Herbert H Samuels

Biosketch / Results /

Herbert Samuels

Helen and Milton A. Kimmelman Professor of Pharmacology, Department of Biochemistry and Molecular Pharmacology
Professor, Department of Medicine

Kimmelman Prof of Pharmacology

Contact Info

Address
455 First Avenue
New York, NY 10016

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

Education

— Dr. Samuels was an Intern and Resident in Medicine at the Albert Einstein College of Medicine completing his training, Residency Training
— NYU School of Medicine, Medical Education

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

Skin Metabolite, Farnesyl Pyrophosphate, Regulates Epidermal Response to Inflammation, Oxidative Stress and Migration
Pastar, Irena; Stojadinovic, Olivera; Sawaya, Andrew P; Stone, Rivka C; Lindley, Linsey Evan; Ojeh, Nkemcho; Vukelic, Sasa; Samuels, Herbert H; Tomic-Canic, Marjana. Skin Metabolite, Farnesyl Pyrophosphate, Regulates Epidermal Response to Inflammation, Oxidative Stress and Migration. Journal of cellular physiology. 2016 Feb 24;:?-? (1965532)

Fas Activated Serine-Threonine Kinase Domains 2 (FASTKD2) mediates apoptosis of breast and prostate cancer cells through its novel FAST2 domain
Das, Sharmistha; Yeung, Kay T; Mahajan, Muktar A; Samuels, Herbert H. Fas Activated Serine-Threonine Kinase Domains 2 (FASTKD2) mediates apoptosis of breast and prostate cancer cells through its novel FAST2 domain. BMC cancer. 2014 Nov 20;14:852-852 (1369062)

A novel cell lysis approach reveals that caspase-2 rapidly translocates from the nucleus to the cytoplasm in response to apoptotic stimuli
Tinnikov, Alexander A; Samuels, Herbert H. A novel cell lysis approach reveals that caspase-2 rapidly translocates from the nucleus to the cytoplasm in response to apoptotic stimuli. PLoS one. 2013 Apr 15;8(4):e61085-e61085 e61085 (301392)

Microcephaly Gene Links Trithorax and REST/NRSF to Control Neural Stem Cell Proliferation and Differentiation
Yang, Yawei J; Baltus, Andrew E; Mathew, Rebecca S; Murphy, Elisabeth A; Evrony, Gilad D; Gonzalez, Dilenny M; Wang, Estee P; Marshall-Walker, Christine A; Barry, Brenda J; Murn, Jernej; Tatarakis, Antonis; Mahajan, Muktar A; Samuels, Herbert H; Shi, Yang; Golden, Jeffrey A; Mahajnah, Muhammad; Shenhav, Ruthie; Walsh, Christopher A. Microcephaly Gene Links Trithorax and REST/NRSF to Control Neural Stem Cell Proliferation and Differentiation. Cell. 2012 Nov 21;151(5):1097-1112 (197612)

A Novel Transcription Complex That Selectively Modulates Apoptosis of Breast Cancer Cells through Regulation of FASTKD2
Yeung, Kay T; Das, Sharmistha; Zhang, Jin; Lomniczi, Alejandro; Ojeda, Sergio R; Xu, Chong-Feng; Neubert, Thomas A; Samuels, Herbert H. A Novel Transcription Complex That Selectively Modulates Apoptosis of Breast Cancer Cells through Regulation of FASTKD2. Molecular & cellular biology. 2011 Mar 28;31(11):2287-2298 (132312)