Ocorr Lab

The Ocorr Lab is investigating the cellular and molecular basis of adult heart function and cardiomyopathies using the genetic model system Drosophila.

We use functional, electrophysiological, biochemical and immunohistochemical techniques that allow us to examine the roles of genes and gene products in cardiac channelopathies and stress-related cardiomyopathies.

Our lab pioneered the development of a novel methodology (Semi-automatic Optical Heartbeat Analysis, SOHA) that permits the quantification of heartbeat parameters in model systems with small hearts.

Using this system we have identified several ion channels in the fly heart that play prominent roles in repolarization of the human heart and cause arrhythmia in both the fly and in humans when mutated. We also have developed a number of other disease models including a diabetic-like cardiomyopathy induced by high sugar diet and hypoxia-induced cardiomyopathy.

Recently we have begun collaborations with NASA (by winning a Space Florida International Space Station Research Competition). We are using the fly to uncover the molecular/cellular basis for cardiac and muscle atrophy in astronauts exposed to extended periods of microgravity despite extensive exercise regimes aboard the ISS. Our flies were launched aboard SpaceX 3 for a month-long exposure to micro-gravity.

Learn more about SOHA Contact the Lab Download Karen Ocorr's CV

Semi-Automated Optical Heartbeat Analysis Software

Click play to watch a video under microscope of the beating heart of a Drosophila melanogaster

SOHA was originally written as a MatLab-based application and its implementation was published in Ocorr et al., 2007. The original program resulted from a collaboration between researchers at the Sanford-Burnham Medical Research Institute and the University of California – San Diego.

A more detailed demonstration of its application to fruit flies and to other model systems with small hearts was presented in Fink et al, 2009 and Ocorr et al, 2009.

Quantifies Movement from Videos

  • Sensitive
  • Non-invasive
  • Good signal/noise ratio
  • Resolution is limited only by the movie frame rate

Successfully used to quantify movement from:

  • Drosophila melanogaster hearts
  • Zebrafish larval hearts
  • Embryonic mouse hearts (E9)
Download SOHA

Publications

PLoS Genetics - Huntington's Disease Induced Cardiac Amyloidosis Is Reversed by Modulating Protein Folding and Oxidative Stress Pathways in the Drosophila Heart. PLoS Genetics - A Drosophila model of high sugar diet-induced cardiomyopathy. Cell - A global in vivo Drosophila RNAi screen identifies NOT3 as a conserved regulator of heart function. Science - Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Molecular Biology of the Cell - Myosin transducer mutations differentially affect motor function, myofibril structure, and the performance of skeletal and cardiac muscles.

Publications by Year

Click into a date range to see the publications for a specific year

Ivy JR, Drechsler M, Catterson J, Bodmer R, Ocorr K, Paululat A., Hartley PS Klf15 Is Critical for the Development and Differentiation of Drosophila Nephrocytes. PLoS One. 2015 Aug 24;10(8):e0134620. doi: 10.1371/journal.pone.0134620. eCollection 2015 PMID:26301956

Zarndt R, Piloto S, Powell F, Haddad G, Bodmer R*, Ocorr K* Cardiac responses to hypoxia and reoxygenation in Drosophila. Am J Physiol Regul Integr Comp Physiol. 2015 Sep 16:ajpregu.00164.2015. doi: 10.1152/ajpregu.00164.2015. [Epub ahead of print] PMID:26377557 *Co-corresponding Authors

Kaushik G, Spenlehauer A, Sessions AO, Trujillo AS, FuhrmannA, Fu Z, Venkatraman V, Pohl D, Tuler J, Wang M, Lakatta EG, Ocorr K, Bodmer R, Bernstein SI, Van Eyk JE, Cammarato A, Engler AJ. Vinculin-network mediated cytoskeletal remodeling and regulation of contractile function in aging myocardium SciTranslMed. 2015 Jun17;7(292):292ra99. doi:10.1126/scitranslmed.aaa5843. PMID:26084806

