Interdisciplinary Stem Cell Institute University of Miami Miller School ...

Interdisciplinary Stem Cell Institute

University of Miami Miller School of Medicine

Executive Briefing Spring 2011

Front coverStem cells and neurons in culture from the lab of Jeffrey Goldberg. Dr. Goldberg’s team is investigating the interaction between stem cells and neurons in the retina. Cell therapy has the potential to treat patients with vision loss due to macular degeneration and other retinal diseases.

Interdisciplinary Stem Cell Institute University of MiamiMiller School of Medicine

Executive Briefing Spring 2011

TRANSFORMATIVE MEDICINEISCI leads the nation in cardiac stem cell clinical trials, pioneering the use of regenerative therapies in patient treatment.

Contents

Message from the Director . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Executive Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Proven Model to Accelerate the Translation of Stem Cell Research into Regenerative Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

The Need to Expand Clinical Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Renowned Scientific and Medical Leadership . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Background and Mission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

A Growing Research Enterprise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10

Key Recent Accomplishments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .13

Extramural Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14

Collaborative Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15

Clinical Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15

Financial Report . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16

Impact . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19

Governance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

Faculty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

Biosketches of the Interdisciplinary Stem Cell Institute’s Primary Investigators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

Members of the Interdisciplinary Stem Cell Institute . . . . . . . . . . . . . . . . . . . . 33

Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38

Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

Report of the Scientific Advisory Board . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

Select Scientific Publications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

Recent Press . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57

Dr. Alan Heldman, Dr. Juan P. Zambrano and team perform percutaneous, trans-endocardial injection of stem cells into a patient with heart failure. Results of this study, recently published in the journal Circulation Research, show reduced heart size, reduced scar tissue, and improved function to injured heart areas.

6 ISCI Executive Briefing Spring 2011

Message from the Director

Many eras have witnessed medical breakthroughs that revolutionize the health of society. Just a few examples include vaccination, antibiotics, modern surgery, and chemotherapy. Although each of these discoveries have led to quantum leaps in patient care and longevity, new problems always arise that dominate human health. For example, infectious disease was the leading cause of death in the late 19th and early 20th century. The introduction of sterile technique and antibiotics changed that, and in the process, paved the way for what is now the current major obstacle in health: chronic diseases such as cancer, cardiovascular disease and neuro-logic disease. Stated differently, the major health risk to today’s popula-tion is from diseases caused by permanent injury to the cells that make up our tissue, maladies affecting all organs including the brain, heart, liver, kidney, bone marrow, bone and skin.

This problem poses the greatest challenge—and opportunity—for modern medicine: can we develop therapeutic strategies to heal these chronic diseases? Indeed, we seem to be on the verge of major progress in this area. The past decade’s research into stem cell biology is poised to yield new cell-based therapies that can address for the first time actual tissue repair and recovery that can restore an organ’s function back to-wards normal and—in the process—treat chronic disease.

The Interdisciplinary Stem Cell Institute (ISCI) at the University of Miami Miller School of Medicine was formed in 2008 to find solutions for medicine’s most challenging problems. ISCI is founded upon three principles: Translational Research, Transdisciplinary Collaboration, and Transformative Medicine.

ISCI’s philosophy is that translational research—moving discover-ies from the lab to the patient—must be conducted ethically, safely and rapidly to provide science and society with critical health benefits as soon as possible. And we have done just that with a series of early stage clinical trials in multiple disease areas that have advanced greatly the insights and opportunities for cell based therapy. Our clinical trials are done in such a way so that we advance our knowledge of potential treatments for patients in the clinic while also advancing our scientific understanding of the basic biology of these treatments and diseases in the lab.

In addition to cutting edge research, we believe greatly that transdis-ciplinary collaboration—work between different medical disciplines such as neurology and oncology—can accelerate medical breakthroughs. So, for example, the identical cells being used to treat heart failure may also treat stroke victims or neonates suffering from poor lung development. ISCI is designed to foster those connections across disease specialties.

Finally, our approach is designed to transform medicine. While we are conducting rigorous and ethical basic and translational science, we are also addressing the ethics of this new area of medicine and evaluating the impact of this new therapy on the economics of health care delivery.

Thank you so much for your interest in ISCI and in our endeavor. We welcome your partnership and support as we strive to transform medi-cine in a way that enhances the health and welfare of our society, now and in the future. And we hope you find the information in this report interesting and informative.

Yours truly,

Dr. Joshua M. Hare

Dr. Joshua Hare with a patient from a cardiac clinical trial. He was the first patient in the first clinical trial testing the safety of delivering bone marrow cells via catheter to heart muscle damaged by a heart attack.

ISCI Executive Briefing Spring 2011 7

Executive Summary

The advent of stem cell therapy as a means to reconstruct damaged tissues and prevent the negative impact of aging on the human organism will one day benefit and lengthen countless lives. The Interdisciplinary Stem Cell Institute (ISCI), founded in 2008 at the University of Miami Miller School of Medicine, is on the cutting-edge of translating stem cell research into therapies. ISCI’s goal is spearheading cell based therapies for a host of untreatable diseases, including diseases of the heart, bone, blood, kidney, nervous system and eyes, as well as cancer and diabetes.

Proven Model to Accelerate the Translation of Stem Cell Research into Regenerative Therapy

ISCI leads in the initiation and enrollment of patients in cardiac stem cell clinical trials. According to ISCI’s Scientific Advisory Board, ISCI succeeded, thus far, in enrolling the largest cohort of patients in the nation for treating heart disease with stem cell therapies. A publication by Dr. Joshua M. Hare, ISCI Founding Director, and Dr. Alan Heldman, Interventional Cardiologist, entitled “Intramyocardial Stem Cell Injection in Patients with Ischemic Cardiomyopathy: Functional Recovery and Reverse Remodeling,” documented for the first time that stem cells injected into enlarged hearts reduced heart size, reduced scar tissue, and improved function to injured heart areas. This publication was accepted within five days for inclusion in the March 18, 2011, issue of Circulation Research, a leading journal of the American Heart Association.

ISCI’s landmark success in moving from the bench to the beside novel therapies for heart disease demonstrates a clear translational path that is a model for other diseases. In addition to four studies in treating heart disease, a fifth study treats patients with chronic wounds and yet another study is planned to treat stroke patients.

All clinical trials at ISCI have a solid, rigorous base in stem cell biology research. ISCI labs collaborate and share findings on a weekly basis. A snapshot of lab research includes: Cardiac Cell Signaling; Stem Cell Biology; Bone Marrow Stem Cells and the Microenvironment of Chronic wounds; Neuronal Regenerative Ganglion Cells; the Role of Endothelial Progenitor Cells in Hypertension; and Adult Stem Cell Transplantation.

The Cell Manufacturing Lab (CML) housed within ISCI accelerates the treatment of stem cell therapies by processing human autologous and allogeneic mesenchymal stem cells (MSC). The lab—a cellular Good Manufacturing Practice facility—isolates and expands MSCs and many other cell types, preparing them for injection into patients enrolled in clinical trials and for their use in pre-clinical trial studies in small and large animals.

ISCI’s 14 primary investigators and 41 scientists and physicians representing 15 academic departments at the Miller School of Medicine. Members expand the opportunities to collaborate in new areas of research engineering new cross-disciplinary solutions. ISCI’s future growth is likely to include the transition from institute to the Department of Cellular and Regenerative Therapies, providing an academic home for investigators focused on regenerative medicine, stem cell therapeutics, and stem cell biology research. A departmental structure will transcend the traditional organ system based organization of academic medicine.

Transcatheter, transendocardial delivery of stem cells to the damaged heart. ISCI scientists are at the forefront of catheter delivery technology, anticipating the day when transcatheter cell therapy for heart disease will benefit large segments of the population.


The Need to Expand Clinical Trials ISCI’s primary investigators receive $6.1 million in annual extramural

funding, which represents a compound growth rate of 40% since ISCI’s inception in 2008. Recently, Dr. Hare received the highest score awarded by the National Institutes of Health (NIH) for a stem cell therapy grant. ISCI scientists and physicians are translating science into the clinical setting without primary industry support. Research is driven by the desire to find cures for common and uncommon diseases irrespective of the therapy’s initial potential for commercialization and profit.

Additional research could include a number of diseases, such as Idiopathic Pulmonary Fibrosis, Alzheimer’s, and Chronic Kidney Disease. Government grants fall short of providing capital for expertise, infrastructure, and the primary research that seeds FDA approval for Investigational New Drugs tested in clinical trials. Philanthropy has the opportunity to set into motion late-stage preclinical trial research for a number of incurable diseases.

Renowned Scientific and Medical LeadershipISCI is led by Dr. Joshua Hare, a pioneer in the field of translational

stem cell research as well as one of the world’s leading clinicians for congestive heart failure. The Institute’s governance includes three boards that advise Dr. Hare. Members of the Scientific Advisory Board are lead-ing national and international scientists from world-renowned institu-tions, including Harvard, University of Maryland, University of Toronto, Cincinnati Children’s Hospital Medical Center, and Hadassah University.

Members of the Governing Board of Directors and the Platform Advisory Committee are leading ISCI and University of Miami Miller School of Medicine scientists and physicians, including Dean Pascal J. Goldschmidt and Dr. Ralph L. Sacco, Professor of Neurology, Epide-miology and Human Genetics and President of the American Heart Association.

ISCI InvestigatorsEvangelos Badiavas, M.D., Ph.D. leads the laboratory on

researching cutaneous wound healing and regeneration. He is the primary investigator on the first human trial administering bone marrow stem and progenitor cells to patients.

Chunming Dong, M.D. researches atherosclerosis and endothelial progenitor cells. He is also the Director of the Center for Medical Relations in China and the Medical Director for Asia in the International Medicine Institute.

Jeffrey L. Goldberg, M.D., Ph.D. leads the laboratory focused on neuronal regenerative ganglion cells. His group is using nanotechnology and magnetopheresis in their quest to cure blindness.

James M. Grichnik, M.D., Ph.D. is the Director of the Melanoma Program, the deadliest form of skin cancer. He is focused on developmental stem and germ cell pathways expressed in melanoma.

Kenneth W. Goodman, Ph.D., F.A.C.M.I. is the Director of the Bioethics Program and Co-Director of the University of Miami Ethics Programs. The Ethics Programs are designated as a World Health Organization (WHO) Collaborating Center in Ethics and Global Health Policy, one of six in the world and the only one in the United States.

Alan W. Heldman, M.D. is an Interventional Cardiologist and Vice Chief of Cardiology at the Miller School of Medicine. He is a world-renowned expert in the treatment and prevention of coronary artery disease and pioneer in cardiac stem cell catheter-delivery systems.

Head MRI reveals large areaof brain tissue damaged bystroke. Neurologist Dileep Yavagal, collaborating with cell biologist Ian McNiece and cardiologist Joshua Hare, is showing major reductions in stroke size due to stem cell infusion.


Ray E. Hershberger, M.D. is Associate Chief of Cardiology, Director of the Advanced Heart Failure Therapies Program, and Director of Translational Cardiovascular Genetic Medicine. He is the principal investigator of the Familial Dilated Cardiomyopathy Research Project.

Tan A. Ince, M.D., Ph.D. researches how characteristics of breast cancer tumors depend on their cells of origin.

Michael S. Kapiloff, M.D., Ph.D., F.A.H.A. is the Director of the Cardiac Signal Transduction and Cellular Biology Laboratory. His group is particularly interested in the role that multimolecular signaling complexes play in the regulation of cellular function.

