Department of Cell and Cancer Biology

William A. Maltese, Ph.D.

Maltese William A. Maltese, Ph.D.
Professor Emeritus

Prior to his retirement, Dr. Maltese's research was funded by the NIH for 34 years. His early work established connections between cholesterol metabolism and tumor development and contributed to the discovery of a novel posttranslational modification termed "isoprenylation", wherein isoprenoid intermediates derived from the cholesterol pathway provide membrane anchors for numerous proteins, including members of the Ras, Rac and Rab GTPase families. Subsequent studies focused on the roles of Rab GTPases in intracellular vesicular trafficking, and utilized dominant-negative Rab mutants to dissect trafficking pathways that contribute to the post-translational proteolytic processing of the Alzheimer's beta-amyloid precursor protein. Dr. Maltese's interest in endocytic trafficking pathways ultimately led his group to study the interface between these pathways and the intracellular "self-eating" process of autophagy, which plays an important role in the survival of glioblastoma cells. An offshoot of his work finally led to the discovery of a new mechanism of cell death that was named 'methusosis' by the Maltese lab. In methuosis, dysregulated vesicle trafficking pathways for micropinocytosis and endocytosis causes catastrophic accumulation of fluid-filled vacuoles and loss of cellular integrity via a mechanism that is distinct from classical programmed cell death (apoptosis). It is now recognized that cancer cells may be particularly vulnerable to this form of cell death. Based on these observations, the Maltese lab launched a collaborative effort with Dr. Erhardt and others in UT's Center for Drug Design and Development to identify new chemical compounds that can trigger methuosis in brain cancers and other types of tumors. These efforts recently led to the development of several patented lead compounds that showed promise in penetrating the blood-brain barrier and slowing the growth of glioblastoma in preclinical models.


Last Updated: 6/27/22