Principal Investigator/Program Director (Last, First, Middle):
BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
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NAME
POSITION TITLE
Eliot M. Rosen, MD, PhD
Professor of Oncology
eRA COMMONS USER NAME
ROSENE
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
DEGREE
(if applicable)
YEAR(s)
FIELD OF STUDY
BS
MS
MD
PhD
1972
1974
1979
1980
Chemical Engineering
Chemical (Biomed) Eng.
Medicine
Physiology (Cellular)
Columbia University, New York City, NY
Mass. Institute of Technology, Cambridge, MA
University of Pennsylvania, Philadelphia, PA
University of Pennsylvania, Philadelphia, PA
Internship and Residency Training:
1980 - 1981
Intern in Medicine, Beth Israel Hospital, Harvard Medical School, Boston, MA
1981 - 1984
Resident in Radiation Therapy, Joint Center, Harvard Medical School, Boston, MA
Research and Professional Experience:
1984
Board Certified in Therapeutic Radiology
1984 - 1985
Instructor in Radiation Therapy, Harvard Medical School
1984 - 1987
Associate in Radiation Therapy & Chief, Gynecological RT, Brigham and Women's Hospital
1985 - 1987
Assistant Professor of Radiation Therapy, Harvard Medical School
1987 - 1993
Assistant Professor of Therapeutic Radiology, Yale University Sch. of Medicine, New Haven, CT
1987 - 1993
Radiotherapist in charge of Pediatric Radiotherapy and total body radiotherapy, Yale Med. Sch.
1993 - 2003
Head, Section of Research, Dept. of Rad. Onc., Long Island Jewish Med. Ctr., New Hyde Park
1993 - 2003
Member, Physician Staff, Long Island Jewish Medical Center
1993 - 1998
Associate Professor of Radiation Oncology, Albert Einstein College of Medicine
1994 - 2003
Member, Cancer Center, Albert Einstein College of Medicine (AECOM)
1998 - 2003
Professor of Radiation Oncology, AECOM, Bronx, NY
2001 - 2003
Professor of Developmental & Molecular Biology and Hormone-Dependent Tumor Biology, AECOM
2003 Professor of Oncology, Biochemistry, and Radiation Medicine, Georgetown University (Tenured)
2003 Member, Executive Committee, Lombardi Comprehensive Cancer Center
2006 Endowed Chair: Charlotte Gragnani Chair in Oncology and Radiation Biology
Awards and Honors: Awards for Highest Scholastic Standing, Dept. of Chemical Engineering, Columbia University,
1971 & 1972; National Science Foundation Traineeship, 1973-1974; Medical Scientist Training Program, NIGMS/NIH,
University of Pennsylvania (PA), 1974-1980; Alpha Omega Alpha Honor Medical Society, University of Pennsylvania,
1978; William Perry Pepper and Rose Meadow Levinson Prizes, University of Pennsylvania; American Heart
Association Established Investigator Award, 1990-1995; Study Section Member (1995): American Heart Association;
California State Breast Cancer Research Project; NIH RFA CA-94-31 (Spore in Prostate Cancer); Site Visit Committee
for Immunobiology Laboratory of NCI, Frederick Cancer Center. Reviewer: Medical Research Council (London); Study
Section, Israel Cancer Research Fund NY. Member, NIH Study Sections, Biochemical Endocrinology (BCE); Chemoand Dietary Prevention (CDP); DOD Ovarian Cancer Study Section (2000-2004); DOD Prostate Cancer Study Section
(2007). Endowed chair (2006-)
Selected Recent Publications: (Out of More Than 136 Total)
1. Fan S, Wang J-A, Meng Q, Yuan R-Q, Ma YX, Erdos MR, Pestell RG, Yuan F, Auborn KJ, Goldberg ID, Rosen
EM. BRCA1 regulates estrogen receptor signaling in transfected cells. Science 284: 1354-1356, 1999.
2. Abounader R, Lal B, Luddy G, Koe G, Davidson B, Rosen EM, and Laterra J. In vivo targeting of SF/HGF and
c-met expression via U1snRNA/Ribozymes inhibits glioma growth and angiogenesis and promotes tumor
apoptosis. FASEB J 16: 108-110, 2002.
3. Carter TH, Liu K, Ralph W Jr., Chen D, Qi M, Fan S, Yuan F, Rosen EM, Auborn KJ. Diindolylmethane alters
gene expression in human keratinocytes in vitro. J Nutr 132: 3314-3324, 2002.
