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Peter Espenshade, Ph.D.

Peter J. Espenshade, Ph.D.

Headshot of Peter Espenshade
  • Associate Dean for Graduate Biomedical Education
  • Professor of Cell Biology

Research Interests

Lipid Metabolism; Cholesterol; Cancer; Pancreas; Sterol Regulatory Element Binding Protein (SREBP); Hypoxia; Homeostasis; Nutrient Sensing ...read more

Background

Dr. Peter J. Espenshade is a professor of cell biology at the Johns Hopkins University School of Medicine. He also serves as the Associate Dean for Graduate Biomedical Education.

The Espenshade Lab studies mechanisms of nutrient sensing with specific interests in regulation of cellular cholesterol homeostasis and the cellular response to hypoxia. The Espenshade Lab initially used fission yeast as a model genetic organism to address these questions but has extended these studies to mice and mammalian cell culture.

Dr. Espenshade earned an A.B. in molecular biology from Princeton University and his Ph.D. in cell biology/genetics from the Massachusetts Institute of Technology. He completed postdoctoral training with Drs. Michael Brown and Joseph Goldstein at UT Southwestern Medical Center in Dallas before joining the Johns Hopkins faculty as an Assistant Professor in 2003.

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Titles

  • Associate Dean for Graduate Biomedical Education
  • Executive Director, Center for Innovation in Graduate Biomedical Education
  • Professor of Cell Biology
  • Professor of Oncology

Departments / Divisions

Centers & Institutes

Education

Degrees

  • Ph.D.; Massachusetts Institute of Technology (Massachusetts) (1998)
  • B.A.; Princeton University (New Jersey) (1990)

Additional Training

  • UT Southwestern Medical Center, Dallas, TX, 2002, Molecular Cell Biology

Research & Publications

Research Summary

Elevated blood cholesterol is a primary risk factor for heart disease, and overaccumulation of cholesterol and fatty acids is toxic to cells. A negative feedback mechanism prevents excessive lipid accumulation in cells by regulating sterol regulatory element-binding proteins (SREBPs), a family of membrane-bound transcription factors that activate genes required for cholesterol and fatty acid synthesis and uptake of cholesterol-rich lipoproteins. Using yeast genetics as a discovery tool, we found that fungal SREBPs respond to environmental oxygen and control cellular adaptation to hypoxia. The fungal SREBP pathway is required for hypoxic growth and importantly for host infection by fungal pathogens, making it a candidate antifungal drug target.

Solid tumors are poorly vascularized, leading to hypoxia and limited nutrient supply. Further, lipid synthesis is highly oxygen-consumptive, so neoplastic cells in a hypoxic environment are challenged with meeting the demand for lipid supply. Our discoveries in fungi motivated us to extend our studies to mammalian cells in order to examine (1) whether the SREBP pathway also responds to hypoxia in mammals and (2) whether SREBPs are required for cancer initiation, progression, and metastasis.

Current project areas:

Mechanisms for regulation of SREBPs - Using genetics and cell biology, we are searching for new regulators of the SREBP pathway and cellular lipid homeostasis.

Regulation of the Hypoxia Inducible Factor (HIF) by lipoproteins – We discovered that HIF responds to changes in lipid supply and are working to describe this mechanism and the physiological implications of this pathway.

SREBP pathway as a therapeutic target in cancer – Using xenograft and genetically engineered mouse models, we are testing whether SREBPs are required for cancer initiation, tumor growth, and metastasis. In parallel, we are developing chemical inhibitors of the pathway as potential cancer therapeutics.

Lab

Lab Website: Espenshade Lab

Selected Publications

View all on PubMed

Esquejo RM, Roqueta-Rivera M, Shao W, Phelan PE, Seneviratne U, Am Ende CW, Hershberger PM, Machamer CE, Espenshade PJ, Osborne TF. 2021. Dipyridamole inhibits lipogenic gene expression by retaining SCAP-SREBP in the endoplasmic reticulum. Cell Chem Biol. 28:169-179

Shao W, Espenshade PJ. 2014. Sterol regulatory element-binding protein (SREBP) cleavage regulates Golgi-to-endoplasmic reticulum recycling of SREBP cleavage-activating protein (SCAP). J Biol Chem. 289:7547-57

Clasen SJ, Shao W, Gu H, Espenshade PJ. 2017. Prolyl dihydroxylation of unassembled uS12/Rps23 regulates fungal hypoxic adaptation. eLife 6:e28563

Shao W, Hwang J, Liu C, Mukhopadhyay D, Zhao S, Shen MC, Selen ES, Wolfgang MJ, Farber SA, Espenshade PJ. 2020. Serum lipoprotein-derived fatty acids regulate hypoxia-inducible factor. J Biol Chem. 295:18284-18300

Shao W, Espenshade PJ. 2012. Expanding roles for SREBP in metabolism. Cell Metab. 16:414-419

Academic Affiliations & Courses

Graduate Program Affiliation

Biochemistry, Cellular and Molecular Biology Graduate Program

Cellular and Molecular Medicine Graduate Program

Activities & Honors

Honors

  • Fellow, American Association for the Advancement of Science, 2014
  • Avanti Young Investigator Award in Lipid Research, American Society for Biochemistry and Molecular Biology, 2012
  • Established Investigator Award, American Heart Association, 2008
  • Investigator in Pathogenesis of Infectious Disease, Burroughs Wellcome Fund, 2006
  • Career Award in the Biomedical Sciences, Burroughs Wellcome Fund, 2001
  • National Research Service Award, National Heart, Lung and Blood Institute, 1998
  • Predoctoral fellowship, National Science Foundation, 1992
  • Phi Beta Kappa Honor Society, Princeton University, 1990

Memberships

  • American Society for Cell Biology
  • American Society for Biochemistry and Molecular Biology
  • American Association for the Advancement of Science
  • Advisory Council, National Institute for General Medical Sciences
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