Webinar Series miRNAs and Cancer · Pre-miRNA (hairpin precursor) Drosha Genome - miRNA gene...
Transcript of Webinar Series miRNAs and Cancer · Pre-miRNA (hairpin precursor) Drosha Genome - miRNA gene...
miRNAs and Cancer
Sponsored by:
Participating Experts:George Calin, M.D./Ph.D.
The University of TexasM.D. Anderson Cancer CenterHouston, Texas
Frank Slack, Ph.D.Department of Molecular, Cellular and
Developmental BiologyYale UniversityNew Haven, CT
Scott Hammond, Ph.D.University North Carolina at Chapel Hill
Chapel Hill, NC
Brought to you by the AAAS/Science Business Office
Webinar SeriesScience
20 February, 2008
A non-codingRNA revolution in the
cancer society
George Adrian Calin, MD, PhD
Associate Professor
Experimental Therapeutics Dept
Univ. Texas, MD Anderson CC
Houston, US
Year 2K “Central dogma” of molecular oncology
Cancer is the GENETIC DISEASE with the most complex mechanism.
Oncogenes and Tumor-suppressors are the two types of PROTEINS deregulated in cancer
cells.
Normal cell
PROTO-ONCOGENES
TUMOR
SUPPRESSORS
Malignant cell
ONCOGENEStumor suppressors
microRNA
I am very smalland non-coding!But I can do a big jobin your cells!Size doesn’t matter!
Really?! Who are you little thing? The son of a new genetics?
messengerRNAs
Cytoplasm
ORF
mRNA cleavage
RISC RISC
RISCTranslation repression
Some miRNAs
Pre-miRNA(hairpin precursor)
Drosha
Genome - miRNA gene
Pri-miRNA
Duplex
Dicer
miRNA
NucleusExportin-5
RISC
3’UTR
Small RNAs make big splash
Lee RC, Feinbaum RL, Ambros V. Cell. 199 3 Dec 3;75( 5):843. Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinge r JC, Rougvie AE, Horvitz HR, Ruvkun G. Nature. 2000 Feb 24;403(6772 ):901.
How many miRNAs are enough for what?
~15,000 conserved human stem loops,
many more non-conserved, but potentially important
(Bentwich et al, Nat Genet, 2005; Berezikov et al, Cell 2005; Cummins et al, PNAS, 2006)
ALTERATIONS OF MICRORNAS ARE FOUND IN EVERY
TYPE OF HUMAN CANCER
miRNA
expression profiles
classify
human leukemias
and
carcinomas
(Calin et al, PNAS 2002; Lu et al, Nature, 2005; Volinia & Calin et al, PNAS 2006; Landgraf et al, Cell 2007)
MNC Ly CD5
Cluster 2 Cluster 1
CLL
A
246
109
544151
63
138
6618 50
LUNG carcinoma
BREAST carcinoma
COLON carcinoma
GASTRIC carcinoma
Endocrine PANCREATIC tumors
PROSTATE cancers
B-CLL
papillary THYROID carcinoma
primary GLIOBLASTOMAS
HEPATOCELLULAR carcinoma
B
836
(Calin et al, PNAS, 2004; Esquela-Kerscher & Slack, Nat Rev Cancer 2006; Calin & Croce, Nat Rev Cancer 2006)
miR Amplification
miR Translocation
miR Mutation
miR Deletion/
Hypermethylation/
Abmormal processing
AAAA
AAAAAAAA
AAAA
AAAA
AAAAAAAA
AAAA
PCG Amplification
PCG Translocation
AAAA
AAAA
PCG Mutation
PCG Deletion/Hypermethylation
AAAA
AAAA
NH2COOH
NH2COOH
NH2COOH
NH2COOH
NH2COOH
NH2COOH
Oncogenic proteins
NH2COOH
NH2COOH
Tumor-suppressor proteins
Low apoptosis
High proliferation
Metastasis
High angiogenesis
NH2COOH
Causing miRNA abnormal expression - the combinatorial “in cascade”model
