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

Research Interests
Research in the Merrins laboratory centers on two features of nutrient metabolism in pancreatic 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 (for example during obesity or pregnancy). These adaptive responses to environmental stress ultimately fail in diabetes (neonatal, type 1, and type 2).

To understand how this occurs, we utilize rodent models of obesity/diabetes in combination with biochemistry, patch clamp electrophysiology, and quantitative imaging. A central focus of the lab is the use of fluorescence microscopy (FRET, optogenetics, and FLIM/2-photon) to monitor biochemical reactions as they occur in living cells. Our recent work – detailed in J Biol Chem. – describes novel biosensors useful for real-time measurements of glycolysis, as well as non-invasive optical approaches to study mitochondrial function. Using these tools, we have been able to monitor metabolite production in a variety of cell types from yeast to human breast cancer cells.

Live-cell imaging of Pancreatic Islet Oscillations (Movie).

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

• Characterization of mitochondrial proteins identified by RNA sequencing as type 2 diabetes-associated loci; we are using optogenetics to elucidate the mechanisms by which these proteins alter mitochondrial dynamics, metabolic oscillations, and insulin secretion.

• Fluorescence lifetime fingerprinting of metabolic defects in aging and diabetes.

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 NIH/NIDDK (National Institute of Diabetes and Digestive and Kidney Disorders).

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

• Watts M, Fendler B, Merrins MJ, Satin LS, Bertram R, and Sherman S (2014) “Calcium and Metabolic Oscillations in Pancreatic Islets: Who's Driving the Bus?” SIAM J. Applied Dynamical Systems 13, 683-703. PMID: 25698909.

• 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 beta cell” Journal of Biological Chemistry 289, 32798–810. PMID: 25271154.

• 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 high-fat diet induces insulin resistance and deterioration of pancreatic β-cell function in adult offspring with sex differences in mice” Journal of Clinical Investigation 306, E1163-75. PMID: 24691028.

• 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, 33312-22. PMID: 24100037.

• 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, 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 & Stuenkel EL (2008) “Kinetics of Rab27a-dependent actions on vesicle docking and priming in pancreatic beta-cells” Journal of Physiology 586, 5367-81. PMID: 18801842.