About the lab
Overview: Synapse formation is an essential task of brain development. Conversely, synapse dysfunction is a core feature of neurodevelopmental disorders including autism, epilepsy, and schizophenia. Our group aims to understand the complex interactions between multiple cell types within the brain, including neurons, astrocytes, and microglia. We also aim to understand how innate immune signals shape healthy brain development, both within the brain and in communication with peripheral immunity. Our goal is to achieve a cellular and molecular understanding of postnatal synaptic development that can inform new immune-based therapies for psychiatric and neurodevelopmental illnesses.
Our findings: We have shown that cytokines can play important roles in regulating synapse numbers in the developing brain. For example, we recently demonstrated that the cytokine Interleukin-33 is produced by developing astrocytes and regulates the synapse-engulfing function of brain-resident immune cells known as microglia. The finding that a locally produced immune signal is required for healthy brain development has important implications for understanding the homeostatic roles of innate immunity in the brain. In related work, we previously demonstrated that astrocytes are functionally heterogeneous in their support of neuronal development. We continue to identify novel markers that distinguish astrocytes in synapse rich regions (gray matter), in order to understand how astrocytes adapt their functions in region specific and context specific ways, including in the setting of neuroinflammation.
Current questions: How do synapses mature, and how do glial cells, including astrocytes and microglia adapt their functions to shape synaptic development? How does the tissue remodeling associated with innate immune responses shape synapses during hippocampal-dependent learning, cortical critical periods, and other forms of brain plasticity. How are these pathways involved in brain disorders such as epilepsy, autism, and schizophrenia? How do cytokines regulate microglial and neuronal function? How does stress, aging, and injury impact neuroimmune signaling in the brain. Can we develop new tools to visualize glial-synaptic interactions?
Our approaches: We use transcriptomics, imaging, electrophysiology, and behavior to characterize glial properties during neural circuit development and function. The lab works mainly with murine models, but is also developing tools in the juvenile zebrafish, and engaging in clinical collaborations to study immune pathways in humans.
About the PI
Education and interests: I completed my undergraduate training in Neuroscience and Chemistry at Amherst College, and subsequently received my MD/PhD from the University of Michigan as part of the Medical Scientist Training Program (MSTP). My training focused on the molecular mechanisms regulating CNS stem cell self-renewal and aging, as well as molecular and functional characterization of glial heterogeneity. The Molofsky lab, established in July of 2015, studies the roles of glial cells and neuroimmunity in brain development and synapse formation.
Clinical training: I completed my residency in adult psychiatry at UCSF and obtained additional training at the San Francisco Psychoanalytic Institute. I maintain a faculty practice at UCSF in the Langley-Porter Psychiatric Institute.
Honors and Awards:
2019 Freedman Award in Basic Research, Brain and Behavior Research Foundation
2019 Joseph Altman Award in Developmental Neuroscience, Japanese Neuroscience Society
2017 NIH New Innovator Award
2017 Pew Biomedical Scholar
2016 Young Investigator Award, Brain and Behavior Research Foundation
2015 Career Award for Medical Scientists, Burroughs Wellcome Fund
2014 ACNP Travel Award, American College of Neuropsychopharmacology
2013 APA-Pfizer MD/PhD Psychiatric Research Fellowship, American Psychiatric Association
2007 Dean’s Award for Research Excellence, University of Michigan Medical School
2006 Harold M. Weintraub Graduate Student Award, Fred Hutchinson Cancer Center
1997 Phi Beta Kappa