Al Bothwell graduated with an A.B. from Washington University in 1971, got a PhD from Yale in Sidney Altman’s lab in 1975 and then did a postdoc with David Baltimore at MIT where he established the genetic basis of the anti-NP idiotypic antibody response. He has been on the Immunobiology faculty at the Yale Medical School since 1982. He continued studies of B cell antibody diversity and memory and then worked on T cell receptor structure/function and signaling. He also developed the molecular genetics of the Ly6 gene family (aka Sca-1/Ly6A and Ly6C). Increasingly his work has shifted to studies of human immunity with development of humanized mouse models of vascular disease/transplantation, type 1 diabetes and cancer. Studies on gut inflammation in a genetic tumor model and Inflammatory Bowel Disease have lead most recently to contributions concerning wnt signaling to infections and asthma. His studies focus on the remarkable immunoregulatory properties of Wnt signaling that is both canonical and non-canonical and involves direct interaction with platelets.This is a basic mechanism for regulating tissue permeability affecting the mobility of lymphocytes and tumor cells.