Mark A. Rizzo
660 West Redwood St.,
Assistant Professor, Department of Physiology 2005-present
Postdoctoral Fellow, Vanderbilt University, 2000-2005
PhD, University of Pittsburgh, 2000 BA, Canisius College, 1996
Insulin secretion from the pancreas
Insulin is a primary and essential regulator of blood glucose, which provides nutrition to cells and tissues in the body. When blood glucose rises, the pancreatic β cells respond by secreting insulin, which in turn enhances glucose uptake by the cells in the body to quickly lower the blood sugar concentration to the correct level. How much and how quickly insulin is secreted is tightly regulated, and this is the focus of our research.
A key protein regulator of insulin secretion is the enzyme glucokinase. Our lab studies how glucokinase is regulated by nitric oxide, which activates glucokinase and regulates its cellular localization. This research is currently supported by a research grant from the NIDDK.
Development of optical biosensors
Fluorescent proteins allow us to examine dynamic regulation of proteins in living cells. We use a structure-based approach to understand the inner workings of these reagents and to build better, brighter probes. Our latest variant, mCerulean3, is an exceptionally bright and stable cyan fluorescent protein. We also have several FRET-based probes in development that can be used to track enzyme activation in living cells through quantitative fluorescence microscopy methods.
Markwardt ML, Seckinger KM, Rizzo MA. Regulation of Glucokinase by Intracellular Calcium Levels in Pancreatic Beta Cells. J Biol Chem. 291: 3000-3009 2016. PMID: 26698632
Desmond PF, Muriel J, Markwardt ML, Rizzo MA, Bloch RJ. Identification of Small Ankyrin 1 as a Novel Sarco(endo)plasmic Reticulum Ca2+-ATPase 1 (SERCA1) Regulatory Protein in Skeletal Muscle. J Biol Chem 290(46):27854-67 2015 PMCID: PMC4646913
Costantini LM, Baloban M, Markwardt ML, Rizzo MA, Guo F, Verkhusha VV, Snapp EL. A palette of fluorescent proteins optimized for diverse cellular environments. Nat Commun. 6:7670 2015 PMCID: PMC4499870
Fairfax ST, Mauban JR, Hao S, Rizzo MA, Zhang J, Wier WG. Ca(2+) signaling in arterioles and small arteries of conscious, restrained, optical biosensor mice. Front Physiol. 2014 Oct 7;5:387. doi: 10.3389/fphys.2014.00387. eCollection 2014. PMCID: PMC4188025
Mauban JR, Fairfax ST, Rizzo MA, Zhang J, Wier WG. A method for noninvasive longitudinal measurements of [Ca2+] in arterioles of hypertensive optical biosensor mice. Am J Physiol Heart Circ Physiol. 2014 Jul 15;307(2):H173-81. doi: 10.1152/ajpheart.00182.2014. Epub 2014 May 23. PMCID: PMC4101644
Markwardt ML, Nkobena A, Ding SY, & Rizzo MA. Association with nitric oxide synthase on insulin secretory granules regulates glucokinase protein levels. Mol Endocinol. 26:1617-29. 2012. PMCID: PMC3434526
Geraedts MC, Takahashi T, Vigues S, Markwardt ML, Nkobena A, Cockerham RE, Hajnal A, Dotson CD, Rizzo MA & Munger SD. Transformation of post-ingestive glucose responses after deletion of sweet taste receptor subunits or gastric bypass surgery. Am J Physiol Endocrinol Metab. 303:E464-72. 2012. PMCID: PMC3423100
Ding SY, Nkobena A, Kraft CA, Markwardt ML & Rizzo MA. Glucagon-like peptide 1 stimulates post-translational activation of glucokinase in pancreatic beta cells. J. Biol. Chem. 286:16768-42. 2011. PMCID: PMC3089519
Markwardt ML, Kremers GK, Kraft CA, Ray K, Cranfill PJC, Wilson KA, Day RN, Wachter RM, Davidson MW & Rizzo MA. An improved Cerulean Fluorescent protein with enhanced brightness and reduced reversible photoswitching. PLoS ONE 6:e17896. 2011. PMCID: PMC3066204
Ding SY, Tribble ND, Kraft CA, Markwardt M, Gloyn AL & Rizzo MA. Naturally occurring glucokinase mutations are associated with defects in post-translational S-nitrosylation. Mol Endocrinol. 24:171-7. 2010. PMCID: PMC2802892
Rizzo MA. & Piston D.W. FRET by Fluorescence Polarization Microscopy Sullivan K.F. (ed). Methods in Cell Biology. 85:415-30. 2008.
Rizzo MA, Springer G, Segawa K, Zipfel W & Piston DW. Optimization of pairings and detection conditions for measurement of FRET between cyan and yellow fluorescent proteins. Microscopy & Microanalysis 12:238-54. 2006.
Rizzo MA & Piston DW. A High Contrast Method for Imaging FRET between Fluorescent Proteins. Biophys J. 88:L14-16. 2005 PMCID: PMC1305173
Rizzo MA. Springer GH, Granada B & Piston D. W. An improved cyan fluorescent protein variant useful for FRET. Nat. Biotechnol. 22:445-49. 2004.
Rizzo MA & Piston DW. Regulation of β-cell glucokinase by S-nitrosylation and association with nitric oxide synthase. J. Cell Biol. 161:243-48. 2003. PMCID: PMC2172922