Faculty & Staff at TUC

Miriam  Gochin

Miriam Gochin

College: COM

Department: Basic Sciences

Title: Professor

Phone: Office: (707) 638-5463; Lab: (707) 638 5482

Fax: (707) 638-5255

E-Mail: miriam.gochin@tu.edu

Office: Administration & Faculty 1, Rm. 128

Website: http://tws.tu.edu/webdocs/TUResearch/MGochin.htm

Institution Degree Field of Study Obtained
Rhodes University, South Africa B.S. Honors Math/Chemistry 1977
Weizmann Institute of Science, Israel M.S. Chemistry 1981
University of California, Berkeley, CA Ph.D. Chemistry 1987

TEACHING EXPERIENCE

Touro University: Didactic instruction in Fundamentals of Osteopathic Medicine; Physician Assistant / Masters in Public Health and Masters in Health Science programs. Lectured in Fundamentals of Genetics and Inherited Diseases, Biochemistry, Basic Virology, Biotechnology

UCSF: Physical Chemistry Lab for Pharmacy students; Theory of NMR course for graduate students.

MENTOR TEACHING EXPERIENCE

Post-doctoral fellows and research personnel mentored:                                                                           

1999 Kechaun Tu University of California, San Francisco, University of the Pacific Dentistry, San Francisco, CA

2004-2008 Dong Wu University of the Pacific School of Dentistry, San Francisco, CA, Touro University – CA. Current position–biotech Startup

2004-2008 Lifeng Cai University of the Pacific School of Dentistry, San Francisco, CA, Touro University – CA. Current position: Associate Professor, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, 100850, China

2006 Yanxia Hou University of California, San Francisco, Touro University California  Current position: Associate Scientist, Département des Microtechnologies pour la Biologie et la Santé (DTBS), Laboratoire d’electronique et de technologies de l’information (LETI), Commissariat a L’Energie Atomique (CEA), 17 Rue Des Martyrs, 38054 Grenoble, France

2007 Shengyong Zhai University of California, San Francisco, Touro University California

2008-2009 Edina Balogh Touro University California

2008-current Guangyan Zhou Touro University California

2010 Aaron Phillips Touro University California Current position: Genentech, South San Francisco, CA

2010-11 Zhuangwu Li Touro University California

2010 Harmeet Kaur Touro University California

2011 Joseph Walsh Touro University California and UCSF

2011-2012 Mamta Chahar Touro University California and San Francisco State University

2011- Shidong Chu Touro University California

2011- Hardeep Kaur Touro University California

2012- Vladimir Sofiyev Touro University California

 

Website: Structural Biology Lab
We are using biochemical and biophysical tools for drug discovery against the Human Immunodeficiency Virus fusion mechanism. Drugs in this class have the potential to prevent the infection of T-cells by invading virus, and are so far limited to peptides that have poor pharmaceutical and bioavailability profiles. We are using techniques such as bio-inorganic chemistry, fluorescence, NMR spectroscopy and solid state biosensors to develop methodology allowing detection of small molecules targeting the viral fusion domain. Such compounds have the potential to be developed into effective drugs.

Current research includes the development of assays for the detection, evaluation and development of fusion inhibitors against HIV.  Methodology includes the use of a fluorescence assay to detect inhibitors binding to the HIV-1 envelope protein gp41, which is responsible for viral fusion. NMR studies have been designed for structural elucidation of bound low molecular weight gp41 inhibitors.  A solid-state (biosensor) assay utilizing an electrochemical quartz crystal microbalance has been developed.  We are also actively engaged in synthetic chemistry and computational chemistry for rational drug design.  Currently three classes of compounds are being investigated: 1) compounds randomly chosen from screening of a large diverse library; 2) Compounds selected from focused combinatorial libraries of peptidomimetics which mimic the natural interaction; 3) Rationally designed compounds based on structure-based drug discovery.  Application of the technology to the trimeric domain of other Class 1 viruses, in particular Influenza virus, as well as other types of pathogens, eg. Tuberculosis, is being considered.

