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Biosketch / Results /

Gregory David, Ph.D.

Associate Professor; Co Course Director
Department of Biochemistry and Molecular Pharmacology [1]

Contact Info

Address
540 First Avenue
NYU School of Medicine Floor 4 Room 5
Skirball Institute
New York, NY 10016

212-263-2926
Gregory.David@nyumc.org

[2]

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Education

1994-1998 — Inst Pasteur, Paris, Graduate Education

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Research Summary

The research interests of our laboratory center on chromatin modifications and its impact on regulation of gene expression and nuclear structure, particularly as it relates changes associated with malignant transformation. Clearly, the interplay between activation and repression of transcription that imposes normal transcriptional control becomes disrupted in cancer. Besides their roles in promoter-specific transcriptional regulation, histone modifiers also play a role in the establishment of large chromosomal domains, and therefore function in maintenance of chromosomal integrity. We and others have shown that deregulation of histone modifying complexes, including Histone Deacetylases (HDACs)-containing complexes, participate to the oncogenic transformation in numerous human cancers. Several studies suggested that blocking the enzymatic activity of HDAC complexes (e.g., using histone deacetylase inhibitors) could prevent tumorigenesis and selectively induce cell death in transformed cells. While HDACs are integral components of several gene regulatory complexes, HDAC inhibitors developed to date exhibit little or no specificity towards individual HDAC-containing complex. Thus, the identification of pathways involved in the modulation of the activities of specific HDAC complexes is a priority in cancer therapy. Knowledge of these control mechanisms in both normal physiology and malignancy is essential for the better understanding of the malignant process that will allow development of novel therapeutic and diagnostic approaches to human disease.
We have recently developed valuable biological tools to study the prominent HDAC-containing complex in mammalian cells, the mSin3-HDAC complex. The mSin3 complex was the first chromatin modifying complex shown to be deregulated in human cancers. However, the molecular basis for the malignant phenotype in those tumors remain unclear, impairing the development of efficient targeted therapies. Using genetic recombination, we generated mouse strains that can be spatially and temporally genetically inactivated for different components of the mSin3-HDAC complex. Those unique reagents will enable the precise delineation of the in vivo consequences of deregulation or inactivation of the complex on mammalian development and oncogenesis, and enable the development of rational targeted therapies.

Research Interests

Chromatin modifications in development and oncogenesis

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All data from NYU Health Sciences Library Faculty Bibliography — -

Contact:
http://hsl.med.nyu.edu/faculty-bibliography-search [7]

Regulation of oncogene-induced cell cycle exit and senescence by chromatin modifiers
David, Gregory
2012 Sep;13(11):992-1000, Cancer biology & therapy
— id: 178052, year: 2012, vol: 13, page: 992, stat: Journal Article,

Sequence Requirements for Combinatorial Recognition of Histone H3 by the MRG15 and Pf1 Subunits of the Rpd3S/Sin3S Corepressor Complex
Kumar, Ganesan Senthil; Chang, William; Xie, Tao; Patel, Anand; Zhang, Yongbo; Wang, Gang Greg; David, Gregory; Radhakrishnan, Ishwar
2012 Sep;422(4):519-531, Journal of molecular biology
— id: 177220, year: 2012, vol: 422, page: 519, stat: Journal Article,

Chromatin associated Sin3A is essential for male germ cell lineage in the mouse
Pellegrino, Jessica; Castrillon, Diego H; David, Gregory
2012 Sep;369(2):349-355, Developmental biology (Orlando)
— id: 175783, year: 2012, vol: 369, page: 349, stat: Journal Article,

Structural basis for molecular interactions involving MRG domains: implications in chromatin biology
Xie, Tao; Graveline, Richard; Kumar, Ganesan Senthil; Zhang, Yongbo; Krishnan, Arvind; David, Gregory; Radhakrishnan, Ishwar
2012 Jan;20(1):151-160, Structure
— id: 155901, year: 2012, vol: 20, page: 151, stat: Journal Article,

Dissecting the complex regulation of Mad4 in glioblastoma multiforme cells
Yang, Wensheng; Yang, Xiaolu; David, Gregory; Dorsey, Jay F
2012 Nov;13(13):1339-1348, Cancer biology & therapy
— id: 185862, year: 2012, vol: 13, page: 1339, stat: Journal Article,

