Stanislaw Stepkowski, D.V.M., Ph.D., D.Sc.
Stanislaw M. Stepkowski, PhD. Professor in the Department of Medical Microbiology and Immunology.
Dr. Stepkowski received his Ph.D. and D.Sc. from the Polish Academy of Sciences, Warsaw, Poland. He carried out his post-doctoral training at Radium Hospital, Oslo, Norway and at Dalhousie University, Halifax, Nova Scotia, Canada. He began his academic career at the rank of Assistant Professor at the University of Texas Medical School, Houston, where he remained until he joined UToledo College of Medicine in 2007.
Dr. Stepkowski’s research interests are in cell and organ transplantation, with focus on improvement of long-term allograft survival and development of new immunosuppressive modalities. More specifically, the laboratory focuses on the cytokine-mediated Jak3/Stat-dependent signals leading to proliferation and differentiation of activated T cells. Based on screening of multiple compounds from NIH database, the laboratory has developed a selective Jak3 inhibitor (NC1153), which may inhibit kidney allograft rejection in rats and cynomolgus monkeys. Most of this work has been published in the Journal of Immunology, Blood, and Transplantation.
Dr. Stepkowski had investigated a sphingosin-1-phosphate receptor (S1P) agonist, FTY720 (2-amino-2-2-[4[octylphenyl]ethyl)propane-1,3-diol hygrochloride), which inhibits allograft rejection. However, this promising compound was abandoned following clinical kidney trials because of its side effects, and in particular bradycardia and hypertension, which occurred because of poor selectivity of this compound. Over the last 2 years, the laboratory has tested a novel compound, KRP203 (2-amino-2-propanediol hydrochloride), with selective agonist activity on S1P1. Recent results showed that KRP203 not only extends allograft survival of kidney allografts but also induces transplantation tolerance to pancreatic islet allografts when combined with local infusion of T regulatory cells. One cannot overemphasize the implication of this work on type 1 diabetes.
More recently, the laboratory showed that a short therapy with anti-T cell receptor (TCR) monoclonal antibody prevented development of Type 1 Diabetes (T1D) as well as blocked onset of the disease in two mouse models. These results correlated with significant expansion of CD4+Foxp3+ regulatory T (Treg) cells. Furthermore, the laboratory has shown that anti-TCR mAb did not produce a cytokine storm similar to anti-CD3 mAb, the latter therapy is currently used in clinical trials. The plan is to produce humanized anti-human TCR mAb, which will be tested in vivo in humanized mouse model of islet and vascularized artery transplantation.
Dr. Stepkowski has developed multiple collaborations with other members of CeDER to investigate the role of the immune response in the pathogenesis of obesity and obesity-induced diseases, including diabetes, non-alcoholic steatohepatitis (NASH) and atherosclerosis.
Dr. Stepkowski has authored more than 150 peer-reviewed articles. His research has been continuously funded by grants from the NIH.