Paul M. Epstein, PhD

Dr. Epstein's laboratory has been studying cyclic nucleotide phosphodiesterases (PDE), a large family of isozymic enzymes which control the cellular levels of two key signal transduction molecules, cAMP and cGMP, and thereby play a role in controlling a wide variety of critical cellular functions. Through cloning and sequence analysis, he is identifying different forms of phosphodiesterase and determining their expression and subcellular localization during normal development and in association with pathophysiological disease states. One disease sate he is concentrating on in particular is leukemia. He has found that a 63 kDa form of calmodulin-dependent PDE (PDE1B1) is expressed in leukemia cells but not in normal quiescent human lymphocytes. He cloned the cDNA for this gene and developed antisense oligonucleotides (ASODNs) against it. When he disrupts the expression of the gene for PDE1B1 with these AS ODNs, it triggers apoptosis in leukemic cells without any effect on normal resting lymphocytes. Hence these studies pioneer the basis for a possible new therapy for leukemia. Similar studies are now being undertaken with respect to breast cancer.

[2022] Editorial: Cyclic Nucleotide Phosphodiesterases (PDEs) in Immune Regulation and Inflammation. [2022] Treatment of Experimental Autoimmune Encephalomyelitis with an Inhibitor of Phosphodiesterase-8 (PDE8) [2022] Cyclic Nucleotide Phosphodiesterases (PDEs) in Immune Regulation and Inflammation [2022] PDE8 controls CD4(+) T cell motility through the PDE8A-Raf-1 kinase signaling complex. [2022] Different phosphodiesterases (PDEs) regulate distinct phosphoproteomes during cAMP signaling. [2022] Differential Expression and Function of PDE8 and PDE4 in Effector T cells: Implications for PDE8 as a Drug Target in Inflammation. [2022] Inhibition of breast cancer cell migration by activation of cAMP signaling. [2022] Effect of cAMP signaling on expression of glucocorticoid receptor, Bim and Ba