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Yale E. Goldman, MD, PhD

Yale E. Goldman, MD, PhD

faculty photo
Professor of Physiology
Department: Physiology

Contact information
400 Curie Boulevard
615B CRB
Philadelphia, PA 19104-6083
Office: (215) 898-4017
Fax: (215) 898-2653
Lab: (215) 898-4247
Education:
B.S. (Electrical Engineering)
Northwestern University, 1969.
Ph.D. (Physiology)
University of Pennsylvania School of Medicine, 1975.
M.D. (Medicine)
University of Pennsylvania School of Medicine, 1975.
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Description of Research Expertise

Research Interests
Relating the structural changes to enzymatic reactions and mechanical steps of the energy transduction mechanism by mapping the real-time domain motions of the motor proteins and ribosomal elongation factors.

Key Words: Actin, Molecular motors, Motility, Myosin, Kinesin, Dynein, Structural dynamics, Fluorescence, Ribosome, Protein synthesis, G-Protein, Optical Trap, Single-Molecule, Nanotechnology

Description of Research
Motor proteins and GTP-binding proteins (G-proteins) share many structural and functional attributes. Molecular motors myosin, dynein and kinesin are prototype biological energy transducers that can be understood at a particularly fine level of detail. The obvious functional output (force and motion) allow the reaction sequence to be probed by single molecule biophysical, chemical and structural studies. A cyclic interaction between actin and myosin transforms free energy of splitting ATP into motion and mechanical work. Modified forms of this mechanism power other cell biological motions such as targeted vesicle transport and cell division. We are using novel biophysical techniques, including nanometer tracking of single fluorescent molecules, bifunctional fluorescent probes and infrared optical traps (laser tweezers) to map the real-time domain motions of the motor proteins.

Although the ribosome has been studied extensively since the unraveling of the genetic code, how it accomplishes the enormous fidelity of messenger RNA translation into amino acid sequences during protein biosynthesis is not understood. The ribosome is a motor translocating along the mRNA exactly 3 bases per elongation cycle. Energy from splitting GTP by G-protein elongation factors (EFs) is transformed into translational accuracy and maintenance of the reading frame. Codon-anticodon base pairing between mRNA and tRNA ‘reads’ the code, but EF-Tu ‘proofreads’ it. EF-G is the motor catalyzing translocation of tRNAs and mRNA. Powerful techniques developed for studies on motor proteins, including single molecule fluorescence and optical traps, may be applied to understand the structural biology, energetics, and function of EFs in their working environment.

Rotation Projects
- Unconventional Myosins
- Dynein/Myosin Interactions
- Protein Synthesis
- Ribosomal Elongation Factors

Lab Personnel:
Dr. Jody Dantzig-Brody, Research Faculty
Xiaonan Cui, Research Technician
Chunlai Chen, post-Doctoral Fellow
Matthew Caporizzo, Material Sciences Graduate Student
Deborah Shroder, Biochemistry and Molecular Biophysics Graduate Student
Lisa Lippert, Biochemistry and Molecular Biophysics Graduate Student
Michael Woody, Biochemistry and Molecular Biophysics Graduate Student
Ryan Jamiolkowski, Bioengineering Graduate and MD Student

Description of Other Expertise

Academic Experience:
1975 Upjohn Achievement Award, University of Pennsylvania;
1971-1975 Trainee, Medical Scientist Training Program, University of Pennsylvania;
1975-1977 Research Fellowship, Muscular Dystrophy Association;
1977-1979 National Research Service Award, (NIH);
1980-1985 Research Career Development Award, (NIH);
1983-1988 Editorial Board Member, Journal of Physiology (London);
1984-1986 Editor for Special Topic Section of Annual Reviews of Physiology;
1985-1987 Elected Councilor of the Society of General Physiology;
1986 Bowditch Lecturer of the American Physiological Society;
1987 Chairman, Gordon Conference on Muscle: Contractile Proteins;
1988-2010 Director, Pennsylvania Muscle Institute, University of Pennsylvania;
1989 Lindback Foundation Award for Distinguished Teaching;
1990 Lamport Lecturer of the University of Washington, School of Medicine;
1990-1995 Elected Councillor (Executive Committee) of Biophysical Society;
1991 Organizer, American Physiological Society Specialty Conference;
1991 Visiting Professor, Osaka University, Japan;
1994,95,97 Visiting Professor, University of Florence, Italy;
1992-2012 Editorial Board Member, Biophysical Journal;
2003 -2004 President, Biophysical Society;
2005-pres Assoc-Director, Nano-Bio Interface Center, University of Pennsylvania;
2005 Stanley N. Cohen School of Medicine Biomedical Research Award;
2006 Fellow of the Biophysical Society;
2007 Fellow of the American Association for the Advancement of Science;
2011 Plenary Lecturer, University of Massachusetts, Amherst;
2011 Plenary Lecturer, Gordon Conference on Molecular Motors;
2013 University of Virginia Distinguished Speaker;
2014 University of Colorado, Boulder, Distinguished Speaker.

