TRAINING IN PHARMACOLOGY, TOXICOLOGY & PHARMACEUTICAL SCIENCES 2008 ASPET SUMMER UNDERGRADUATE RESEARCH FELLOWSHIP OPPORTUNITY at the UNIVERSITY OF CINCINNATI
The Department of Pharmacology & Cell Biophysics, College of Medicine is pleased to offer this research project as part of the 2008 summer ASPET SURF Training Program offered by the Department of Pharmacology & Cell Biophysics.  Students interested in this project are encouraged to contact Professor Kirley to discover more about the project, learn what your responsibilities will be during the ten-week research training program.
2008 ASPET SURF Project #:  08-017 Faculty Supervisor/Mentor: Terence L. Kirley, Ph.D., Professor Pharmacology & Cell Biophysics College of Medicine, University of Cincinnati Email: terry.kirley@uc.edu
Project Title: Epitope Mapping of Inhibitory Antibodies as a First Step to Develop Specific Inhibitors for Ecto-Nucleotidases
Research Program Description: The long-term goal of my laboratory is the determination of the structures and functions of the cell membrane and soluble ecto-nucleotidases. Receptors for extracellular nucleotides (purinergic and pyrimidinergic receptors) occur in many parts of the body, perform many different physiological functions, and respond to different types of nucleotides (e.g., ATP vs. UTP), as well as to different phosphorylation states of each nucleotide (e.g., ATP vs. ADP vs. AMP vs. adenosine). The ecto-nucleotidases are important for the regulation of the many physiological and pathological signaling processes under purinergic control, including pain perception and maintenance of hemostasis via hydrolysis of the platelet activator, ADP. Ecto-nucleotidases have also been implicated as important for cell adhesion, angiogenesis, and cancer development.  Unfortunately, no good specific inhibitors for these enzymes are known, hampering progress in determining the physiological functions of the different members of this family of enzymes. We employ immunological, molecular biological, biophysical, structural biological and basic biochemical techniques to study the structures and functions of these enzymes. We are currently studying two unrelated families of ecto-nucleotidases – the ecto-Nucleoside Triphosphate Diphosphohydrolases (NTPDases) and the calcium activated nucleotidases.  The first enzyme family is being examined to learn how to modulate purinergic signaling and all the biological processes that it controls, while the second enzyme family is being studied in order to generate a new and efficacious injectable anti-coagulant proteins, to be developed for the treatment of heart attacks, ischemic strokes, and other clotting pathologies.
ASPET SURF Project Description: We have obtained inhibitory monoclonal antibodies that are specific for human NTPDase3 ecto-nucleotidase.  We are currently attempting to localize the inhibitory epitope.  This is important since, given our knowledge of the structures of the NTPDases and the many mutations and biochemical tools we have developed to study NTPDase3, we plan to use the additional knowledge of the epitope location to design inhibitors for not just this enzyme, but for the other members of this family of enzymes.  If successful, this project would be a significant advancement in the field and the beginning of a new direction for our laboratory.  The ASPET SURF student would work closely with Dr. Kirley and members of his laboratory to define a specific sub-project involved in this larger project that would result in publishable data within the 10 week training period. The student would be expected to do background literature reading, participate in lab group meetings, and interact with other lab personnel working on other projects.  The ASPET SURF student would learn many biochemical, immunological and molecular biological techniques during the training experience. Significant research program contributions made by the ASPET SURF student will earn co-authorship on presentations and publications arising from this federally funded research.