44846-Flak, Jonathan

Jonathan N. Flak, PhD

Assistant Professor of Pharmacology & Toxicology

Email jflak@iu.edu
Phone 317-983-3315
MS A420
Indianapolis, IN
Pubmed Logo
Download CV


Jonathan Flak joined IU in September 2019. Immediately upon arrival he began setting up his own lab within the IBRI Diabetes Center. In his lab, Jonathan is focusing on studying the central nervous system’s regulation of glucose metabolism as it relates to diabetes.

More specifically, Jonathan will build on work he began at the University of Michigan that is aimed at distinguishing markers for ventromedial hypothalamic neurons involved in glycemic regulation from the rest of the nucleus, a known brain area critical to balancing glucose, to help determine new targets/brain systems that may prove important in future therapeutics. He plans to identify the downstream systems from these subsets of ventromedial hypothalamic neurons to establish the mechanisms of how the brain can tune metabolic function (e.g. energy expenditure, glucose uptake and glucose mobilization).

Prior to establishing his lab at the IBRI, Jonathan worked in the lab of Martin Myers at the University of Michigan. This project was an outgrowth from his work in this lab, where he began using cre-dependent mouse models and viral systems to study leptin action in the brainstem periaqueductal gray and lateral parabrachial nuclei. His work with Prof. Myers led to research published in Nature Neuroscience and the Journal of Clinical Investigation.

Jonathan received his Bachelor of Science degree in Biopsychology and Cognitive Sciences with honors from the University of Michigan in 2004. And, he obtained his PhD in Neuroscience from the University of Cincinnati in 2011.

Key Publications

Flak J.N., Goforth P.B., Dell’Orco J., Sabatini P.V., Li C., Bozadjieva N., Sorenson M., Valenta A., Cras-Meneur C., Ansari A., Sacksner J., Kodur N., Sandoval D., Kennedy R.T., Olson D.P., Myers M.G. Jr. Ventromedial hypothalamic neuronal subset regulates blood glucose independently of insulin. Journal of Clinical Investigation (2020); 130(6): 2943-2952. 

Bozadjieva N., 
Ross R.A., Johnson D.Q., Haggerty D.L., Atwood B., Lowell B.B., Flak J.N. The role of mediobasal hypothalamic PACAP in the control of body weight and metabolism.  Endocrinology (2021); 162(4). 

Flak J.N., Arble D., Pan W., Patterson C.M., Lanigan T., Sacksner J., Joosten M., Morgan D., Allison M.B., Hayes J., Feldman E., Seeley R.J., Olson D.P., Rahmouni K., Myers M.G. Jr. A leptin-regulated neural circuit that modulates glucose mobilization in response to noxious stimuli. Journal of Clinical Investigation (2017); 127(8): 3103-3113. 

Flak J.N., Patterson C.M., Garfield A.S., D’Agostino G., Goforth P.B., Sutton A.K., Malec P.A., Wong J.M., Germani M., Jones J.C., Rajala M., Satin L., Rhodes C.J., Olson D.P., Kennedy R.T., Heisler L.K., Myers M.G. Jr.  Leptin-inhibited PBN neurons enhance responses to hypoglycemia in negative energy balance.  Nature Neuroscience (2014); 17 (12): 1744-50. 

Titles & Appointments

  • Assistant Professor of Pharmacology & Toxicology
  • Education
    2011 PhD University of Cincinnati
    2004 BS University of Michigan
  • Research

    It is well understood that the brain can control energy balance via descending connections (i.e. sympathetic nervous system) with peripheral organs (e.g. pancreas, heart, liver, adrenal). However, the details of these brain systems have not yet been established. While therapies exist that can successfully target the sympathetic nervous system to restore normal function in obese and diabetic patients, these tools also produce deleterious effects on unwanted and unrelated processes (e.g. cardiovascular disease, renal failure). Thus, the upstream neural system that can specifically target, for example, glucose mobilization, represents the ideal target to curb medical issues associated with complications such as hypoglycemia. Yet, there is only a superficial understanding, at this time, of the unique cellular components (e.g. neurotransmitters, receptors, and/or transcription factors) contained within the neural circuits that control these processes. 

    Dr. Jonathan Flak, who joined the IBRI in the fall of 2019, and his team, are investigating how the brain can separately initiate the glucose mobilization and glucose uptake, with the help of the ADA Pathway Program. Dr. Flak’s goal is to identify ways to target these circuits to promote glucose mobilization during hypoglycemia or curb diabetic hyperglycemia.

    In addition to the control of glucose, many overlapping components in the brain that influence glucose homeostasis also can influence energy expenditure. Concurrently, the Flak Lab also aims to understand the circuits in the brain that separately control energy expenditure, especially those circuits that can be promoted during periods of exercise. Moreover, the Flak Lab is additionally examining whether these same neural systems are engaged by current obesity therapies and whether dysfunction within these circuits contribute to cancer cachexia.

    Using mouse models, the Flak Lab is working to identify the neural circuits, as well as the essential components (e.g. receptors, transmitters, transcription factors) within these circuits, that are responsible for generating these responses. These studies may reveal new targets for future treatments. 

    Within the last few years, Dr. Flak has revealed brainstem -->hypothalamus circuits that can mobilize blood glucose during periods of hypoglycemia and pain/inflammation.  Dr. Flak is working to establish the downstream connections from the hypothalamus to understand how these signals communicate with the peripheral organs in order to generate the mobilization of blood glucose, glucose uptake and facilitate energy expenditure.

  • Professional Organizations
    American Diabetes Association
    Society for Neuroscience
    The Obesity Society

Research Labs

Faculty research at IU School of Medicine is transforming health. Details about the medical research being conducted in faculty labs throughout IU School of Medicine are available in the Research section of this site.

Faculty Labs