Funded – Current

12/13/2010-12/12/2012 AI093243-01 R21 (Principal Investigator) “Rational design of indole compounds as HIV fusion inhibitors”, NIH/NIAID $275,000 direct costs

9/13/2010-8/12/2014 GM087998-01A1 R01 (Principal Investigator) “Structure-based discovery and development of HIV-1 gp41 fusion inhibitors”, NIH/NIGMS $207,649 direct / year

Funded – Past

10/1/2009-9/30/2010 NS066469-01A1 R21 (Principal Investigator) “Assay development for high affinity non-peptide HIV-1 gp41 inhibitors” NIH/NINDS $100,000 direct / year

8/1/2008-2/21/2010 NS059403-S1 (Principal Investigator) (Supplement) Application of HIV-1 fusion inhibitor assay at MLSCN, project approval April 2, 2009 ($25,000 direct)

3/1/2007-2/28-2009 NS059403 R21 (Principal Investigator) “A high throughput screening assay for HIV-1 fusion inhibitors”, NIH/NINDS $125,000 direct (extended through 2/28/2010)

9/1/2005-8/31/2008 ID05-TOURO-041 (Principal Investigator)”A Biosensor for detection of HIV fusion inhibitors” Universitywide AIDS Research Program, $50,000 direct / year

5/1/2004–4/31/2006 AI060361 R21 (Principal Investigator) “Metallopeptides in HIV-1 Fusion Inhibition”  NIH/NIAID $150,000 direct / year

1/1/2003-12/31/2003 106388-33-RGGN  (Principal Investigator) “A Mimic of the gp41 Coiled Coil in Inhibition of HIV” American Foundation for AIDS Research $90,000 direct

7/1/2003-7/1/2004 PDRF522 (Principal Investigator) “Expression of HIV-1 gp41 Peptides in E. coli” Pacific Dental Research Foundation, $3604

2003 DRES-023 Research Committee grant (Principal Investigator) “NMR Studies of Designed Metal-binding Peptides”, University of the Pacific School of Dentistry, $3000

7/1/2000 – 6/31/2002  R00-UP-092 (Principal Investigator) “Targeting HIV by Disruption of the Fusion Mechanism” Universitywide AIDS Research Program, $75,000 direct / year

7/1/1995–6/30/1999 GM53164 R29 (Principal Investigator) “Paramagnetic Ions in NMR Structure Determination” NIH/NIGMS 75,000 direct / year

 

Peer-Reviewed Publications:

1980      Gochin, M. and Moss, J.R., "On the Structure of H2Os3(CO)12", Organometallic Chemistry 192, 409

1981      Degani, H., Gochin, M., Karlish, S.J.D. and Schechter, Y., "EPR Studies and Insulin-like Effects of Vanadium in Rat Adipocytes", Biochemistry  20, 5795

1984       Gochin, M., James, T.L. and Shafer, R.H., "In Vivo 19F NMR of 5-fluorouracil Incorporation into RNA and Metabolites in E. coli cells", Biochim. Biophys. Acta 804, 118

1985      Gochin, M. and Degani, H., "1H NMR Studies of a Two-Iron Two-Sulphur Ferredoxin from Halobacterium of the Dead Sea", J. Inorg. Biochem. 25, 151

1985      Gochin. M., Weitekamp, D.P. and Pines, A., "A SHARP Method for High Resolution NMR of Heteronuclear Spin Systems in Inhomogeneous Fields", J. Magn. Reson. 63, 431

1985      Gochin, M. and Pines, A., "High Resolution NMR with a Surface Coil", J. Am. Chem. Soc. 107, 7193

1986      Gochin, M., Schenker, K.V., Zimmerman, H. and Pines, A., "Determination of Dipole-dipole Couplings in Oriented n-Hexane by Two-dimensional NMR", J. Am. Chem. Soc. 108, 6813

