Dr. Ilya Levental
The University of Texas Health Science Center at Houston
McGovern Medical School
Department of Integrative Biology and Pharmacology
Though the structure-function relationship of polypeptides is one of the core dogmas of molecular cell biology, the functional aspects of lipid structure have been little explored. The existence of lipid rafts, i.e. lateral membrane domains arising from preferential interactions between specific lipids, suggests that such structure could be an important contributor to cell function and pathophysiology. The involvement of these domains in diverse cellular functions (e.g. growth factor signaling and membrane trafficking) and disease processes - including cancer, autoimmunity, and Alzheimer’s disease - has confirmed this potential and energized the field. Recent compelling evidence has definitively resolved the controversy about the existence of membrane domains; however, the mechanisms by which they regulate cell function remain speculative due to a lack of quantitative, robust tools for their investigation.
Our primary research goals are: (1) to investigate the physical principles behind the formation of membrane domains; (2) to uncover the mechanisms by which these domains regulate cell signaling; and (3) to develop strategies to modulate these mechanisms for treatment of human disease.
Ongoing project #1: using an exciting and novel tool in membrane biology, phase separation in Giant Plasma Membrane Vesicles (GPMVs) to assay raft-dependent ligand binding and oligomerization of the Epidermal Growth Factor Receptor (EGFR) and its oncogenic homolog HER2.
Ongoing project #2: measuring changes in raft formation, physical properties, and composition of plasma membranes of mesenchymal stem cells as they proceed through terminal differentiation
Ongoing project #3: developing a quantitative protein lipidation assay and using it to characterize palmitoylation dynamics in immune and cancer cell signaling
Ongoing project #4: designing transmembrane domain mutants of EGFR to determine the requirements for its raft association and oligomer formation
Ongoing project #5: developing drugs to specifically target protein transmembrane domains