Krishna Komanduri, M.D. is the Director of the Sylvester Stem Cell Transplantation Program. His group aims to better understand how the immune system functions in order to coax T cells into maintaining their beneficial immunologic functions, without attacking the host.

Ian McNiece, Ph.D. is the Director of the Experimental and Clinical Cell-Based Therapies Program. His group provides the infrastructure to rapidly translate novel stem cell products from research to clinical therapeutic applications.

Claudia Rodrigues, M.S., Ph.D. is investigating the molecular mechanisms involved in neoangiogenesis - the development of new blood vessels from pre-existing ones.

Ivonne H. Schulman, M.D. is focused on mechanisms by which aging impairs the cardiovascular regenerative capacity of mesenchymal stem cells (MSCs) as well as cardiac, renal, and endothelial progenitor cells.

David Min Suk Seo, M.D. is Co-Medical Director of Clinical Informatics and the Director of the Genomics Registry. He is exploring the use of MSCs to repair atherosclerosis.

TRANSLATIONAL RESEARCHISCI specializes in translating research from the lab to the clinic and back to the lab – simultaneously advancing basic scientific discoveries and novel medical therapies.


Regenerative medicine is an emerging multidisciplinary field involving biology, medicine, and engineering that will revolutionize approaches to treating patients and broadly improve human health and the quality of life. With the ability of stem cells to develop into specialized tissue cells, understanding fundamental features of stem cell biology and harnessing this regenerative potential into high impact treatments for devastating diseases are some of the high priorities of current basic and clinical science. The Interdisciplinary Stem Cell Institute of the Miller School of Medicine aims to generate therapeutics for the repair and regeneration of damaged and diseased organs. Today, research into regenerative medicine is invariably a transdisciplinary exercise, bringing together clinicians from every medical and surgical discipline, and incorporating basic scientists with expertise in biochemistry, molecular biology, stem cell biology, and computer science. The interactions promoted by ISCI’s establishment dramatically increase the potential of cross-fertilization between disciplines.

ISCI houses a comprehensive research program aimed at fostering the translation of basic stem cell biology into stem cell therapeutics and regenerative medicine for the use in patients as quickly as is ethical and efficacious. Through the repair and replacement of non-functional tissues, we expect that stem cells will provide the basis for the future treatment of diseases such as myocardial infarction (heart attack), poor wound healing, vascular dysfunction, spinal cord injury, blindness, arthritis, diabetes and cancer. Realization of these goals requires a commitment to the translation of the basic mechanisms underlying developmental biology and regenerative medicine into therapeutic strategies that will repair and restore organ function in patients.

The study of stem cell therapeutics and regenerative medicine is considered by many to be the most important field of research in medicine in nearly seventy-five years. This is recognized nationally by the formation of new departments at major medical schools, the initiation of new professional journals, and the targeting of major funding through the National Institutes of Health (NIH) and other agencies. The study and translation of stem cell therapies offers new and innovative approaches to curing human disease, offering solutions that meet major unmet medical needs. The Interdisciplinary Stem Cell Institute of the Miller School of Medicine is committed to the development of these therapies for the benefit and well-being of all humanity.

Background and Mission

Reconstructed blood vessel due to MSC infusion in a damaged heart. The cells with pink dots in their nucleus are injected mesenchymal stem cells that have regenerated a new blood vessel. The idea for this research came from observations made from clinical trial data.


A Growing Research Enterprise

❍❍ The Interdisciplinary Stem Cell Institute was chartered by the University of Miami Faculty Senate in March, 2008. Based at the oldest medical school in South Florida and serving a population exceeding 7 million, ISCI is the leading stem cell institute in Florida and the dominant presence in this discipline in South Florida.

❍❍ Since July, 2009, ISCI is housed on the eighth and ninth floors of the new Biomedical Research Building (BRB) within 26,000 sq. ft. that includes laboratory space, tissue culture rooms, general equipment rooms, administrative and faculty offices. The GMP laboratory began operation after receiving Clinical Laboratory Improvement Amendments (CLIA) certification from the Agency for Healthcare Administration (AHCA) in January, 2010, followed that summer by the Large Animal Imaging Facility.

❍❍ ISCI includes a large group of clinicians and researchers who are experts in the areas of clinical medicine where regenerative therapeutics is rapidly becoming important. With the recruitment of 14 independent in-house investigators and 41 affiliated junior and non-resident faculty members, we have established an unparallel presence in the state of Florida in the field of regenerative medicine.

❍❍ In its first two years of its existence, ISCI has enjoyed major growth in extramural funding, membership, and high priority publications, despite decreasing overall federal and non-govermental support for biomedical research.

❍❍ The external scientific advisory board of ISCI noted in October, 2010, that ISCI scientists have the largest national impact on cardiac stem cell therapy in the United States.


ISCI Faculty MembershipISCI’s faculty has grown to 55, representing 15 departments at the University of Miami

ISCI Scientific Research PlatformsPercentage Per Primary Platform Affiliation

TRANSDISCIPLINARY COLLABORATIONISCI fosters partnerships across disciplines, cross-fertilizing among different scientific fields to accelerate new breakthroughs.


Key Recent Accomplishments

❍❍ Scientific accomplishments have been extensive, both in transla-tional and fundamental areas. These include:

❍ Ongoing enrollment in The PercutaneOus StEm Cell Injection Delivery Effects On Neomyogenesis (POSEIDON) trial.

❍ Completion of key milestones in the TAC-HFT (catheter delivery) trial.

❍ Approval of the POSEIDON in Dilated Cardiomyopathy protocol by the FDA and UM Internal Review Board. An NHLBI grant was awarded, receiving the highest priority score given.

❍ Initiation of enrollment of patients in wound healing trial.

❍ Approval of “A Pilot Study of the Administration of Mesenchymal Stem Cells in the Treatment of Chronic Wounds” clinical protocol by the FDA.

❍ Multiple scientific publications, including many high impact and collaborative papers.

❍❍ ISCI faculty serve on NIH and other national and international study sections and boards of major scientific organizations and present at national and international scientific conferences, advancing UM’s scientific stature and influence in the field.

❍❍ To date, 55 full-time faculty members of the Miller School of Medicine have been granted membership within ISCI. Of these faculty members, 14 are occupying labs within Biomedical Research Building (BRB). ISCI membership now represents 15 academic departments in the Miller School of Medicine, the School of Engineering, and the Miami Veterans Affairs Healthcare System.

❍❍ ISCI has recently developed key programs in areas such as orthopedics, vascular surgery, and neurology, programs which are housed outside the BRB.

❍❍ Governance procedures have been introduced, with three ongoing advisory boards consisting of ISCI investigators, senior leaders from the UM Miller School, community members and international scientific leaders.

❍❍ ISCI cellular Good Manufacturing Practice c(GMP) laboratory initiated operations and received Foundation for the Accreditation of the Cellular Therapy (FACT) accreditation in March, 2011. It also has received the Agency for Healthcare Administration (AHCA) accreditation.

❍❍ A documentary entitled “Stem Cell Therapy: Healing Force of the Future” focused on ISCI’s translational pipeline as part of the Breakthrough Medicine series and received a 2010 Suncoast Regional Emmy.

The receptor for Growth Hormone Releasing Hormone (GHRHR) found in cardiac cells. Working in experimental models, Nobel Prize winning endocrinologist Andrew V. Schally, cardiologist Joshua Hare and their team found that administering GHRH after a heart attack resulted in dramatic improvement to damaged cardiac tissue. The discovery will aid future research in both endocrinology and cardiology.


PrinicipalInvestigator

Project Title Co-Investigators Funding Agency

Project Dates

Annual Funding

Hare Cardioprotective Effect Of Growth Hormone Releasing Hormone

Schally NHLBI 1-Jan-201130-Nov-2015

$644,337

Hare Nitroso/Redox Balance In Myocardial Infarction

NHLBI 15-Feb-2009 31-Dec-2013

$408,969

Hare Autologous Adult Myocardial Cardioblasts To Treat Ischemic Heart Failure

McNiece NHLBI 1-Apr-2010 31-Mar-2012

$764,867

Hare Cellular Cardiomyoplasty For Chronic Heart Failure

NHLBI 5-Jul-2007 30-Jun-2012

$382,500

Hare Stem Cells for Dilated Cardiomyopathy NHLBI 1-Jul-20116-Jun-2016

$673,200

Goldberg Kruppel-Like Transcription Factors In Retinal Ganglion Cell Regeneration

NEI 1-Aug-2010 30-Jun-2014

$483,549

Goldberg Retinal Scaffolds: Synaptic And Stem Cell Integration

OD 30-Sep-2009 29-Sep-2011

$380,387

Goldberg Walt and Lilly Disney Award for Amblyopia Research

RPB 1-Jul-2010 30-Jun-2011

$100,000

Goldberg Developmental Control Of Axon Regeneration In RGCs

NINDS 1-Jun-2007 31-May-2011

$298,206

Komanduri Improving Cord Blood Transplant Via Expansion Of Myeloid And Regulatory T Cells

McNiece State of Florida

1-Jul-2010 30-Jun-2015

$240,000

Komanduri Immune Reconstitution After Cord Blood Transplantation

Szabolcs NHLBI 11-Feb-2008 31-Dec-2011

$386,750

Komanduri T Cell Reconstitution After Allogeneic SCT

NCI 28-Sep-2005 31-May-2011

$257,865

Hershberger Familial Dilated Cardiomyopathy: Detection/Gene Mapping

NHLBI 1-May-1998 31-May-2012

$663,954

Kapiloff Role Of The mAKAP Complex In Cardiac Hypertrophy

NHLBI 8-Dec-2003 30-Jun-2015

$382,500

Badiavas Bone Marrow Stem Cells And The Microenvironment Of Chronic Wounds

NIA 15-Jun-2007 29-Feb-2012

$304,303

Rodrigues Molecular Mechanisms Of Stem Cell Engraftment

NHLBI 1-Aug-2010 31-May-2015

$132,163

Rodrigues Mechanisms of Intercellular Communication During Angiogenesis

State Of Florida

1-Jul-2009 30-Jun-2011

$125,000

Li Regulation Of Cardiac Hypertrophy By mAKAP-Calcineurin Complexes

AHA 1-Jul-2010 30-Jun-2014

$77,000

Hu Neurotrophic Effect Of A Novel TrkB Agonist On Retinal Ganglion Cells After Ischemic Axon Injury

AHA 1-Jul-2010 30-Jun-2012

$46,612

Kritzer-Cheren Regulation Of Cardiac Myocyte Camp Levels By The AC5-mAKAP Complex

AHA 1-Jul-2010 30-Jun-2012

$21,770

Total Extramural Funding $6,773,932

Extramural Funding


Collaborative Funding With Non-ISCI Principal Investigators

PrinicipalInvestigator

Project Title Co-Investigators Funding Agency

Project Dates

Annual Funding

Young Epigenomic Mapping In Human Tumor Stem Cells

Ince NCI 21-Aug-2009 30-Jul-2014

$640,619

Daley Comparative Phenotypic, Functional, And Molecular Analysis Of ESC And IPSC

Ince NHLBI 30-Sep-2009 31-Aug-2011

$1,683,978

Marban Cellular Cardiomyoplasty For Acute And Chronic Ischemic Cardiomyopathy

Hare, McNiece NHLBI 30-Sep-2005 31-Aug-2011

$2,523,072

Beecham Individualized Risk Stratification Using The Genomic Contribution

Seo NHLBI 8-Sep-2010 31-May-2015

$757,801

Total Collaborative Funding $5,605,470

Clinical Trials

Start Date Status Study Title Phase Division

03/10/08 Active, Not Recruiting

A Phase I/II, Randomized, Double-Blinded, Placebo-Controlled Study of the Safety and Efficacy of Intramyocardial Injection of Autologous Human Mesenchymal Stem Cells (MSCs) in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction (MI) Undergoing Cardiac Surgery for Coronary Artery Bypass Grafting (CABG). [20070598 - NIH/NHLBI - Hare | See “Prometheus” at ClinicalTrials.gov]