Martinez-Morentin L, Martinez L, Piloto S, Yang H, Schon E, Garesse R, Bodmer R, Ocorr K*, Cervera M*, Arredondo J*. Cardiac deficiency of single cytochrome oxidase assembly factor scox induces p53-dependent apoptosis in a Drosophila cardiomyopathy model. Hum Mol Genet.. 2015 Mar 19. pii: ddv106. [Epub ahead of print] PMID:25792727 *Co-corresponding authors

Diop S, Bisharat-Kernizan J, Birse R, Oldham S, Ocorr K, Bodmer R. PGC-1/Spargel Counteracts High-Fat-Diet-Induced Obesity and Cardiac Lipotoxicity Downstream of TOR and Brummer ATGL Lipase. Cell Reports . 2015 S2211-1247(15)00168-0. doi: 10.1016/j.celrep.2015.02.022. PMID:25753422

Smith KA, Voiriot G, Tang H, Fraidenburg DR, Song S, Yamamura H, Yamamura A, Guo Q, Wan J, Pohl NM, Tauseef M, Bodmer R, Ocorr K, Thistlethwaite PA, Haddad GG, Powell FL, Makino A, Mehta D, and Yuan J X-L. Notch Activation of Ca2+ Signaling Mediates Hypoxic Pulmonary Vasoconstriction and Pulmonary Hypertension. Am. J Resp. Cell Mol. Biol. 2015 PMID:25569851

Cammarato A, Ocorr S, Ocorr K. Enhanced assessment of contractile dynamics in Drosophila hearts. BioTechniques. 2015 58(2):77-80. doi: 10.2144/000114255. PMID:25652030

Lim H-Y, Wang W, Chen J, Ocorr K, Bodmer R. ROS Regulate Cardiac Function via a Distinct Paracrine Mechanism. Cell Reports. 2014 7, 35–44.

Nishimura M, Kumsta C, Kaushik G, Ding Y,Bisharat-Kernizan J,Cammarato A, Ross RS, Engler AJ, Bodmer R, Hansen M, and Ocorr K. Dual Role of Integrin and Integrin-Linked Kinase in Cardiac Aging and Integrity. Aging Cell. 2014 13, 431-40.

Tang M, Yuan W, Bodmer R, Wu X, Ocorr K. The role of pygopus in the differentiation of intra-cardiac valves in Drosophila. Genesis. 2014 Jan;52(1):19-28. PMID:24265259.

Melkani GC, Trujillo AS, Ramos R, Bodmer R, Bernstein SI, Ocorr K. Huntington's Disease Induced Cardiac Amyloidosis Is Reversed by Modulating Protein Folding and Oxidative Stress Pathways in the Drosophila Heart. PLoS Genet. 2013 9(12): :e1004024 PMID:24367279. (Cover Image; Image of the Week in The Scientist)

Tang M, Yuan W, Bodmer R, Ocorr K*, Wu X*. Pygopus Maintains Drosophila Heart Function with Age Independently of Canonical Wnt Signaling. Circ Cardiovasc Genet. 2013 6(5):472-80 PMID:24046329. *Co-corresponding authors

Wang X, Liao P, Fan X, Wan Y, Wang Y, Li Y, Jiang Z, Ye X, Mo X, Ocorr K, Deng Y, Wu X. Yuan W. CXXC5 Associates with Smads to Mediate TNF. Current Molecular Medicine. 2013 13:1385-1396 PMID: 23906331

Zhang R, Han P, Yang H, Ouyang K, Lee D, Lin YF, Ocorr K, Kang G, Chen J, Stainier DY, Yelon D, Chi NC. In vivo cardiac reprogramming contributes to zebrafish heart regeneration. Nature. 2013 Jun 27;498(7455):497-501. doi: 10.1038/nature12322. Epub 2013 Jun 19.

Harpaz N, Ordan E, Ocorr K, Bodmer R, Volk T. Multiplexin Promotes Heart but Not Aorta Morphogenesis by Polarized Enhancement of Slit/Robo Activity at the Heart Lumen. PLoS Genet. 2013 Jun;9(6):e1003597. PMID:23825967.

