Thomas Smithgall, PhD

Dr. Smithgall’s research is centered on drug discovery related to HIV/AIDS and cancer.  While antiretroviral drugs have transformed HIV infection from a life-threatening illness to a chronic condition, they do not clear the virus from the patient and require life-long administration.  The Smithgall group has discovered small molecules that block the functions of the HIV-1 Nef virulence factor.  These compounds potently suppress HIV replication and restore immune recognition of HIV-positive cells, raising the exciting possibility of their translational potential in new strategies to eliminate latent viral reservoirs.  Non-receptor protein-tyrosine kinases, including members of the Src family, represent exciting drug targets for leukemia and many other cancers.  Most current kinase inhibitors compete for ATP binding at the kinase domain active site.  However, structural conservation of kinase active sites limits the clinical applications of ATP-competitive kinase inhibitors as well as their utility as chemical probes of individual kinase functions.  To address these issues, the Smithgall laboratory is pursuing drug discovery strategies to find small molecules that enhance the natural allosteric mechanisms associated with kinase regulation.  Promising drug candidates have been identified with potential clinical utility in acute myeloid leukemia, either as stand-alone drugs or in combination with existing ATP-site inhibitors.