Matthew J. Merrins

Matthew Merrins

Assistant Professor

(also Medicine)

C4134A VA Hospital (4th floor - C wing)

Merrins Lab Dept. of Medicine Webpage

Phone: (608) 256-1901 x12848

Email: merrins@wisc.edu

 

Education

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

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

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 of Note
Perform a customized PubMed literature search for Dr. Merrins.

•   Merrins MJ and Stuenkel EL (2008) “Kinetics of Rab27a-dependent actions on vesicle docking and priming in pancreatic β-cells” Journal of Physiology 586, 5367–5381. PMID: 18801842.

Highlighted in: Ullrich S. (2008) “Glucose-induced insulin secretion: is the small G-protein Rab27A the mediator of the KATP channel-independent effect?” Journal of Physiology 586, 5291. PMID: 19011133.

•   Merrins MJ, Fendler B, Zhang M, Sherman A, Bertram R, Satin LS (2010) “Metabolic oscillations in pancreatic islets depend on the intracellular Ca2+ level but not Ca2+ oscillations” Biophysical Journal 99, 76–84. PMID: 20655835.

•   Merrins MJ, Bertram R, Sherman A, Satin LS (2012) “Phosphofructo-2-kinase/fructose-2,6-bisphosphatase modulates oscillations of pancreatic islet metabolism” PLOS one 7, e34036. PMID: 22532827.

•   Merrins MJ, Van Dyke AR, Mapp AK, Rizzo MA, Satin LS (2013) “Direct measurements of oscillatory glycolysis in pancreatic islet β-cells using novel FRET biosensors for pyruvate kinase M2 activity” Journal of Biological Chemistry 288, 33312–33322. PMID: 24100037.

•   Merrins MJ, Poudel C, McKenna JP, Ha J, Sherman A, Bertram R, and Satin LS (2016) “Phase Analysis of Metabolic Oscillations and Membrane Potential in Pancreatic β-cells” Biophysical Journal 110, 691–699. PMID: 27129239.

•   McKenna J, Ha J, Merrins MJ, Sherman A, Satin LS, and Bertram R (2016) “Ca2+ Effects on ATP Production and Consumption Have Key Regulatory Roles on Oscillatory Islet Activity” Biophysical Journal 110, 733-742. PMID: 26840737.

•   Kim SY, Lee JH, Merrins MJ, Gavrilova O, Bisteau X, Kaldis P, Satin LS, and Rane SG (2017) “Loss of Cyclin Dependent Kinase 2 in the Pancreas Links Primary β-cell Dysfunction to Progressive Depletion of β cell Mass and Diabetes” Journal of Biological Chemistry 292(9), 3841-3853. PMID: 28100774.

•   Gregg T, Poudel C, Schmidt BA, Dhillon RS, Sdao SM, Truchan NA, Baar EL, Fernandez LA, Denu JM, Eliceiri KW, Rogers JD, Kimple ME, Lamming DW, and Merrins MJ (2016) “Pancreatic β-cells from Mice Offset Age-Associated Mitochondrial Deficiency with Reduced KATP Channel Activity” Diabetes 65(9), 2700-2710. PMID: 27284112.

•   Fontana L, Cummings NE, Arriola Apelo SI, Neuman JC, Kasza I, Schmidt BA, Cava E, Spelta F, Tosti V, Syed FA, Baar EL, Veronese N, Cottrell SE, Fenske RJ, Bertozzi B, Brar HK, Pietka T, Bullock AD, Fiigenshau RS, Andriole GL, Merrins MJ, Alexander CM, Kimple ME, and Lamming DW (2016) “Decreased Consumption of Branched Chain Amino Acids Improves Metabolic Health” Cell Reports 16(2), 520-530. PMID: 27346343.

•   Neuman JC, Schaid MD, Brill AL, Fenske RJ, Kibbe CR, Fontaine DA, Sdao SM, Brar HK, Connors KM, Wienkes HN, Eliceiri KW, Merrins MJ, Davis DB, and Kimple ME (2017) “Enriching Islet Phospholipids with Eicosapentaenoic Acid Reduces Prostaglandin E2 Signaling and Enhances Diabetic β-cell Function” Diabetes 66(6), 1572-1585. PMID: 28193789.

•   Hernandez R, Graves SA, Gregg T, VanDeusen HR, England CG, Valdovinos HF, Jeffery JJ, Barnhart TE, Severin GW, Nickles RJ, Merrins MJ#, and Cai W# (2017) “Assessing Functional β-cell Mass with Radiomanganese PET” Diabetes 66(8), 2163-2174. PMID: 28515126. #Corresponding authors.