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Medicinal and Biological Chemistry
Katherine A. Wall
Professor and Chair, Department of Medicinal and Biological Chemistry
|B.S., 1971||Montana State University|
|Ph.D., 1977||University of California at Berkeley|
|Damon Runyon-Walter Winchell
Cancer Research Fellowship
|Massachusetts Institute of Technology|
|NIH Fellowship, 1980-82||University of Chicago|
|Visiting Investigator 2000-01||University of Michigan|
|Visiting Professor 2010||University of Rochester Medical Center|
Immunology and biochemistry; molecular analysis of the autoimmune disease myasthenia gravis using a murine model system; design of immunomodulatory drugs.
I have three major projects ongoing in my laboratory.
1) Cytokines in Myasthenia Gravis
Myasthenia gravis is an autoimmune disease characterized by autoantibodies to the nicotinic acetylcholine receptor. Over the past 20 years, my collaborators and I have defined the T cell response to the acetylcholine receptor in a murine model of myasthenia gravis, experimental autoimmune myasthenia gravis (EAMG). Currently we seek to determine the mechanisms by which factors other than antibody titer affect disease severity in myasthenia gravis. We are studying the role of the cytokine interleukin 12 (IL-12) in enhancing passive transfer of EAMG. We have shown that interferon gamma is important in enhancing disease and are determining the source of interferon gamma and its effects on muscle tissue
2) Glycopeptide-Based Cancer Antigen Vaccines
This project is a collaboration with Dr. Steve Sucheck of the UT Dept. of Chemistry. We have been studying the immune response of mice to cancer vaccines containing synthetic cancer glycopeptide antigens with a covalently attached rhamnose epitope. This is designed to take advantage of anti-rhamnose antibodies that occur naturally in humans and can be generated in mice. We are developing additional synthetic vaccines that take advantage of antibody targeting.
3) CD38 and NAD Metabolites in Lymphocyte Signaling
I have a longstanding interest in the role of NAD metabolites in lymphocyte function. During a sabbatical with Dr. Frances Lund in Rochester, NY in 2010, I began a study of CD38 and NAD metabolites in T cell function. My lab is continuing a collaboration with Dr. James Slama to examine the role of NAADP, a newly discovered calcium mobilizing agent, in lymphocyte signaling and function.
- A disease-related epitope of Torpedo acetylchone receptor: residues involved in IAb
binding, self-nonself discrimination, and TCR antagonism. K. A. Wall, J.-y. Hu, P.
Currier, S. Southwood, A. Sette, and A. J. Infante. J. Immunol. 152:4526-4536, 1994.
- Restricted T cell receptor repertoire for acetylcholine receptor in murine myasthenia
gravis. E. Kraig, J. L. Pierce, K. Z. Clarkin, N. E. Standifer, P. Currier, K. A.
Wall, and A. J. Infante.. J. Neuroimmunol. 71: 87-95, 1996.
- Inhibition of the intrinsic NAD+ glycohydrolase activity of CD38 by carbocyclic NAD
analogues. K. A. Wall, M. Klis, J. Kornet, D. Coyle, J.-C. Amé, M. K. Jacobson, and
J. T. Slama. Biochemical J. 335: 631-636, 1998.
- Interleukin-12 enhances clinical experimental autoimmune myasthenia gravis in susceptible
but not resistant mice. S. Sitaraman, D. W. Metzger, R. J.Belloto, Jr., A. J.Infante,
and K. A. Wall. J. Neuroimmunol. 107: 73-82, 2000.
- Split tolerance in a novel transgenic model of autoimmune myasthenia gravis. S. Stacy,
B. Gelb, B. A. Koop, J. J. Windle, K. A. Wall, K. A. Krolick, A. J. Infante, and E.
Kraig. J. Immunol. 169: 6570-6579, 2002.
- Recall immune memory: A new tool for generating late onset autoimmune myasthenia gravis.
S. Stacy, A. J.Infante, K. A. Wall, K. Krolick, and E. Mechanisms of Ageing and Development 124: 931-940, 2003.
- Cowpea mosaic virus capsid: a promising carrier for the development of carbohydrate
based antitumor vaccines. A. Miermont, H. Barnhill, E. Strable, X. Lu, K. A. Wall,
Q. Wang, M. G. Finn, and X. Huang. Chemistry - A European Journal 14: 4939-4947, 2008.
- Synthesis of a single molecule L-rhamnose-containing three component vaccine and evaluation of antigenicity in the presence of anti-L-rhamnose antibodies. S. Sarkar, S. A. Lombardo, D. N. Herner, R. S. Talan, K. A. Wall, and S. J. Sucheck. J. Amer. Chem. Soc. 132: 17236-17246, 2010.