MICHAEL J. RUDOLPH, PH.D.
mrudolph@nysbc.org
My blog: http://michaeljrudolph.blogspot.com/
Linked in: http://www.linkedin.com/pub/michael-rudolph/13/33/378
PHARMACEUTICAL/BIOTECHNOLOGY
Results driven scientist with extensive experience in molecular biology, protein biochemistry, and macromolecular crystallography research tempered by a tremendous enthusiasm for drug discovery and design. Creative problem solver employing newest technology to overcome research obstacles and obtain core elements needed to complete investigations. Team-spirited collaborator with extensive leadership skills and an unflagging determination to find answers to complex scientific questions.
SELECT ACCOMPLISHMENTS:
* Spearheaded a SNF1 project using complex molecular biological processes encompassing the engineering of a tri-cistronic vector containing the correct regions of all three SNF1 genes to produce and crystallize high-quality proteins.
* Created crystals using robotics as well as the microseeding process to deliver diffraction-quality crystals.
* Overcame the problem of obtaining quality crystals for a Molybdopterin synthase project by conducting trials in a non-equilibrating environment.
* Performed structure determination, protein biochemical, and enzymatic studies on SNF1, Molybdopterin Synthase, and Cytochrome b5 domain from human sulfite oxidase.
* Published in such peer-reviewed journals as Nature, The Journal of Biological Chemistry, Structure, and Nature Structural Biology.
Drug Discovery * Drug Design * Scientific Research * Project Management
Experimental Design * Public Speaking * Problem Resolution * Mentoring
RESEARCH PROFESSIONAL EXPERIENCE
NEW YORK STRUCTURAL BIOLOGY CENTER , New York, New York • 2011-Present
Research Scientist
Currently working on a project in contract with the Department of Defense to structurally design small molecule inhibitors of biological pathogens in ultra high throughput mode.
COLUMBIA UNIVERSITY, New York, New York * 2003-2011
Associate Research Scientist (2009-2011)
Consultant for Sirtris Pharmaceuticals (2008-2009)
Post-doctoral Research Fellow (2003-2009)
Researched the biochemical and structural components of AMP-activated protein kinase (AMPK), a major drug discovery advance for diseases such as cancer and diabetes. Investigated SNF1, the AMPK homolog in S. cerevisiae, strengthening knowledge of AMPK function and auto-inhibition mechanisms through biochemical and structural research. Published an article about the investigation in Nature, a well-respected industry journal.
Select Key Highlights
* Directed subcloning, purification, and biochemical/biophysical characterization of various proteins involved in metabolic regulation.
* Orchestrated biochemical and structural analysis of S. cerevisiae AMPK kinase domain, AMPK bateman2 domain, and AMPK heterotrimeric core
* Completed protein oligomerization state analysis by gel filtration, static light scattering, native polyacrylamide gel electrophoresis.
* Performed site-directed mutagenesis.
* Employed thermal shift assay methodologies to characterize protein-ligand interactions.
* Performed crystallization trials using protein reductive methylation and/or surface entropy reduction.
* Design and execution of a gene to structure project including biochemical/biophysical characterization of protein-ligand interactions in support of drug discovery for Sirtris Pharmaceuticals.
HARVARD UNIVERSITY, Boston, Massachusetts * 2002-2003
Post-Doctoral Research Fellow, Joslin Diabetes Center
Constructed expression vectors for proteins linked to metabolic regulation and autoimmune disease. Performed large-scale expression and purification of AIRE proteins and AMPK. Conducted crystallization trials of the AIRE protein.
STONY BROOK UNIVERSITY, Stony Brook, New York * 1996-2002
Ph.D. Student
Explored the biochemical/biophysical characterization and structure determination of Molybdopterin Synthase, an enzyme involved in the biosynthesis of the Molybdenum Cofactor. Discovered a structural similarity between the small subunit of Molybdopterin Synthase and ubiquitin demonstrating the evolutionary antecedence of the Moco biosynthetic pathway to the ubiquitin-dependent protein degradation pathway. Published findings in Nature Structural Biology.
Select Accomplishments:
* Discovered structural distinctions in the human sulfite oxidase b5 domain which promote optimal electron transport from sulite oxidase to cytochrome c after solving the crystal structure of the Cytochrome b5 domain from human sulfite oxidase.
* Characterized protein-ligand interactions using isothermal titration calorimetry assays.
* Studied protein stability using circular dichroism assay.
* Used crystallization and structure determination techniques on Cytochrome b5 domain of human sulfite oxidase and Enoyl-CoA hydratase.
TEACHING/MANAGEMENT EXPERIENCE
COLUMBIA UNIVERSITY, New York, New York * 2003-5/2010
Supervisor, Graduate Students and Postdoctoral Fellows
STONY BROOK UNIVERSITY, Stony Brook, New York * 1995-1997
Graduate Assistant, Molecular Biology Techniques Lab/BIO311 (1997)
Graduate Assistant, Biochemistry Lab BIO365 (1996)
Teaching Assistant, Organic Chemistry, CHE321/322 (1995-1996)
EDUCATION
Doctor of Philosophy in Biochemistry/Molecular Biology
Stony Brook Univ., Stony Brook, New York
Bachelor of Science in Ex. Physiology
Hofstra University, Hempstead, New York
INVITED LECTURES
* May 1999, Long Island Structural Biology Meeting. “Evolutionary and mechanistic insight from the crystallographic studies of Molybdopterin Synthase.”
