Mark R. Philips, MD

  • Specialty: Rheumatology
  • Language: English
  • Phone: 212-263-7404
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Credentials

Positions
  • Professor, Department of Medicine
  • Professor, Department of Cell Biology
  • Professor, Department of Biochemistry and Molecular Pharmacology
  • Director for Basic Research CI
Board Certifications
  • American Board of Internal Medicine (Rheumatology), 1988
  • American Board of Internal Medicine - Internal Medicine, 1985
Education and Training
  • Fellowship, NYU Medical Center, Rheumatology, 1988
  • Residency, NYU Medical Center, Internal Medicine, 1985
  • MD from Columbia University, 1982

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Locations and Appointments

522 First Avenue, Smilow Research Building Rm. 1205
New York, NY 10016

Research My Research

Interests

processing and membrane targeting of GTPases, cancer, immunology, pharmacology

Research Summary

Our laboratory is primarily interested in the cell biology of GTPases. GTPases are ubiquitous elements of signaling pathways, including those regulating cell growth and differentiation. Virtually all cellular processes utilize GTPases as regulatory elements including processes that control the immune response. Thus, although our work has immediate relevance to cancer, insights from our studies may be relevant to a wide variety of human diseases including inflammatory and autoimmune disorders.

The protooncogene ras and closely related GTPases are among a class of proteins that are synthesized as soluble molecules in the cytosol and are then targeted to membranes by a series of posttranslational modifications of a C-terminal CAAX sequence that includes prenylation, proteolysis, and carboxyl methylation. Of these modifications, only carboxyl methylation is reversible and may therefore have a signaling function. We therefore focused on the enzyme that catalyzes this modification, prenylcysteine carboxyl methyltransferase, and recently cloned its gene.

Prenylcysteine carboxyl methyltransferase proved to be a multiple membrane spanning protein that is expressed in ER and Golgi but not plasma membrane (see figure). This observation was surprising since it implied that ras, synthesized in the cytosol and destined for the plasma membrane, must make a detour to the ER to complete processing. The ER processing of ras led us to hypothesize that ras is transported to plasma membrane via the vesicular transport system. Using green fluorescent protein-tagged ras proteins we showed that this model is correct. We also showed that carboxyl methylation is required for vesicular transport of ras. We hope to exploit this previously unappreciated aspect of ras biology to develop novel anticancer therapies.

In more recent work we have tested the hypothesis that intracellular ras can be activated and regulate signaling pathways and proved it correct. We accomplished this by developing a novel fluorescent probe that reports when and where Ras becomes activated in living cells. We consider our probe for activated ras a prototyped of a class of molecules that can serve as fluorescent reporters of signaling events in living cells and thereby elucidate many previously inaccessible aspects of signal transduction.

Academic Contact

Lab Website

Research Interests Timeline

These focus areas and their associated publications are derived from PubMed and the MeSH term library.
represents one publication
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Publications

  • Regulation of NOTCH signaling by RAB7 and RAB8 requires carboxyl methylation by ICMT

    Court, Helen; Ahearn, Ian M; Amoyel, Marc; Bach, Erika A; Philips, Mark R Court, Helen; Ahearn, Ian M; Amoyel, Marc; Bach, Erika A; Philips, Mark R
    Journal of cell biology. 2017 Oct 19. 216 (12): 4165-4182

  • Evaluation of the selectivity and sensitivity of isoform- and mutation-specific RAS antibodies

    Waters, Andrew M; Ozkan-Dagliyan, Irem; Vaseva, Angelina V; Fer, Nicole; Strathern, Leslie A; Hobbs, G Aaron; Tessier-Cloutier, Basile; Gillette, William K; Bagni, Rachel; Whiteley, Gordon R; Hartley, James L; McCormick, Frank; Cox, Adrienne D; Houghton, Peter J; Huntsman, David G; Philips, Mark R; Der, Waters, Andrew M; Ozkan-Dagliyan, Irem; Vaseva, Angelina V; Fer, Nicole; Strathern, Leslie A; Hobbs, G Aaron; Tessier-Cloutier, Basile; Gillette, William K; Bagni, Rachel; Whiteley, Gordon R; Hartley, James L; McCormick, Frank; Cox, Adrienne D; Houghton, Peter J; Huntsman, David G; Philips, Mark R; Der, Channing J
    Science signaling. 2017 Sep 26. 10 (498): ?-?
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  • Nitrogen Cavitation and Differential Centrifugation Allows for Monitoring the Distribution of Peripheral Membrane Proteins in Cultured Cells

    Zhou, Mo; Philips, Mark R Zhou, Mo; Philips, Mark R
    Journal of visualized experiments : JoVE. 2017 Aug 18. (126): ?-?

Read All Publications (110)