Zhang Z, Hsieh B, Poe A, Anderson J, Ocorr K, Gibson G, Bodmer R. Complex Genetic Architecture of Cardiac Disease in a Wild Type Inbred Strain of Drosophila melanogaster. PLoS One. 2013 Apr 29;8(4):e62909. PMID:23638165.

Na J, Musselman LP, Pendse J, Baranski TJ, Bodmer R, Ocorr K*, Cagan R. A Drosophila Model of High Sugar Diet-Induced Cardiomyopathy. PLoS Genet. 2013 9(1):e1003175. PMID:23326243. *Corresponding author (Cover Image)

Spindler SR, Li R, Dhahbi JM, Yamakawa A, Mote P, Bodmer R, Ocorr K, Williams R, Wang Y, & Ablao KP. Statin treatment increases lifespan and improves cardiac health in Drosophila. PLoS One. 2012;7(6):e39581 PMID: 22737247.

Hong TT, Smyth JW, Chu KY, Vogan JM, Fong TS, Jensen BC, Fang K, Halushka MK, Russell SD, Colecraft H, Hoopes CW, Ocorr K, Chi NC, Shaw RM. BIN1 is reduced and Cav1.2 trafficking is impaired in human failing cardiomyocytes. Heart Rhythm. 2012;9(5):812-20. Epub 2011 Dec 2.

Grossman T, Gamliel A, Wessells RJ, Taghli-Lamallem O, Jepsen K, Ocorr K, Korenberg J, Kirk L. Peterson KL, Rosenfeld MG, Bodmer R, Bier E. Over-expression of DSCAM and COL6A2 cooperatively generates congenital heart defects. PloS Genetics 2011 11:e100234 PMID:22072978.

Nishimura M, Ocorr K, Bodmer R, Cartry J. Drosophila as a model to study cardiac aging. Exp. Gerontology. 2011 46: 326-30. PMID:21130861.

Melkani G, Bodmer R, Ocorr K* and Bernstein SI*. The UNC-45 chaperone is critical for establishing myosin-based myofibrillar organization and cardiac contractility in the Drosophila heart model. PLoS One. 2011;6(7):e22579. PMID: 21799905. *Co-corresponding authors

Eleftherianos I, Won S, Chtarbanova S, Squiban B, Ocorr K, Bodmer R, Beutler B, Hoffmann A and Imler J-L. KATP channel-dependent regulation of cardiotropic viral infections. Proc Natl Acad Sci USA. 2011 108(29):12024-9. PMID:21719711.

Qian L, Wythe JD, Liu J, Cartry J, Vogler G, Mohapatra B, Otway RT, Huang Y, King IN, Maillet M, Zheng Y, Crawley T, Taghli-Lamallem O, Semsarian C, Dunwoodie S, Winlaw D, Harvey RP, Fatkin D, Towbin JA, Molkentin JD, Srivastava D, Ocorr K, Bruneau BG, Bodmer R. Tinman/Nkx2-5 acts via miR-1 and upstream of Cdc42 to regulate heart function across species. J Cell Biol. 2011 193(7):1181-96. PMID:21690310.

Lim HY, Wang W, Wessells RJ, Ocorr K, Bodmer R. Phospholipid homeostasis regulates lipid metabolism and cardiac function through SREBP signaling in Drosophila. Genes Dev. 2011 25(2):189-200. PMID:21245170.

Fan X, Yang Q, Wang Y, Zhang Y, Wang J, Yuan J, Li Y, Wang Y, Deng Y, Yuan W, Mo X, Wan Y, Ocorr K, Yang X, Wu X. Cloning and characterization of the cardiac-specific Lrrc10 promoter. BMB Rep. 2011;44(2):123-8.

Luo N, Li G, Li Y, Fan X, Wang Y, Ye X, Mo X, Zhou J, Yuan W, Tan M, Xie H, Ocorr K, Bodmer R, Deng Y, Wu X. SAMD4B, a novel SAM-containing protein, inhibits AP-1-, p53- and p21-mediated transcriptional activity. BMB Rep. 2010 43(5):355-61. PMID:20510020.

