Tom Van Blarcom thomasv[at]che.utexas.edu
Academic Background
B.S. North Carolina State University, Chemical Engineering, 2003
currently: Doctoral Student, Department of Chemical Engineering, U.T. Austin
Research Description
Engineering high affinity antibodies for the treatment of tumor necrosis factor alpha (TNF-a) related autoimmune diseases
My research projects focus on engineering antibody fragments for therapeutic applications. In particular, I am involved in developing protein engineering and biotechnology based approaches for the treatment of tumor necrosis factor alpha (TNF-a) related autoimmune diseases. These include rheumatoid arthritis, multiple sclerosis, psoriasis, and inflammatory bowel disease.[1],[2] The underlying purpose of my research project is to engineer therapeutics for the cure of TNF-a related autoimmune diseases. My broad objective is to gain a better understanding of the mechanism of interaction between recombinant antibodies and their specific ligands, and of the molecular determinants of antibody affinity and specificity. In physiological conditions, TNF-a activates signal transduction via the interaction with two specific receptors (TNF-a Receptor Type I and II). The pleiotropic effect of this interaction involves a number of cellular responses including cell differentiation and proliferation, cellular metabolism and cachexia, apoptosis, and inflammation.[3] Tremendous progress has been made recently in the understanding of the pathophysiology of TNF-a related autoimmune diseases, but there are still many unresolved issues. Recent studies show that the TNF-a/TNF receptor interaction is responsible for the activation of signal transduction cascades mechanisms that can initiate, promote and downregulate cellular pathways associated with the pathogenesis of the disease.[4] However, it is still unclear how these ligand-receptor interactions can be responsible for such pleiotropic effects and the onset of various autoimmune diseases. In general, the deregulation of TNF-a expression has been correlated with the onset of autoimmune diseases. As a result, one strategy for effective treatment involves preventing the interaction between TNF-a and its receptors at the cell surface.[5] My research projects focus on engineering antibody fragments for the specific binding of either TNF-a or the receptors to prevent the TNF-a/TNF receptor interaction from taking place.
Publications
Kollias, G. et al. On the role of tumor necrosis factor and receptors in models of multiorgan failure, rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. Immunological Reviews . 169, 175-194 (1999)
Schottelius, A. J. G. et al. Biology of tumor necrosis factor-a – implications for psoriasis. Experimental Dermatology. 13, 193-222 (2004)
Schottelius, A. J. G. et al. Biology of tumor necrosis factor-a – implications for psoriasis. Experimental Dermatology. 13, 193-222 (2004)
Kollias, G. et al. On the role of tumor necrosis factor and receptors in models of multiorgan failure, rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. Immunological Reviews . 169, 175-194 (1999)
Schottelius, A. J. G. et al. Biology of tumor necrosis factor-a – implications for psoriasis. Experimental Dermatology. 13, 193-222 (2004)
