William A. Maltese, Ph.D.
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William A. Maltese, Ph.D. Professor Emeritus William.Maltese@utoledo.edu |
RESEARCH INTERESTS :
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.