Matthew J. Merrins

Credentials: Metabolic regulation of insulin secretion in aging, obesity, and diabetes

Position title: Associate Professor - Department of Medicine

Email: merrins@wisc.edu

Address:
6107 WIMR1, 1111 Highland Ave, Madison WI 53705

The Merrins Lab Website

Education

B.A., Oberlin College
Ph.D, University of Michigan
Postdoctoral Fellow at University of Michigan Brehm Diabetes Center

Honors & Awards

2010 Ruth L. Kirschstein National Research Service Award
2014 NIDDK Research Scientist Development Award
2016 American Diabetes Association Innovative Basic Sciences Award
2017 Wisconsin Partnership Program New Investigator Award
2017 Central Society for Clinical and Translational Research Early Career Development Award

Research Interests

Keywords: metabolism, mitochondrial biology, exocytosis, insulin secretion, fluorescence microscopy, electrophysiology

Research in the Merrins laboratory centers on the control of insulin release from the endocrine pancreatic islets of Langerhans, and how this is disrupted in diabetes. Our main interests lie in two features of nutrient metabolism in islet beta cells, (1) the ability to trigger pulses of insulin release, and (2) the ability to trigger cell proliferation, when the demand for insulin increases (e.g. during aging and obesity). These adaptive responses to environmental stress ultimately fail in diabetes.

To understand how this occurs, we utilize rodent models of obesity and aging in combination with biochemistry, patch clamp electrophysiology, and quantitative imaging. A central focus of the lab is the use of fluorescence microscopy (FRET, optogenetics, super-resolution and FLIM/2-photon) to monitor biochemical reactions as they occur in living cells. Our recent work is focused on the design and utilization of biosensors useful for real-time measurements of glycolysis, as well as the development of NAD(P)H FLIM as a non-invasive optical approach to study the TCA cycle and electron transport chain. Using these tools, we have been able to monitor metabolite production and second messenger signaling in a variety of pathways.

Live-cell imaging of Pancreatic Islet Oscillations (movie):

Active Projects

•  Regulation of pulsatile insulin secretion by pyruvate kinase M2 (PKM2), and its dynamic control by allosteric regulation and post-translational modifications.

•   Mechanisms of communication between metabolism and the cell cycle mediated by cyclin dependent kinases (CDKs) and their regulators.

•  Characterization of metabolic enzymes identified by RNA sequencing as type 2 diabetes-associated loci; we are using live-cell imaging to elucidate the mechanisms by which these proteins control mitochondrial fluxes, metabolic oscillations, and insulin secretion.

•   Development of NAD(P)H FLIM to study metabolic defects in aging and diabetic islets.

Postdoctoral, PhD students, MD/PhD students, and undergraduates interested in pursuing research in the laboratory should contact Dr. Merrins directly at merrins@wisc.edu.

The Merrins lab is supported by the National Institute of Diabetes and Digestive and Kidney Disorders, the National Institute of Aging, and the American Diabetes Association.

Publications

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