PHS 398/2590 (Rev. 09/04)
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Dilmanian FA, Button TM, Le Duc G, Zhong N, Pena LA, Martinez SR, Bacarian T, Tammam J, Ren B, Farmer
PM, Kalef-Ezra J, Micca PL, Nawrocky MM, Niederer JA, Recksiek FP, Smith JAL, Fuchs A, Rosen EM.
Response of the rat intracranial 9L gliosarcoma to microbeam radiation therapy (MRT). Neuro-Oncology 4: 2638, 2002.
Fan S, Wang J-A, Ma YX, Yuan R-Q, Meng Q, Erdos MR, Pestell RG, Goldberg ID, Rosen EM. p300
modulates BRCA1 inhibition of estrogen receptor activity. Cancer Res 62: 141-151, 2002.
Ma YX, Fan S, Xiong J, Yuan RQ, Meng Q, Gao M, Goldberg ID, Fuqua SA, Pestell RG, Rosen EM. Role of
BRCA1 in heat shock response. Oncogene 22: 10-27, 2003.
Xiong J, Fan S, Meng Q, Wang C, Zhou J, Zafonte B, Goldberg ID, Pestell RG, Rosen EM. BRCA1 inhibition of
telomerase activity in cultured cells. Mol Cell Biol 23: 8668-8690, 2003.
Jeon KY, Rih JK, Kim HJ, Lee YJ, Cho CH, Goldberg ID, Rosen EM, Bae I. Pretreatment of Indole 3-Carbinol
augments TRAIL-induced apoptosis in a prostate cancer cell line, LNCaP. FEBS Lett 544: 246-251, 2003.
Auborn KJ, Fan S, Rosen EM, Goodwin L, Chandraskaren A, Williams DE, Chen D, Carter TH. Indole-3carbinol is a negative regulator of estrogen. J Nutr 133(7 Suppl): 2470S-2475S, 2003.
Rosen EM, Fan S, Pestell RG, Goldberg ID. BRCA1 in hormone-responsive cancers. Trends Endocrinol
Metab 14: 378-385, 2003.
Razandi M, Pedram A, Rosen EM, Levin ER. BRCA1 inhibits membrane estrogen and growth factor receptor
signaling to cell proliferation in breast cancer. Mol Cell Biol 24: 5900-5913, 2004.
Abounader R, Reznik T, Colantuoni C, Martinez-Murillo F, Rosen EM, Laterra J. Regulation of c-Metdependent gene expression by PTEN. Oncogene 23: 9173-9182, 2004.
Bae I, Fan S, Meng Q, Rih JK, Kim HJ, Kang HJ, Xu J, Goldberg ID, Jaiswal AK, Rosen EM. BRCA1 induces
antioxidant gene expression and resistance to oxidative stress. Cancer Res 64: 7893-7909, 2004.
Ma YX, Tomita Y, Fan S, Wu K, Tong Y, Zhao Z, Song L-N, Goldberg ID, Rosen EM. Structural determinants
of the BRCA1: estrogen receptor interaction. Oncogene 24: 1831-1846, 2005.
Fan S, Gao M, Meng Q, Laterra JJ, Symons M, Goldberg I, Pestell RG, Coniglio S, Rosen EM. Role of NF-kB
signaling in hepatocyte growth factor/scatter factor mediated cell protection. Oncogene 24: 1749-1766, 2005.
Zhang Y, Fan S, Meng Q, Ma Y, Katiyar P, Schlegel R, Rosen EM. BRCA1 interaction with human
papillomavirus oncoproteins. J Biol Chem 280: 33165-33177, 2005.
Xian Ma Y, Katiyar P, Jones LP, Fan S Zhang Y, Furth PA, Rosen EM. The breast cancer susceptibility gene
BRCA1 regulates progesterone receptor signaling in mammary epithelial cells. Mol Endocrinol 20: 14-34, 2006.
Epub 2005 Aug 18.
Bae I, Rih JK, Kim HJ, Kang HJ, Haddad B, Kirilyuk A, Fan S, Avantaggiati ML, Rosen EM. BRCA1 regulates
gene expression for orderly mitotic progression. Cell Cycle 4: 1641-1466, 2005.
Xia S, Rosen EM, Laterra J. Sensitization of glioma cells to Fas-dependent apoptosis by chemotherapyinduced oxidative stress. Cancer Res 65: 5248-5255, 2005.
