My laboratory focuses on understanding the pathophysiology of inherited cancer syndromes such as Neurofibromatosis 2(NF2) and Tuberous Sclerosis type 1 and type 2 (TSC1 and TSC2). The NF2 protein merlin belongs to a family of proteins that are known to connect the plasma membrane proteins to the actin cytoskeleton. One aspect of our work involves understanding the role of merlin in cellular signaling to the actin cytoskeleton. We have recently identified NHE-RF, a regulatory protein for many ion channels as an interacting protein for merlin. NHE-RF appears to function as a key adaptor protein involved in many signaling pathways and our efforts are to define the role of NHE-RF in cell proliferation.
Tuberous sclerosis results from mutations in either of the two genes TSC1 and TSC2 and functions of the protein products hamartin and tuberin respectively are largely unknown. We have generated valuable antibodies for these proteins and defined their subcellular pattern of expression in kidney, one of the affected organs in TSC. Work is in progress to isolate, characterize other proteins that interact with these two proteins. The ultimate goal is to define the physiological functions of these proteins and how their absence results in this multisystem disorder.