Matthew J. Merrins

Assistant Professor (also Medicine)

merrins@wisc.edu

(608) 256-1901 x12848

C4134A VA Hospital (4th floor - C wing)

Matthew Merrins

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

• 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.

•   Hennings TG, Chopra DG, DeLeon ER, VanDeusen HR, Sesaki H, Merrins MJ, Ku GM (2018) In vivo Deletion of Beta Cell Drp1 Impairs Insulin Secretion without Affecting Islet Oxygen Consumption. Endocrinology Jul 19: Pubmed Record.

•  Sharick JT, Favreau PF, Gillette AA, Sdao SM, Merrins MJ, Skala MC (2018) Protein-bound NAD(P)H Lifetime is Sensitive to Multiple Fates of Glucose Carbon. Sci Rep 8(1):5456 (PMC5883019).

•   Cummings NE, Williams EM, Kasza I, Konon EN, Schaid MD, Schmidt BA, Poudel C, Sherman DS, Yu D, Arriola Apelo SI, Cottrell SE, Geiger G, Barnes ME, Wisinski JA, Fenske RJ, Matkowskyj KA, Kimple ME, Alexander CM, Merrins MJ, Lamming DW (2018) Restoration of metabolic health by decreased consumption of branched-chain amino acids. J. Physiol. (Lond.) 596(4):623-645 (PMC5813603).

•   Hernandez R, Graves SA, Gregg T, VanDeusen HR, Fenske RJ, Wienkes HN, England CG, Valdovinos HF, Jeffery JJ, Barnhart TE, Severin GW, Nickles RJ, Kimple ME, Merrins MJ, Cai W (2017) Radiomanganese PET Detects Changes in Functional β-Cell Mass in Mouse Models of Diabetes. Diabetes 66(8):2163-2174 (PMC5521871).

•   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, Kimple ME (2017) Enriching Islet Phospholipids With Eicosapentaenoic Acid Reduces Prostaglandin E Signaling and Enhances Diabetic β-Cell Function. Diabetes 66(6):1572-1585 (PMC5440023).

•   Kim SY, Lee JH, Merrins MJ, Gavrilova O, Bisteau X, Kaldis P, Satin LS, 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. J. Biol. Chem. 292(9):3841-3853 (PMC5339765).

•   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, Merrins MJ (2016) Pancreatic β-Cells From Mice Offset Age-Associated Mitochondrial Deficiency With Reduced KATP Channel Activity. Diabetes 65(9):2700-10 (PMC5001174).

•   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, Figenshau RS, Andriole GL, Merrins MJ, Alexander CM, Kimple ME, Lamming DW (2016) Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health. Cell Rep 16(2):520-530 (PMC4947548).

•   Wynn ML, Yates JA, Evans CR, Van Wassenhove LD, Wu ZF, Bridges S, Bao L, Fournier C, Ashrafzadeh S, Merrins MJ, Satin LS, Schnell S, Burant CF, Merajver SD (2016) RhoC GTPase Is a Potent Regulator of Glutamine Metabolism and N-Acetylaspartate Production in Inflammatory Breast Cancer Cells. J. Biol. Chem. 291(26):13715-29 (PMC4919454).

•   McKenna JP, Ha J, Merrins MJ, Satin LS, Sherman A, Bertram R (2016) Ca2+ Effects on ATP Production and Consumption Have Regulatory Roles on Oscillatory Islet Activity. Biophys. J. 110(3):733-742 (PMC4744176) .

•   Merrins MJ, Poudel C, McKenna JP, Ha J, Sherman A, Bertram R, Satin LS (2016) Phase Analysis of Metabolic Oscillations and Membrane Potential in Pancreatic Islet β-Cells. Biophys. J. 110(3):691-699 (PMC4744170).

•   Johnson JS, Kono T, Tong X, Yamamoto WR, Zarain-Herzberg A, Merrins MJ, Satin LS, Gilon P, Evans-Molina C (2014) Pancreatic and duodenal homeobox protein 1 (Pdx-1) maintains endoplasmic reticulum calcium levels through transcriptional regulation of sarco-endoplasmic reticulum calcium ATPase 2b (SERCA2b) in the islet β cell. J. Biol. Chem. 289(47):32798-810 (PMC4239629).

•   Alejandro EU, Gregg B, Wallen T, Kumusoglu D, Meister D, Chen A, Merrins MJ, Satin LS, Liu M, Arvan P, Bernal-Mizrachi E (2014) Maternal diet-induced microRNAs and mTOR underlie β cell dysfunction in offspring. J. Clin. Invest. 124(10):4395-410 (PMC4191023).

•   Merrins MJ, Van Dyke AR, Mapp AK, Rizzo MA, Satin LS (2013) Direct measurements of oscillatory glycolysis in pancreatic islet β-cells using novel fluorescence resonance energy transfer (FRET) biosensors for pyruvate kinase M2 activity. J. Biol. Chem. 288(46):33312-22 (PMC3829177) .