Herbert H Samuels

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Herbert H Samuels, M.D.

Professor; Helen and Milton A. Kimmelman Professor of Pharmacology; Kimmelman Prof of Pharmacology
Departments of Biochemistry and Molecular Pharmacology and Medicine (Endocrinology Div)

Contact Info

Address
455 First Avenue
Floor 8 Room 835
Public Health Lab
New York, NY 10016

212-263-6279
212-263-6279
Herbert.Samuels@nyumc.org

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Education

— Dr. Samuels was a Research Associate in the lab of Dr. Gordon M. Tomkins' Laboratory of Molecular Biology at the NIAMD until 1970.|, PostDoctoral Training
1965 — NYU School of Medicine, Medical Education
1967 — Dr. Samuels was an Intern and Resident in Medicine at the Albert Einstein College of Medicine completing his training, Residency

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Research Summary

Our research involves the broad aspect of hormone action with a major focus on transcriptional regulation by the nuclear receptors for glucocorticoid hormones, thyroid hormone (T3R), all trans-retinoic acid (RAR), 9-cis retinoic acid (RXR), and vitamin D (VDR). These receptors are members of a subfamily of the steroid hormone receptor superfamily which recognizes similar DNA sequences that contain two or more hexanucleotide DNA-binding half-sites arranged as direct repeats or inverted repeats. We identified a dimerization domain which is embedded within the ligand-binding region in the C-terminal half of T3R, RXR, and RAR which consists of nine hydrophobic heptad repeats. These receptors play important roles in mediating gene expression, development, and differentiation. T3R, RAR, and VDR primarily bind their DNA elements as heterodimers with RXR, which was established using Escherichia coli expressed T3R, RAR, and RXR, purified to homogeneity, as well as with receptors expressed using eukaryotic systems. Our current studies focus on identifying the nuclear factors, including the core transcription factors such as TFIIB and TFIID, which interact with T3R, RAR, and RXR and defining their role(s) using in vitro transcription systems. These studies have defined a region in the N-terminus of T3R which specifically interacts with TFIIB. In addition, we are: 1) defining the precise motifs involved in mediating homo- and/or heterodimer formation and transcriptional activation with site-directed mutagenesis; 2) using protein purification and the yeast two-hybrid system to identify novel cDNAs which encode factors that interact with different domains of the T3Rs and are functionally important for transcriptional activation or repression; 3) defining the mechanism of action of the verbA oncogene, an avian retroviral counterpart of the a-form of T3R; 4) analyzing the functional role of T3R mutations found in the clinical syndrome of generalized thyroid hormone resistance; and 5) identifying novel antagonists for the RARs and the T3Rs using a computational approach based on the known crystal structure of nuclear hormone receptors (with Matthieu Schapira and Ruben Abaygan).

Research Interests

Hormonal Regulation of Gene Expression

Research Keywords

gene transcription, hormones, nuclear receptors, transcription factors