Bradford B. Lowell

Biosketch

Bradford B. Lowell, MD PhD is a Professor of Medicine at Harvard Medical School and is Director of the Transgenic Program at Beth Israel Deaconess Medical Center (BIDMC). He earned his BA in Physiological Psychology from the University of Massachusetts Amherst (1980) studying hypothalamic lesions that cause overeating and obesity. He then obtained MD and PhD degrees in Medicine and Physiology from Boston University School of Medicine (1986) working on muscle fuel metabolism with Neil Ruderman. As an Intern and Resident in Medicine, and then Endocrine Fellow at Beth Israel Hospital (now Beth Israel Deaconess Medical Center), he studied adipocyte gene expression with Jeffrey Flier, and learned to genetically manipulate the mouse genome. He has been a faculty member at Beth Israel Deaconess Medical Center and Harvard Medical School since 1992. Early on, he used mouse genetic engineering to establish the role of brown adipose tissue and beta-adrenergic receptors in preventing obesity. Since the mid 1990s, his focus returned to the brain where he has been using neuron-specific recombinase driver mice, in combination with recombinase-enabled neuroscience “tools”, to elucidate the neural basis for brain control of hunger/satiety, metabolism, neuroendocrine systems, and the gastrointestinal tract. He is a member of the Association of American Physicians and the National Academy of Sciences.

Research Interests

My lab seeks to identify the neural mechanisms responsible for brain control of homeostatic motivational drives (e.g. hunger), energy balance, the autonomic nervous system, neuroendocrine systems and the gastrointestinal tract. To achieve this, we interrogate the function, regulation and the input/output connectivity of genetically-identified neurons. This is done by combining mice genetically engineered to express DNA recombinases (Cre, Flp, etc.) in transcriptionally-defined neurons with viral vectors or mice that express, in a recombinase-dependent fashion, a panel of “neuroscience tools”. Using these approaches, we then manipulate that neuron’s firing rate to determine its role in regulating behavior and physiology, measure its activity to establish how it responds to discrete sensory, behavioral and physiologic perturbations, and map that neuron’s upstream and downstream synaptic connectivity to uncover its underlying neural “wiring diagram”. Combined, this information is used to construct mechanistic models of how the brain controls physiology and behavior. Techniques utilized include: electrophysiology, optogenetics, chemogenetics, rabies monosynaptic mapping, ChR2-assisted circuit mapping, in vivo assessments of neuronal activity, and single neuron transcriptomics (the latter to discover the neuron subtypes, and their genetic markers, that constitute the key regulatory nodes in the brain).