1987      Gochin, M., Hugi-Cleary, D., Zimmerman, H. and Pines, A., "Two-dimensional Multiple Quantum NMR of Isotopic Mixtures in Liquid Crystals", Mol. Phys. 60, 205

1987      Gochin, M., Zimmerman, H. and Pines, A., "Assignment of Dipolar Couplings and Estimation of Conformational Probabilities in Partially Oriented Hexane", Chem. Phys. Lett. 137, 51

1989      James, T.L., Kerwood, D.J., Gochin, M., Mills, P.A., Borgias, B.A. and Basus, V.J., "Refinement of Three-dimensional Protein and DNA Structures in Solution from Two-dimensional NMR Spectra", 4th Cyprus Conference on New Methods in Drug Research, Proceedings, Ed. A. Makriannis

1990      Borgias, B.A., Gochin, M., Kerwood, D.J. and James, T.L., "Relaxation Matrix Analysis of 2D NMR Data",Prog. Nucl. Magn. Reson. Spectr. 22, 83

1990      Gochin, M., Pines, A., Rosen, M.E., Rucker, S.P. and Schmidt, C., "Two-dimensional NMR Studies of Flexible Molecules in  Liquid Crystals: Orientations and Conformations of n_Hexane:, Mol. Phys. 69, 671

1990      Gochin, M., Zon, G. and James, T.L., "Solution Structure of [d(AC)4•d(GT)4] via Two-dimensional COSY and 2D NOE Spectroscopy", Biochemistry  22, 11161

1990      Gochin, M. and James, T.L., "Restrained Molecular Dynamics Simulations on [d(AC)4•d(GT)4] using NMR Constraints Derived from Two-dimensional NOE and DQF-COSY Experiments", Biochemistry  29, 11172

1991      Gochin, M. "Determination of Proton Transverse Relaxation Times in Homonuclear Coupled Spin Systems",J. Magn. Reson. 95, 299

1995      Gochin. M. and Roder, H., "The use of Pseudocontact shifts in NMR Structure Determination; Application to Wild-type and mutant Cytochrome c", Protein Science, 4, 296

1995      Hom, K., Gochin, M., Peumans, W.J. and Shine, N., "Ligand-Induced Perturbations in Urtica Dioica Agglutinin", FEBS Letts, 361, 157

1995      Gochin, M. and Roder, H., "Use of the Pseudocontact Shift as a Structural Constraint for Macromolecules in Solution", Bulletin of Magnetic Resonance

1997      Gochin, M. " Nuclear Magnetic Resonance Studies of a Paramagnetic Metallo-DNA Complex", J. Am. Chem. Soc., 119: 3377-8

1998      Gochin, M, "Nuclear Magnetic Resonance Characterization of a Paramagnetic DNA-Drug complex with High Spin Cobalt: Assignment of 1H and 31P Spectra and Determination of Electronic, Spectroscopic and Molecular Properties", J. Biomolec. NMR, 12:243-25

1999      Desvaux, H and Gochin, M. " Coherence Transfer Between Nuclear Spins in Paramagnetic Systems:  Effects of Nucleus-Electron Dipole-Dipole Cross-Correlation", Mol. Phys., 9: 1317-33

1999      Tu, K. and Gochin, M., "Structure Determination by Restrained Molecular Dynamics using NMR Pseudocontact Shifts as Experimentally Determined Constraints", J. Am. Chem. Soc., 121: 9276-85

1999      Buchko, G.W., Daughdrill,G.W., de Lorimer, R., Rao, S., Isern, N.G., Lingbeck, J., Taylor, J-S., Wold, M.S., Gochin, M., Spicer, L.D., Lowry, D.F., and Kennedy, M.A.. "Interactions of Human Nucleotide Excision Repair Protein XPA with RPA70 and DNA: Chemical Shift Mapping and 15N NMR Relaxation Studies", Biochemistry, 38:15116-28