Hu J, Yuan W, Tang M, Wang Y, Fan X, Mo X, Li Y, Ying Z, Wan Y, Ocorr K, Bodmer R, Deng Y, Wu X. KBTBD7, a novel human BTB-kelch protein, activates transcriptional activities of SRE and AP-1. BMB Rep. 2010 43(1):17-22. PMID:20132730.

Birse RT, Choi J, Reardon K, Rodriguez J, Graham S, Diop S, Ocorr K, Bodmer R, Oldham S. High-fat-diet-induced obesity and heart dysfunction are regulated by the TOR pathway in Drosophila. Cell Metab. 2010 12(5):533-44. PMID: 21035763.

Huang W, Deng Y, Dong W, Yuan W, Wan Y, Mo X, Li Y, Wang Z, Wang Y, Ocorr K, Zhang B, Lin S, Wu X. The effect of excess expression of GFP in a novel heart-specific green fluorescence zebrafish regulated by nppa enhancer at early embryonic development. Mol Bio Rep. 2011;38(2):793-9. Epub 2010 Apr 10.

Lee JH, Budanov AV, Park EJ, Birse R, Kim TE, Perkins GA, Ocorr K, Mark H. Ellisman, Bodmer R, Bier E, Karin M. Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science. 2010 327(5970):1223-8. PMID: 20203043.

Neely GG, Kuba K, Cammarato A, Isobe K, Amann S, Zhang L, Murata M, Elmén L, Gupta V, Arora S, Sarangi R, Dan D, Fujisawa S, Usami T, Xia C, Keene AC, Alayari NN, Yamakawa H, Elling U, Berger C, Novatchkova M, Koglgruber R, Fukuda K, Nishina H, Isobe M, Pospisilik JA, Imai Y, Pfeufer A, Hicks AA, Pramstaller PP, Subramaniam S, Kimura A, Ocorr K, Bodmer R, Penninger JM. A global in vivo Drosophila RNAi screen identifies NOT3 as a conserved regulator of heart function. Cell. 2010 141:142-53. PMID:20371351.

Shahrestani P, Leung HT, Le PK, Pak WL, Tse S, Ocorr K, Huang T. Heterozygous mutation of Drosophila Opa1 causes the development of multiple organ abnormalities in an age-dependent and organ specific manner. PLoS One. 2009 4(8):e6867. PMID:19718456.

Akasaka T and Ocorr K. Functional screening in the Drosophila Heart Model. Methods Mol Biol. 2009 577:235-49. PMID:19718521.

Alayari NN, Vogler G, Taghli-Lamallem O, Ocorr K, Bodmer R, Cammarato A. Fluorescent Labeling of Drosophila Heart Structures. JoVE. 2009 doi:10.3791/1423.

Vogler G, Ocorr K. Visualizing the beating heart in Drosophila. JoVE. 2009 doi:10.3791/1425.

Ocorr K*, Fink M, Cammarato A, Bernstein S, Bodmer R. Semi-automated Optical Heartbeat Analysis of Small Hearts. JoVE. 2009 doi:10.3791/1435. *Corresponding author

Wessells R, Fitzgerald E, Piazza N, Ocorr K, Morley S, Davies C, Lim H-Y, Elmen L, Hayes M, Oldham S, Bodmer R. d4eBP acts downstream of both dTOR and dFoxo to modulate cardiac functional aging in Drosophila. Aging Cell. 2009 8:542-52 PMID:19594484.

Buechling T, Akaksaka T, Vogler G, Ruiz-Lozano R, Ocorr K, Bodmer R. Non-autonomous modulation of heart rhythm, contractility, and morphology in adult fruit flies. Dev. Biol. 2009 328: 483-92. PMID:19233157.

