Brandon Holmes, MD, PhD

I am a physician-scientist with the longstanding goal of generating fundamental discoveries in molecular and cellular neurobiology that can be translated to human diagnostics and therapeutics. During my PhD training with Dr. Marc Diamond, I explored the cellular and molecular mechanisms mediating the transcellular propagation of protein aggregates. My efforts led to the discovery that the cell-surface complex heparan sulfate proteoglycans govern the cellular internalization and seeding of tau and a-synuclein aggregates. This work motivated my fascination with the cell-surface compartment as a critical regulator of cellular signaling. In parallel, I developed cell-based biosensors that permit femtomolar detection of protein aggregates and are now enabling therapeutic efficacy predictions of novel drugs in pre-clinical trials. These projects, which reside at the interface of translational biology, diagnostic assay design, and therapeutic discovery, have inspired my passion for engineering molecular tools to precisely characterize and manipulate biological systems. Combined with my ardor for understanding neurological disease, I continue to dream of novel methods that will enhance our knowledge and treatment of neurodegeneration. It is in pursuit of this vision that I am now completing my post-doctoral research training with Dr. Jim Wells who has pioneered phage display and surface proteomic strategies to understand how the cell-surface is remodeled in health and disease.