Director, Center for Protein Therapeutics with research focusing on the utilization of pharmacokinetic and pharmacodynamic analyses and mathematical modeling to guide the discovery and development of new immunotherapies for cancer and autoimmunity.

Research Interests and Projects:

1. Development of new therapies for immune thrombocytopenia (ITP). This laboratory has developed new animal models ITP, and these models now allow systematic, mechanistic investigation of new therapies for this common autoimmune disease. Current research is investigating the therapeutic utility of: (a) "Opsisomes" (antibody-coated liposomes) that are designed to block pathways of platelet destruction inITP, (b) an extracorporeal bioreactor that is designed to remove pathogenic autoantibodies, and (c) "Macro-block" a new therapy that is designed to utilize endogenous antibodies and a triggering agent to form immune complexes that block the phagocytic activity of macrophages.
2. Development of FcRn inhibitors. This project focuses on the design and evaluation of inhibitors of FcRn, a transport protein that protects IgG from intracellular catabolism. The inhibitors may have broad utility in the treatment of antibody mediated auto- and allo- immune conditions.
3. Targeting tissue plasminogen activator (tPA). This project will be performed in collaboration with Dr. Victor Yang at the University of Michigan. Research conducted at UB will investigate the utility of novel delivery strategies for selective alteration in the pharmacokinetics and pharmacodynamics of tPA.
4. Targeting chemotherapy with novel derivatives of the TAT peptide. This project represents another collaborative effort between UB and Dr. Yang‘s group at the University of Michigan. Research conducted at UB will investigate the utility of novel delivery strategies that attempt to enhance the pharmacokinetic, pharmacodynamic, and therapeutic selectivity of anti-cancer drugs.
5. Inverse targeting for ovarian cancer. This project employs anti-drug antibodies to alter the distribution and elimination kinetics of chemotherapeutics as a means to provide targeted drug therapy of peritoneal metastases of ovarian cancer. Our approach combines intraperitoneal administration of antineoplastic agents with systemic administration of anti-drug antibodies. The presence of anti-drug antibodies in the systemic circulation leads to rapid binding of drug diffusing out of the peritoneum and entering the blood, thereby reducing the extravascular distribution of the chemotherapeutic. It is anticipated that resultant alterations in the pharmacokinetics of the chemotherapeutic will lead to a reduction in the fraction of drug delivered to tissues associated with toxicity (e.g., bone marrow), without affecting peritoneal drug exposure or peritoneal cytotoxic activity. Thus, this drug targeting approach may beneficially alter the efficacy v. toxicity profile of antineoplastics utilized in the treatment of ovarian cancers.