The human ankyrin insulator supports production of therapeutic levels of adult hemoglobin following beta-globin gene transfer in hematopoietic cells derived from thalassemic and sickle cell patients
Breda, L; Casu, C; Bianchi, N; Cartegni, L; Yazdanbakhsh, K; Manwani, D; Mohandas, N; Jelinic, P; David, G; Gardner, L B; Kleinert, D A; Prus, E; Fibach, E; Giardina, P; Gambari, R; Rivella, S
2011 18 Nov 2011;118(21):-, Blood
— id: 169672, year: 2011, vol: 118, page: , stat: Journal Article,

A Novel Mammalian Complex Containing Sin3B Mitigates Histone Acetylation and RNA Polymerase II Progression within Transcribed Loci
Jelinic, Petar; Pellegrino, Jessica; David, Gregory
2011 Jan;31(1):54-62, Molecular & cellular biology
— id: 115424, year: 2011, vol: 31, page: 54, stat: Journal Article,

Ras-induced senescence and its physiological relevance in cancer
Dimauro, Teresa; David, Gregory
2010 Dec;10(8):869-876, Current cancer drug targets
— id: 138210, year: 2010, vol: 10, page: 869, stat: Journal Article,

The Mammalian sin3 proteins are required for muscle development and sarcomere specification
van Oevelen, Chris; Bowman, Christopher; Pellegrino, Jessica; Asp, Patrik; Cheng, Jemmie; Parisi, Fabio; Micsinai, Mariann; Kluger, Yuval; Chu, Alphonse; Blais, Alexandre; David, Gregory; Dynlacht, Brian D
2010 Dec;30(24):5686-5697, Molecular & cellular biology
— id: 114827, year: 2010, vol: 30, page: 5686, stat: Journal Article,

Chromatin modifications: The driving force of senescence and aging?
Dimauro, Teresa; David, Gregory
2009 ;1(2):182-190, Aging
— id: 107286, year: 2009, vol: 1, page: 182, stat: Journal Article,

Sin3B expression is required for cellular senescence and is up-regulated upon oncogenic stress
Grandinetti, Kathryn B; Jelinic, Petar; DiMauro, Teresa; Pellegrino, Jessica; Fernandez Rodriguez, Ruben; Finnerty, Patricia M; Ruoff, Rachel; Bardeesy, Nabeel; Logan, Susan K; David, Gregory
2009 Aug 15;69(16):6430-6437, Cancer research
— id: 101640, year: 2009, vol: 69, page: 6430, stat: Journal Article,

Specific requirement of the chromatin modifier mSin3B in cell cycle exit and cellular differentiation
David, Gregory; Grandinetti, Kathryn B; Finnerty, Patricia M; Simpson, Natalie; Chu, Gerald C; Depinho, Ronald A
2008 Mar 18;105(11):4168-4172, Proceedings of the National Academy of Sciences of the United States of America
— id: 78025, year: 2008, vol: 105, page: 4168, stat: Journal Article,

Sin3B: an essential regulator of chromatin modifications at E2F target promoters during cell cycle withdrawal
Grandinetti, Kathryn B; David, Gregory
2008 Jun 1;7(11):1550-1554, Cell cycle
— id: 86646, year: 2008, vol: 7, page: 1550, stat: Journal Article,

The F-box protein Fbl10 is a novel transcriptional repressor of c-Jun
Koyama-Nasu, Ryo; David, Gregory; Tanese, Naoko
2007 Sep;9(9):1074-1080, Nature cell biology
— id: 75366, year: 2007, vol: 9, page: 1074, stat: Journal Article,

mSin3A corepressor regulates diverse transcriptional networks governing normal and neoplastic growth and survival
Dannenberg, Jan-Hermen; David, Gregory; Zhong, Sheng; van der Torre, Jaco; Wong, Wing H; Depinho, Ronald A
2005 Jul 1;19(13):1581-1595, Genes & development
— id: 63113, year: 2005, vol: 19, page: 1581, stat: Journal Article,

Cdk5/p35 phosphorylates mSds3 and regulates mSds3-mediated repression of transcription
Li, Zhen; David, Gregory; Hung, Kwok-Wang; DePinho, Ronald A; Fu, Amy K Y; Ip, Nancy Y</