Michael Roe, Ph.D.

Mechanisms that Regulate Intracellular Calcium Ion Signaling and Insulin Secretion, Pathophysiology of Diabetes Mellitus

Research Summary

Dr. Roe's laboratory is focused on understanding the regulation of insulin secretion and the pathophysiology of diabetes. He has concentrated on
[1] defining the subcellular Ca²⁺ signaling mechanisms which regulate insulin secretion from the perspectives of biophysics, physiology, biochemistry and molecular biology, and [2] determining the role of Ca²⁺ signaling defects in the pathophysiology of Type 1 and Type 2 diabetes mellitus.

Projects are underway to
[1] understand the role of endoplasmic reticulum (ER) Ca²⁺ the regulation of glucose-stimulated intracellular Ca²⁺ responses and insulin secretion,
[2] define the interrelationship between defects in ER Ca²⁺ signaling and beta-cell dysfunction in a mouse model of Type 2 diabetes mellitus, and
[3] determine the role of ER stress in beta-cell apoptosis associated with Type 1 diabetes mellitus.

Using newly developed Ca²⁺ biosensors targeted to the lumen of the ER, Dr. Roe is studying ER Ca²⁺ signaling in normal and diabetic mouse islets. Dr. Roe's group is also utilizing genetically-targeted fluorescent indicators to define mechanisms that regulate Ca²⁺ fluxes in the nucleus and mitochondria of insulin-secreting cells, and developing transgenic mice in which Ca²⁺ biosensors are specifically expressed in beta-cells. Most recently, Dr. Roe's laboratory has initiated the
[1] construction and testing new optical biosensors that will enable real-time measurements of insulin and insulin-like growth factor 1 receptor tyrosine kinase activity, [2] development of a new red light emitting genetically targeted fluorescence resonance energy transfer indicator of intracellular calcium concentration, and
[3] application of interfering RNA technology to define the effects of selective gene ablation on islet cell biology, signal transduction, and apoptosis.

Selected Papers

Pulver RA, Rose-Curtis P, Phillips CC, Roe MW, Wellman GC and Lounsbury KM. (2004). Store-operated Ca²⁺ entry mediates activation of the CREB transcription factor in vascular smooth muscle. Circulation Research 94: 1351-1358

Houamed K, Fu J, Roe MW and Philipson LH. (2004). Electrophysiology of the pancreatic beta cell. In: Diabetes Mellitus: a fundamental text (D. LeRoith, S.I Taylor, and J.M. Olefsky, editors), Third Edition, Lippincott Williams & Wilkins: Philadelphia, 51-68

Philipson LH and Roe MW. (2004). Imaging metabolic and signaling targets in the pancreatic beta cell. Current Medicinal Chemistry-Immunological, Endocrine and Metabolic Agents 4: 333-337.

Zhou* XY, Shibusawa* N, Naik K, Porras D, Temple K, Ou H, Kaihara K, Roe MW, Brady MJ and Wondisford FE. (2004). Insulin regulation of hepatic gluconeogenesis through CREB Binding Protein (CBP) phosphorylation. Nature Medicine 10: 633-637 [* Both authors contributed equally to this paper]

Hara M, Bindokas V, Lopez JP, Kaihara K, Landa LR Jr, Harbeck M and Roe MW. (2004). Imaging endoplasmic reticulum calcium with a fluorescent biosensor in transgenic mice. American Journal of Physiology-Cell Physiology 287: C932-C938.

Wang C-Z, Wang Y, Di A, Magnuson MA, Ye H, Roe MW, Nelson DJ, Bell GI and Philipson LH. (2005). 5-amino-imidazole carboxamide riboside (AICAR) promotes glucose-stimulated insulin secretion from mouse pancreatic islets by KATP channel-dependent and -independent pathways. Biochemical Biophysical Research Communications 330: 1073-1079.

Kang G, Chepurny OG, Rindler MJ, Collis L, Chepurny Z, Harbeck M, Roe MW and Holz GG. (2005). A cAMP and Ca²⁺ coincidence detector in support of Ca²⁺-induced Ca²⁺ release (CICR) in pancreatic beta-cells. Journal of Physiology 566: 173-188.

Landa* L Jr, Harbeck* M, Kaihara K, Kitiphongspattana K, Graf O, Chepurny O, Nikolaev VO, Lohse MJ, Holz GG and Roe MW. (2005) Interplay of Ca²⁺ and cAMP signaling in the insulin-secreting MIN6 beta cell line. Journal of Biological Chemistry 280: 31294-31302. [* Both authors contributed equally to this paper.]

Roe MW, Fiekers JF, Philipson LH and Bindokas VP. (2005). Visualizing calcium signaling in cells by digitized conventional wide-field and confocal fluorescence microscopy. In: Cell Imaging and Techniques: Methods and Protocols (D.J. Taatjes and B.T. Mossman, editors), Humana Press: Towanda, NJ, in press