Photo of Paul M. Epstein, Ph.D.

Paul M. Epstein, Ph.D.

Associate Professor, Department of Cell Biology
Academic Office Location:
Cell Biology
UConn Health
263 Farmington Avenue
Farmington, CT 06030-6125
Phone: 860-679-2810
Fax: 860-679-3693

Cell Biology Graduate Program

Genetics & Developmental Biology Graduate Program

Neuroscience Graduate Program

Skeletal Biology and Regeneration Graduate Program

Epstein Publication Bibliography

Epstein Researcggate Profile

Curriculum Vitae:

Name of Award/HonorAwarding Organization
Principal inventor on US Patent Application No. 20090105281 on “Methods of Treating Inflammation”United States Patent and Trademark Office
Principal inventor on US Patent No. 5,885,834 on “Synthesis of Antisense Oligodeoxynucleotide of Phosphodiesterase and Inducement of Apoptosis in Human Lymphoblastoid CellsUnited States Patent and Trademark Office
Fellow of the Rosalie B. Hite Foundation for Cancer Research Rosalie B. Hite Foundation
NIH Predoctoral Trainee NIH
Scholarship for Woods Hole Marine Biological Laboratory Physiology Program Marine Biological Laboratory
Dean’s List Columbia College Columbia College
New York State Regents Scholarship New York State
Name & DescriptionCategoryRoleTypeScopeStart YearEnd Year
Committee on Undergraduate Medical Education (CUME)Education CommitteeChairUConn HealthUniversity20232028
CellsProfessional/Scientific JournalEditorial BoardExternalInternational2020
UCH Medical School Coaching ProgramAdvisory CommitteeAdvisorUConn HealthUniversity20162020
American Association for Cancer ResearchProfessional/Scientific OrganizationMemberExternalNational2007
Biochemical JournalEditorial BoardEditorial AdvisorExternalInternational2003
Medical and Dental Student Research Day CommitteeResearch CommitteeMember and ChairUConn HealthUniversity19962012
Committee on Student ResearchResearch CommitteeChairUConn HealthUniversity19942012
NIH Physiological Chemistry Study SectionStudy SectionMemberExternalNational1989
Director of the Graduate Program in Cell and Molecular PharmacologyEducation CommitteeDirectorUConn HealthUniversity19881999
Society for NeuroscienceProfessional/Scientific OrganizationMemberExternalNational1983
American Society for Pharmacology and Experimental TherapeuticsProfessional/Scientific OrganizationMemberExternalInternational1975
New York Academy of SciencesProfessional/Scientific OrganizationMemberExternalInternational1975
American Association for the Advancement of ScienceProfessional/Scientific OrganizationMemberExternalInternational1975
Sigma XIProfessional/Scientific OrganizationMemberExternalInternational1975

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.

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.

Journal Articles


  • Paul M. Epstein, Stefan Brocke, Michy P. Kelly, Leila Gobejishvili Cells Special Issue on "Phosphodiesterases (PDEs): Therapeutic Targets in Human Health and Disease." see: 2024 Jul;
  • Cyclic Nucleotide Phosphodiesterases (PDEs) in Immune Regulation and Inflammation
    Stefan Brocke, Paul M. Epstein, Robert Nelson and Tim Vanmierlo Electronic Book for Frontiers in Pharmacology 2022 Jun;
  • Epstein Paul M, editor Cyclic nucleotide phosphodiesterases (PDEs) in immune regulation and inflammation

Book Chapters


  • Methods of Treating Inflammation
    Epstein, P.M., Brocke, S., Dong, H. and Dall, A. United States Patent Publication Number US20090105281 2009 Jan;1-45
  • Synthesis of Antisense Oligodeoxynucleotide of Phosphodiesterase and Inducement of Apoptosis in Human Lymphoblastoid Cells
    Epstein P.M. United States Patent Publication Number US005885834 1999 Mar;


Title or AbstractTypeSponsor/EventDate/YearLocation
PDEs in Vascular and Metabolic ProcessesPanel DiscussionGordon Research Conference on Cyclic Nucleotide Phosphodiesterases2022Gordon Research Conference, Les Diablerets Switzerland
Cyclic Nucleotide Phosphodiesterase 8 as a Target to Treat Autoimmune InflammationTalkGordon Reseach Conference on Cyclic Nucleotide Phosphodiesterases2022Gordon Research Conference, Les Diablerets Switzerland
"Phosphodiesterase 8A domains at the site of leucocyte-endothelial cell adhesion in ulcerative colitis submucosa." Poster13th Congress of ECCO. Inflammatory Bowel Disease201913th Congress of ECCO, Inflammatory Bowel Disease
Novel Approaches to Overcoming Glucocorticoid Resistance in the Treatment of Lymphoid LeukemiasPosterGordon Research Conference2018Sunday River Maine
Targeting Phosphodiesterase-8: PDE8 Controls Autoimmune Inflammation by Mechanisms Distinct from PDE4 InhibitionTalkGordon Research Conference2018Sunday River Maine
Modulating inflammatory properties of brain derived endothelial cells through PDE8PosterMS Society2016Rocky Hill Connecticut
Targeting the PDE8A-Raf-1 kinase signaling complex to treat autoimmune inflammationPosterMS Society2016Rocky Hill Connecticut
Discovering New Medicines with a Novel Drug Target - PDE8TalkCURE2014UConn Health
Targeting PDE8 to treat inflammation in vivoGordon Research Conference2014Mt Holyoke MA
The Role of PDE8 in EAEPoster2014Mt Holyoke MA
Inhibition of Breast Cancer Cell Migration by Activation of cAMP SignalingTalkGordon Research Conference2014Mt Holyoke MA
Interplay Between Glucocorticoid and cAMP Signaling on Induction of Apoptosis in Leukemia and Multiple Myeloma CellsTalkGordon Research Conference2010Waterville Valley NH
Inhibition of Breast Cancer Metastasis by Activation of cAMP SignalingTalkConnecticut Breast Health Initiative2008New Britain CT
PDE8 as a Potential Target for Inhibition of Lymphocyte ChemotaxisTalkGordon Research Conference2006U. of New England Biddeford ME
Interplay Between Glucocorticoid and cAMP Signaling Pathways on Induction of Apoptosis in Leukemic CellsTalkGordon Research Conference2004Barga Italy
Exisulind and Its Derivatives Inhibit Jurkat Cell Proliferation by an Apparent Non-cGMP Dependent MechanismPosterGordon Research Conference2002Mt Holyoke MA
PDE as a potential target for inducing apoptosis of breast cancer cellsTalkGordon Research Conference2000Oxford U. England
Co-Expression of Four Splice Variants of cGMP-Stimulated Phosphodiesterase (PDE2) in Rat BrainTalkGordon Research Conference1999Waterville Valley ME
Cloning of the Human PDE1B1 Gene and its Potential as a Therapeutic Target for Treatment of LeukemiaTalkGordon Research Conference1998New London NH
PDE1 Molecular Biology and TherapeuticsTalkWilliam Harvey Research Conference1997Royal College of Physicians, London England