University Of Kentucky - Thomas C. Vanaman

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Thomas C. Vanaman
Professor
B.S. University of Kentucky
Ph.D. Duke University
vanaman@pop.uky.edu
859-257-1347

Research Interests | Publications | PubMed

Research Interests:
The structure, function and molecular biology of Ca²⁺ dependent regulatory proteins (particularly calmodulin) and the target proteins which they regulate is under study. One primary focus is the plasma membrane Ca²⁺-pumping ATPase (PMCA) in eucaryotes. Multiple isoforms of this enzyme are produced by alternative splicing of primary transcripts of four distinct genes. By artificial manipulation of expression through recombinant DNA methods, we have shown that products of one of these genes is required for proper cell adhesion, expression of a specific cell adhesion moleucle and for proper nerve growth factor action in a neuronal cell paradigm. We have also shown that the plasma membrane calcium pump is regulated by contact mediated tyrosine phosphorylation in both excitable cells and platelets. Studies are currently in progress using a variety of biochemical, immunological and molecular biological approaches to further elucidate the functions, expression, localization and physiological roles of specific PMCA isoforms and their regulation during normal animal cell development and in proceseses such as cell movement and attachment - linked to cell contact mediated tyrosine phosphorylation. Studies also are in progress to determine whether natural alterations in PMCA expression and/or function play a causal role in cancer, neurological disorders or other diseases linked to abnormal Ca²⁺-signaling. A second major area of study concerns depolarization depemndent reversible phodsphorylation of various protein factors of the vesicular neurosecretory apparatus and the possible dysfunction in this system in epilepsy. A final area of study involves molecular modeling based approaches to develop new photoactive arylazide derivatives of anti-schizophrenic phenothiazines and the use of these reagents to study the primary targets for their neuropharmacological action, dopamine receptors. Parallel studies are investigating their interaction with secondary targets such as calcineurin and calmodulin which may be responsible for unwanted side effects and the multidrug resistance drug transporter, P-glycoprotein, where interaction may enhance potential for cancer chemotherapy.

Representative Publications:

Barnes, G. N., Slevin, J. T., and Vanaman, T. C. Rat Brain Protein Phosphatase 2A: An Enzyme Which May Regulate Autophosphorylated Protein Kinases. J. Neurochem. 64: 340-353, 1995.
DeLaLuz, P., Golinski, M., Watt, D. S. and Vanaman, T. C. Synthesis and use of a biotinylated 3-azido phenothiazine to photolabel both amino and carboxyl terminal sites in calmodulin. Bioconjugate Chem., 6: 558-566, 1995.
Brandt, P., Sisken, J. and Vanaman, T. C. The Plasma Membrane Calcium Pumping ATPase Isoform I is Essential for Neurite Extension in Pheochromocytoma Cells. Proc. Nat'l Acad. Sci. submitted, 1996.