Michael Bonaguidi

PIBBS Mentor

Assistant Professor
Department of Stem Cell Biology & Regenerative Medicine
Keck School of Medicine/ Broad CIRM Center
Associate Member, Zilkha Neurogenetic Institute

Research Topics

  • Neural Stem Cells
  • Brain Injury & Repair
  • Aging
  • Single Cell Analysis
  • Systems Biology
  • Neural Circuits

Research Overview

We investigate how stem cells act to adapt and repair the adult brain. Using endogenous neural stem cells as a model system, our approach incorporates principles from neuroscience, single cell molecular and cellular biology, computational & systems biology, imaging and engineering to unravel brain plasticity. We focus on the reciprocal interaction between neural stem cells and newly generated cells with their surroundings during normal, aging, injured and diseased states.

Our group developed new approaches to visualize the entire neurogenesis process within the mouse hippocampus at single cell resolution. In doing so, we provided the first evidence of individual stem cell existence within the adult mammalian brain. Our subsequent studies revealed mechanisms linking neural stem cell adaptation to changes in the brain under normal conditions and during injury. We are currently examining how neural stem cells - including a newly discovered second population - modify the brain from development to old age. These efforts are highlighted by three areas of interest: (1) How do neural stem cells adapt their behavior to meet needs of the injured or diseased brain? What are the molecular mechanisms mediating the production of newborn stem cells, neurons, astrocytes and oligodendrocytes? (2) How does time, both developmentally and during aging, influence the ability of neural stem cells to generate or remodel tissue homeostasis? (3) How do newborn cells remodel the existing neural circuit, at local and global levels?

We believe that analysis of neurogenesis from multiple perspectives will illuminate the capacity of brain plasticity resulting from dynamic stem cell regulation. Our long-term goal evaluates the capacity of endogenous stem cells to serve as a cellular mediator of neural function and as a therapeutic source of cognitive rejuvenation.