(Calin & Croce, Cancer Res, 2006; Calin & Croce, J Clinical Inv 2007)
MICRORNAS AS ONCOGENES AND TUMOR
SUPPRESSORS
miRNAs as
tumor sup pressors
(e.g.miR-16/15a, let-7) or
oncogenes
(e.g. miR-155, miR-21,
miR17-92 cluster,
miR-10b)
(Johnson et al, Cell 2005; He et al, Nature 2005; O’Donnell et al, Nature 2005;
Cimmino et al, PNAS 2005; He et al, Nature 2007; Chang et al, Mol Cell 2007;
Raver-Shapira et al, Mol Cell 2007; Ma et al, Nature 2007;
Fabbri et al, PNAS 2007; Chang et al, Nat Genet 2008; Tavazoie et al,Nature 2008)
Akt-PKB
Proliferation
Apoptosis
PDCD4
c-JUN
miR-21
PTEN
PI3K
miR-17-92 E2F1 c-MYC
MAPK pathway RAS let-7
ERK5 miR-143/145
TCL1miR-29b
miR-181b
ARFTP53
TP53INP1
miR-155
BCL6
miR-127
miR-15a/16-1
BCL2
TSGs
DNMT3A/3B
miR-29a, -29b, -29c
miR-34
ALTERATIONS OF MICRORNAS AND/OR TARGET
INTERACTION MAY CAUSE CANCER PREDISPOSITION
Mutations
in miRNAs and
“interactor” SNPs
as possible
predisposing
factors in human
cancers
Germline abnormalities in miR15a/miR16-1 transcript are associated with
CLL and breast cancer aggregation
mir-16-1 normal genome
precursor
mir-16-1 (CtoT)+7
+1 +7precursor
A
U6
A
P
miR
16
WT
Em
pty
V
29
3
miR
16
-1
MU
T
miR
16
WT
Em
pty
V
29
3
miR
16
-1
MU
T
GFP
miR-16-1 miR-15a
C
0
5
10
15
20
25
30
35
Mutant 15-16 Empty
vector
Non
transfected
Ct
va
lue
s
1ng RNA
5ng RNA
10ng RNA
miR-16-1
MEG01 cells
DB
NB Ratio 0.25 0.50 2.07 1.22
MAr Ratio 1.01 3.25 9.20 6.24
miR-16-1
NB Ratio 0.29 0.51 1.97 1.37
MAr Ratio 0.95 1.30 3.50 2.30
miR-15a
U6
(Calin et al, N Engl J Med, 2005; Raveche et al, Blood 2007)
SNPs in interactor sites could predispose to familial breast cancer by
affecting the microRNA targeting
(Nicoloso & Sun et al, in preparation, 2008)
CC
/TT
0.7
0.8
0.9
1
1.1
1.2
miR-101 scrambled
TP53BP2_miR-101
T/C
0.8
0.9
1
1.1
1.2
1.3
miR-638 scrambled
BRCA1
AAGUC
AAUAgUG uCAUGACAU
TAATtAC gGTACTGTA
ACATC T
miR-101TP53BP2_T
-16.82 151
miR-101TP53BP2_C
-11.41 123
AAGUC A A
A UAgUG uCAUG CAU
T ATtAC gGTAC GTA
ACATC A T C
p 0.0039
C A
UC CGG CgGUgggCG GgC G UAgGG
AG GCC GtCAtttGC CtG C AAgCC
C A T TTTT A A
-25.53 94
miR-638BRCA1_T
C U A
UC CGG CgGUgggCGgG GC AggG
AG GCC GtCAtttGCtC CG TttC
C A T A
-27.52 114
miR-638BRCA1_C
p 0.0163
miR binding site containingTARGET SNP
Promoterluciferase
disrupting allele
HIGH
Promoter
luciferaseactivating allele
Low
LUCIFERASE ACTIVITY
pGL3-SNP ALLELIC
PAIRS
disrupting allele
activating allele
Expected
> 1RATIO of pGL3-SNP
LUC ACTIVITY
disrupting allele
activating allele
RA
TIO
C/T
RA
TIO
T/C
pGL3-TP53BP2 C/T pGL3-BRCA1 T/C
MIRNA PROFILING AS A NEW DIAGNOSTIC & PROGNOSTIC
TOOL FOR CANCER PATIENTS
miRNAs expression
signatures associated
with diagnosis and
prognostic factors
(CLL, DLBCL, Lung,
Colon, Pancreas,
Brain ca.)
(Michael et al, Molec Cancer Res 2003; Lu et al, Nature, 2005; Eis et al, PNAS, 2005
Lui et al, Cancer Res 2007, Bloomston et al, JAMA 2007; Mi et al, PNAS, 2007; Garzon et al, Blood in press 2008)
A unique miRNA signature is associated with
lung cancer prognosis
Table 5.