Fink M, Callol-Massot C, Chu A, Ruiz-Lozano P, Belmonte JC, Giles W, Bodmer R, and Ocorr K. A new method for the detection and quantification of heartbeat parameters in Drosophila, zebrafish, and embryonic mouse hearts. Biotechniques. 2009 46:101-113. PMID: 19317655.

Shahrestani P, Leung HT, Le PK, Pak WL, Tse S, Ocorr K, Huang T. Heterozygous mutation of Drosophila Opa1 causes the development of multiple organ abnormalities in an age-dependent and organ-specific manner. PLoS One 2009;4(8):e6867.

Qian L, Mohapatra B, Akasaka T, Liu J, Ocorr K, Towbin JA, Bodmer R. Transcription factor neuromancer/TBX20 is required for cardiac function in Drosophila with implications for human heart disease. Proc Natl Acad Sci USA. 2008 105:19833-8. PMID: 19074289.

Yu W, Li Y, Zhou X, Deng Y, Wang Z, YuanW, Zhao X, MoX, Huang W, Luo N, Yan Y, Ocorr K, Bodmer R, Wang Y, and Wu X. A novel human BTB-kelch protein KLHL31, strongly expressed in muscle and heart, inhibits transcriptional activities of TRE and SRE. Mol. Cells. 2008 26: 1-10. PMID:18719355.

Taghli-Lamallem O, Akasaka T, Ocorr K, Bodmer R. Drosophila Dystrophin is required for cardiac physiology and maintenance of heart structure integrity. Aging Cell. 2008 7:237-49. PMID:18221418.

Cammarato A, Dambacher CM, Reedy MC, Knowles AF, Kronert WA, Bodmer R, Ocorr K*, Bernstein SI*. Myosin Transducer Mutations Differentially Affect Motor Function, Myofibril Structure, and the Performance of Skeletal and Cardiac Muscles. Molecular Biol. Cell. 2008 19(2):553-62. PMID:18045988. *Co-corresponding authors (Highlighted in "InCytes", Cover Image)

Li Y,Yang D, Bai Y, Mo X, Huang W, Yuan W, Yin Z, Deng Y, Murashko O, Wang Y, Fan X, Zhu C, Ocorr K*, Wu X*. ZNF418, a Novel Human KRAB/C2H2 Zinc Finger Protein, Suppresses MAPK Signaling Pathway. Mol Cell Biochem. 2008 310:141-51. PMID:18084723. (*co-corresponding authors)

Shaw P, Ocorr K, Bodmer R, Oldham S. Drosophila aging Exp. Gerontol. 2008 43:5-10. PMID:18061385.

Mery A, Taghli-Lamallem O, Clark KA, Beckerle MC, Ocorr K, Bodmer R*. The Drosophila muscle LIM protein, Mlp84B, is essential for cardiac function. J. Exp. Biol. 2008 211:15-23. PMID:18083727.

Jing Li; Yuequn Wang; Xiongwei Fan; Xiaoyang Mo; Zequn Wang; Yongqing Li; Zhaochu Yin; Yun Deng; Na Luo; Chuanbing Zhu; Mingyao Liu; Qian Ma; Karen Ocorr; Wuzhou Yuan; Xiushan Wu. ZNF307, a novel zinc finger gene suppresses p53 and p21 pathway. Biochem Biophys Res Comm. 2007 363: 895-900. PMID:17910948.

Ocorr K, Crawley T, Gibson G, Bodmer R. Genetic variation for cardiac dysfunction in Drosophila. PLoS ONE. 2007 2:e601. PMID:17622346.

Ocorr K, Perrin L, Lim H-Y, Qian L, Wu X, Bodmer R. Genetic control of heart function and aging in Drosophila. Trends Cardiovasc Med. 2007 17(5):177-82. PMID:17574126.

Ocorr K, Reeves N, Wessells RJ, Fink M, Chen H-SV, Akasaka T, Yasuda S, Metzger J, Giles W, Posakony JW, and Bodmer R. KCNQ potassium channel mutations cause cardiac arrhythmias in Drosophila that mimic the effects of aging. Proc Natl Acad Sci USA. 2007 104:3943-8. PMID:17360457.

