Matthew J. Merrins

Position title: Associate Professor (also Medicine)

Phone: (608) 256-1901 x12848

Address:
C4134A VA Hospital (4th floor - C wing)

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

Perform a customized PubMed literature search for Matthew J. Merrins

Lin, H., N. Smith, A.F. Spigelman, K. Suzuki, M. Ferdaoussi, T.A. Alghamdi, S.L. Lewandowski, Y. Jin, A. Bautista, Y.W. Wang, J.E. Manning Fox, M.J. Merrins, J. Buteau, and P.E. MacDonald. (2021). β-Cell Knockout of SENP1 Reduces Responses to Incretins and Worsens Oral Glucose Tolerance in High-Fat Diet-Fed Mice. Diabetes, 70: 2626-2638.
Corkey, B.E., J.T. Deeney, and M.J. Merrins. (2021). What Regulates Basal Insulin Secretion and Causes Hyperinsulinemia? Diabetes, 70: 2174-2182.
Adams, M.T., J.M. Dwulet, J.K. Briggs, C.A. Reissaus, E. Jin, J.M. Szulczewski, M.R. Lyman, S.M. Sdao, V. Kravets, S.D. Nimkulrat, S.M. Ponik, M.J. Merrins, R.G. Mirmira, A.K. Linnemann, R.K. Benninger, and B. Blum. (2021). Reduced synchroneity of intra-islet Ca oscillations in vivo in Robo-deficient β cells. eLife, 10: .
El, K., S.M. Gray, M.E. Capozzi, E.R. Knuth, E. Jin, B. Svendsen, A. Clifford, J.L. Brown, S.E. Encisco, B.M. Chazotte, K.W. Sloop, D.J. Nunez, M.J. Merrins, D.A. D'Alessio, and J.E. Campbell. (2021). GIP mediates the incretin effect and glucose tolerance by dual actions on α cells and β cells. Science advances, 7: .
Sdao, S.M., T. Ho, C. Poudel, H.R. Foster, E.R. De Leon, M.T. Adams, J.H. Lee, B. Blum, S.G. Rane, and M.J. Merrins. (2021). CDK2 limits the highly energetic secretory program of mature β cells by restricting PEP cycle-dependent K channel closure. Cell reports, 34: 108690.
Abulizi, A., R.L. Cardone, R. Stark, S.L. Lewandowski, X. Zhao, J. Hillion, L. Ma, R. Sehgal, T.C. Alves, C. Thomas, C. Kung, B. Wang, S. Siebel, Z.B. Andrews, G.F. Mason, J. Rinehart, M.J. Merrins, and R.G. Kibbey. (2020). Multi-Tissue Acceleration of the Mitochondrial Phosphoenolpyruvate Cycle Improves Whole-Body Metabolic Health. Cell metabolism, 32: 751-766.e11.
Lewandowski, S.L., R.L. Cardone, H.R. Foster, T. Ho, E. Potapenko, C. Poudel, H.R. VanDeusen, S.M. Sdao, T.C. Alves, X. Zhao, M.E. Capozzi, A.H. de Souza, I. Jahan, C.J. Thomas, C.S. Nunemaker, D.B. Davis, J.E. Campbell, R.G. Kibbey, and M.J. Merrins. (2020). Pyruvate Kinase Controls Signal Strength in the Insulin Secretory Pathway. Cell metabolism, 32: 736-750.e5.
de Souza, A.H., J. Tang, A.K. Yadev, S.T. Saghafi, C.R. Kibbe, A.K. Linnemann, M.J. Merrins, and D.B. Davis. (2020). Intra-islet GLP-1, but not CCK, is necessary for β-cell function in mouse and human islets. Scientific reports, 10: 2823.
Douros, J.D., J. Niu, S. Sdao, T. Gregg, M.J. Merrins, J. Campbell, J. Tong, and D. D'Alessio. (2019). Temporal plasticity of insulin and incretin secretion and insulin sensitivity following sleeve gastrectomy contribute to sustained improvements in glucose control. Molecular metabolism, 28: 144-150.
Gregg, T., S.M. Sdao, R.S. Dhillon, J.W. Rensvold, S.L. Lewandowski, D.J. Pagliarini, J.M. Denu, and M.J. Merrins. (2019). Obesity-dependent CDK1 signaling stimulates mitochondrial respiration at complex I in pancreatic β-cells. The Journal of biological chemistry, 294: 4656-4666.