(Yanaihara et al, Cancer Cell, 2006)
A unique miRNA signature is associated with CLL prognosis
Nr. Crt.
Component Map P value
Aggressive CLL **
Observation***
1 miR-15a 13q14.3 0,018 high cluster 15a/16-1 del CLL & Prostate ca.
2 miR-195 17p13 0,017 high del HCC
3 miR-221 Xp11.3 0,010 high cluster 221/222
4 miR-23b 9q22.1 0,009 high cluster 24-1/23b FRA 9D; del Urothelial ca.
5 miR-155 21q21 0,009 high amp child Burkitt’s lymphoma 6 miR-223 Xq12-
13.3
0,007 low normally expression restricted to myeloid lineage
7 miR-29a-2 7q32 0,004 low cluster 29a-2/29b-1 FRA7H; del Prostate ca.
8 miR-24-1 9q22.1 0,003 high cluster 24-1/23b FRA 9D; del Urothelial ca.
9 miR-29b-2 1q32.2-32.3
0,0007 low
10 miR-146 5q34 0,0007 high
11 miR-16-1 13q14.3 0,0004 high cluster 15a/16-1 del CLL, prostate ca.
12 miR-16-2 3q26.1 0,0003 high identical miR-16-1
13 miR-29c 1q32.2-32.3
0,0002 low
Note: * - All the members of the signature are mature microRNAs; ** - Aggressive CLL is represented by group 1 includes patients with IgVh unmutated and Zap-70 positive (high), both predictors of poor prognosis. *** - FRA = fragile site; del = deletion; HCC = hepatocellular carcinoma; ca. = carcinoma.
(Calin et al, N Engl J Med, 2005)
MICRORNAS AS NEW THERAPEUTIC TARGETS &
NEW DRUGS
miRNAs as cancer drugs
miRNAs as targets
for cancer drugs
(Krutzfeldt et al, Nature 2005; Weidhaas et al, Cancer Res 2007)
Principles of
microRNA-based
Gene Therapy
MIRNA EXPRESSION
IN NORMAL CELL
(Tili et al, Future Oncology, 2007)
NH2COOH
NH2COOH
NH2COOH
NH2COOH
NH2COOH
NH2COOH
NH2COOH
NH2COOH
NH2COOH
miR-16 & miR-15 based Gene Therapy in CLL
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
7 15 21
Days
Tum
or V
olu
me (
mm
3)
Mock pRS-E pRS15/16A MEG01
MOCKMEG01pRS-E
MEG01pR15/16
B
C
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
Mock pRS-E pRS15/16
Day 28
(Calin, Cimmino & Fabbri et al, PNAS in press, 2008)
Opening Pandora’s box:
Revisiting the molecular oncology dogma
Mad spirit
of cancer
proteins
miRNAs
supressorsmiRNAs
activators
protein
s
megaRNAs
Ultraconserved
Genes
UCG expression profiles classify human cancers
* 50 UCRs differentiate
human cancers
(P<0.005)
* half of them Non-exonic
* 6/12 Exonic UCRs represent
ANTISENSE transcripts with
host gene
CLL
CRC
HCC
133 cancer samples
(Calin & Liu & Ferracin et al, Cancer Cell, 2007)
MicroRNAs and genomic dark matter alterations in human leukemias
and carcinomas
CCC-OSU
Croce’s laboratory
Carlo M. Croce
Amelia Cimmino,
Sylwia Wojcik,
Muller Fabri,
Ramiro Garzon,
Arriana Bottoni,
Gianpiero di Leva,
Esmerina Tili,
Jean-Jacques Michaille,
Cristian Taccioli,
Hansjuerg Alder,
Stefano Volinia,
Chang-gong Liu,
A. de la Chapelle’s lab
Huiling He,
Krystian Rajewsky
Univ of Ferrara
Negrini’s lab
Massimo Negrini,
Manuela Ferracin.
