Cells are encased within a semipermeable barrier known as the plasma membrane. This is a dynamic structure programmed to be responsive to environmental cues that affect cellular physiology. Importantly, key enzyme assemblies that reshape the membrane properties, resulting in the regulation of cellular metabolism and proliferation are associated with the plasma membrane. Failures to regulate these membrane-associated signaling ensembles can lead to excessive cell proliferation, which is one of the hallmarks of cancer. Accordingly, dysfunction and dysregulation of lipid-altering enzymes are frequently associated with cancer. Currently, how membrane-associated signaling mechanisms are regulated...

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Cells are encased within a semipermeable barrier known as the plasma membrane. This is a dynamic structure programmed to be responsive to environmental cues that affect cellular physiology. Importantly, key enzyme assemblies that reshape the membrane properties, resulting in the regulation of cellular metabolism and proliferation are associated with the plasma membrane. Failures to regulate these membrane-associated signaling ensembles can lead to excessive cell proliferation, which is one of the hallmarks of cancer. Accordingly, dysfunction and dysregulation of lipid-altering enzymes are frequently associated with cancer. Currently, how membrane-associated signaling mechanisms are regulated in health and disease remain very poorly understood. My goal as a first-time tenure-track faculty member at University of Texas Health San Antonio (UTHSA) is to understand the regulation of these enzyme ensembles under normal physiological conditions and to determine how this regulatory process becomes dysfunctional in cancer. To accomplish this, we will reconstitute salient membrane-protein complexes to define their structure, function, and regulation germane for deciphering their signaling roles. We will also interrogate how mutations in these enzyme ensembles lead to gastric cancer, which is significantly more prevalent in the Hispanic population in South Texas and thus represents a major health disparity. Insights from our work will set the stage for developing chemical compounds that target these enzyme ensembles in collaboration with our Center for Innovative Drug Discovery. These compounds will provide a valuable tool for the research field and could be further developed into novel gastric cancer therapeutics. Together, our endeavors will make significant contributions toward understanding the etiology of gastric cancer and provide a promising avenue for future cancer drug development.

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