2000      Gochin, M, "A High Resolution Structure of a DNA-Chromomycin-Cobalt Complex Determined from Paramagnetic Shifts in Nuclear Magnetic Resonance", Structure with Folding and Design, 8: 441-52

2002      Gochin, M., Khorosheva, V. and Case, M.A., “Structural Characterization of a Paramagnetic Metal Ion – Assembled Three Stranded a-Helical Coiled Coil”, J. Am. Chem. Soc., 124, 11018-28

2003      Gochin, M., Guy, R.K. and Case, M.A. “A metallopeptide assembly of the HIV-1 gp41 coiled coil is an ideal receptor in fluorescence detection of ligand binding”, Angew. Chem. Int. Ed., 42: 5325-8

2006      Gochin, M., Savage, R., Hinckley, S. and Cai, L. “A fluorescence assay for rapid detection of ligand binding affinity to HIV-1 gp41”, Biol. Chem, 387: 477-83

2006      Le TQ, Gochin M, Featherstone JD, Li W, DenBesten PK. “Comparative calcium binding of leucine-rich amelogenin peptide and full-length amelogenin”, Eur J Oral Sci. 114 Suppl 1:320-6; discussion 327-9, 382

2007      Cai, L. and Gochin, M. “A Novel Fluorescence Intensity Screening Assay Identifies New Low Molecular Weight Inhibitors of the gp41 Coiled Coil Domain of HIV-1”, Antimicrob. Agents Chemotherapy, 51: 2388-95

2007      Cai, L. and Gochin, M. “Colloidal aggregate detection by rapid fluorescence measurement of liquid surface curvature changes in multi-well plates”, J. Biomol. Screen. 12(7):966-71

2008      Hou, Y. and Gochin, M.An Artificial Ion Channel Biosensor in Human Immunodeficiency Virus gp41 Drug Sensing”, Anal. Chem., 80(15):5924-9

2009      Balogh E, Wu D, Zhou G, Gochin M., “NMR Second Site Screening for Structure Determination of Ligands Bound in the Hydrophobic Pocket of HIV-1 gp41”, J. Am. Chem. Soc. Feb 10. 131(8): 2821–2823

2009      Cai L, Balogh E, Gochin M. “A stable extended HIV-1 gp41 coiled coil as an effective target in an assay for high affinity fusion inhibitors.” Antimicrob. Agents Chemother. Jun; 53(6): 2444-9

2009      Gochin, M. and Cai, L. “The Role of Amphiphilicity and Negative Charge in Glycoprotein 41 Interactions in the Hydrophobic Pocket” J. Med. Chem, June 17 52(14), 4338-44

2010      Zhou, G., Wu, D., Hermel, E., Balogh, E. and Gochin, M., “Design, Synthesis and Evaluation of Indole Compounds as Novel Inhibitors targeting Gp41” Bioorg. Med. Chem. Lett., 20, 1500-3

2011      Gochin, M., Zhou, G. and Phillips, A.H.  “Paramagnetic Relaxation Assisted Docking of a Small Indole Compound in the HIV-1 gp41 Hydrophobic Pocket”, ACS Chem. Biol. 6, 267-74.

2011      Cai, L., Gochin, M. and Liu, K. “A facile surfactant critical micelle concentration determination” Chem. Commun., 2011, 47 (19), 5527 - 5529

2011      Gochin, M. and Zhou, G. “Amphipathic properties of HIV-1 gp41 fusion inhibitors”, Curr. Top. Med. Chem., 11 (24): 3022-32

2011      Cai, L., Gochin M. and Liu, K. “Biochemistry and Biophysics of HIV-1 gp41 – membrane interactions: Implications for HIV-1 Envelope Protein Mediated Viral-Cell Fusion and Fusion Inhibitor Design”, Curr. Top. Med. Chem., 11 (24): 2959-84