I/II Cardiology

5/1/09 Enrolling A randomized Study to Evaluate to the Safety of Bone Marrow Aspirate Plus Cultured Bone Marrow Cells Versus Bone Marrow Aspirate Alone Versus Cultured Bone Marrow Aspirate Cells Alone in the Treatment of Chornic Wounds [20080299 - NIH/NIA - Badiavas]

I/II Dermatology

7/14/08 Enrolling A Phase I/II, Randomized, Double-Blinded, Placebo-Controlled Study of the Safety and Efficacy of Transendocardial Injection of Autologous Human Cells (Bone Marrow or Mesenchymal) in Patients with Chronic Ischemic Heart Failure Secondary to Myocardial Infarction. The Transendocardial Autologous Cells (hMSC or hBMC) in Ischemic Heart Failure Trial (TAC-HFT) [20070443 - Biocardia - Heldman | See “TAC-HFT” at ClinicalTrials.gov]

I/II Cardiology

8/20/07 Enrolling Gene Expression Profiling and Prognosis in Cardiomyopathy [20070495 - Intramural - Hare]

N/A Cardiology

9/10/07 Enrolling A Phase II, multi-center, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of PROCHYMAL® (ex vivo cultured adult human mesenchymal stem cells) intravenous infusion following acute myocardial infarction: The Osiris 403 study [20090602 - OSIRIS - HELDMAN | See “Osiris” at ClinicalTrials.gov]

II Cardiology

9/21/09 Enrolling A Phase I/II, Randomized Pilot Study of the Comparative Safety and Efficacy of Transendocardial Injection of Autologous Mesenchymal Stem Cells Versus Allogeneic Mesenchymal Stem Cells in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction. The Percutaneous Stem Cell Injection Delivery Effects On Neomyogenesis Pilot Study (The POSEIDON-Pilot Study) [20090352 - NIH-NHLBI BioCardia - Hare | See “Poseiden” at ClinicalTrials.gov]

I/II Cardiology


The Interdisciplinary Stem Cell Institute (ISCI) is a transdisciplinary institute which fosters and houses cutting edge basic and translational research oriented towards regenerative medicine. Fiscal Year 2010 (FY10) was the Institute’s first full year of operation in its new location within the Biomedical Research Building (BRB).

Based on combined operations budget for FY10, ISCI is projecting that its total budget expenses for FY11 will be approximately $8.06 Million (M), which represents a 13.3% increase over FY10. ISCI’s research programs will rely more on grant revenues and less on start-up funds in FY11, in keeping with its transition from start-up mode. The cGMP facility is on a three year plan to transition reliance from chair-package funding to grants and contracts for cell production. ISCI expects contract revenue to increase from $90,000 to $308,000 from FY10 to FY11, an impressive increase of 342%. Accordingly, ISCI has been highly successful in initiating a trajectory of growth and scientific excellence despite the current financial challenges.

ISCI’s financial plan for FY11 continues this trajectory and needs for expansion have been selected only in essential areas. This coming year is a pivotal year for ISCI, since moving into the Biomedical Research Building (BRB). ISCI will see a nearly 90% allocation of BRB 8th and 9th floors by the first quarter of FY11. Investing in a new facility is essential to meet projected growth in members, to increase revenues from self-sustaining programs, and to support all of ISCI’s research platforms and deliver the innovative team-based approach to learning. Maximizing ISCI’s facility is also critical towards our efforts to recruit and retain leading faculty, while building stronger ties to the business community.

ISCI investigators have been highly successful in receiving both governmental and agency awards for funding research endeavors. However, one of ISCI’s main goals during this fiscal year was to support and promote each principal investigators. Each investigator was expected to submit at least one grant per cycle, thus increasing overall funding opportunities for the Institute. ISCI has actively encouraged grant submissions from newly recruited research faculty and existing faculty with adequate time devoted to research, in order to increase government funding. In addition, ISCI has encouraged extramural research funding from public and private sources, to be able to increase research funded by industry sources as well as private foundations. In addition to a large increase in federal funding, ISCI has also had large increases in Florida State grant support and has had success in obtaining a shared instrumentation grant for a cardiac bi-plane, which was delivered in the fourth quarter of FY10.

Financial Report

$0

$1,000,000

$2,000,000

$3,000,000

$4,000,000

$5,000,000

FY2010FY2009FY2008

ISCI NIH funding increased by 66.8% in FY 2009-2010


Trends of Total ISCI Investigator Funding

All Sponsored Activities NIH Sponsored Activities


NOGA electroanatomical map of the left ventricle of the heart. This technology is used to localize scar tissue for stem cell injection.

Impact

Impact of ISCI on Training and Mentorship at The University of Miami Miller School of Medicine

❍ Several junior faculty have achieved crucial early-stage funding for regenerative medicine projects, including K08 awards (Rodrigues) and an internal UM award (Yavagal).

❍ Numerous ISCI post-docs and trainees advanced to UM clinical training programs.

❍ Junior faculty have had important publications in their fields resulting from their work at ISCI (Young).

Impact of ISCI on NIH Funding ❍ Total funding increased over 51.4% relative to FY09.

This increase is an underestimate given the number of awards still residing within home departments.

❍ A significant number of major new awards are antici-pated to be funded in the upcoming council, reflecting ISCIs ongoing track record. These include the new RC4 program.

❍ ISCI research benchmarks compare very favorably to school averages.

Clinical Impact of ISCI at UHealth ❍ ISCI clinical trial programs have a major effect on pa-

tient referrals to UHealth. ❍ The University of Miami research office has calculated

that 13 patients are referred for every patient enrolled in an ISCI clinical trial.

❍ The cardiac clinical trial program enrolled 58 patients in FY10 resulting in 502 referrals.

❍ On average, each patient referred to UHealth and not enrolled generates approximately $6,275 in clinical revenue.

❍ ISCI has received major local and national press, raising its profile with the public as a leader in this cutting edge field and drawing patients from around the nation. ISCI faculty are frequently asked for comment in major news media, in-cluding ABC News, CNN and Time Magazine, and in the most prestigious scientific journals such as Nature and Circulation on the issues surrounding the stem cell field.

Impact of ISCI on South Florida Economy ❍ There are 87 ISCI employed faculty and staff. ❍ 107 jobs have been created in South Florida due to the

inception of ISCI.

Collaborations ❍ Biological Delivery Systems. ❍ Kardia Therapeutics, Inc. – NIH STTR 5R42HL080888

Adult Human Progenitor Cells for Cardiac Regeneration. ❍ Biocardia – providing catheters for TAC-HFT and

POSEIDON trials. ❍ Proteonomix – providing regulatory support and cellular

manufacturing for ongoing clinical trial.


ISCI administration includes three levels of governance. All governing boards advise Dr. Joshua M. Hare, Founding Director, Interdisciplinary Stem Cell Institute.

Governing Board of DirectorsThe ISCI Governing Board of Directors (GAB) oversees and provides

input on ISCI governance and operations, ensuring a clear vision and strategic direction, setting goals and policies. In addition, the GAB identifies collaborative leadership and effective partnerships, assists in fundraising and government and community relations, identifies novel therapies that have commercial potential for possible spin-off companies and reviews the performance of ISCI and its Director. Members of the GAB include:

Eduardo C. Alfonso, M.D., Professor of Ophthalmology, Kathleen and Stanley J. Glaser Chair in Ophthalmology, Chairman, Department of Ophthalmology, Director, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine.

W. Dalton Dietrich, III, Ph.D., Professor of Neurological Surgery, Neurology and Cell Biology and Anatomy, Scientific Director, The Miami Project to Cure Paralysis.

Pascal J. Goldschmidt, M.D., Senior Vice President and Dean, Chief Executive Officer, University of Miami Health System.

Joshua M. Hare, M.D., F.A.C.C., F.A.H.A., Louis Lemberg Professor of Medicine, Founding Director, Interdisciplinary Stem Cell Institute.

Norma S. Kenyon, Ph.D., Martin Kleiman Professor of Surgery, Microbiology & Immunology and Biomedical Engineering, Diabetes Research Institute, Executive Director, Wallace H. Coulter Center for Translational Research, Senior Associate Dean for Translational Science, University of Miami Miller School of Medicine.

Jeffrey D. Molkentin, Ph.D., Professor, Howard Hughes Medical Institute, Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center.

Ralph L. Sacco, M.D., M.S., F.A.H.A., F.A.A.N., Professor of Neurology, Epidemiology and Human Genetics, Olemberg Family Chair in Neurological Disorders, University of Miami Miller School of Medicine, Chief of Neurology Services, Jackson Memorial Hospital.

H. Allan Shore, Esq., Partner, Wealth Transfer Co-Chair, Bilzin, Sumberg, Baena, Price, & Axelrod, LLP.

Bernard Siegel, Founder and Executive Director, Genetics Policy Institute.

Scientific Advisory Committee The ISCI Scientific Advisory Committee (SAC) provides recommen-

dations on all scientific, technical and policy issues and on future devel-opments required to maintain ISCI’s scientific and technical productivity at the highest possible level. The SAC reviews existing and proposed new programs, considering the mix of scientific research platforms and their ancillary laboratories and equipment. Members of the SAC include:

Piero Anversa, M.D., Director Center for Regenerative Medicine, Professor of Medicine, Brigham and Women’s Hospital, Harvard Medical School.

Governance

Progenitor cells isolated from the kidney differentiate into endothelial cells and form vascular networks in vitro. Dr. Ivonne Schulman, Dr. Joshua Hare, and their team have isolated kidney-derived progenitor cells and are studying their ability to differentiate into various kidney cell lineages, with the goal of developing cell-based therapies for kidney diseases.

Melanoma cells engineered to have red chromosomes, blue spindles, and turn green when instability pathways are turned on. James Grichnik is studying this genomic instabilty, which is a hallmark of cancer and a problem for stem cells.


Curt Civin M.D., Associate Dean for Research, Director, Center for Stem Cell Biology & Regenerative Medicine, Professor of Pediatrics, University of Maryland, School of Medicine.

Joshua M. Hare, M.D., F.A.C.C., F.A.H.A., Louis Lemberg Professor of Medicine and Founding Director, Interdisciplinary Stem Cell Institute.

Armand Keating, M.D., Professor of Medicine, Director, Center for Stem Cell Biology & Regenerative Medicine, University of Toronto in Toronto, Canada.

Jeffery D. Molkentin, Ph.D., Professor, Howard Hughes Medical Institute, Cincinnati Children’s Hospital Medical Center, Molecular Cardiovascular Biology.

Joseph Wu, M.D., Ph.D., Assistant Professor in the Department of Medicine (Cardiology) and Department of Radiology at the Stanford School of Medicine.

Benjamin Reubinoff M.D. Ph.D., Director, The Hadassah Human Embryonic Stem Cell Research Center, Sidney Swartz Chair in Human Embryonic Stem Cell Research, The Department of Gynecology and The Goldyne Savad Institute of Gene Therapy, Hadassah University Medical Center, Jerusalem, Israel.

