Department of PhysiologyResearch Highlights

www.AbisambraLab.com

Joe Abisambra, PhDAssistant Professor

Sanders-Brown Center on AgingAlzheimer’s Disease Research CenterDepartment of PhysiologySpinal Cord and Brain Injury Research Center

http://doraziolab.uky.edu/

John D’Orazio, MD, PhDProfessor

PediatricsMD/PhD Program Co-DirectorMD/PhD Program MentorPhysiology - Joint FacultyPharmacology & Nutritional Sciences - Joint FacultyToxicology - Joint Faculty

Lawrence, M.… E. Lander and G. Getz, Nature, 2013.

Melanoma has the most mutations…

Somatic mutation frequencies observed in exomes from 3,083 tumor–normal pairs

… and almost all are “UV signature” mutations

Regulation of melanocyte DNA

repair by the MC1R-cAMP

signaling axis

John D’Orazio, MD, PhDjdorazio@uky.edu

859-323-6238

Jarrett, S. … and J. D’Orazio, Mol Cell 2014, Nucl Acids Res, 2016

• We’re studying a hormonal pathway in the skin that regulates melanocyte DNA repair of UV lesions.

• This targetable pathway may be exploitable to prevent UV-induced melanoma.

http://www.uky.edu/coa/about-us/faculty/steven-estus-phd

Steve Estus, PhDProfessor

Sanders-Brown Center on AgingAlzheimer’s Disease Research CenterMD/PhD Program MentorDepartment of Physiology – Department Leadership

Estus Lab: Molecular Genetics of Alzheimer’s Disease

Genetic variants account for 70% of risk of Alzheimer’s Disease (AD).Recent genome wide studies have identified multiple AD variants.

Underlying mechanisms are investigated with molecular and cellular biology, human brain autopsy tissue, cell culture and mice.

Long-term goal: translate mechanisms into prevention therapies

Note: Picture from 2015, Lab currently much smaller

Lance Johnson, PhDAssistant Professor

Department of Physiology

www.LJohnsonLab.com

Johnson Lab

Research in our lab is devoted to exploring the metabolic effects of the E4 isoform of apolipoprotein E (apoE), a

major genetic risk factor for both cardiovascular disease and Alzheimer's disease.

Our translational studies tackle a critical central question: are the cognitive and cerebrovascular impairments

associated with E4 metabolic in nature?

www.LJohnsonLab.com

Mariana Nikolova-Karakashian, PhDProfessor

Department of PhysiologyCardiovascular Research Center – Affiliated FacultyMarkey Cancer Center – Affiliated Faculty

http://physiology.med.uky.edu/users/mnikolo

Effects of aging on cell signaling pathwaysin the liver

Changes in the steady state of key bioactive lipids

in the cells lead to hypersensitivity and hyper

response

Increased occurrence of steatosis, diabetes,

cardiovascular diseases, and AD

Chronic, low grade inflammation in the elderly

(TNF, IL-1, oxidative stress)

Change in systemic lipid metabolism favoring fat

accumulation

Aleken Skywalker

Mariss Karakashian

Princess Geri-Endor

An ORPHAN, recently made liver specific knockout mouse is seeking a caring and reliable graduate student for possible adoption.The HOPE is to find a cure for the mouse’s problem: Albeit resistant to diet-induced steatosis, she still develops awful fibrotic plaques (in spite that she never drinks alcohol, or even carbonated drinks) which worries her greatly.The AWARD: a personalized star war cartoon, and a 3 letter abbreviation after your name.

Dr. MarianaNikolova-Karakashian

Master Deep Yoda Princess Leah-oua-Shi Padme Krassi

Hiroshi Saito, PhDAssociate Professor

Department of PhysiologyDepartment of SurgeryMarkey Cancer Center – Affiliated Faculty

https://physiology.med.uky.edu/users/hsa225

• Hiroshi Saito, Ph.D.• Associate Professor

• MS-476, Medical Science Bldg.

• Dept. of Surgery & Physiology

• University of Kentucky• Lexington 40536-0298, KY• Email: hiroshi.saito@uky.edu

RESEARCH GOALAging is associated with reduced stress tolerance. Elderly people become very sick and often die by mild injury or infection which are not serious for younger people. Our laboratory has been trying to understand the mechanisms for such age-dependent vulnerability to physiological stresses by using mouse models of aging. We are also actively investigating the mechanisms of chronic muscle weakness after severe sepsis using our novel clinically relevant mouse model.

RESEARCH KEY WORDSSepsis, Aging, Inflammation, Thrombosis, Oxidative Damage

ONGOING RESEARCH PROJECTS(1) Muscle dysfunction after sepsis (infection).(2) Role of adipose tissue in systemic inflammation & aging.(3) Effects of diet on systemic inflammation and sepsis.(4) Age-dependent severity of sepsis & acute pancreatitis.

RECENT FUNDINGR01-AG039732 (NIH/NIA, 2011-2017) R01-GM126181 (NIH/NIGMS, 2017-2022)F31-GM117868 (NIH/NIGMS, 2016-2019)

SAITO LABORATORY

Donna Wilcock, PhDAssociate Professor

Department of PhysiologyDepartment of SurgeryMarkey Cancer Center – Affiliated Faculty

http://www.uky.edu/coa/about-us/faculty/donna-m-wilcock-phd

Wilcock Lab – Alzheimer’s Disease

• Project 1: The impact of different inflammatory phenotypes on disease progression and response to therapies.

• Project 2: The comorbidity of vascular dementia and Alzheimer’s disease.

Alzheimer’s disease is the only major disease that has an increased mortality rate. Most other major causes of death including cancer and heart disease have declined in mortality.