Alfred L.M. Bothwell, PhD

Dr. Bothwell received his AB from Washington University and his PhD from Yale University in Sidney Altman’s lab studying RNA biogenesis in bacteria and human cells.  He did postdoctoral research at MIT in David Baltimore’s lab where he developed molecular probes for antibody genes and defined molecular properties of the murine antibody response and their genes.  He joined the Yale Medical School faculty and has studied basic properties of lymphocytes and their receptors in mouse models of infection, autoimmunity, transplantation and novel humanized mouse models of vascular disease, type 1 diabetes and cancer. Studies of human complement regulation by CD59 lead to intellectual property that was the basis for founding Alexion Pharmaceuticals.  He has published over 190 papers and reviews on his research.

Cancer Focus 

Current studies are focused on the immunoregulatory properties of regulatory T cells, myeloid derived suppressor cells and other lymphocytes in immune responses to cancer in both mice and human models. The roles of Wnt ligands DKK1 and DKK2 in regulating the development of tumors is studied in mouse models and in human patient derived xenograft models.  Organoids are being used to define mechanisms of tumor development from stem cells and formation of tumor microenvionmental niches. New insight is being developed from studies of lymphocytes from the same patient as tumors growing in humanized mice. These strategies can be used to evaluate candidate drug therapies and cellular properties in vivo.