Joseph M Castellano, PhD

Across his career, Dr. Castellano has studied molecular mechanisms underlying aging and Alzheimer's pathogenesis. Early in his training, he used in vivo microdialysis to show in behaving mice that clearance of the amyloid-beta peptide is impeded by the presence of APOE4, the strongest genetic risk factor for AD, whereas clearance is faster in the context of more neutral or protective forms. As he transititoned into postdoctoral training, Dr. Castellano became fascinated by the possibility that brain function may be, in part, shaped by the immune system and by unexplored activities present within the periphery. In postdoctoral work with Tony Wyss-Coray, Dr. Castellano sought to identify and characterize youth-associated factors in the periphery that reverse features of brain aging, finding that systemic treatment with umbilical cord plasma revitalizes hippocampal function in aged mice. The Castellano laboratory now focuses on characterizing the activity of proteins, including TIMP2, and their action in mediating long-range effects on circuits in the brain in the context of Alzheimer's disease and other disorders. His lab broadly focuses on how blood-CNS interactions regulate synaptic and neuroimmune function to influence aging and AD pathology.