OSU-Pharmacology
Tom Schmittgen,
Eun Joo
TJU-KCC
Philadelphia
Cinzia Sevignani,
Terry Hyslop,
Linda Siracusa
Romania
Dragos Stefanescu,
Vlad Herlea
(Fundeni Hospital)
Natl Inst Cancer, Genoa
Simona Zuppo
MD Anderson CC
Calin’s laboratory
(CLL Global Research Found. &
MD Anderson Trust &
Regents Research Scholar )
Milena S. Nicoloso, MD
Riccardo Spizzo, MD
Masayoshi Shimizu, BS
Simona Rossi, PhD
Sumaiyah Rehman, PhD student
CLL research
Thomas J. Kipps
Michael Keating
Kanti Ray
Neil Kay
Susan Slager
Laura Rassenti
Donna Neuberg
John Byrd
How can we find targets?I am getting crazy to find them!
It is very difficult…we could do…cfyyou… gvcjgyf? Buywe? hegruey?!
534uiytfdu3..12:1247 = fybrbc + fxnvhr jhwhuerh .34@ = fshxbf
LKM / KUHF..23649 % 7(346) IWRE CIRE
I am not sure that is going to work and it will take forever?!
Maybe we could askin the microarray facility to customize microchips for miRNA genes!
ihsa-miR-143
ugagaugaagc
acuguagcuca
Cinzia Sevignani 2005
Enjoy the ncRNA revolution!
miRNAs and Cancer
Sponsored by:
Participating Experts:George Calin, M.D./Ph.D.
The University of TexasM.D. Anderson Cancer CenterHouston, Texas
Frank Slack, Ph.D.Department of Molecular, Cellular and
Developmental BiologyYale UniversityNew Haven, CT
Scott Hammond, Ph.D.University North Carolina at Chapel Hill
Chapel Hill, NC
Brought to you by the AAAS/Science Business Office
Webinar SeriesScience
20 February, 2008
MicroRNAs and cancer
Frank Slack
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
Thousands of microRNAs act in multiple
biological events
Aging
Metabolism
Developmental
timing
Apoptosis
Cell fate/differentiation, Cell cycle…
Differentiation
…Cancer
MicroRNAs were discovered by V. Ambros
and G. Ruvkun in C. elegans
cuticle
mouth
Lee et al. 1993 Cell
Reinhart et al. 2000 Nature
MicroRNAs were discovered by V. Ambros
and G. Ruvkun in C. elegans
cuticle
mouth
Lee et al. 1993 Cell
Reinhart et al. 2000 Nature
Calin, G.A., et al., 2004. PNAS 101:2999-3004
microRNA genes map to cancer loci
MicroRNAs
are mis-
expressed in
cancer
Down-regulated in colon
Down-regulated in lung
Down-regulated in thyroid
Down-regulated in all
Down-regulated in breast
Up-regulated in all
Up-regulated in allD. Brown, 2002
Calin et al. (2004) Proc. Natl. Acad. Sci. USA 101, 2999-3004
Oncomirs - miRNAs and cancer
Oncogene miRNAsmir-17-92; mir-155, mir-21
Tumor suppressor genesLATS; RB1; PTEN
Tumor suppressor miRNAsmir-15/16; let-7; mir-34 Oncogenes
RAS; MYC
BCL2; MET
TSG
ONCOGENE
Oncogenic microRNA
TSG
ONCOGENE
Oncogenic microRNA
Normal cell Tumor cell
Normal cell Tumor cell
TS microRNA TS microRNA
TSG
OncoProtein
MicroRNAs act as oncogenes and tumor suppressors in
cancer
MicroRNAs commonly associated
with human cancerTable 1. MicroRNAs associated with human cancers
miRNA Gene Loci Cancer association Function* References
miR15,
miR-16
chromosome 13q14
Frequently deleted/downregulated in B-cell chronic
lymphocytic leukemia.
Negatively regulates the anti-apoptotic gene, BCL2.
TS
Calin, 2002
Cimmino, 2005
miR-143,
miR-145
chromosome 5q32-33
Decreased abundance in colorectal cancer.
Down-regulated in breast, prostate, cervical, and
lymphoid cancer cell lines.
miR-145 decreased in breast cancer.
TS
Michael, 2003
Iorio, 2005
miR-21
chromosome 17q23.2
Antiapoptotic factor.
Upregulated in glioblastomas and breast cancer.
OG
Chan, 2005
Ciafre, 2005
Iorio, 2005
let-7
multiple loci
Negatively regulates the Ras oncogene.
Directs cell proliferation, differentiation.
Decreased abundance in lung cancer.
TS
Johnson, 2005
Takamizawa, 2004
miR-142
chromosome 17q22
t(8,17) translocation that places the MYC oncogene
downstream of the mir-142 hairpin resulting
in an aggressive B cell leukemia due to
MYC over-expression.
