Professor & Associate Head of Department Georgia Cancer Coalition Scholar Our lab uses a variety of technical approaches to better understand how post-translational modifications regulate the function of CaaX-type proteins. These proteins are subject to an ordered series of C-terminal modifications: isoprenylation, proteolysis, and carboxylmethylation. Prominent examples of CaaX proteins can be found among the Ras family of oncoproteins that are often mutated in cancer. Standard v. Shunt Pathway: We recently discovered that certain CaaX proteins follow an isoprenylation-only branch of the standard modification pathway that we refer to as the shunt pathway. Pathway preference appears linked to optimal CaaX protein function. We are determining the pathway followed by various CaaX protein reporters and detailing the consequences of altering their modification preference. These consequences range from altered protein activity, to differential localization, to changes in cellular phenotypes.The CaaX Proteases: Rce1p and Ste24p are ER membrane-localized proteases. Our research centers on their proteolytic mechanisms, substrate profiles, and biological roles in the cell. We expect to gain a better understanding of their function as gatekeepers for CaaX protein modificaiton via the standard pathway and their utility as targets for disease therapy (e.g. cancer treatment).The M16A Proteases: Ste23p and Axl1p are zinc-dependent metalloproteases that are part of the M16A subfamily of metalloproteases. They are related to the insulin-degrading enzyme (IDE) that has a proposed protective function in Alzheimer's disease (AD). Our research on Ste23p and Axl1p is designed is to gain a better understanding of the largely uncharacterized M16 metalloprotease family as a whole, thus potentially providing novel insight into new methods for the treatment of AD and possibly other diseases.The RAS Initiative: Want to learn more about Ras and therapeutic approaches aimed at interfering with Ras biology? The National Cancer Institute recently launched a national campaign to develop resources and new knowledge about Ras biology. Education Education: PostDoc: Johns Hopkins University School of Medicine, 2001 PhD: University of California (Berkeley), Ph.D., 1995 Undergraduate: Rice University, B.A., 1989 Highschool: Weslaco High School, 1985 Research Research Areas: Cancer Biology Cell Biology Cellular & Molecular Neuroscience Drug Discovery & Development Fungal Biology Selected Publications Selected Publications: NCBI MyBibliography Google Scholar Pubmed Courses Regularly Taught Courses Regularly Taught: BCMB 3100 BCMB 8214 Other Website Other Website: https://schmidtlab.uga.edu/ Grants Grants: 2016-20 National Institutes of Health R01 (R01 GM117148) - Role of proteolysis in regulating CaaX protein function. 2019-24 National Institutes of Health R01 (R01 GM132606) - Determining the scope of prenylatable protein sequences.