Platform Advisory Committee The ISCI Platform Advisory Committee (PAC) ensures that the vision

of the SAC and GAB is executed across platform activities. Comprised of faculty members, the PAC identifies collaborations and effective partnerships as important means for quality enhancement, adding value and continuous improvement to ISCI Platforms. In addition, the PAC identifies novel therapies that have commercial potential for possible spin-off companies and makes recommendations regarding research on emerging therapies using stem cells. PAC members include:

Herman Cheung, Ph.D., James L. Knight Professor of Biomedical Engineering, Senior VA Research Career Scientist, Professor of Medicine and Orthopedic Surgery.

Robin N. Fiore, Ph.D., Associate Professor (pending), Department of Medicine, Co-Director, Ethics Program.

Kenneth W. Goodman, Ph.D., F.A.C.M.I., Bioethics Program Director and Co-Director, Ethics Programs.

James M. Grichnik, M.D., Ph.D., Professor, Department of Dermatology and Cutaneous Surgery, Director, Melanoma Program.

Joshua M. Hare, M.D., F.A.C.C., F.A.H.A., Louis Lemberg Professor of Medicine and Founding Director, Interdisciplinary Stem Cell Institute.

Michael S. Kapiloff, M.D., Ph.D., F.A.H.A., Associate Professor, Division of Cardiology, Departments of Pediatrics and Medicine, Director, Cardiac Signal Transduction and Cellular Biology Laboratory.

Krishna Komanduri, M.D., Director, Sylvester Stem Cell Transplantation Program, Associate Director, Translational Research, Miami Transplant Institute, Jackson Memorial Hospital.

Ian K. McNiece, Ph.D., Professor of Medicine, Department of Medicine, Director, Experimental and Clinical Cell Based Therapies Program.

Dileep R. Yavagal, M.D., Assistant Professor of Clinical Neurology and Neurosurgery, Director of Interventional Neurology, Co-Director of Endovascular Neurosurgery.

MSCs differentiating into fat cells in vitro. MSCs have the capacity to differentiate into multiple cell lineages, including fat cells. Understanding the mechanisms directing cell differentiation are key to the development of organ specific cell-based therapies and are the research focus of ISCI laboratories.

MSCs differentiating into bone cells in vitro. Exploring the potential of MSCs to differentiate into bone forming cells will lead to innovative stem cell-based therapies for osteoporosis.


ISCI faculty intellect and talents represent the broadest scope of modern translational research and include the areas of fundamental basic science, clinical expertise and specialization necessary for a well-rounded approach to discovering the treatments for common complex human diseases. Faculty members are medical doctors and/or doctors of philosophy. They have expertise ranging from molecular biology to bioethics. In addition, the faculty has diverse clinical expertise including licensed, board-certified cardiologists pediatricians, neurologists, internists, and psychiatrists. Described below are the established investigators who direct in-house ISCI laboratories.

Evangelos Badiavas, M.D., Ph.D.Dr. Evangelos Badiavas is the Director of the Interdisciplinary Stem

Cell Institute Laboratory on Cutaneous Wound Healing and Regenera-tion. He received his B.A. in Biochemistry from Rutgers College in New Brunswick, New Jersey. He went on to obtain a Ph.D. in Pharmacology at Thomas Jefferson University in Philadelphia, PA where he worked under the direction of Dr. Hideko Kaji studying gene expression in bone mar-row stem cells. After graduate school he began a postdoctoral fellowship under the direction of Drs. Jaimie Caro and Alan Erslev, the discoverer of erythropoietin, at the Cardeza Institute, Jefferson Medical College, Philadelphia, PA. During his postdoctoral fellowship, he was also enrolled in medical school at Jefferson Medical College, Philadelphia, PA. After obtaining his M.D. degree from Jefferson Medical College, he went on to an internship in Internal Medicine at the Medical College of Pennsylvania and then completed a residency in Dermatology at the Uni-versity of Miami Miller School of Medicine. After finishing his residency in Dermatology, Dr. Badiavas completed a fellowship in Dermatopathol-ogy at the University of Miami Miller School of Medicine. Following his training and obtaining board certification in Dermatology and Der-matopathology, he became an Assistant Professor of Dermatology and Cutaneous Surgery at the University of Miami Miller School of Medicine. He later took academic positions at Boston University School of Medi-cine and Brown University School of Medicine. In 2008, Dr. Badiavas returned to Miami to join the Interdisciplinary Stem Cell Institute and is currently Associate Professor of Dermatology and Cutaneous Surgery at the University of Miami Miller School of Medicine. He has been the recipient of several research awards and funding from the American So-ciety for Dermatologic Surgery, Dermatology Foundation, and National Institutes of Health. He has served as a reviewer for several funding agencies including the Department of Defense and National Institutes of Health. He has also serves as a reviewer for many dermatology, wound healing and basic science journals.

Dr. Badiavas’ research efforts involve the treatment of chronic wounds and other skin diseases with bone marrow cells. He was the principal investigator on the first human trial administering bone mar-row stem and progenitor cells to patients. He was first to report on bone marrow stem cell trafficking and differentiation in wounds in a rodent model. He holds two IND’s from the FDA for the treatment of chronic wounds using bone marrow cells. He is the principal investigator on a

Faculty

Evangelos Badiavas

Opposite PagePositive results from the first clinical trial for non-healing wounds using cultured bone marrow cells. The study’s principal investigator, Evangelos Badiavas, was also the first to report on bone marrow stem cell trafficking and differentiation in wounds in animal models.


federally funded award examining the mechanisms of bone marrow cells in wound healing. He currently has two open clinical trials for patients with chronic wounds that have failed to heal by basic and advanced treat-ments. In addition, his laboratory focuses on the cutaneous delivery of stem and progenitor cells for the treatment of systemic disorders.

Kowalcz yk J and Badiavas EV: Bone Marrow Adult Stem and Progenitor Cells in the Treatment of Chronic Wounds. Advances in Wound Care 2010, (1) 490-494.

Badiavas EV, Ford D, Liu P, Kouttab N, Morgan J, Richards A, Maizel A: Long term bone marrow culture and its clinical potential in chronic wound healing. Wound Repair Regeneration 2007, Nov;15(6):856-865.

Luo L, Badiavas E, Luo JZ, Maizel A: Allogeneic bone marrow supports human islet beta cell survival and function over six months. Biochem Biophys Res Commun 2007, Oct 5;361(4):859-64.

Chunming Dong, M.D., F.A.C.C.Chunming Dong, M.D., F.A.C.C., Associate Professor of Medicine is

a board-certified physician in internal medicine and general cardiology. Dr. Dong is an outstanding scientist with a track record of productive research in molecular and cellular biology, vascular biology, epigenomics, genomics and cell therapeutics. He is an author of more than 44 peer-reviewed articles, including those published in top-notch journals, such as Molecular Cell, PNAS, PLoS Medicine, Circulation Research and Circulation. His current research focuses on the role of DNA methylation and microRNAs in regulating stem cell senescence and atherosclerosis development. At the Miller School, Dr. Dong is also the Director of the Center for Medical Relations in China and the Medical Director for Asia in the International Medicine Institute. Dr. Dong is spearheading a program to establish the University of Miami’s international medicine programs and facilities in China; he also liaises the exchange between UHealth specialists and Chinese patients.

Zhu S, Malhotra A, Zhang L, Deng S, Zhang T, Freedman NJ, Storms R, Peppel K, Goldschmidt-Clermont PJ, and Dong C. Human umbilical cord blood endothelial progenitor cells decrease vein graft neointimal hyperplasia in SCID mice. Atherosclerosis 2010, Sep:212 (1):63-9.

Zhu S, Evans S, Yan B, Povsic TJ, Tapson V, Goldschmidt-Clermont PJ, and Dong C. Transcriptional regulation of Bim by FOXO3a and Akt mediates sclero-derma serum-induced apoptosis in endothelial progenitor cells. Circulation 2008, Nov 18;118(21):2156-65.

Zhu S, Liu X, Li Y, Goldschmidt-Clermont PJ, Dong C. Aging in the Atheroscle-rosis Milieu May Accelerate the Consumption of Bone Marrow Endothelial Progenitor Cells. Arteriosclerosis, Thrombosis, and Vascular Biolog y 2007, Jan;27(1):113-9.

Jeffrey L. Goldberg, M.D., Ph.D.Dr. Goldberg is an Associate Professor of Ophthalmology, with sec-

ondary appointments in Cell Biology and Anatomy, Program in Neuro-science, and the Department of Molecular and Cellular Pharmacology. Dr. Goldberg’s laboratory is investigating the developmental control of axon growth by retinal ganglion cells and other central nervous system neurons as they try to explain why retinal ganglion cells fail to survive and regenerate after injury. He uses a combination of cellular and mo-lecular approaches to address these questions.

Retinal degeneration often end with the death of retinal neurons, such as the rod and cone cells that sense light in age-related macular degen-eration and retinitis pigmentosa, and retinal ganglion cells in glaucoma. Although it may be possible to salvage these cells before they die, for

Chunming Dong


the many patients who have lost these cells, we must figure out a way to replace them. Dr. Goldberg’s group is approaching these problems from multiple directions. For example, they are studying the molecular signals that regulate how neural progenitor cells differentiate into particular neural cell fates, including proteins like Math5 that regulate gene expres-sion in the eye. Recently, it was demonstrated that in adult humans, a small population of stem cells reside at the edge of the retina, called the ciliary marginal zone. Dr. Goldberg is optimizing the isolation of these retinal progenitor cells and studying how these cells proliferate, differ-entiate, and integrate into adult retinas in culture. They expect that their experiments will lead to a method for the biopsy, isolation and growth of retinal progenitor cells. In preparation for stem cell transplantation, Dr. Goldberg’s group is utilizing nanotechnology. They hope to use “mag-netopheresis,” or magnetic field-induced cellular translocation, to direct retinal progenitor cells into their proper retinal locations, to enhance cell replacement therapies. Ultimately, such nanoparticles could also be man-ufactured to contain critical drugs or trophic factors to further enhance stem cell survival, differentiation, or integration into the diseased retina.

Moore DL, Blackmore MG, Hu Y, Kaestner KH, Bixby JL, Lemmon VP, Goldberg JL. KLF Family Members Regulate Intrinsic Axon Regeneration Ability. Science 2009, Oct 9;326(5950):298-301.

Blackmore MG, Moore DL, Smith RP, Goldberg JL, Bixby JL, Lemmon VP. High Content Screening of Cortical Neurons Identifies Novel Regulators of Axon Growth. Molecular and Cellular Neuroscience 2010, May;44(1):43-54.

Goldberg JL, Klassen MP, Hua Y, Barres BA. Amacrine-Signaled Loss of Intrinsic Axon Growth Ability by Retinal Ganglion Cells. Science 2002, Jun 7;296(5574):1860-4.

James M. Grichnik, M.D., Ph.D.James M Grichnik, M.D., Ph.D. is a Professor of the Department of

Dermatology and Cutaneous Surgery. Dr. Grichnik, an expert in early detection of melanoma, was recruited from Duke University where he served as the Director of the Melanocytic Diseases Section in the Divi-sion of Dermatology for 14 years.