Jones L, Li M, Halama ED, Ma Y, Lubet R, Grubbs CJ, Deng C, Rosen EM, Furth P. Promotion of mammary
cancer development by tamoxifen in a mouse model of Brca1-mutation related breast cancer. Oncogene 24:
3554-3562, 2005.
Wang C, Fan S, Ma YX, Fu M, Reutens A, Francis R, Katzenellenbogen B, Kushner P, Weber B, Rosen EM,
Pestell RG. BRCA1 repression of the transcriptional activity of the estrogen receptor (ER-) is inhibited by
cyclin D1. Cancer Res 65: 6557-6567, 2005.
Rosen EM, Fan S, Isaacs C. BRCA1 in hormonal carcinogenesis: basic and clinical research. Invited Review.
Endocrine-Related Cancers 12: 533–548, 2005.
Fan S, Meng Q, Auborn K, Carter T, Rosen EM. BRCA1 and BRCA2 as molecular targets for phytochemicals
indole-3-carbinol and genistein in breast and prostate cancer cells. Br J Cancer 94: 407-426, 2006.
Kang JK, Kim HJ, Kim SK, Barouki R, Cho CH, Khanna KK, Rosen EM, Bae I. BRCA1 modulates xenobiotic
stress-inducible gene expression by interacting with ARNT in human breast cancer cells. J Biol Chem 281:
14654-14662, 2006.
Katiyar P, Ma Y, Fan S, Pestell RG, Furth PA, Rosen EM. Regulation of progesterone receptor signaling by
BRCA1 in mammary cancer. Nuclear Receptor Signaling, 2006; 4:e006. Epublished April 28.
Ma Y, Yuan R-Q, Fan S, Hu C, Goldberg ID, Abounader R, Laterra JJ, Rosen EM. Determinants of U373MG
human glioblastoma cell chemosensitivity. Anti-Cancer Drugs 17: 733-751, 2006.
Dilmanian FA, Zhong Z, Bacarian T, Benveniste H, Romanelli P, Wang R, Welwart J, Yuasa T, Rosen EM,
Anschell DJ. Interlaced X-ray microplanar arrays: A novel radiosurgery approach with clinical potential. Proc
Natl Acad Sci USA 103: 9709-9714, 2006.
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Principal Investigator/Program Director (Last, First, Middle):
29. Fan S, Meng Q, Laterra JJ, Rosen EM. Ras effector pathways modulate scatter factor-stimulated NFkappaB signaling and protection against DNA damage. Oncogene 26: 4774-4496. Epub 2007 Feb 12.
30. Xu J, Gao M, Fan S, Meng Q, Goldberg ID, Abounader R, Ressom H, Laterra JJ, Rosen EM. Effect of Akt
inhibition on scatter factor-regulated gene expression in DU-145 human prostate cancer cells. Oncogene 26:
2925-2938, 2007. Epublished 2006 Nov 13.
31. Ma Y, Hu C, Riegel AT, Fan S, Rosen EM. Growth factor signaling pathways modulate BRCA1 repression
of estrogen receptor-alpha activity. Mol Endocrinol 21: 1905-1923, 2007. Epub 2007 May 15.
32. Jones LP, Tilli MT, Assefnia S, Torre K, Halama ED, Parrish A, Rosen EM, Furth PA. Activation of estrogen
signaling pathways collaborates with loss of Brca1 to promote development of ERalpha-negative and
ERalpha-positive mammary preneoplasia and cancer. Oncogene. 2007 Jul 23; [Epub ahead of print]
33. Xia S, Li Y, Rosen EM, Laterra J. Ribotoxic stress sensitizes glioblastoma cells to death receptor induced
apoptosis: requirements for c-Jun NH2-terminal kinase and Bim. Mol Cancer Res 5: 783-792, 2007.
34. Reznik TE, Sang Y, Ma Y, Abounader R, Rosen EM, Xia S, Laterra J. Transcriptionally dependent
epidermal growth factor receptor activation by hepatocyte growth factor. Mol Cancer Res 6: 139-150, 2008.
RESEARCH PROJECTS ONGOING OR COMPLETED DURING THE LAST THREE YEARS:
Active Projects
R01-CA82599 (Rosen)
09/01/99 - 11/30/09
BRCA1 Modulates Estrogen Receptor Response in Breast Ca
The major goals of this project are: SA1. To precisely identify the molecular determinants of the BRCA1:ER-
interaction; SA2. To determine the mechanisms by which oncogene signaling rescues BRCA1 inhibition of ER; SA3. To determine the role of acetylation in regulating ER- resistance to BRCA1; SA4. To examine the
interaction between estrogen and Brca1 in mammary tumorigenesis in vivo.
