Program Director/Principal Investigator (Last, First, Middle): Ostap, E. M. SENIOR/KEY PERSONNEL. See instructions. Use continuation pages as needed to provide the required information in the format shown below. Start with Program Director(s)/Principal lnvestigator(s). List all other senior/key personnel in alphabetical order, last name first. Name eRA Commons User Name Organization Role on Project E. M. Ostap Ostapm University of PA Pl Roberto Dominguez Dominguez University of PA Investigator Henry Shuman shuman University of PA Investigator Charles Sindelar Csindelar Yale University Consortium Pl OTHER SIGNIFICANT CONTRIBUTORS Name Organization Role on Project Human Embryonic Stem Cells Ii] No Dves If the proposed project involves human embryonic stem cells, list below the registration number of the specific cell line(s) from the following list: cells/registry/current.htm. Use continuation pages as needed. If a specific line cannot be referenced at this time, include a statement that one from the Registry will be used. Cell Line 0MB No. 0925-0001 PHS 398 (Rev. 01/18 Approved Through 03/31/2020) Page] Form Page 2-continued Number the following pages consecutively throughout the application. Do not use suffixes such as 4a, 4b. BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FIVE PAGES. NAME: E. Michael Ostap eRA COMMONS USER NAME (credential, e.g. , agency login): OSTAPM POSITION TITLE: Professor of Physiology and Director of the Pennsylvania Muscle Institute EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.) INSTITUTION AND LOCATION DEGREE Completion (if Date applicable) MMNYYY Illinois State University, Normal IL University of Minnesota, Minneapolis, MN B.S. 05/1988 Ph .D. 09/1993 Johns Hopkins University School of Medicine, Baltimore MD Post-doc 12/1996 FIELD OF STUDY Chemistry Biochemistry, Molecular Biology, & Biophysics Biochemistry & Cell Biology A. Personal Statement I have a strong background in the investigation of the biochemistry and biophysics of cytoskeletal motors. I have developed and utilized advanced biophysical & biochemical techniques (ensemble and single-molecule). I was the first to characterize the detailed ATPase kinetic mechanism of an unconventional myosin motor, and my laboratory has been a leader in the characterization of the force-dependent kinetics of muscle and non- muscle myosins. Much of our recent focus has been on the use of single-molecule and structural methods to investigate myosin-I motors, where we described the biophysics of membrane binding and the relationship between their mechanical and biochemical activities. Our recent work resulted in the determination of the structural mechanism of myosin force-sensing at near atomic resolution using cryo-EM, and we published the first unitary measurements of the force-dependence of cardiac myosin-I1. Notably, we recently discovered the importance of the myosin-I motor domain in establishing cell and organismal chirality. We have a strong interest in muscle cell biology and contractility, where we use advanced biophysical and imaging techniques. am the director of the Pennsylvania Muscle Institute (, I was chair of the 2014 Gordon Research Conference on Muscle and Molecular Motors, and I chaired the 2016 Biophysical Society Meeting in Los Angeles, CA. In 2006, I initiated a NIAMS-supported T32-based program focused on Muscle Biology and Muscle Disease for pre- and post-doctoral trainees, which is in its 13th year. Finally, I am currently chair of the NIH study section , Molecular Structure Function-C. B. Positions and Honors Professional Experience 2010-present Director, Pennsylvania Muscle Institute University of Pennsylvania School of Medicine 2009 Acting Director, Pennsylvania Muscle Institute University of Pennsylvania School of Medicine 2009-present Professor of Physiology University of Pennsylvania School of Medicine 2003-2009 Associate Professor of Physiology University of Pennsylvania School of Medicine 1997-2003 Assistant Professor of Physiology University of Pennsylvania School of Medicine 1993-1996 Postdoctoral Fellow, Department of Cell Biology and Anatomy Johns Hopkins School of Medicine

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Method to Extend Research in Time (MERIT) Award (R37)
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Study Section
Special Emphasis Panel (NSS)
Program Officer
Ainsztein, Alexandra M
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University of Pennsylvania
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Mentes, Ahmet; Huehn, Andrew; Liu, Xueqi et al. (2018) High-resolution cryo-EM structures of actin-bound myosin states reveal the mechanism of myosin force sensing. Proc Natl Acad Sci U S A 115:1292-1297
Lebreton, G; Géminard, C; Lapraz, F et al. (2018) Molecular to organismal chirality is induced by the conserved myosin 1D. Science 362:949-952
Woody, Michael S; Capitanio, Marco; Ostap, E Michael et al. (2018) Electro-optic deflectors deliver advantages over acousto-optical deflectors in a high resolution, ultra-fast force-clamp optical trap. Opt Express 26:11181-11193
Iwamoto, Daniel V; Huehn, Andrew; Simon, Bertrand et al. (2018) Structural basis of the filamin A actin-binding domain interaction with F-actin. Nat Struct Mol Biol 25:918-927
Greenberg, Michael J; Shuman, Henry; Ostap, E Michael (2017) Measuring the Kinetic and Mechanical Properties of Non-processive Myosins Using Optical Tweezers. Methods Mol Biol 1486:483-509
Ghiretti, Amy E; Thies, Edda; Tokito, Mariko K et al. (2016) Activity-Dependent Regulation of Distinct Transport and Cytoskeletal Remodeling Functions of the Dendritic Kinesin KIF21B. Neuron 92:857-872
McIntosh, Betsy B; Ostap, E Michael (2016) Myosin-I molecular motors at a glance. J Cell Sci 129:2689-95
Pyrpassopoulos, Serapion; Arpa?, Göker; Feeser, Elizabeth A et al. (2016) Force Generation by Membrane-Associated Myosin-I. Sci Rep 6:25524
Greenberg, Michael J; Arpa?, Göker; Tüzel, Erkan et al. (2016) A Perspective on the Role of Myosins as Mechanosensors. Biophys J 110:2568-76
Arif, Ehtesham; Sharma, Pankaj; Solanki, Ashish et al. (2016) Structural Analysis of the Myo1c and Neph1 Complex Provides Insight into the Intracellular Movement of Neph1. Mol Cell Biol 36:1639-54

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