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Yale E. Goldman, MD, PhD
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Emeritus Professor of Physiology
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Department: Physiology
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Graduate Group Affiliations
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Contact information
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415 Curie Boulevard
47 615B Clinical Research Building
Philadelphia, PA 19104-6083
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47 615B Clinical Research Building
Philadelphia, PA 19104-6083
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Office: (215) 898-4017
34 Fax: (215) 898-2653
34 Lab: (215) 898-4247
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34 Fax: (215) 898-2653
34 Lab: (215) 898-4247
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Publications
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Education:
21 9 B.S. 23 (Electrical Engineering) c
30 Northwestern University, 1969.
21 a Ph.D. 17 (Physiology) c
46 University of Pennsylvania School of Medicine, 1975.
21 9 M.D. 15 (Medicine) c
46 University of Pennsylvania School of Medicine, 1975.
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21 9 B.S. 23 (Electrical Engineering) c
30 Northwestern University, 1969.
21 a Ph.D. 17 (Physiology) c
46 University of Pennsylvania School of Medicine, 1975.
21 9 M.D. 15 (Medicine) c
46 University of Pennsylvania School of Medicine, 1975.
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Links
7e Search PubMed for articles
79 Department of Physiology
83 Pennsylvania Muscle Institute
8b Biochemistry and Molecular Biophysics
90 Cell and Molecular Biology Grad Group
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3
3
90
Permanent link7e Search PubMed for articles
79 Department of Physiology
83 Pennsylvania Muscle Institute
8b Biochemistry and Molecular Biophysics
90 Cell and Molecular Biology Grad Group
c
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5e
d9 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.
8
ce Key Words: Actin, Molecular motors, Motility, Myosin, Kinesin, Dynein, Structural dynamics, Fluorescence, Ribosome, Protein synthesis, G-Protein, Optical Trap, Single-Molecule, Nanotechnology
8
26 Description of Research
381 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.
8
370 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.
8
20 Rotation Projects
21 - Unconventional Myosins
25 - Dynein/Myosin Interactions
1c - Protein Synthesis
27 - Ribosomal Elongation Factors
8
1e Lab Personnel:
30 Dr. Jody Dantzig-Brody, Research Faculty
28 Xiaonan Cui, Research Technician
2a Chunlai Chen, post-Doctoral Fellow
3d Matthew Caporizzo, Material Sciences Graduate Student
4f Deborah Shroder, Biochemistry and Molecular Biophysics Graduate Student
4c Lisa Lippert, Biochemistry and Molecular Biophysics Graduate Student
4d Michael Woody, Biochemistry and Molecular Biophysics Graduate Student
40 Ryan Jamiolkowski, Bioengineering Graduate and MD Student
6e
42 1975 Upjohn Achievement Award, University of Pennsylvania;
5a 1971-1975 Trainee, Medical Scientist Training Program, University of Pennsylvania;
46 1975-1977 Research Fellowship, Muscular Dystrophy Association;
39 1977-1979 National Research Service Award, (NIH);
3b 1980-1985 Research Career Development Award, (NIH);
49 1983-1988 Editorial Board Member, Journal of Physiology (London);
53 1984-1986 Editor for Special Topic Section of Annual Reviews of Physiology;
49 1985-1987 Elected Councilor of the Society of General Physiology;
45 1986 Bowditch Lecturer of the American Physiological Society;
49 1987 Chairman, Gordon Conference on Muscle: Contractile Proteins;
56 1988-2010 Director, Pennsylvania Muscle Institute, University of Pennsylvania;
42 1989 Lindback Foundation Award for Distinguished Teaching;
52 1990 Lamport Lecturer of the University of Washington, School of Medicine;
52 1990-1995 Elected Councillor (Executive Committee) of Biophysical Society;
4c 1991 Organizer, American Physiological Society Specialty Conference;
39 1991 Visiting Professor, Osaka University, Japan;
45 1994,95,97 Visiting Professor, University of Florence, Italy;
3e 1992-2012 Editorial Board Member, Biophysical Journal;
32 2003 -2004 President, Biophysical Society;
58 2005-pres Assoc-Director, Nano-Bio Interface Center, University of Pennsylvania;
4c 2005 Stanley N. Cohen School of Medicine Biomedical Research Award;
2f 2006 Fellow of the Biophysical Society;
4f 2007 Fellow of the American Association for the Advancement of Science;
45 2011 Plenary Lecturer, University of Massachusetts, Amherst;
46 2011 Plenary Lecturer, Gordon Conference on Molecular Motors;
3b 2013 University of Virginia Distinguished Speaker;
43 2014 University of Colorado, Boulder, Distinguished Speaker.
e 29
27
Description of Research Expertise
2a Research Interestsd9 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.
