Paul M. Epstein, Ph.D.Associate Professor, Department of Cell Biology
|Ph.D.||Albert Einstein School of Medicine||Molecular Biology|
|Name of Award/Honor||Awarding Organization|
|Principal inventor on US Patent Application No. 20090105281 on “Methods of Treating Inflammation”|
|Principal inventor on US Patent No. 5,885,834 on “Synthesis of Antisense Oligodeoxynucleotide of Phosphodiesterase and Inducement of Apoptosis in Human Lymphoblastoid Cells|
|Fellow of the Rosalie B. Hite Foundation for Cancer Research|
|NIH Predoctoral Trainee|
|Scholarship for Woods Hole Marine Biological Laboratory Physiology Program|
|Dean’s List Columbia College||Columbia College|
|New York State Regents Scholarship|
Not accepting lab rotation students at this time
Lab Rotation Projects
Most of the emphasis of the lab at the moment is identifying forms of PDE as targets for inducing apoptosis of cancer cells. We are also collaborating with two colleagues in Pharmacology, Drs. Joel Pachter and Stefan Brocke, to examine a potential role for inhibitors of PDE to strengthen the blood brain barrier as a means of treating Alzheimer’s Disease, and to examine a potential role for PDEs in regulating lymphocyte chemotaxis and transendothelial migration in relation to treating multiple sclerosis. Students are free to design their own projects, but possibilities are:
Project 1: We have found that stimulating the cAMP signaling pathway can overcome the resistance to inducing apoptosis in leukemic cells from patients that have developed glucocorticoid resistance (see: Tiwari, S. et al. “Type 4 cAMP Phosphodiesterase (PDE4) Inhibitors Augment Glucocorticoid-Mediated Apoptosis in B Cell Chronic Lymphocytic Leukemia (B-CLL) in the Absence of Exogenous Adenylyl Cyclase Stimulation.” Biochem. Pharmacol. 69:473-483, 2005). The mechanism of this effect is, however, still unknown. One hypothesis we have is that cAMP signaling may enhance the expression and/or function of the BH3-only proapoptotic proteins BAD and BIM, leading to apoptosis of these resistant cells, and this could be examined as a rotation project.
Project 2: Work from Dr. Pachter’s laboratory has pioneered a method for culturing primary brain microvascular endothelial cells (BMEC) in a manner in which the tight junctions of the endothelial cells are preserved (see: Song, L. and Pachter, J. S. Culture of murine brain microvascular endothelial cells that maintain expression and cytoskeletal association of tight junction-associated proteins. In Vitro Cell Dev Biol Anim, 39: 313-320, 2003). This therefore provides a model in vitro system in which to examine the effects of agents on the blood brain barrier. We hypothesize that PDE inhibitors will strengthen the blood brain barrier by enhancing the expression of expression of the tight junction-associated proteins, claudin-5, occludin, and zona occludin-1 (ZO-1), and this could be examined as a rotation project.
Project 3: PDE4 inhibitors have been shown to be effective in ameliorating the pathogenesis associated with multiple sclerosis (MS) in EAE animal models of this disease, though it is unclear how they work in this regard. We hypothesize that PDE4 inhibitors block T lymphocyte chemotaxis and transendothelial migration through their ability to induce phosphorylation and inactivation of rhoA resulting in decreased phosphorylation of myosin light chain, and, with the help of Dr. Brocke who is a renowned expert in this area, this can be tested in a rotation project.