Andrew Scharenberg, MD
My lab has two distinct areas of focus. The first of these is the role of ion channels in immune cell signaling and biology. Our work in this area has identified two novel ion channel/enzyme fusions, designated TRPM2 and TRPM7, which are expressed in a diverse array of immune cells. Ongoing studies are involved in 1) defining 2nd messenger pathways which regulate the function of TRPM2, as well as downstream effector pathways which are impacted by TRPM2 activation; and 2) understanding the role of TRPM7-mediated Mg2+ uptake in the regulation of immune cell growth, as well as the reciprocal impact of growth regulatory signaling on Mg2+ uptake mediated by TRPM7 and other plasma membrane Mg2+ transporters. The second major focus of the lab is the design of novel homing endonucleases and their application for gene repair. Homing endonucleases are a class of DNA cleavage proteins which have long recognition sites (in the range of 20 base pairs), and thus are able to generate precise double strand breaks. Ongoing work in the lab is involved in designing novel homing endonuclease proteins able to cleave desired target sites through a combination of computational and directed evolution approaches. Additional work is aimed at delivering these proteins to hematopoietic stem cells for the purpose of repairing genes mutated in common primary immunodeficiencies.