Laboratory of Orian Shirihai
MD, PhD, Technion, Israel
General field of research:
Affiliations other than medicine:
Evans Center for Interdisciplinary Biomedical Research
Room 847, X-building, 650 Albany St, Boston MA 02118
Phone: (617)-230 8570
Other research websites:
Mitochondria; Diabetes; Erythroid differentiation; Beta cell; Insulin
Summary of research interest:
Mitochondrial oxidative damage plays a key role in degeneration, aging and metabolic diseases. Our goal is to determine how damage is prevented or contained, how dysfunctional mitochondria are recognized and removed, and how mitochondrial networks participate in these processes.
We study two disease models in which oxidative damage to mitochondria play a key role in the development of pathology. In diabetes, nutrient-induced oxidative damage has been shown to be a major mediator of endocrine dysfunction and beta cell loss. In bone marrow, oxidative damage induced by iron and heme-intermediates, leads to the development of sideroblastic anemia and myelodysplastic syndrome.
Cellular imaging is central to our research and much effort is dedicated to developing of novel techniques for monitoring living cells under the microscope. The lab has enjoyed long term collaborations in both academia and industry. Funding is divided such that 25% is received from industry and the rest from NIH.
Wikstrom JD, Katzman SM, Mohamed H, Twig G, Graf SA, Heart E, Molina AJ, Corkey BE, de Vargas LM, Danial NN, Collins S, Shirihai OS. 2007. beta-Cell mitochondria exhibit membrane potential heterogeneity that can be altered by stimulatory or toxic fuel levels. Diabetes 56:2569-2578.
Haigh SE, Twig G, Molina AA, Wikstrom JD, Deutsch M, Shirihai OS. 2007. PA-GFP: a window into the subcellular adventures of the individual mitochondrion. Novartis Found Symp 287:21-36.
Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, Stiles L, Haigh SE, Katz S, Las G, Alroy J, Wu M, Py BF, Yuan J, Deeney JT, Corkey BE, Shirihai OS. 2008. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 27:433-446.
Danial NN, Walensky LD, Zhang CY, Choi CS, Fisher JK, Molina AJ, Datta SR, Pitter KL, Bird GH, Wikstrom JD, Deeney JT, Robertson K, Morash J, Kulkarni A, Neschen S, Kim S, Greenberg ME, Corkey BE, Shirihai OS, Shulman GI, Lowell BB, Korsmeyer SJ. 2008. Dual role of proapoptotic BAD in insulin secretion and beta cell survival. Nat Med. Feb;14(2):144-53
Twig G. Hyde B, and Shirihai OS. 2008. Mitochondrial fusion, fission and autophagy as a quality control axis. Biochemica and Biophysica Acta. 1777(9):1092-7.
Elorza A., Hyde B., Mikkola HK, Collins S, and Shirihai OS. 2008. UCP2 modulates cell proliferation through the MAPK/ERK pathway during erythropoiesis and has no effect on heme biosynthesis. J. Biol. Chem. 283(45):30461-70. PMCID: PMC2576537
Mouli P, Twig G, and Shirihai OS. 2009. Selectivity and Frequency of mitochondrial fusion is essential to its quality control maintenance. Biophysical Journal. In Press. Available online.
Molina AJ, Shirihai OS. 2009. Quantification of Mitochondrial Dynamics. Methods in Enzymology. In Press.
Technologies available for sharing upon request:
Confocal microscopy of mitochodnria in living cells.
Oxygen consumption of isolated mitochondria, cells and tissue.
Erythroid differentiation in vitro from blood projenitors and from ES cells.