Philip D. Stahl, Ph.D.

Professor
Cell Biology and Physiology

Molecular Cell Biology Program
Immunology Program

  • 314-362-6913

  • 314-362-1081

  • 314-362-1490

  • 8228

  • 4912 South Building

  • pstahl@wustl.edu

  • human-specific genes, signal transduction, endocytosis

  • Hominoid-specific genes such as TBC1D3, that regulate growth factor receptor signaling, may explain why human physiology and pathobiology differs from lower species.

Research Abstract:

Cell Biology of Human-Specific Genes--understanding why humans are human at the protein level.The cell and molecular biology of human-specific genes—a virtually untouched field of investigation--will significantly enlarge our understanding of human biology and disease. The human genome contains a relatively small number of genes that are hominoid- or human-specific; not present in mice or other model organisms. Human/hominoid-specific genes may modulate signaling or regulatory pathways that have evolved to a higher level of complexity and that distinguish humans from less complex species. Human-specific genes may operate at the transcriptional level, thereby influencing gene expression, or by regulating translation, altering protein deployment or turnover at the cellular level. They may impose control by regulating the assembly of macromolecular complexes that orchestrate cellular signaling events. The identification, expression and function of human-specific genes will advance our understanding of human biology and pathobiology into a uniquely new domain. Our lab has identified TBC1D3, a breast- and prostate cancer oncogene, as a very promising model. TBC1D3 is hominoid-specific with no known orthologs outside the primate lineage. TBC1D3 expression enhances cell proliferation by enhancing the response to growth factors such as EGF and Insulin. We are currently trying to understand the intracellular targeting, degradation and signal-enhancing properties of TBC1D3.

Rab Cell Biology. A second area of research activity in our lab is focused on the low molecular weight Rab GTPases, the “gatekeepers” of endocytosis and receptor signaling/trafficking. We are currently studying the Rab5 isoforms 5a, 5b and 5c and other endocytic Rabs that regulate growth factor receptors and transporters, such as the fatty acid transporter, CD36, that recycle from the cell surface to and from an intracellular endocytic compartment.

Selected Publications:

Stahl PD, Wainszelbaum MJ. Human-specific genes may offer a unique window into human cell signaling. Sci Signal. 2009 2(89):pe59. http://www.ncbi.nlm.nih.gov/pubmed/19797272

Chen PI, Kong C, Su X, Stahl PD. Rab5 isoforms differentially regulate the trafficking and degradation of epidermal growth factor receptors. J Biol Chem. 2009 284:30328-38. http://www.ncbi.nlm.nih.gov/pubmed/19723633

Wainszelbaum MJ, Charron AJ, Kong C, Kirkpatrick DS, Srikanth P, Barbieri MA, Gygi SP, Stahl PD. The hominoid-specific oncogene TBC1D3 activates Ras and modulates epidermal growth factor receptor signaling and trafficking. J Biol Chem. 2008 283:13233-42. http://www.ncbi.nlm.nih.gov/pubmed/18319245

Last Updated: 8/4/2011 12:26:12 PM

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