Evan Macosko, MD, PhD

Prize Winner

Position

Associate Professor Stanley Center for Psychiatric Research

Prize

MIND Prize

Cohort

2023

Program

MIND Prize

Institution

Broad Institute of MIT and Harvard; Harvard Medical School

Website

macoskolab.com

Project

Cell Fusion: A novel therapeutic modality for neural restoration and rejuvenation

Vision

The brain is a non-regenerating organ that needs to remain healthy and functional for our entire lives. We need new approaches that can deliver restorative, rejuvenating factors to aging neurons, especially for the treatment of neurodegenerative diseases. My lab is leveraging cutting-edge single-cell and spatial genomics technology we have developed over the past ten years to uncover the secrets of the poorly understood neurobiological phenomenon: neural cell fusion. By learning the mechanisms behind this fusion process, we hope to build a new therapeutic platform for cell therapy in the human brain.

About

Dr. Macosko is a neuroscientist and psychiatrist focused on developing new genomics technologies to study brain diseases. Technological innovations he has led include Drop-seq, the first high-throughput single cell analysis method, and Slide-seq, a method for localizing gene expression within intact tissue sections. His lab works to extend these technologies to measure connections amongst neurons in the brain, and to uncover molecular mechanisms of schizophrenia and Parkinson’s disease. He is the co-director of the newly established Center for Human Brain Cell Variation at the Broad, funded by the NIH Brain Initiative. Macosko is an attending psychiatrist at Massachusetts General Hospital, an institute member of the Broad Institute, and an associate professor of psychiatry and neurobiology at Harvard Medical School.

As a physician-scientist, my ultimate goal is to have our science impact human health through making tangible improvements to disease treatments and overall well-being.

Neurons of the human brain cannot regenerate, and so must continue functioning across many decades when damage can accumulate. Our project will explore the development of novel platform for therapeutics in which cells deliver restorative molecules to neurons in the brain. The launching point of the platform is an endogenous phenomenon where peripheral blood cells are known to spontaneously fuse with certain neurons. We will learn the mechanisms by which this phenomenon works, and adapt it to ferry cargoes of proteins, nucleic acids, and other macromolecules to neurons in need.

"With the help of the MIND Prize, we are able to explore a hugely understudied phenomenon of neurobiology with potentially transformative impact on how therapeutics are conceived, and delivered, to the nervous system."