Melanoma is the deadliest form of skin cancer. It develops in cells that give rise to skin pigment cells called melanocytes. Melanocytes produce melanin, which protects skin from ultraviolet light and provides skin its natural pigment or color. Benign clusters of melanocytes are called moles (or nevi) malignant clusters of melanocytes are melanoma. Dr. Grichnik’s research efforts are focused on developmental stem and germ cell pathways expressed in melanoma that may serve both to specifically identify lethal tumors and serve as targets for therapy. “In our basic research laboratory we are working toward the development of improved tumor markers and new therapeutic approaches by focusing our attention on understanding the basic developmental biology of melanoma. We have determined that melanoma tumors are best viewed as developmental systems (a heterogeneous collection of cells, generally attempting to dif-ferentiate toward pigment cells).” These tumors include a sub-population of cells with stem-cell-like features. The tumor stem cells have the capac-ity to differentiate towards a number of different developmental direc-tions including germ cell pathways. “We believe that it is the expression of the germ cell pathways that allow the cancer process to progress. Our laboratory is currently focusing on germ cell pathway protein expression as markers of lethal tumors and therapeutic targets. We are especially interested in meiomitosis, a process we theorize causes genomic instabil-ity due to the collision of meiosis and mitotic pathways. We are utilizing

Jeffrey L. Goldberg

James M. Grichnik


fluorescence based tools and confocal microscopy to visualize chromo-some dynamics during malignant progression.”

Dr. Grichnik received his baccalaureate from Washington University in St Louis, his Ph.D. in Cell Biology from Baylor College of Medicine College and his medical degree from Harvard University. He completed a medical internship at Beth Israel Hospital in Boston and dermatology residency at Duke University.

Ross AL, Sanchez MI, Grichnik JM. Molecular Nevogenesis, Dermatolog y Research and Practice, in press 2011.

Grichnik JM. Stratum corneum RNA levels are diagnostic for melanoma, British Journal of Dermatolog y (commentary, in press 2011).

Grichnik JM. Melanoma, Nevogenesis, and Stem Cell Biolog y, Journal of Investiga-tive Dermatolog y 2008, Oct;128(10):2365-80.

Joshua M. Hare, M.D.Dr. Joshua Hare is the founding Director of the University of Miami

Interdisciplinary Stem Cell Institute, the Louis Lemberg Professor of Medicine and Professor of Molecular and Cellular Pharmacology, and Biomedical Engineering. He has obtained over 20 Million dollars in NIH funding (including multiple R01s, a U54 and a P20 award) over the past decade to support basic research of cell therapy strategies, has published more than 175 original research articles, editorials, and review articles, and holds three Food and Drug Administration Investigational New Drug (IND) for cell therapy in patients with heart disease. Dr. Hare has enrolled the largest cohort of patients in novel stem cell trials for heart disease in the United States, studying multiple delivery systems and cell types. Dr. Hare has an extensive track-record of translational research, performing studies in both experimental systems, preclinical animal models and in humans. He is extensively involved in clinical studies of new therapies for congestive heart failure, in research involving gene expression profiling in heart failure, and is a leader in the application of new stem cell-based cardiac therapies. Prior to coming to University of Miami, Dr. Hare was Professor of Medicine and Biomedical Engineer-ing and Director of the Cardiac Transplant and Heart Failure Program at Johns Hopkins University School of Medicine. At Johns Hopkins, Dr. Hare directed the NHLBI-funded Johns Hopkins Specialized Center for Cellular Therapeutics and the Cardiobiology section of the Johns Hop-kins Institute for Cell Engineering (ICE), and was an investigator in the Donald W. Reynold’s Center for Translational Research.

Dr. Hare is an internationally recognized cardiologist and stem cell scientist and chairs the Cardiac Contractility and Heart Failure (CCHF) study section of the National Institutes of Health and the stem cell working group of the American Heart Association. He sits on multiple advisory boards, guiding stem cell initiatives at the NIH and at profes-sional societies.

Williams, AR, Trachtenberg B, Velazquez DL, McNiece I, Altman P, Rouy D, Mendizabal AM, Pattany PM, Lopera GA, Fishman J, Zambrano JP, Heldman AW, Hare JM. Intramyocardial stem cell injection in patients with ischemic cardiomy-opathy: Functional recovery and reverse remodeling. Circulation Research, 2011;108:792-296

Hatzistergos KE, Quevedo HC, Oskouei BN, Hu Q, Feigenbaum GS, Margitich IS, Mazhari R, Boyle AJ, Zambrano JP, Rodriguez JE, Dulce RA, Pattany PM, Valdes D, Revilla C, Heldman AW, McNiece I, Hare JM. Bone marrow mesenchy-mal stem cells stimulate cardiac stem cell proliferation and differentiation. Circulation Research 2010,107;913-22.

Joshua M. Hare


Kanashiro-Takeuchi RM, Tziomalos K, Takeuchi LM, Treuer AV, Lamirault G, Dulce R, Hurtado M, Song Y, Block NL, Rick F, Klukovits A, Hu Q, Varga JL, Schally AV, Hare JM. Cardioprotective effects of growth hormone-releasing hormone agonist after myocardial infarction. Proceedings of the National Academy of Sciences, U S A 2010, 107(6):2604-9.

Hare JM, Traverse JH, Henry TD, Dib N, et al. A randomized, double–blind, placebo–controlled, dose–escalation study of intravenous adult human mesenchymal stem cells (Prochymal™) following acute myocardial infarction. Journal of the American Col-lege of Cardiolog y 2009, 54:2287-2289.

Barouch LA, Harrison RW, Skaf MM, Rosas GO, Cappola TP, Kobeissi ZA, Hobai IO, Lemmon CA, O.Rourke B, Rodriguez ER, Burnett A, Huang PL, Lima JAC, Berkowitz DE and Hare JM. Nitric oxide regulates the heart by spatial confine-ment of nitric oxide synthase isoforms. Nature 2002, 416:337-339.

Alan W. Heldman, M.D. Alan W. Heldman, M.D., is a Professor of Medicine and Vice Chief

of Cardiology. Educated at Harvard College, University of Alabama at Birmingham School of Medicine, and trained in internal medicine, car-diovascular disease, and interventional cardiology all at Johns Hopkins University, Dr. Heldman spent 12 years on the faculty in cardiology at Johns Hopkins, where he was director of Interventional Cardiology Inno-vation & Research, a high volume interventional operator, and associate professor of medicine.

Dr. Heldman was a member of the first team to produce and test an effective drug-eluting stent, and he is expert in the treatment and pre-vention of coronary restenosis. He is involved with the development of new techniques to treat myocardial infarction and heart failure with the catheterdelivery of stem cells to the heart. His clinical practice focuses on techniques for a number of interventional problem areas, including procedures in the elderly, in vein graft disease, in acute myocardial infarc-tion, and in patients with vascular disease. He also coordinates a multi-disciplinary clinical effort for the evaluation and care of patients with hypertrophic cardiomyopathy.

Williams, AR, Trachtenberg B, Velazquez DL, McNiece I, Altman P, Rouy D, Mendizabal AM, Pattany PM, Lopera GA, Fishman J, Zambrano JP, Heldman AW, Hare JM. Intramyocardial stem cell injection in patients with ischemic cardiomy-opathy: Functional recovery and reverse remodeling. Circulation Research, 2011;108:792-296

Ghersin E, Soto V, Heldman AW. Multidetector computerized tomography can guide and document alcohol septal ablation in hypertrophic obstructive cardiomyopathy. Circulation 2011, Jan 18;123(2):e5-7.

Heldman AW, Wu KC, Abraham TP, Cameron DE. Myectomy or alcohol septal ablation: Surgery and percutaneous intervention go another round. Journal of the Ameri-can College of Cardiolog y 2007, Jan 23;49(3):358-60.

Ray E. Hershberger, M.D.Ray E. Hershberger, M.D., is Professor of Medicine, Associate Chief

of Cardiology, Director of the Advanced Heart Failure Therapies Pro-gram, and Director of Translational Cardiovascular Genetic Medicine. Dr. Hershberger received his medical degree from the University of Nebraska College of Medicine and trained in internal medicine at the Washington Hospital Center in Washington, D.C. and the University of Kansas School of Medicine. He completed fellowships in Cardiology at the University of Utah and cardiac transplant at the Utah Cardiac Trans-plant Program in Salt Lake City, Utah. Before joining the University of Miami, Dr. Hershberger served as the Director of Cardiac Transplanta-

Alan W. Heldman

tion at the Oregon Health & Science University in Portland, Oregon. He is the founder and principal investigator of the Familial Dilated Cardio-myopathy Research Project that seeks to identify and understand the genetic causes of cardiomyopathy and heart failure.

Norton N, Li D, Rieder MJ, Sieg fried JD, Rampersaud E, Zuchner S, Mangos S, Gonzalez-Quintana J, Wang L, McGee S, Reiser J, Martin E, Nickerson DA, and Hershberger RE. Genome-wide Studies of Copy Number Variation and Exome Sequencing Identify Rare Variants in BAG3 as a Cause of Dilated Cardiomyopathy. The American Journal of Human Genetics 2011, Mar 11;88(3):273-82.

Morales A, Painter T, Li R, Sieg fried JD, Li D, Norton N, Hershberger RE. Rare Variant Mutations in Pregnancy-Associated or Peripartum Cardiomyopathy. Circulation 2010, May 25;121(20):2176-82.

Hershberger RE, Norton N, Morales A, Li D, Sieg fried JD, and Gonzalez-Quin-tana, J. Coding Sequence Rare Variants Identified in MYBPC3, MYH6, TPM1, TNNC1, and TNNI3 From 312 Patients With Familial or Idiopathic Dilated Cardiomyopathy. Circulation: Cardiovascular Genetics 2010, Apr;3(2):155-61.

Tan A. Ince, M.D., Ph.D.Dr. Tan Ince is an Associate Professor Pathology who recently joined

the faculty from Harvard University. Dr. Ince’s research focuses on the role of cell-of-origin in determining tumor phenotype and development of culture systems for in vitro culture of primary human tissues and tumors. The normal human breast tissue has many different cell types; among these, Dr. Ince and colleagues converted two different normal human breast cell types into tumorigenic cells through the introduction of an identical set of gene mutations. The resulting tumors differed sig-nificantly despite having identical DNA mutations. The tumors created from one cell type (BPECs) exhibited the typical features of tumor stem cells (TSC) and formed tumors in mice when only 10 cells were injected. These cells formed adenocarcinoma-like tumors in mice associated with desmoplastic reaction similar to human breast tumors, and frequently metastasized to the lungs. In contrast, the tumors derived from another normal breast cell type (HMECs) formed squamous carcinomas with no desmoplastic reaction, never spread to other organs and required injection of 100,000 cells to form tumors in mice. Since these cells were ostensibly isogenic, Ince and colleagues concluded that the phenotypic differences of these tumors, including the dramatic difference in the fre-quency of TSC-like cells result from epigenetic differences between their different normal cell origins. The follow up studies that expand on this initial work are designed to describe the histone modification and DNA methylation patterns that are associated with tumor phenotypes and tumor stem cells. Additional areas of investigation in this laboratory are examination of heat shock protein (HSP) influence on ovarian and breast tumor stem cell phenotype, development of genetically engineered hu-man malignant mesothelioma and ovarian carcinoma models, analysis of cell origin influence on the phenotype of induced pluripotent stem cells (iPS), and development of culture systems for carcinoid tumors, adenoid cystic carcinoma, ovarian and breast carcinomas.

Lin MC, Lomo L, Baak JP, Eng C, Ince TA, Crum CP, Mutter GL. Squamous morules are functionally inert elements of premalignant endometrial neoplasia. Modern Patholog y 2009, Feb;22(2):167-74.

Elmasri H, Karaaslan C, Teper Y, Ghelfi E, Weng M, Ince TA, Kozakewich H, Bischoff J, Cataltepe S. Fatty acid binding protein 4 is a target of VEGF and a regula-tor of cell proliferation in endothelial cells. FASEB Journa 2009, Nov;23(11):3865-73.