2011      Gochin M. “Lipophilic and Amphiphilic Interactions in Glycoprotein 41: Targets for Therapy” Curr. Top. Med. Chem. 11 (24): 2945-6

2011      Zhou, G., Wu, D. Snyder, B.c, Ptak, R.G c, Kaur, H.a and Gochin, M. ”Development of indole compounds as small molecule fusion inhibitors targeting HIV-1 glycoprotein-41”, J. Med. Chem. 54 (20), pp 7220–7231. http://dx.doi.org/10.1021/jm200791z

2012      Holden, P.M., Kaur, H., Goyal, R., Gochin, M. and Robert C. Rizzo, R.C. “Footprint-based identification of viral entry inhibitors targeting HIV gp41Bioorg. Med. Chem. Lett., in press

2012      Whitby, L.R., Boyle, K.E., Cai, L., Yu, X., Gochin, M. and Boger, D.L. “Discovery of HIV fusion inhibitors targeting gp41 using a comprehensive α-helix mimetic library” Bioorg. Med. Chem. Lett., in press

University Service

1999-2002 Admissions Committee, UCSF School of Pharmacy

2003 Student Welfare Committee, UCSF

2005-present Research Committee, Touro University

2005- Institutional Commitment to Outcomes, Touro University

2009- Assessment Development, Touro University

2009-present Translational Research Committee, Touro University

2009 WASC steering committee, Touro University

2009-2011 Program Review Committee, Touro University

2009-present Institutional Biosafety Committee, Touro University

2010-present Secretary, Faculty Benefits and Renention Committee

Professional Service

1994-present   Ad hoc reviewer, American Chemical Society, Biophys J, Biochemistry, FEBS Letts, J. Biomolec NMR, Bioorg and Med Chemistry Letts, Eur. J. Biochem.

2006-7 Reviewer, National Science Foundation, Division of Chemistry      

2009-10 E-mentoring program with students at Hogan High School, Project SEED with ACS

2010 Reviewer, NIH-NIAID

2011 Guest Editor, Hot Topic: “Lipophilic and Amphiphilic Interactions in Glycoprotein 41: Targets for Therapy”, Current Topics in Medicinal Chemistry, November

2011 Reviewer, AIDS Fellowship Study Section ZRG1 AARR, July 15

2012 Administrative/Scientific Review Committee, Veterans Health Administration Clinical Case Registry Data Repository

Societies

1999-present   American Chemical Society

2003-present   American Association for the Advancement of Science

2004-present   International Society for Antiviral Research

1974-1976       Rhodesian Government University Scholarship, Rhodes University

1975-1976       Good Hope Textile Corporation Bursary for Chemistry, Rhodes   University

1975               Sydney Cruise Memorial Prize for Mathematics, Rhodes University

1976               David Williams Memorial Prize for Mathematics, Rhodes University

1980               Recipient of Award for Distinction, Weizmann Institute of Science

1984               Regent's fellowship, University of California, Berkeley

2008               Dean’s Recognition for Excellence in Teaching, UCSF School of Pharmacy

2010–present  Professor, Department of Basic Sciences; Touro University California.

2004-2010Associate Professor; Department of Basic Sciences; Touro University CA

1997-present Adjunct Professor, Department of Pharmaceutical Chemistry, UCSF.

1995-2005 Adjunct Professor, University of the Pacific School of Dentistry, San Francisco.

1993-1994 Associate Scientist, California Pacific Medical Center Research Institute.

1991-1993 Senior Research Associate, Fox Chase Cancer Center, Philadelphia, PA. 

1990-1991 Assistant Research Chemist, University of California, San Francisco, CA.

1987-1990 Postdoctoral Research Associate, Department of Pharmaceutical Chemistry, UCSF.

1979 Lecturer, Rhodes University, Grahamstown, South Africa. 

1978-79 Research Assistant, Weizmann Institute of Science, Rehovot, Israel. 

Last Updated: 5/5/17