N/A
Lagos-Quintana, 2002
BIC/miR-155
chromosome 21q21
Upregulated in pediatric Burkitt’s lymphomas,
Hodgkins, primary mediastinal and
diffuse large B cell lymphomas.
Upregulated in human breast cancer.
OG
Eis, 2005
Kluiver, 2005
van den Berg, 2003
Metzler, 2003
Iorio, 2005
miR-17-19b
cluster
chromosome 13q31-32
Upregulated by the c-Myc oncogene.
Negatively modulates E2F1 oncogene.
Loss-of-heterozygosity of cluster in
hepatocellular carcinoma.
Over-expressed in B-cell lymphomas.
TS/
OG
He, 2005
O’Donnell, 2005
*Abbreviations: TS, tumor-suppressor gene; OG, oncogene; N/A, not applicable
MiRNAs and cancer- a summary
• miRNAs control cell cycle, cell differentiation and
apoptosis by regulating oncogenes and TS genes
• miRNAs are misexpressed in cancer and are therefore
excellent diagnostic/prognostic markers in cancer
• Some miRNAs e.g. mir-155, can cause cancer and
oncogenic miRNAs may be therapeutic targets in
cancer
• Other miRNAs like let-7, may prevent cancer and may
be therapeutic molecules themselves.
• MicroRNAs could augment current cancer therapies.
Thanks to all members of the Slack LabCurrent Post-docs:Shih-Peng ChanAlex deLencastre Masaomi KatoPedro Medina Ryusuke NiwaZach PincusGiovanni StefaniPhong Trang
Current Grad students:Imran BabarKatherine Carter Lena Chin Sirie Godshalk Sarah Roush Mike Turner
Technician:Xianping Liang
Collaborators:Joanne Weidhaas at Yale UniversityDavid Brown/Lance Ford at Ambion/Asuragen
Former Post-docs:E-Y. Choi, Helge Grosshans, Gopi Ramaswamy,Diya Banerjee, Aurora Kerscher
Former Grad students:Steven Johnson, Monica VellaBetsy Schulman, Mona NoldeMichelle BoehmFormer Technicians:Shin-Yi Lin, Kristy Reinert
Thanks to:NIH, NSF, Patterson Trust, YCCMSD, Rockefeller Fund, Asuragen, CT Dept of Public Health, Ellison Medical Foundation, AFAR, McDonnell Foundation
miRNAs and Cancer
Sponsored by:
Participating Experts:George Calin, M.D./Ph.D.
The University of TexasM.D. Anderson Cancer CenterHouston, Texas
Frank Slack, Ph.D.Department of Molecular, Cellular and
Developmental BiologyYale UniversityNew Haven, CT
Scott Hammond, Ph.D.University North Carolina at Chapel Hill
Chapel Hill, NC
Brought to you by the AAAS/Science Business Office
Webinar SeriesScience
20 February, 2008
miRNAs and Cancer
Scott Hammond, Ph.D.
University North Carolina at Chapel Hill
Chapel Hill, NC
Do microRNAs play a causal role in human cancer?
Identification of microRNA genes
Analysis of microRNA expression in cancer
Do microRNAs play a causal role in human cancer?
How do microRNAs promote/suppress cancer?
Regulation of cell proliferation
Regulation of apoptosis
Propagation of tumor stem cells
miR p27
miR Bax
Identification of microRNA genes
Analysis of microRNA expression in cancer
Do microRNAs play a causal role in human cancer?
How do microRNAs promote/suppress cancer?
Regulation of cell proliferation
Regulation of apoptosis
Propagation of tumor stem cells
miR p27
miR Bax
Identification of microRNA genes
Analysis of microRNA expression in cancer
Can microRNAs be targeted for therapy?