Chan EM, Ratanasirintrawoot S, Park IH, Manos PD, Loh YH, Huo H,

Ray E. Hershberger

Tan A. Ince


Miller JD, Hartung O, Rho J, Ince TA, Daley GQ, Schlaeger TM. Live cell imaging distinguishes bona fide human iPS cells from partially reprogrammed cells. Nature Biotechnolog y 09 Nov;27(11):1033-7.

Michael S. Kapiloff, M.D., Ph.D.Dr. Kapiloff is the Director of the Cardiac Signal Transduction and

Cellular Biology Laboratory and an Associate Professor of Medicine and Pediatrics. Prior to joining the University of Miami, Dr. Kapiloff was an Assistant Professor of Pediatrics at the Oregon Health and Science University in Portland. Dr. Kapiloff received his B.A from The Johns Hopkins University in 1984 and his Ph.D. in Biomedical Sciences in 1991 after completing his dissertation in the laboratory of Dr. M. Geoffrey Rosenfeld, a member of the National Academy of Sciences at the Univer-sity of California, San Diego. He graduated from UCSD with a Doctor-ate of Medicine in 1992 and then completed a residency in Pediatrics at Primary Children’s Medical Center and the University of Utah in 1995. In 1997, Dr. Kapiloff became a Research Assistant Professor, performing research in the laboratory of Howard Hughes Medical Institute Investiga-tor Dr. John Scott at the Vollum Institute in Portland, OR. Although Dr. Kapiloff was at one time a Board-Certified General Pediatrician, he is currently involved in full-time basic science.

Research in Dr. Kapiloff’s lab targets the elucidation of the signal transduction pathways of heart muscle cells along with the role that multimolecular signaling complexes play in the regulation of cellular function. Intracellular signal transduction is mediated by a network of molecules that are often ubiquitous and widely distributed. It is the par-ticular combination of these protein kinases, phosphatases, ion channels and other types of macromolecules that defines the individual signaling pathway and the specific cellular response to each unique extracellular stimulus. An emerging concept in the field of signal transduction is the existence of nodes within this network where multiple signaling pathways converge and share common molecules, thereby facilitating crosstalk be-tween pathways. Molecules that participate in these centers of integration are of special therapeutic interest. The Cardiac Signal Transduction and Cellular Biology Laboratory at the University of Miami Miller School of Medicine is committed to the elucidation of the signal transduction path-ways within the cardiac myocyte and stem cell progenitors. In particular, we are interested in the role that multimolecular signaling complexes play in the regulation of cellular function.

Dodge-Kafka, K.L., Soughayer, J., Pare, G.C., Michel, J.J.C., Langeberg, L.K., Kapiloff, M.S., and Scott, J.D. The Protein Kinase A Anchoring Protein mAKAP Co-ordinates Two cAMP Effector Pathways. Nature 2005, Sep 22;437(7058):574-8.

Kapiloff, M.S.*, Piggott, L.A., Sadana, R., Li, J., Heredia, L., Henson, E., Efendiav, R. and Dessauer, C.W.* An Adenylyl Cyclase-mAKAP Signaling Complex Regulates cAMP Levels in Cardiac Myocytes. Journal of Biological Chemistry 2009, Aug 28;284(35):23540-6.

Li, J., Negro, A., Lopez, J., Bauman, A.L., Henson, E., Dodge-Kafka, K.L., and Kapiloff, M.S. The mAKAP Scaffold Regulates Cardiac Myocyte Hypertrophy via Recruitment of Activated Calcineurin. Journal of Molecular and Cellular Cardiolog y 2010, Feb;48(2):387-94.

Krishna Komanduri, M.D.Krishna Komanduri, M.D., Professor of Medicine, Microbiology and

Immunology is the Director of the UM/Sylvester Stem Cell Transplanta-tion Program and associate director of translational research at the Mi-ami Transplant Institute at Jackson Memorial Hospital. Prior to joining

Michael S. Kapiloff


the UM faculty, Dr. Komanduri was a physician-scientist who cared for stem cell transplant recipients and performed research in human T cell immunology at M.D. Anderson’s Department of Stem Cell Transplanta-tion and Cellular Therapy. His research focus is in immune reconstitution after stem cell transplantation and human T cell immunity to pathogenic viruses and fungi, and in characterizing how subsets of T cells may medi-ate post-transplant complications. Dr. Komanduri’s lab was among the first to apply novel techniques in functional immune assessment by flow cytometry to study virus-specific T cells and those capable of recognizing foreign tissues.

For patients with high-risk or relapsed multiple myeloma, lymphoma and many subsets of leukemia, stem cell transplantation, performed by infusing donor grafts containing both stem cells and T cells following the administration of chemotherapy to the recipient with cancer, remains the standard of care. While stem cell transplantation offers the best chance of cure for these patients, scientific challenges remain. Stem cell grafts obtained from either the peripheral blood or marrow contains T cells, which normally play a key role in protecting healthy individuals and cancer patients from infections. T cells contained in donor stem cell products may also attack residual cancer cells, performing a critical function in maintaining remissions in stem cell transplant recipients. However, the benefits may stop there for some patients. Those same T cells that have helped rebuild the stem cell transplant patient’s immunity and attack the residual cancer may also turn on healthy tissue in the recipient. That phenomenon, called graft vs. host disease, is a primary area of interest for Dr. Komanduri. Work in his laboratory is aimed at trying to better understand how the immune system functions, in order to coax T cells into maintaining their beneficial immunologic functions, without attacking the host. Unfortunately, the risk of graft vs. host disease also requires the use of closely matched donors for potential recipients, excluding many current patients from potentially lifesaving treatment options. Dr. Komanduri is working with other ISCI scientists to improve outcomes in cord blood transplantation, a promising alternative for patients lacking such donors. By engineering stem cell grafts to contain an optimal combination of blood-forming stem cells and subsets of T cells with desired properties, stem cell transplantation would become safer and more effective, and be available to a wider range of patients, including those lacking sufficiently matched donors to allow them to be safely transplanted today. Dr. Komanduri’s expectation is that multidisciplinary research in stem cell biology, immunology and clinical transplantation will provide a brighter future for patients facing life-threatening cancers of the blood and marrow.

Kim TK, St John LS, Wieder ED, Khalili J, Ma Q, Komanduri KV. Human late memory CD8+ T cells have a distinct cytokine signature characterized by CC chemokine production without IL-2 production. Journal of Immunolog y 2009, Nov 15;183(10):6167-74.

Kim TK, Billard MJ, Wieder ED, McIntyre BW, Komanduri KV. Co-engagement of alpha(4)beta(1) integrin (VLA-4) and CD4 or CD8 is necessary to induce maximal Erk1/2 phosphorylation and cytokine production in human T cells. Human Immunol-og y 2010, Jan;71(1):23-8.

Decker WK, Xing D, Li S, Robinson SN, Yang H, Steiner D, Komanduri KV, Shpall EJ. Th-1 polarization is regulated by dendritic-cell comparison of MHC class I and class II antigens. Blood 2009, Apr 30;113(18):4213-23.

Krishna Komanduri


Ian McNiece, Ph.D.Dr. Ian McNiece is ISCI’s Director of the Experimental and Clinical

Cell-Based Therapies Program. Prior to joining the faculty, he was at Johns Hopkins University where he was Professor of Oncology, and also served as the Director of the Graft Engineering Laboratory at Johns Hopkins Medicine and chaired the Division of Biomedical Sciences, Johns Hopkins in Singapore. He received his Ph.D. in 1986 from the University of Melbourne undertaking his thesis work in studies of blood cell development at the Peter MacCallum Cancer Institute in Melbourne. An Australian by birth, McNiece is internationally renowned for his contributions as a researcher in stem cell biology and clinical marrow and stem cell transplantation. He trained at Melbourne University in Australia, where he received his B.Sc. in Biochemistry (1979), an M.Sc. (1981) and Ph.D. (1986) degrees in Physiology. He completed his thesis work at the Peter MacCallum Cancer Institute in Melbourne. McNiece subsequently came to the United States as a postdoctoral fellow at the University of Virginia. In 1988, he joined Amgen,Inc., Thousand Oaks, California, as a Research Scientist and became Laboratory Head in the Department of Developmental Hematology in 1994. In 1995, he was appointed to head the Amgen Central Laboratory at Saint Luc University Hospital in Belgium. Before joining Johns Hopkins Medicine, as a professor, McNiece worked at the University of Colorado Health Science Center where he was Director of Research for the Bone Marrow Transplant Program and Director of the Stem Cell Biology Program.

Dr. McNiece directs the Experimental and Clinical Cell-Based Therapies Program that provides the infrastructure to rapidly translate novel stem cell products form research to clinical therapeutic application. The central feature of the program is the cGMP manufacturing faculty housed on the 9th floor of the Biomedical Research Building. In the Clinical Development Laboratory, Dr. McNiece scales up processes for all cellular manufacturing, develops standard operating procedures and undertakes validation studies for IND submission. Dr. McNiece’s group also provides support for preclinical validation and animal models, assisting faculty in the identification of cGMP reagents for clinical applications, process development, and production of cellular products for large animal models and testing. His program provides regulatory consultation and oversight for IND submissions and the production of human cell products.

The research focus of Dr. McNiece’s laboratory is stem cell biology with an emphasis on the applications of mesenchymal stem cells for therapeutic approaches to regenerative medicine. His laboratory has pioneered procedures for ex vivo expansion of cord blood products used in bone marrow transplantation and he currently working to develop clinical trials to utilize expansion of cord blood in clinical protocols.

Hatzistergos K, Quevedo H, Oskouei BN, Hu Q, Freigenbaum GS, Margitich IS, Mazhari R, Boyle AJ, Zambrano PJ, Rodriguez JE, Pattany PM, Valdes D, Revilla C, Heldman AW, McNiece IK, Hare JM. Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation. Circulation Research 2010, Oct 1;107(7):913-22.

Wang Y, Nathanson L, McNiece IK. Differential hematopoietic supportive potential and gene expression of stromal cell lines from midgestation mouse placenta and adult bone marrow. Cell Transplantation. In Press.

McNiece IK. Ex vivo expansion of cord blood hematopoietic cells. Umbilical Cord Blood: A future for regenerative medicine. S. Kadereit, G. Udolph, eds., World Scientific Publishing Co, Singapore. 2010. pp. 77-88.

Ian McNiece

Claudia O. Rodrigues, Ph.D.Dr. Claudia Rodrigues is a Research Assistant Professor of Molecular

and Cellular Pharmacology. Dr. Rodrigues’ laboratory is investigating the molecular mechanisms involved in neoangiogenesis--the development of new blood vessels from pre-existing ones.

The vascular system supplies all organs in the body with oxygen and nutrients required for tissue survival. Lack of blood supply such as what occurs during myocardial infarction can lead to tissue death. Induction of neovascularization is a major approach currently being tested for tissue survival and regeneration. Dr. Rodrigues’ group targets neoangiogenesis from two different aspects. In one approach, she is trying to determine the intracellular mechanisms involved in endothelial cell functions required for neoangiogenesis and activation mechanisms after endothelial stimulation. These include basement membrane degradation, migration and proliferation. In another approach, her group is studying the crosstalk between progenitor cells and endothelial cells to find the molecular determinants of this activation process. Recently, it has been demonstrated that progenitor cells can differentiate into endothelial and smooth muscle cells which can assemble into new blood vessels. However, progenitor cells can also be found incorporated in the vicinity of blood vessels, suggesting that they might have a stimulatory role. As part of this approach, Dr. Rodrigues’ group is developing new methods to improve stem cell engraftment after cell transplantation that can prolong their stimulatory properties. They expect that their findings can be applied to conditions in which neoangiogenesis is needed, such as in tissue survival and regeneration. In addition, their findings will also be applied to pathological angiogenic conditions, in which neoangiogenesis must be blocked.

