Frankie D. Heyward, Ph.D.

Frankie D. Heyward is a postdoctoral research fellow jointly in endocrinology, diabetes and metabolism at Beth Israel Deaconess Medical Center and at Harvard Medical School, where he is working in the lab of Evan Rosen.

During his postdoctoral research, Frankie investigated a small population of AgRP hunger neurons in the hypothalamus that coordinate homeostatic changes in appetite associated with fluctuations in food availability and leptin signaling. To identify the relevant transcriptional regulatory pathways in these neurons, he generated mouse AgRP neuron-specific transcriptomic and chromatin accessibility profiles during three distinct hunger states of satiety, fasting-induced hunger, and leptin-induced hunger suppression. Cis-regulatory analysis of these integrated datasets enabled the identification of Interferon regulatory factor 3 (IRF3) as a leading candidate mediator of leptin-induced hunger suppression. Gain- and loss-of-function experiments in vivo confirm the role of IRF3 in mediating the acute satiety-evoking effects of leptin in AgRP neurons, while live-cell imaging in vitro indicated that leptin can activate neuronal IRF3 in a cell-autonomous manner. Finally, Frankie employed CUT&RUN to uncover direct transcriptional targets of IRF3 in AgRP neurons in vivo. Thus, his work identified AgRP neuron-expressed IRF3 as a key transcriptional effector of the hunger-suppressing effects of leptin.

Frankie earned his doctorate in neurobiology from the University of Alabama at Birmingham (UAB) while working with David Sweatt to study the epigenetic basis of obesity-induced cognitive impairment in mice. During this time, he earned the UAB Nutrition and Obesity Research Center Predoctoral Kirschstein-NRSA T32 fellowship, a UNCF/Merck Graduate Science Research Dissertation fellowship, a Comprehensive Minority Faculty and Student Development Program fellowship, and a NIDDK Network of Minority Health Research Investigators Excellence in Research Award (Basic Science). He was also the founding chair of the UAB Graduate in Biomedical Sciences Student Outreach Committee, and a mentor for the UAB Blazer Male Enrichment Network, a mentoring network that paired Black male graduate student mentors with Black male freshmen.

In addition to conducting research, Frankie yearns to make the biomedical sciences more inclusive. Promoting diversity, equity and inclusion within biomedical science drove him to become the founding chair of the Harvard Medical School Black Postdoctoral Association and founder and president of the National Black Postdoctoral Association. Today, he is also a member of the Harvard Medical School Diversity, Equity and Inclusion Committee, and co-director of the Nutrition and Obesity Research Center of Harvard Associate Member Committee.

In addition to being named an inaugural Simons Collaboration on Plasticity and the Aging Brain Transition to Independence fellow, Frankie’s recent accolades include an American Heart Association postdoctoral fellowship (2018), a Burroughs Wellcome Fund Postdoctoral Enrichment Program fellowship (2018), an American Diabetes Association Minority Postdoctoral fellowship (2018), a Nutrition and Obesity Research Center of Harvard Pilot and Feasibility (P&F) Grant for under-represented minorities (2019 and 2021), a Brain and Behavior Research Foundation Young Investigator award (2020), a Boston Nutrition and Obesity Research Center P&F Program grant (2022), and a Duke Next Generation Leader award (2022).

Research Plan

The overarching goal of my lab will be to understand how neurotoxic insults caused by an obesogenic diet contribute to persistent, epigenetically encoded impairments in the properties of cell types in the brain that control appetite and cognition. We will study this broad topic by employing a combination of low-input cell-type specific, and single-cell, genome-wide assessments of gene expression, epigenetic modifications, chromatin accessibility, and transcription factor DNA binding dynamics, as well as mouse genetic and epigenome engineering tools, in vitro and in vivo assessments of transcription factor activation, and animal behavioral assessments. The specific major research programs we will pursue include: a) identifying novel transcriptional pathways that regulate synaptic plasticity events controlling hunger and the development of obesity; b) understanding the transcriptional basis for alterations in synaptic plasticity underlying the anorexia of aging; and c) elucidating the epigenetic basis of obesity-induced age-related cognitive decline.