CAPAAAAAAAAAAAAAAAA
TTTTTTTTTTTTTTT
Most microRNAs were discovered by cloning
mRNA
CAPAAAAAAAAAAAAAAAA
P OH
TTTTTTTTTTTTTTT
Most microRNAs were discovered by cloning
mRNA
microRNA
CAPAAAAAAAAAAAAAAAA
P OH
TTTTTTTTTTTTTTT
P OHP OH
Most microRNAs were discovered by cloning
mRNA
microRNA
PP OH AAAAAAAAAAAAAAAA
TTTTTTTTTTTTTTT
541 microRNAs have been identified in the human genome
Taken from: Mariana Lagos-Quintana, Reinhard Rauhut, Winfried Lendeckel, Thomas Tuschl, Science, 294: 853-858 (2001)
MicroRNA expression analysis using microarrays
Thomson et al, Nature Methods 1(1): 47-53 (2004)
MicroRNA expression during
Mouse development
A polycistronic cluster of microRNAs are overexpressed in cancer
Ch13-ORF25
Proliferation
Apoptosis
Angiogenesis
Invasiveness
OncomiR-1 (Oncogenic microRNA-1)
OncomiR-1 expression accelerates lymphoma development
He et al, Nature 435(7043): 828-833 (2005)
Matsubara H, et al. Apoptosis induction by antisense oligonucleotides against miR-17-5p
and miR-20a in lung cancers overexpressing miR-17-92. Oncogene. 2007 Mar 26;
[Epub ahead of print]
Wang CL, et al. Activation of an oncogenic microRNA cistron by provirus integration.
Proc Natl Acad Sci U S A. 2006 103(49):18680-4.
Volinia S, et al. A microRNA expression signature of human solid tumors defines cancer
gene targets. Proc Natl Acad Sci U S A. 2006 103(7):2257-61.
Hayashita Y, et al. A polycistronic microRNA cluster, miR-17-92, is overexpressed in
human lung cancers and enhances cell proliferation. Cancer Res. 2005 65(21):9628-32.
O’Donnell KA, et al. c-Myc-regulated microRNAs modulate E2F1 expression. Nature.
2005 435(7043):839-43.
Dews et al. Augmentation of tumor angiogenesis by a Myc regulated microRNA
Nature Genetics 38(9): 1060-1065 (2006)
Do microRNAs play a causal role in human cancer?
How do microRNAs promote/suppress cancer?
Regulation of cell proliferation
Regulation of apoptosis
Propagation of tumor stem cells
miR p27
miR Bax
Identification of microRNA genes
Analysis of microRNA expression in cancer
Can microRNAs be targeted for therapy?
MicroRNAs as therapeutic targets
AAAAAAAAAAAA
oncomiR containing RISC
Translational arrest
(Oncogenic microRNA)
MicroRNAs as therapeutic targets
AAAAAAAAAAAA
oncomiR containing RISC
Translational re-activation
(Oncogenic microRNA)
AntagomiR
MicroRNAs as therapeutic targets
AAAAAAAAAAAA
Insufficient TS-miR RISC
Translational activation
(Tumor suppressor microRNA)
MicroRNAs as therapeutic targets
AAAAAAAAAAAA
Translational arrest
(Tumor suppressor microRNA)
TS-miR containing RISC
miR mimic
The microRNA hypothesis of cancer
Tumors downregulate many microRNAs to promote
a “stem cell” like state
Selected microRNAs (oncomiRs) are expressed at a
high level to promote proliferation, suppress apoptosis
What is the mechanism for widespread alterations in gene
expression? Transcriptional, processing, turnover?
Drosha processing of “tumor suppressor” miRNAs
is inhibited in early development (and cancer?)
Acknowledgements
Chuck Perou
Joel Parker
Gerry Usary
Jason Leib
Cheol-koo Lee
Joel Parker
Tricia Wright
Elizabeth Morin
James Tsuruta
Debra O-Brien
Yi Zhang
Dazhi Wang
Hammond lab members:
Mike Thomson
Summer Goodson
Keith Woods
Marty Newman
Handan Kaygun
Andrew Baraniak
Vidya Mani
Former lab members:
Jerry Bernards
Emily Kuty
UNC Microarray Facility
Software from Michael Eisen
Department of Cell and Developmental Biology
General Motors Cancer Research Foundation
NIH-NIGMS
American Cancer Society
American Association for Cancer Research
Greg Hannon
Lin He
Jidong Lu
Michelle Carmell
David Mu
Scott Powers
Carlos Cordon-Cardo
Scott Lowe
Mike Hemann
Yue Xiong
Antonio Giraldez
Paul Barnes
Tom Maynard
Look out for more webinars in the series at:
www.sciencemag.org/webinar
miRNAs and CancerWebinar SeriesScience
20 February, 2008
Brought to you by the AAAS/Science Business Office
For related information on this webinar topic, go to: www.stratagene.com/miRNA
To provide feedback on this webinar, please e-mail
your comments to [email protected]