Rodrigues, C. O., Nerlick, S., White, E. L., Cleveland J. L., and King, M. L. A Myc-Twist-Slug Regulatory Circuit Directs Vascular Development. Development 135:1903-1911, 2008.

Ivonne H. Schulman, M.D. Ivonne H. Schulman, M.D. is an Assistant Professor of Clinical

Medicine in the Division of Nephrology and Hypertension at the University of Miami Miller School of Medicine. Dr. Schulman received her medical degree from the University of Miami. She completed her internship, residency, and nephrology clinical and research fellowships at University of Miami/Jackson Memorial Hospital and Veterans Affairs Medical Center and joined the University of Miami School of Medicine faculty in 2004. In addition to working as a clinical nephrologist and hypertension specialist, Dr. Schulman is a researcher with expertise in vascular biology, including basic mechanisms underlying cardiovascular and renal injury in animal models of aging, hypertension, and diabetes. She has previously studied the interaction between estrogen and the insulin-like growth factor-1 system in the progression of diabetic renal disease as well as the role of renal progenitors in the development of diabetic glomerulosclerosis. In addition, she has investigated the interaction between the renin-angiotensin system, nitric oxide, and estrogen in hypertensive and age-related cardiovascular and renal injury. Her current research focuses on mechanisms by which aging impairs the cardiovascular regenerative capacity of mesenchymal stem cells as well as cardiac, renal, and endothelial progenitor cells, particularly the role of the renin-angiotensin system and oxidative stress.

Claudia O. Rodrigues

Ivonne H. Schulman


Schulman IH, Aranda P, Raij L, Veronesi M, Aranda FJ, Martin R. Surgical Menopause Increases Salt Sensitivity of Blood Pressure. Hypertension, 47: 1168-1174, 2006.

Schulman IH, Zhou M-S, Jaimes EA, Raij L. Dissociation between Metabolic and Vascular Insulin Resistance in Aging. American Journal of Physiolog y: Heart and Circulatory Physiolog y, 293: H853-H859, 2007.

Schulman IH, Zhou MS, Treuer AV, Chadipiralla K, Hare JM, Raij L. Altered Renal Expression of Angiotensin II Receptors, Renin Receptor, and ACE-2 Precede the Development of Renal Fibrosis in Aging Rats. American Journal of Neprholog y, 32(3): 249-261, 2010.

David Min Suk Seo, M.D.David Seo, M.D. is Associate Professor of Medicine in the Division

of Cardiology at University of Miami Miller School of Medicine. He serves as Co-Medical Director of Clinical Informatics and Director of the Genomic Medicine Registry for the School of Medicine. Dr. Seo received his medical degree from Duke University. He completed his internship and residency at the Beth Israel Deaconess Medical Center of Harvard Medical School and returned to Duke for his cardiology fellowship. On completion of his cardiology fellowship, he remained on faculty at Duke University Medical Center in the Division of Cardiovascular Medicine prior to coming to the University of Miami School of Medicine. In addition to working as a clinical cardiologist, Dr. Seo is a researcher using genomic technologies to determine the genes that contribute to cardiovascular disorders such as coronary artery disease and atrial fibrillation. He is exploring the use of bone marrow derived stem cells to repair atherosclerosis.

Seo D, Goldschmidt-Clermont PJ, Velazquez O and Beecham G. Genomics of premature atherosclerotic vascular disease. Current Atherosclerosis Reports 2010, May;12(3):187-93.

Clarke J and Seo D. An ensemble approach to improved prediction from multitype data. Institute of Mathematical Statistics Collections 3:302-317, 2008.

Karra R, Vemullapalli S, Dong C, Herderick EE, Song X, Slosek K, Nevins JR, West M, Goldschmidt-Clermont PJ, Seo D. Molecular evidence for arterial repair in atherosclerosis. Proceedings of the National Academy of Sciences, U S A 2005, Nov 15;102(46):16789-94

ISCI MEMBERSEvangelos V. Badiavas, M.D., Ph.D.Associate ProfessorDepartment of Dermatology & Cutaneous Surgery

Wayne E. Balkan, Ph.D.Research Associate ProfessorDepartment of Medicine

Cara Benjamin, Ph.D. Research Assistant ProfessorDepartment of Medicine

Nanette H. Bishopric, M.D.Professor of Pharmacology, Medicine and PediatricsDirector, University of Miami / Florida Heart Research Institute Cardiovascular Genomics Laboratory

David Min Suk Seo


Norman L. Block, M.D.Professor of Urology, Oncology and Biomedical EngineeringDepartment of Urology

Mary Bartlett Bunge, Ph.D.Christine E. Lynn Distinguished Professor in NeuroscienceProfessor, Cell Biology & Anatomy, Neurological Surgery and NeurologyThe Miami Project to Cure Paralysis

Herman S. Cheung, Ph.D. James L. Knight Professor of Biomedical EngineeringSenior VA Research Career ScientistProfessor of Biomedical Engineering, Medicine, and Orthopedic Surgery

Jose Santos Da Silva, Ph.D. Associate Scientist , Walter H. Coulter Center for Translational Research

W. Dalton Dietrich, Ph.D., IIIScientific Director, The Miami Project to Cure ParalysisKinetic Concepts Distinguished Chair in NeurosurgerySenior Associate Dean for Discovery of ScienceProfessor, Neurological Surgery, Neurology and Cell Biology and Anatomy

Gianluca D’Ippolito, Ph.D.Research Assistant Professor GRECC Investigator, University of Miami Tissue Bank Department of Orthopaedic Surgery

Chunming Dong, M.D., F.A.C.C.Associate Professor of Medicine, Cardiovascular Division

Shahnaz Duara, M.D. Professor of Pediatrics, Obstetrics & GynecologyMedical Director, Neonatal Intensive Care Unit

Robin N. Fiore, Ph.D.Associate Professor of Medicine (pending)Co-Director, Ethics Program

Joel E. Fishman, M.D. Associate Professor of RadiologyDirector, UM Miller School of Medicine Radiology Services

Eli Gilboa, Ph.D.Dodson Professor of Microbiology and ImmunologyDirector, Dodson Interdisciplinary Immunotherapy InstituteCo-leader, Tumor Immunology Research ProgramUM/Sylvester Cancer Center

Marilyn K. Glassberg, M.D.Associate Professor of Medicine and Surgery

Jeffrey L. Goldberg, M.D., Ph.D.Associate Professor of Ophthalmology, Cell Biology and Anatomy, Molecular and Cellular Pharmacology


Kenneth W. Goodman, Ph.D., F.A.C.M.I.Professor of Medicine and PhilosophyDirector, Bioethics Program

James M. Grichnik, M.D., Ph.D.Professor, Department of Dermatology and Cutaneous SurgeryDirector, Melanoma Program

Joshua M. Hare, M.D., F.A.C.C., F.A.H.A.Louis Lemberg Professor of MedicineProfessor of Molecular & Pharmacology, and Biomedical EngineeringFounding Director, Interdisciplinary Stem Cell Institute

Alan W. Heldman, M.D., F.S.C.A.I.Professor of Medicine, Interventional CardiologyVice Chief, Cardiovascular Division

Ray E. Hershberger, M.D.Professor of MedicineAssociate Chief, Cardiovascular Division Director of Advanced Heart Failure

Qinghua Hu, M.D., Ph.D.Assistant Professor of Medicine, Cardiovascular Division

Tan Ince, M.D., Ph.D. Associate Professor of Pathology Director, Tumor Stem Cell Division, Interdisciplinary Stem Cell Institute

Rosemeire M. Kanashiro-Takeuchi, D.V.M., Ph.D.Research Assistant Professor of Pharmacology

Michael Kapiloff, M.D., Ph.D., F.A.H.A.Associate Professor of Pediatrics and Medicine, Cardiovascular DivisionDirector, Cardiac Signal Transduction and Cellular Biology Laboratory

Lee D. Kaplan, M.D.Associate Professor of Clinical OrthopaedicsChief of UHealth Sports Medicine Division

Norma S. Kenyon, Ph.D., Martin Kleiman Professor of Surgery, Microbiology & Immunology and Biomedical Engineering, Diabetes Research InstituteExecutive Director, Wallace H. Coulter Center for Translational ResearchSenior Associate Dean for Translational Science, University of Miami Miller School of Medicine.

Gary I. Kleiner, M.D.,Ph.D.Associate Professor of Pediatrics and Surgery

Krishna Komanduri, M.D. Professor of Medicine and Microbiology & ImmunologyDirector, Sylvester Stem Cell Transplantation ProgramAssociate Director, Translational Research, Miami Transplant Institute

Duanxiang Li, M.D., M.S. Assistant Professor of Medicine, Cardiovascular Division


Zhao-Jun Liu, M.D., Ph.D.Research Assistant Professor, Department of Surgery

Ian K. McNiece, Ph.D.Professor of MedicineDirector, Experimental and Clinical Cell Based Therapies Program

Paula V. Monje, Ph.D.Research Assistant Professor Department of Neurological SurgeryThe Miami Project to Cure Paralysis

Dominique L. Musselman, M.D., M.S. Associate Professor of Clinical Psychiatry, Department of Psychiatry & Behavioral SciencesDirector, Adult Consultation-Liaison Service Jackson Memorial Hospital

Seigo Nishida, M.D. Professor of Clinical SurgeryAssociate Director of the Adult Intestinal Transplant Program

Nadine Norton, Ph.D. Research Assistant Professor of Medicine, Cardiovascular Division

Pradip M. Pattany, Ph.D. Research Associate ProfessorChief, Section of MR Physics

Damian D. Pearse, Ph.D.Associate Professor of Neurological SurgeryThe Miami Project to Cure Paralysis

Claudia Rodrigues, M.S., Ph.D.Research Assistant ProfessorDepartment of Molecular and Cellular Pharmacology

Andrew V. Schally, Ph.D., MDhc (Multi), D.ScDistinguished Medical Research Scientist Head of The Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center Distinguished Leonard M. Miller Professor of PathologyProfessor of Hematology, Oncology Recipient of The Nobel Prize in Physiology or Medicine 1977

Paul Schiller, Ph.D.Research Associate ProfessorDepartments of Medicine and Biochemistry & Molecular BiologyDirector, Stem Cell Research Program GRECC Veterans Affairs Medical Center

Ivonne H. Schulman, M.D.Assistant Professor of Clinical MedicineDivision of Nephrology and Hypertension


David Min Suk Seo, M.D.Associate Professor of Cardiology Co-Medical Director of Clinical Informatics Director of the Genomic Medicine Registry

Lina A. Shehadeh, Ph.D.Research Assistant Professor Department of Molecular and Cell Pharmacology

Xiaohua Song, M.D.Research Assistant Professor of MedicineCardiovascular Division

H. Thomas Temple, M.D.Professor, Orthopaedics and PathologyVice Chair and Chief, Oncology DivisionDirector, University of Miami Tissue Bank

Andreas G. Tzakis, M.D. Professor of Surgery Director, Liver/GI and Transplant ProgramDiabetes Research Institute

Roberto Vazquez-Padron, Ph.D. Assistant Professor of SurgeryCardiothoracic Transplantation Research Laboratory

Omaida C. Velazquez, M.D. Associate Professor of Surgery Chief, Division of Vascular and Endovascular Surgery

Keith A. Webster, Ph.D. Professor of Pharmacology Director of the Vascular Biology InstituteWalter G. Ross Chair of Vascular Biology

Eric Wieder, Ph.D. Associate Professor of MedicineSylvester Comprehensive Cancer Center Dileep R. Yavagal, M.D.Assistant Professor of Clinical Neurology and NeurosurgeryDirector of Interventional NeurologyCo-Director of Endovascular Neurosurgery

Karen C. Young, M.D.Assistant Professor of Clinical Pediatrics Department of Pediatrics

Juan P. Zambrano, M.D. Assistant Professor of Clinical MedicineAssistant Program Director, Cardiovascular DivisionDirector of the Vascular Section of Interventional Cardiology

Shoukang Zhu, M.D. Research Assistant Professor of Medicine, Cardiovascular Division


ISCI leads the Miller School of Medicine’s effort to

advance the new field of cellular and regenerative

medicine. As such, the Miller School joins with

other leading American medical schools that have

formed vibrant stem cell biology and regenerative

medicine institutes. Recent recruiting efforts

combined with existing strengths in regenerative

medicine provide the opportunity to nurture a

world-class environment for research and education

in regenerative therapeutics. Furthermore, ISCI

has created an academic home for cell-based

therapy research at the University. ISCI has rapidly

become one of the leading centers in the US for

translational research into cell-based therapies. The

overall goal of ISCI is to conduct research that will

impact clinical practice and human health through

the investigation of basic mechanisms of tissue and

cellular regeneration strategies, ultimately helping

large numbers of patients suffering from a panoply

of chronic and incurable diseases.