8
ce Key Words: Actin, Molecular motors, Motility, Myosin, Kinesin, Dynein, Structural dynamics, Fluorescence, Ribosome, Protein synthesis, G-Protein, Optical Trap, Single-Molecule, Nanotechnology
8
26 Description of Research
381 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.
8
370 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.
8
20 Rotation Projects
21 - Unconventional Myosins
25 - Dynein/Myosin Interactions
1c - Protein Synthesis
27 - Ribosomal Elongation Factors
8
1e Lab Personnel:
30 Dr. Jody Dantzig-Brody, Research Faculty
28 Xiaonan Cui, Research Technician
2a Chunlai Chen, post-Doctoral Fellow
3d Matthew Caporizzo, Material Sciences Graduate Student
4f Deborah Shroder, Biochemistry and Molecular Biophysics Graduate Student
4c Lisa Lippert, Biochemistry and Molecular Biophysics Graduate Student
4d Michael Woody, Biochemistry and Molecular Biophysics Graduate Student
40 Ryan Jamiolkowski, Bioengineering Graduate and MD Student
6e
Description of Other Expertise
2c Academic Experience:42 1975 Upjohn Achievement Award, University of Pennsylvania;
5a 1971-1975 Trainee, Medical Scientist Training Program, University of Pennsylvania;
46 1975-1977 Research Fellowship, Muscular Dystrophy Association;
39 1977-1979 National Research Service Award, (NIH);
3b 1980-1985 Research Career Development Award, (NIH);
49 1983-1988 Editorial Board Member, Journal of Physiology (London);
53 1984-1986 Editor for Special Topic Section of Annual Reviews of Physiology;
49 1985-1987 Elected Councilor of the Society of General Physiology;
45 1986 Bowditch Lecturer of the American Physiological Society;
49 1987 Chairman, Gordon Conference on Muscle: Contractile Proteins;
56 1988-2010 Director, Pennsylvania Muscle Institute, University of Pennsylvania;
42 1989 Lindback Foundation Award for Distinguished Teaching;
52 1990 Lamport Lecturer of the University of Washington, School of Medicine;
52 1990-1995 Elected Councillor (Executive Committee) of Biophysical Society;
4c 1991 Organizer, American Physiological Society Specialty Conference;
39 1991 Visiting Professor, Osaka University, Japan;
45 1994,95,97 Visiting Professor, University of Florence, Italy;
3e 1992-2012 Editorial Board Member, Biophysical Journal;
32 2003 -2004 President, Biophysical Society;
58 2005-pres Assoc-Director, Nano-Bio Interface Center, University of Pennsylvania;
4c 2005 Stanley N. Cohen School of Medicine Biomedical Research Award;
2f 2006 Fellow of the Biophysical Society;
4f 2007 Fellow of the American Association for the Advancement of Science;
45 2011 Plenary Lecturer, University of Massachusetts, Amherst;
46 2011 Plenary Lecturer, Gordon Conference on Molecular Motors;
3b 2013 University of Virginia Distinguished Speaker;
43 2014 University of Colorado, Boulder, Distinguished Speaker.
e 29
23
10e 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.
12a 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.
111 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.
fd 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.
f7 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.
146 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.
e8 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.
187 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.
118 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.
113 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(9): 2676-2682, Jul 2009.
10f 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.
11a 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.
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Selected Publications
10d 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, 2003.10e 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.
12a 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.
111 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.
fd 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.
f7 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.
146 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.
e8 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.
187 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.
118 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.
113 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(9): 2676-2682, Jul 2009.
10f 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.
11a 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.
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