Selected Publications

Yildiz, A., Forkey, J.N., McKinney, S.A., Ha, T., Goldman, Y.E., and Selvin, P.R.: Myosin V Walks Hand-over-hand: Single Fluorophore Imaging with 1.5-nm Localization. Science 300: 2062-2065, 2003.

Forkey, J.N., Quinlan, M.E., Shaw, M.A., Corrie, J.E., and Goldman, Y.E.: Three-dimensional Structural Dynamics of Myosin V by Single-molecule Fluorescence Polarization. Nature 422: 399-404, 2003.

Quinlan, M.E., Forkey, J.N., and Goldman, Y.E. : Orientation of the Myosin Light Chain Region by Single and Multiple Molecule Total Internal Reflection Fluorescence Polarization Microscopy. Acc. Chem. Res. 38: 583-593, 2005.

Ross, J.L., Shuman, H., Holzbaur, E.L.F., and Goldman, Y.E.: Kinesin and Dynein-Dynactin at Intersecting Microtubules: Motor Number Affects Dynein but not Kinesin Function. Biophys. J. 92: 941a, 2007.

Sun, Y., Schroeder, H.W. 3rd, Beausang, JF, Homma, K, Ikebe, M, and Goldman, YE. : Myosin VI Walks "Wiggly" on Actin with Large and Variable Tilting. Mol Cell. 28: 954-964, 2007.

Arsenault, M.E., Zhao, H., Purohit, P.K., Goldman, Y.E., and Bau, H.H.. : Confinement and Manipulation of Actin Filaments by Electric Fields. Biophys J. 93: L42-L44, 2007.

Stapulionis R., Wang Y., Dempsey G.T., Khudaravalli R., Nielsen K.M., Cooperman B.S., Goldman Y.E., and Knudsen C.R.: Fast in vitro Translation System Immobilized on a Surface via Specific Biotinylation of the Ribosome. Biol Chem. 389: 1239-1249, 2008.

Dixit R., Ross J.L., and Goldman Y.E., and Holzbaur E.L. : Differential Regulation of Dynein and Kinesin Motor Proteins by Tau. Science 319: 1086-1089, 2008.

Beausang , J.F., Sun, Y., Quinlan, M.E., Forkey, J.N., and Goldman, Y.E. : Orientation and Rotational Motions of Single Molecules by Polarized Total Internal Reflection Fluorescence Microscopy. In: Single-Molecule Techniques. A Laboratory Manual. Eds. Selvin, P.R. and Ha, T. Cold Spring Harbor Press. Page: 507, 2008.

Dixit, R., Barnett, B., Lazarus, J.E., Tokito, M., Goldman, Y.E. and Holzbaur, E.L.F.: Microtubule Plus-End Tracking by CLIP-170 Requires EB1. , 106: 492-492. 2009. Proc. Nat. Acad. Sci. 106: 492-297, 2009.

Sun, Y., Dawicki McKenna, J., Murray, J.M., Ostap, E.M., and Goldman, Y.E. : Parallax: High Accuracy Three-Dimensional Single Molecule Tracking Using Split Images. Nano Lett. 7: 2676-2682, 2009.

Schroeder Harry W, Mitchell Chris, Shuman Henry, Holzbaur Erika L F, Goldman Yale E: Motor Number Controls Cargo Switching at Actin-Microtubule Intersections In Vitro. Current biology : CB Apr 2010.

Sun Yujie, Sato Osamu, Ruhnow Felix, Arsenault Mark E, Ikebe Mitsuo, Goldman Yale E: Single-molecule stepping and structural dynamics of myosin X. Nature structural & molecular biology 17(4): 485-91, Apr 2010.

Holzbaur Erika L F, Goldman Yale E: Coordination of molecular motors: from in vitro assays to intracellular dynamics. Current opinion in cell biology 22(1): 4-13, Feb 2010.

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Last updated: 09/24/2014
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