Phone: 607 253 3336
Fax: 607 253 4447
E-mail: mik7@cornell.edu
Smooth muscle-specific
Cre/eGFP mouse
Light (left) and fluorescent (right) images of mouse urinary bladder (top), mesentery (middle) and heart (below) showing smooth muscle-specific expression of eGFP. (click for larger image)
Dr. Kotlikoff (fifth from right) and the members of his lab.
(click for larger image)
Left column, immunohistochemical staining of GCaMP molecules confined to the smooth muscle layers of the bladder (above), coronary artery (middle), and airway (below). At right the function of the reporter is seen in tissues before and after nerve stimulation of urinary bladder smooth muscle (above), exposure of a mesenteric artery to norepinephrine (middle), and contraction of an airway with methacholine (below). Ca2+ fluorescence is psuedo color-coded from blue to red (see Ji et al, J. Biol. Chem. 279: 21461-21468, 2004).(click for larger image)
Mice with glowing hearts shed light on living cells.
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LAB LINKS
RESEARCH INTERESTS
My laboratory focuses on the molecular processes underlying excitation-contraction coupling and rhythmicity in cardiac and smooth muscle cells. Current studies seek to understand the role of specific sarcoplasmic reticular calcium release channels and sarcolemmal ion channels in cellular excitation and relaxation. A major goal of the laboratory is to understand processes of intercellular communication and the generation of spontaneous electrical activity. Techniques used to study these processes include gene targeting, development of in vivo imaging methods using genetically targeted cell sensors, embryonic stem cell engraftment, patch clamp measurements of ion channel function, and in vivo confocal and wide-field imaging.
Current projects in the laboratory include the study of the development of electrical activity in the embryonic heart, the use of embryonic cardiomyocytes and embryonic stem cells to alter electrical rhythm disturbances that occur after cardiac injury, the basis of spontaneous rhythm in smooth muscle tissues, and the development of genetically encoded sensors of cell signaling.
EDUCATION
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1973
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B.A.
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University of Pennsylvania, Philadelphia
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Literature
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1981
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V.M.D.
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University of Pennsylvania, Philadelphia
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Vet. Medicine
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1984
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Ph.D.
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University of California, Davis
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Physiology
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SELECTED PUBLICATIONS
- Collier, M.L., G. Ji, Y.-X. Wang, and M.I. Kotlikoff. Calcium-induced calcium release in smooth muscle: Loose coupling between the action potential and calcium release. J Gen Physiol 115:653-62, 2000.
Xin, H-B, T Senbonmatsu, D Cheng, Y-X Wang, J Copello, G Ji, ML Collier, K-Y Deng, LH Jeyakumar, MA Magnuson, T Inagami, MI Kotlikoff, and S Fleischer. Estrogen protects FKBP12.6 null mice from cardiac hypertrophy. Nature 416:334-337, 2002.
Rishniw, M., J Wilson, and MI Kotlikoff. Skeletal myogenesis in the mouse esophagus does not occur through transdifferentiation. Genesis 36:81-82, 2003.
Ji, G, ME Feldman, KS Greene, V Sorrentino, H-B Xin, and MI Kotlikoff. RYR2 proteins contribute to the formation of Ca2+ sparks in smooth muscle. J Gen Physiol 123:377-386, 2004.
Ji, G. M.E. Feldman, K.-Y. Deng, K.S. Greene, J. Wilson, J.C. Lee, R.C. Johnston, M. Rishniw, Y. Tallini, J. Zhang, W.G. Wier, M.P. Blaustein, H.-B. Xin, J. Nakai and M.I. Kotlikoff. Ca2+ -Sensing Transgenic Mice: Postsynaptic Signaling in Smooth Muscle. J Biol Chem 279:21461-21468, 2004.
Xin, H-B, KY Deng, B Shui, S Qu, Q Sun, J Lee, KS Greene, J Wilson, M Feldman, and MI Kotlikoff. Gene trap and gene inversion methods for conditional gene inactivation in the mouse. Nucleic Acids Research 33:e14,1-10, 2005.
Kotlikoff, MI and NY Tallini. Imaging dynamic cellular events in the lung. J Gen Physiol 125:529-530, 2005.
Ji, G, M Feldman, R Doran, W Zipfel, and MI Kotlikoff. Ca2+ -induced Ca2+ release through localized Ca2+ uncaging in smooth muscle. J Gen Physiol 127:225-235, 2006.
Tallini, NY, M Ohkura, B-R Choi, G Ji, K Imoto, R Doran, J Lee, P Plan, J Wilson, H-B Xin, A Sanbe, J Gulick, J Robbins, G Salama, J Nakai, and MI Kotlikoff. Imaging Cellular Signals in the Heart in Vivo: Cardiac expression of the high signal Ca2+ indicator GCaMP2. Proc Natl Acad Sci, USA 103:4753-4758, 2006.
Moo YL, H Song, J Nakai, M Ohkura, MI Kotlikoff, SP Kinsey, VA Golovina, and MP Blaustein. Local, Sub-plasma Membrane Ca2+ Signals Detected by a Tethered Ca2+ Sensor. Proc Natl Acad Sci, USA 103:13232-13237, 2006.
Tallini, YN, Shui, B, Deng, K-Y, Doran, Y, Fisher, P, Zipfel, W, Summers, B, Kotlikoff, MI. BAC Transgenic Mice Express Enhanced Green Fluorescent Protein in Central and Peripheral Cholinergic Neurons. Physiol Genomics 27:391-397, 2006.
Qu, S, Rinehart, C, Wu, H-H, Wang, SE, Carter, B, X, H-B, Kotlikoff, M, and Arteaga, CL. Gene targeting of ErbB3 using a Cre-mediated unidirectional DNA inversion strategy. Genesis 44:477-486, 2006.
Rishniw M, Fisher PW, Doran RM, Meadows E, Klein WH, Kotlikoff MI.
Smooth muscle persists in the muscularis externa of developing and adult
mouse esophagus. J Muscle Res Cell Motil. 28:153-65, 2007
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