Gregory David

Gregory David, PhD

Associate Professor, Department of Biochemistry and Molecular Pharmacology

Associate Professor, Department of Urology

Keywords
chromatin modifications in development and oncogenesis, cancer, genome integrity, pharmacology, stem cell biology
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.

Phone

212-263-2926

Fax

212-263-8166

Academic office

550 First Avenue, Medical Science Bldg.

4, 411

New York, NY 10016

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Associate Professor, Department of Biochemistry and Molecular Pharmacology

Associate Professor, Department of Urology

Co-Director, Medical Scientist Training Program

Co-Director, Pharmocology and Drug Development

Graduate Advisor, Molecular Pharmocology Training Program

PhD from Pasteur Institute

Graveline, Richard; Marcinkiewicz, Katarzyna; Choi, Seyun; Paquet, Marilene; Wurst, Wolfgang; Floss, Thomas; David, Gregory

Molecular & cellular biology. 2017 Feb 15; 37(5):?-?

Lau, Lena; David, Gregory

Methods in molecular biology. 2017; 1534:17-30

Graveline, R; Marcinkiewicz, K; Choi, S; Paquet, M; Wurst, W; Floss, T; David, G

Molecular & cellular biology. 2017; 37(5):e00522-16

Mita, Paolo; Savas, Jeffrey N; Briggs, Erica M; Ha, Susan; Gnanakkan, Veena; Yates, John R 3rd; Robins, Diane M; David, Gregory; Boeke, Jef D; Garabedian, Michael J; Logan, Susan K

Journal of biological chemistry. 2016 Dec 02; 291(49):25516-25528

Cantor, David J; David, Gregory

Blood. 2016 Nov 2; 129(1):60-70

Bansal, N; David, G; Farias, E; Waxman, S

Advances in cancer research. 2016; 130:113-135

Porciuncula, A; Hajdu, C; David, G

Advances in cancer research. 2016; 131:1-20

DiMauro, T; Cantor, D J; Bainor, A J; David, G

Oncogene. 2015 Jul 23; 34(30):4011-4017