MCBB PhD candidate Rhushikesh Phadke of the Cruz-Martín Lab is the recipient of this year’s Brenton R. Lutz Award. Rhushikesh’s research explores the impact of the immune complement (C) pathway on synaptic plasticity in neurological disorders like schizophrenia (SCZ) and Alzheimer’s disease. By increasing levels of complement component 4 (C4), a risk gene for SCZ, Rhushikesh and the Cruz-Martín Lab observed a disruption in the connectivity of developing cortical neurons. Contrary to previous beliefs, C4 acts through a non-canonical mechanism independent of complement receptor 3 (CR3). They discovered an interaction between C4 and Sorting Nexin 27 (SNX27), an endosomal protein, which, when introduced together, restored normal neuronal activity. Their microscopy analysis revealed altered distribution of AMPA receptor subunit GluR1 and colocalization of C4 and SNX27 in dendritic spines. These findings highlight how C4 impairs SNX27 function, leading to endosomal dysregulation, GluR1 degradation, and decreased connectivity. This novel model provides insights into neuron-autonomous mechanisms of complement-dependent synaptic weakening and its relation to microglia-mediated synaptic engulfment.
This award provides support for PhD candidates conducting research in neurobiology or neuroscience and have made significant contributions to their field. Brenton R. Lutz was the first person to receive an MD/PhD at Boston University, receiving his PhD in 1916. He later became a Professor and Chairman of BU’s Department of Biology. Dr. Lutz also gave the first University Lecture at BU on December 11, 1950 “The Living Blood Vessels.”
Congratulations, Rhushikesh!