Summary

Appendix


Report of the Scientific Advisory Board

November 5, 2010

Pascal J. Goldschmidt, MDSenior Vice President for Medical Affairs and DeanMiller School of MedicineUniversity of Miami

Report of the ISCI Scientific Advisory Board

There has been a general consensus among the members of the Scientific Advisory Board (SAB) that the Inter-disciplinary Stem Cell Institute (ISCI) at the University of Miami has achieved in a very short time important targets. The laboratory space, equipment, and Core facilities are of high quality and will allow expansion of personnel and scientific goals. Currently, the cardiovascular component predominates, although most disciplines are represented and are in a phase of rapid growth. The major objective of the ISCI is translational research with a strong mechanistic underpinning which reflects the leadership of the Director, Dr. Joshua Hare.

Dr. Hare has played a critical role in the recruitment and coordination of various independent groups, which make the ISCI a diverse but cohesive structure, covering several aspects of medicine. The board appreciated a strong sense of the collaborative nature of the ISCI research groups, despite the diversity of disciplines.

Dr. Hare has been a pioneer in the implementation of cell therapy in the failing heart and is responsible for sev-eral ongoing clinical trials involving the use of mesenchymal stromal cells in the management of ischemic and non-ischemic cardiomyopathy. The members of the SAB were impressed by the number of patients which have been enrolled and treated with autologous bone marrow-derived stromal cells. To the best of our knowledge, this represents, thus far, the largest cohorts of patients injected with stem cells in the United States.

An additional important point that has to be made relates to the dramatic increase in the number of NIH projects awarded to the ISCI, shortly after its official birth. This success is consistent with the new direction of the NIH that emphasizes strongly the development of strategies positively affecting public health. In particular, one com-ponent needs to be discussed in view of its potential impact on the entire operation, the University of Miami, and the cardiovascular community at large.

With Dr. Hare as principal investigator, the ISCI has acquired a Phase I Cardiac Translational Research Imple-mentation Program (C-TRIP) (P20) sponsored by the NIH. This highly competitive RFA has funded only 12 centers throughout the United States. Data on large animal models and a team of physician scientists has to be in place by April 2011 in order to apply for a Phase II award in support of a clinical trial with an April 1, 2012 starting date. Although the number of ultimately awarded grants is not completely clear, it can be assumed that no more than 2 of the 12 C-TRIP centers will be eventually funded. The members of the SAB feel strongly that the team in Miami led by Dr. Hare has an extremely good chance of succeeding in this effort, bringing to the Institute a five years sponsored NIH clinical trial. This conviction is based on the progress made by the Hare’s group in terms of accumulation of high quality pre-clinical data in large animals and the long-standing experi-ence of Dr. Hare’s team in cell therapy.

The interdisciplinary nature of the ISCI has created a pleasant and stimulating environment which has favored the growth of another outstanding program. Dr. Ince and his collaborators are actively involved in the identifi-


cation and characterization of the cell populations implicated in the homeostasis of normal breast tissue. This work has formed the basis for the recognition of the molecular mechanisms responsible for the acquisition of a malignant cell phenotype and the onset and evolution of breast cancer. This cutting edge research has significant clinical outcome and falls into the major focus of the ISCI. The likelihood to translate this basic science endeavor to the clinic is very high and the members of SAB recommend that this program be supported by the Institution.

Diversity is critical for cross-interaction, and physically adjacent but distinct disciplines facilitate the exchange of reagents, experimental protocols and methods of analysis. Cardiovascular research and cancer research have opposite objectives concerning the modulation of cell growth. Myocyte regeneration is the goal in the treatment of heart failure while cell death and inhibition of cell proliferation constitute the targets of cancer therapy. Addi-tionally, the cardiotoxicity of powerful anticancer drugs has limited the use of effective pharmaceutical com-pounds. The research being conducted at the ISCI may result in the development of novel drugs, which retain high efficacy and avoid unwanted side-effects. However, stem cell therapy may prevent or reverse the pathologi-cal alterations of the myocardium and ventricular dysfunction in cancer patients.

The members of SAB commend Dr. Hare’s vision in assembling a program of great potential biologically and clinically for the two major causes of death in the Western world.

Translational research characterizes the efforts of Dr. Kapiloff’s team as well. The most relevant aspect of the work aims at the recognition of molecular targets to be employed in the development of drugs which interfere with the negative aspects of myocyte remodeling in heart failure. The generation of scaffolds able to disrupt protein-to-protein interaction is complex but extremely novel. The committee was positively impressed by the thoughtful and sophisticated approach assembled by Dr. Kapiloff.

Additionally, the intent to introduce iPS cells as a tool to ask biological questions related to the dilated cardiomy-opathy present in patients carrying mutations in the lamin A/C gene was viewed as an important new direction to be pursued aggressively.

This is another example of the leadership of Dr. Hare. iPS cells are a new powerful class of primitive progenitors which may become a form of cell therapy for the damaged heart and other organs. The autologous nature of iPS cells makes them very attractive and potentially superior to embryonic stem cells clinically.

The possibility to treat acute stroke by infusing mesenchymal stem cells has created great enthusiasm in the members of the SAB. Dr. Yavagal has proposed the intra-arterial route of administration of mesenchymal stro-mal cells as a more efficient strategy to enhance functional recovery and attenuate disability in patients suffering from acute ischemic stroke. The data in small animals were encouraging and the safety results in dogs prompted an IND application.

The Committee is extremely supportive of this line of research and encourages the Institution to help in this endeavor. With respect to other fields, cell therapy in the context of stroke is relatively understudied and efforts should be made to implement this strategy in animal models and later in patients to improve the prognosis of this devastating disease.

The mentorship of Dr. Hare has been perceived as critical in the development of this important area of clinical investigation within the ISCI.

Dr. Seo has been addressing a fundamental question concerning the etiology of atherosclerosis and the potential mechanisms of vascular repair. Whether progenitor cells contribute to vessel wall pathology or have a beneficial effect remains a matter of intense debate in the scientific community. The long-term association and collabora-tion with Dr. Pascal Goldschmidt a leading investigator in this area has helped in developing a clever and insight-ful approach to decipher the complexity of atherogenesis and define strategies that may lead to positive vascular wall remodeling. By combining in vitro and in vivo studies, Dr. Seo has convincingly proven that bone marrow cell therapy interferes with plaque formation in a mouse model of accelerated atherosclerosis.

The SAB committee favorably viewed this program. In fact, it was perceived as very promising and highly rel-evant, since it integrates perfectly with the translational goal of the ISCI and complements the objectives of Dr. Hare’s work.


Dr. Young, an early stage investigator, was an interesting surprise. She presented provocative data pointing to c-kit-positive cells, nested within the wall of pulmonary vessels, as key mediator of the plexiform lesions, and smooth muscle cell accumulation in the arterioles of neonates with pulmonary arterial hypertension (PAH). The quality of the work was superb and raised the challenging possibility that the pathology of PAH may be the result of excessive activation of c-kit-positive progenitor cells in the pulmonary circulation. The findings in the animal model were also remarkable.

Great enthusiasm was felt by the members of SAB for this project. It was apparent that Dr. Hare was extremely supportive of this young, talented physician scientist. The interaction with Dr. Hare will help Dr. Young to ac-quire a completely independent status and pursue successfully this highly important area of research.

Dr. Goldberg, a young investigator of the Bascom Palmer Eye Institute and ISCS, has dramatically advanced our understanding and treatment of patients affected by retinal diseases. He has made important contribution to this field and has obtained independent support from the NIH. The SAB committee found his work of the highest quality and hopes that the Institution will favor the expansion of this program.

In summary, the entire operation of the ISCI is extremely promising and composed of highly qualified estab-lished and young investigators which, under the leadership of Dr. Hare, have a great opportunity to impact on several major human diseases.

However, potential problems were identified concerning the future of the ISCI. These are not scientific in nature, but essentially financial. They involve the need for a commitment from the University of Miami for continuous support for a period of at least five years. Additionally, the Cores are not financially independent and the Univer-sity of Miami should sustain the running expenses.

It was felt that efforts should be made to encourage pilot studies supported by the ISCI to attract young talented investigators across Florida. This strategy may favor expansion of the research program and faculty within the ISCI.

The structure of the ISCI is young, which is viewed as very positive, but vulnerable in these difficult times of funding from the NIH. The possibility to create the number one center in the United States for cell therapy of the failing heart is within reach. Dr. Hare is leading the field and should be given the opportunity to achieve this goal.

The rapid growth in personnel of the Institute will soon make the responsibilities of Dr. Hare difficult to man-age. The SAB committee strongly encourages a national search for an Associate Director. This should not be an internal recruitment. This individual should be chosen from an outside Institution.

Finally and most importantly, the ISCI should be transformed and combined into a Department. The departmen-tal configuration would enhance the stability of the Institute and provide larger financial benefits.

This document has been approvcd by all of the SAB membcrs and is signed by the chairman of this committee.

With kindest regards,

Sincerely,

Piero Anversa MDBrigham and Women’s Hospital, Professor of AnaesthesiaProfessor of MedicineDirector, Center for Regenerative Medicine,Brigham and Women’s Hospital, Harvard Medical School


Select Scientific Publications


Recent Press

Stem cells differentiate into cardiac and endothelial lineages. Cardiac stem cells after differentiation expressing cardiac and smooth muscle markers.

For more information Please ContactOlga M. Bellido de LunaSenior Development DirectorInterdisciplinary Stem Cell Institute Leonard M. Miller School of Medicine at the University of MiamiP.O. Box 016960 (R-125)Biomedical Research Building1501 N.W. 10 Avenue, Suite 818Miami, Florida 33136Phone: 305-243-3903Cell: 305-431-3851Fax: 305-243-5584

Interdisciplinary Stem Cell Institute University of Miami Miller School ...

Documents

Transcript of Interdisciplinary Stem Cell Institute University of Miami Miller School ...