Penn Cardiovascular Institute

Lazar Lab

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Mitchell A. Lazar, MD, PhD

Mitchell A. Lazar, MD, PhD
Principal Investigator

Mitchell A. Lazar, MD, PhD
Sylvan Eisman Professor of Medicine
Chief, Division of Endocrinology, Diabetes, and Metabolism
Director, Institute for Diabetes, Obesity, and Metabolism
Perelman School of Medicine at the University of Pennsylvania
12-102 Smilow Center for Translational Research
3400 Civic Center Blvd., Bldg. 421
Philadelphia, PA 19104
Office: 215-898-0198
lazar@mail.med.upenn.edu

Overview

The Lazar Lab is interested in the transcriptional regulation of metabolism by nuclear receptors, particularly in the context of obesity, insulin resistance and diabetes. Lazar Lab members are studying how nuclear receptor signaling and adipocytokines contribute to cardiovascular disease, which is the leading cause of death in diabetes.

Research Projects

The Lazar laboratory is studying the transcriptional and epigenomic regulation of metabolism with a keen focus upon the role played by nuclear receptors (NRs). In the absence of ligand, NRs bind to DNA and function as potent transcriptional repressors by recruiting corepressor complexes that include the chromatin modulating histone deacetylase HDAC3. The Lazar Lab investigates all aspects of these interactions, using a combination of epigenomic, bioinformatic, and genetic approaches, with particular attention to the nuclear receptors for thyroid hormone as well as the orphan receptor Rev-erbα.

Rev-erbα is a key repressive component of the circadian clock that senses heme levels to coordinate metabolism and biological rhythms. The molecular, cellular, and integrative biology of these factors are being studied in mouse and human cell lines, as well as in mouse knock-in and knock-out models.

The Lab is also studying PPARγ, a nuclear receptor that is a master regulator of adipocyte (fat cell) differentiation using ChIP-sequencing and computational biological methods to identify the entire set of genes bound to PPARγ in adipocytes and other cell types, and linking this to epigenomic regulation of transcription and metabolism. Ligands for PPARγ have potent antidiabetic activity, and thus PPARγ represents a long sought-after link between obesity and diabetes.

The Lab discovered resistin, a novel hormone and target of PPARγ made and secreted by fat cells in rodents and by macrophages in humans, has demonstrated that resistin regulates insulin responsiveness, and is now using mice humanized for resistin to test the hypothesis that resistin links metabolism to inflammation in human metabolic diseases.

Members

The Lazar Lab is comprised of post-doctoral researchers, research specialists and graduate students.

  • Shannon Mullican, PhD
    Post-doc
  • David Steger, PhD
    Research Assistant Professor
  • Seo-Hee You, PhD
    Post-doc
  • Ana Cristancho MD
    PhD Student
  • Dan Feng
    Graduate Student
  • Fenfen Wang
    Graduate Student
  • Sonia Step
    Graduate Student
  • Ray Soccio, MD, PhD
    Post-doc
  • Zheng Sun, PhD
    Post-doc
  • Joanna DiSpirito, PhD
    Post-doc
  • Logan Everett, PhD
    Post-doc
  • Jennifer Jager, PhD
    Post-doc
  • Zachary Gerhart-Hines, PhD
    Post-doc
  • Bin Fang, PhD
    Post-doc
  • Jill Marinis, PhD
    Post-doc
  • Sean Armour, PhD
    Post-doc
  • Erika Briggs
    Research Specialst
  • Lindsey Peed
    Research Specialist
  • Eric Chen
    Research Specialist
  • Jessa Tunacao
    Research Specialist
  • Joe Weaver
    Lab Manager

Selected Publications

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