Ocorr K, Akasaka T, and Bodmer R. Age-related cardiac disease model of Drosophila. Mech. Ageing and Dev. 2007 128: 112-116. PMID:17125816.

Li J, Wang Y, Fan X, Mo X, Wang Z, Li Y, Yin Z, Deng Y, Luo N, Zhu C, Liu M, Ma Q, Ocorr K, Yuan W, Wu X. ZNF307, a novel zinc finger gene suppresses p53 and p21 pathway. Biochem Biophys Res Commun. 2007;363(4):895-900. Epub 2007 Sep 10.

Akasaka T, Klinedinst S, Ocorr, K, Bustamante EL, Kim SK, Bodmer R. The ATP-sensitive potassium (KATP) channel-encoded dSUR gene is required for Drosophila heart function and is regulated by tinman. Proc Natl Acad Sci USA. 2006 103(32):11999-2004. PMID:16882722.

Ocorr K and Osgood M. Self or Help: An evaluation of traditional and “self-paced” learning in undergraduate biochemistry courses. Biochem. & Mol. Biol. Education. 2003 31:308–312.

Venkatesh TV, Park M, Ocorr K, Nemaceck J, Golden K, and Bodmer R. Cardiac enhancer activity of the homeobox gene tinman depends on CREB consensus binding sites in Drosophila. Genesis. 2000 26:55-66. PMID:10660673.

Bodmer R, Golden K, Lockwood W, Ocorr K, Park M, Su M-T, and Venkatesh TV. Heart Development in Drosophila. Advances in Dev. Biology 1997 5: 201-236..

Ocorr K, Schulman H. Activation of multifunctional Ca2+/calmodulin-dependent kinase in intact hippocampal slices. Neuron. 1991;6(6):907-14.

Lemos JR, Lee CJ, Ocorr K, Dayanithi G, Nordmann JJ. Possible role for neurosecretory granule channel that resembles gap junctions. Ann N Y Acad Sci. 1991;635:480-2.

Lemos JR, Ocorr K, Nordmann JJ. Possible role for ionic channels in neurosecretory granules of the rat neurohypophysis. Soc Gen Physiol Ser. 1989;44:333-47.

Lemos JR, Ocorr K, Nordmann JJ. Ca2+ activated cation channel in neurosecretory granules from rat neural lobe. Soc Gen Physiol Ser. 1989 44: 132 144. PMID:1720606.

Ocorr K, Byrne JH. Evidence for separate receptors that mediate parallel effects of serotonin and small cardioactive peptideB (SCPB) on adenylate cyclase in Aplysia californica. Neurosci Lett. 1986;70(2):283-8.

Ocorr K, Tabata M, Byrne JH. Stimuli that produce sensitization lead to elevation of cyclic AMP levels in tail sensory neurons of Aplysia. Brain Res. 1986;371(1):190-2.

Ocorr K, Byrne JH. Membrane responses and changes in cAMP levels in Aplysia sensory neurons produced by serotonin, tryptamine, FMRFamide and small cardioactive peptideB (SCPB). Neurosci Lett. 1985;55(2):113-8.

Ocorr K, Walters ET, Byrne JH. Associative conditioning analog selectively increases cAMP levels of tail sensory neurons in Aplysia. Proc Natl Acad Sci U S A. 1985;82(8):2548-52.

Ocorr K, Berlind A. The identification and localization of a catecholamine in the motor neurons of the lobster cardiac ganglion. J Neurobiol. 1983;14(1):51-9.

The Absolute, Ultimate Guide to Lehninger Principles of Biochemistry

Principles of Biochemistry Study Guide

This is the official study guide for Lehninger’s Principles of Biochemistry. This study guide uses guided reading, interactive web-based questions, puzzles , test questions and other study aids to help students assimilate information about the chemistry of biological systems. Much of what is used in the guide emanates from over 10 years of teaching Introductory Biochemistry at the University of Michigan.

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