R01-CA80000-06A3 (Rosen)
09/01/99 - 09/30/09
Role of BRCA1 as a human prostate tumor suppressor gene
The major goals of this project are: SA1. To delineate the roles of BRCA1 in TERT regulation and telomere
maintenance; SA2. To assess the roles of BRCA1 in antioxidant defense pathways in cultured cells; and SA3. To
assess the physiologic consequences of the loss of functional Brca1 in the mouse mammary gland.
*Competing renewal scored 142.
R01-NS43987 (PI: JJ Laterra; EM Rosen Co-PI)
04/01/03 - 03/31/08*
Mechanisms of Chemo/Radioresistance in Human Gliomas
The major goals of this project are: SA1. Identification of novel gene products involved in SF/HGF-mediated
protection of human glioma cells against DNA damaging agents; SA2. Effector mechanism(s) of DNA damageinduced apoptosis and its inhibition by HGF/SF; SA3. Transcriptional mechanisms of SF/HGF-mediated glioma
cytoprotection; and SA4. Effect of inhibition of SF/HGF:c-Met signaling pathways on glioma xenograft
responses to cytotoxic agents in vivo.
R01-CA104546 (Rosen)
04/01/05 - 03/31/10
BRCA Genes in Breast Cancer Chemoprevention
The major goals of this project are: SA1. To determine the contribution of the BRCA genes to the molecular
and cellular actions of I3C; SA2. To assess contribution of BRCA1 and BRCA2 to DIM-induced changes in
mammary gene expression; and SA3. To confirm the in vitro findings using experimental animal models of I3Cmediated chemoprevention to determine if I3C causes up-regulation of mammary Brca1 expression.
R01-ES09169 (Rosen)
03/01/98 - 06/30/08
Protection Against Apoptosis by Scatter Factor
The major goals of this project are: SA1. Mechanism of SF protection of human breast carcinoma cells against
apoptosis: Signal transduction from the c-Met receptor; SA2. Mechanism of SF protection of human breast
carcinoma cells against apoptosis: Downstream regulation of the apoptotic process; SA3. In vivo
chemoprotection by SF in an experimental breast cancer model.
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Principal Investigator/Program Director (Last, First, Middle):
Completed Projects
BCTR0503799 (Rosen)
05/01/05 - 04/30/07
Susan G. Komen Breast Cancer Foundation
BRCA1 regulation of progesterone receptor function in breast cancer
The major goals of this project are: SA1. High resolution mapping of BRCA1: PR interaction; SA2.
Mechanism(s) of BRCA1 inhibition of PR activity; and SA3. Progesterone stimulation of mammary
tumorigenesis in vivo.
Susan G. Komen Beast Cancer Foundation (Rosen) Post-Doctoral Fellowship) 07/01/04 - 06/30/07
Mechanism for BRCA1 regulation of genomic stability
Role on Project: Supervisor for Post-Doctoral Fellowship (Dr. Jeong Keun Rih)
The major goals of this proposal are: SA1. To confirm selected findings in mammary epithelial and cancer
cells by independent mRNA and protein assays; SA2. To demonstrate that BRCA1 regulates the mitotic
spindle checkpoint in mammary epithelial cell types; SA3. To determine if knockdown of endogenous BRCA1
confers genomic instability in mammary epithelial cells; and SA4. To identify the BRCA1 target genes
responsible for loss of genomic stability due to BRCA1 inactivation.
BCTR0201295 (Rosen) Susan G. Komen Breast Cancer Foundation
04/01/03-03/31/05
BRCA1 as a Target for Chemoprevention Agents
Role on Project: PI
The major goals of this project are: SA1. To determine the role of BRCA1 in the molecular and cellular actions
of I3C in breast cancer cells; and SA2. To assess the contribution of BRCA1 to DIM-induced changes in
mammary gene expression.
R21-NS43231-01A1 (Dilmanian)
12/01/02 - 11/30/04
Role on Project: Co-Investigator (2% Effort)
Microbeam Radiation Therapy for Gliomas
The major goals of this project are: SA1. To determine if dose-fractionation improves the therapeutic index of
the unidirectional MRT for intracerebral CNS-1 rat glioma tumors; and SA2. To determine if Gadovist increases
the therapeutic index of unfractionated unidirectional MRT applied to intracerebral CNS-1.
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