Earlanda L. Williams, Ph.D.Lecturer III
University of Texas Health Science Center San Antonio, 2009
Dr. Williams earned her Ph.D. from the Department of Cellular and Structural Biology in April 2009. She is a former UTHSCSA Presidential Ambassador Scholar for the Graduate School of Biomedical Sciences, a three-time Minority Access for Research Careers scholarship recipient and was awarded an R36 Research Dissertation Award to Increase Diversity from the National Institute of Aging. She is currently a lecturer and lab instructor in Dental Gross Anatomy and an instructor in Dental Neuroscience for first-year dental students. These courses primarily focus on head and neck anatomy, embryology, and neuroanatomy. Dr. Williams is also course director for Anatomy I for first-year physical therapy and physician's assistant students and Anatomy II for third-year physical therapy students. These courses provide the basic principles of human anatomy with concentration on osteology, radiology, musculoskeletal, cardiopulmonary, neuromuscular, and basic systems anatomy as they apply to clinical practice. Her research focuses on the molecular mechanisms that establish and break T cell tolerance to the acetylcholine receptor (AChR), the autoantigen in myasthenia gravis (MG).
In MG, destructive autoantibodies are generated to AChRs located at the neuromuscular junctions, and T cells have been shown to play a pivotal role in regulating these pathogenic autoantibodies. Using a transgenic mouse model which expresses the Torpedo (T)AChR alpha chain as a self protein in the appropriate tissues (muscle>>brain>thymus), our laboratory is investigating whether AChR expression in the thymus and/or the periphery (muscle) is important for T cell tolerance. Studies using TAChR-alpha transgenic nude mice coupled with thymic transfer approaches have shown that peripheral expression (muscle only) of the TAChR is sufficient to induce T cell tolerance, while central (thymic) expression is dispensable (see below). Further investigations have revealed a role for Foxp3+CD25+ T regulatory cells as important mediators of T cell tolerance to the AChR in this model.
Peripheral expression of AChR elicits T cell tolerance. Thymus transplants were performed to generate mice in which the TAChR-alpha transgene was present in thymus and/or the periphery (muscle). Mice were immunized with the immunodominant peptide, p146-162/CFA, T cells were harvested seven days later and in vitro stimulated with peptide or intact TAChR as indicated in the figure legend. Cells were pulsed with [3H]-thymidine and proliferation was reported as mean cpm of triplicate wells-background (no stimulus). T cell tolerance is indicated by diminished proliferation to p146-162 and TAChR.
Quantitative real-time PCR
Paralumbar laparotomy (thymus transplant beneath kidney capsule)
T cell proliferation assays
ELISA to analyze antibody titers
FACS analysis of specific T cell subsets
Stacy S, Williams EL, Standifer NE, Pasquali A, Krolick KA, Infante AJ, Kraig E. (2010) Maintenance of immune tolerance to a neo-self acetylcholine receptor antigen with aging: implications for late-onset autoimmunity. J Immunol. 2010 Jun 1;184(11):6067-75. Epub 2010 Apr 30.
Williams, E., S. Stacy, A.J. Infante, and E. Kraig (2009) Chapter 13. Mechanisms of tolerance in experimental models of myasthenia gravis. In P. Christadoss (ed.), Myasthenia gravis (pp. 235-257).
Walter RB, Rains JD, Russell JE, Guerra TM, Daniels C, Johnston DA, Kumar J, Wheeler A, Kelnar K, Khanolkar VA, Williams EL, Hornecker JL, Hollek L, Mamerow MM, Pedroza A, Kazianis S. (2004) A microsatellite genetic linkage map for Xiphophorus. Genetics. 2004 Sep;168(1):363-72.
Kazianis S, Nairn RS, Walter RB, Johnston DA, Kumar J, Trono D, Della-Coletta L, Gimenez-Conti I, Rains JD, Williams EL, Pino BM, Mamerow MM, Kochan KJ, Schartl M, Vielkind JR, Volff JN, Woolcock B, Morizot DC. (2004) The genetic map of Xiphophorus fishes represented by 24 multipoint linkage groups. Zebrafish. 2004;1(3):287-304.
Kazianis S, Khanolkar VA, Nairn RS, Rains JD, Trono D, Garcia R, Williams EL, Walter RB. (2004) Structural organization, mapping, characterization and evolutionary relationships of CDKN2 gene family members in Xiphophorus fishes. Comp Biochem Physiol C Toxicol Pharmacol. 2004 Jul;138(3):291-9.