Return to list Jesse Gray, PhD


Jesse Gray, PhD


Assistant Professor of Genetics, Harvard Medical School





I have a demonstrated record of innovative and creative research projects in neural circuits and genomics over the past twelve years. My graduate work with Cori Bargmann advanced our basic understanding of neural circuits. During my graduate thesis, I identified a neuronal circuit controlling navigation (Gray et al.,2005), laying the foundation for a genetic strategy to determine the neurotransmitters acting at each synapse in the circuit (Chalasani, Chronis, Tsunozaki, Gray et al., 2007). During my Ph.D. thesis work, I also discovered that soluble guanylate cyclases (sGCs) can detect oxygen (Gray* and Karow* et al., 2004), and I used the expression patterns of these genes to define an aerotaxis circuit (Zimmer and Gray et al., 2009). Finally, I showed that behaviors that were originally considered “social” in C. elegans were in part aerotactic in nature, arising from a shared preference of animals for small, oxygen-depleted microenvironments (Gray* and Karow* et al., 2004). My postdoctoral genomics work with Mike Greenberg led to fundamental advances in our understanding of transcription. During my postdoctoral fellowship, I adapted emerging RNA-Seq and ChIPSeq technologies (still in their infancy at the time) to the neuronal cell-biological systems used in Mike Greenberg’s lab. I discovered thousands of neuronal activity-regulated enhancers and showed that at such enhancers, cells transcribe a novel class of RNAs, enhancer RNAs (Kim*, Hemberg*, Gray* et al., 2010).

The strategy of my laboratory is to combine in one lab both molecular genomic and circuit-level approaches to understanding long-term fear memory. This two-pronged approach is designed to facilitate transformative synergies. In the first prong of our research plan, we are developing a genomic and systemsbiological understanding of the activity-regulated transcriptional gene program, which is required for long-term memory formation. Relying on the “parts list” I developed as a fellow, we are defining how different patterns of neural activity are translated into distinct patterns of gene expression – and how the "transfer function" that relates neural activity to gene expression is encoded in gene regulatory sequences. In the second prong, we are establishing brain slice and in vivo experimental systems in which we can manipulate the activity-regulated transcriptional network in an intact microcircuit. In this context, we will apply electrophysiological, optogenetic, and behavioral tools to assess how these manipulations affect the neural circuit rewiring that occurs during consolidation of long-term fear memories. Our approaches hold promise in unraveling the cellular and molecular basis of memory and leading to an understanding of neuropsychiatric disorders that connects symptoms to specific defects in neural circuitry.

R01 MH101528