Research Summary

IBRI DIABETES CENTER (IDC) - FLAK LAB

Focus: The CNS control of individual aspects of energy balance and glucose homeostasis.

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.

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 the treatment of obesity and diabetes. 

Within the last few years, Dr. Flak has revealed brainstemàhypothalamus circuits that can mobilize blood glucose during periods of hypoglycemia and pain/inflammation, leading to publications in Nature Neuroscience and the Journal of Clinical Investigation. 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.

Lab Team

Jonathan Flak, PhD

Senior Research Scientist, IBRI Diabetes Center

Assistant Professor of Pharmacology and Toxicology, Indiana University

Postdoctoral Training 2016 University of Michigan

PhD 2011 University of Cincinnati | BSc 2004 University of Michigan

Read JONATHAN's Bio

Jonathan Flak

Jonathan Flak

Assistant Investigator, IBRI Diabetes Center

Jonathan Flak

Jonathan Flak

Assistant Investigator, IBRI Diabetes Center

Jonathan Flak joined the IBRI in September 2019. Immediately upon arrival he began setting up his own lab within the IBRI Diabetes Center. In his lab, Jonathan will focus 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 here 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.

David Johnson

David Johnson

Assistant Research Associate, IBRI Diabetes Center

David Johnson

David Johnson

Assistant Research Associate, IBRI Diabetes Center

David Johnson joined the IBRI in November 2019 as an assistant research associate in the IBRI Diabetes Center (IDC). In this role, he will work with Johnathan Flak to study the central nervous system’s regulation of glucose metabolism as it relates to diabetes.

David was previously a study technician at Covance Laboratories in Greenfield, IN, where he performed absorption, distribution, metabolism and excretion (ADME), good laboratory practice and toxicology research studies. He also was responsible for the collection and documentation of pertinent data, including test material administration, sample collections and sample processing. While studying at Michigan State University, he served as a teaching assistant in the Charles Drew Science Scholars Program and was an undergraduate research intern in the College of Veterinary Medicine.

David received his bachelor’s degree in neuroscience – cognitive and computational from Michigan State University in East Lansing, Mich.