* Sept 2002, Institute of Cellular and Developmental Biology: “Evolutionary and mechanistic insight from the crystallographic studies of Molybdopterin Synthase.”
* Sept. 2004, Columbia Univ. Biology Department Retreat: “Crystal structure of the AMPK kinase domain from S. cerevisiae.”
* Dec. 2008, Indiana University, Dept. of Biochemistry and Molecular Biology: “Biochemical and structural analysis of AMP-activated protein kinase (AMPK).”
* March 2009, Merck Pharmaceuticals, Global structural biology group: “Biochemical and structural analysis of AMP-activated protein kinase (AMPK).”
* March 2010, Centocor, J&J: “Biochemical and structural analysis of AMP-activated protein kinase (AMPK).”
PUBLICATIONS
* Michael J. Rudolph, Margot M. Wuebbens, K.V. Rajagopalan and Hermann Schindelin. “Crystal structure of molybdopterin synthase and its evolutionary relationship to ubiquitin activation.” Nature Structural Biology. 2001 Jan; 8(1):42-6.
* Michael J. Rudolph and J. Peter Gergen. “DNA-binding by Ig-fold proteins.” Nature Structural Biology. 2001 May;8(5):384-6.
* Alasdair F. Bell, Yuguo Feng, Hilary A. Hofstein, Jiaquan Wu, Michael J. Rudolph, Caroline Kisker and Peter J. Tonge. “Stereoselectivity of enoyl-CoA hydratase results from preferential activation of one of two bound substrate conformers.” Chemistry & Biology. 2002 Nov;9(11):1247-55.
* Michael J. Rudolph, Margot M. Wuebbens, K.V. Rajagopalan and Hermann Schindelin. “Structural studies of molybdopterin synthase provide insights into its catalytic mechanism.” Journal of Biological Chemistry. Vol. 278 No.16 pp 14514-22 (April 2003).
* Michael J. Rudolph, Jean L. Johnson, K.V. Rajagopalan and Caroline Kisker. “The 1.2 Å Crystal Structure of the Human Sulfite Oxidase Cytochrome b5 Domain.” Acta Cryst. D Biological Crystallography. 2003 Jul;59(Pt 7):1183-91.
* Michael J. Rudolph, Gabe A Amodeo, Yun Bai and Liang Tong. “Crystal structure of the protein kinase domain of yeast AMP-activated protein kinase Snf1.” Biochem. Biophys Res Commun. 2005 Dec 2;337(4):1224-8
* Michael J. Rudolph, Gabe A Amodeo, Surtaj H. Iram, Seung-Pyo Hong, Giorgia Pirino, Marian Carlson and Liang Tong. “Structure of the Bateman2 domain of yeast Snf4: dimeric association and relevance for AMP binding.” Structure. 2007 Jan;15(1):65-74.
* Gabe A Amodeo* , Michael J. Rudolph* and Liang Tong. “Crystal structure of the heterotrimer core of the S. cerevisiae AMPK homolog SNF1.” Nature. 2007 Sep 27;449(7161):492-5 (* Equal authorship)
* Michael J. Rudolph, Gabe A Amodeo and Liang Tong. “A new, inhibited conformation for the protein kinase domain of the Saccharomyces cerevisiae AMPK homolog Snf1.” Acta Cryst F Struct Biol Cryst Commun. 2010 Sep 1;66(Pt 9):999-1002.
AWARDS
* NIH Postdoctoral Fellowship Award
* Excellence in research award, Institute for Cell and Developmental Biology
* Science magazine editor's choice for the crystal structure of Molybdopterin Synthase and its evolutionary relationship to ubiquitin activation.
* NSLS science highlights 2008 for the crystal structure of the heterotrimer core of the S. cerevisiae AMPK Homolog SNF1.
TECHNICAL SKILLS
* Molecular Biology: Subcloning; engineering of expression vectors; site-directed mutagenesis
* Biochemistry: Protein/Enzyme engineering; enzymology; expression of recombinant proteins (E. coli); protein quantification; affinity chromatography, HIC, ion exchange, gel filtration, HPLC, FPLC; western blotting; mass spectrometry (MALDI-TOF); fluorescence; light scattering (DLS and SEC-MALLS); circular dichroism; isothermal titration calorimetry (ITC).
* Structural Biology: Extensive experience in all aspects of macromolecular crystallography, including high throughput crystallization using robotics, crystallization, data collection and evaluation, phase determination by multi/single-wavelength anomalous dispersion, multiple isomorphous replacement and molecular replacement, model building, structure refinement and analysis
* Computer Skills: Use of Linux/UNIX; Windows; use of crystallography software (HKL2000 package, CCP4 suite, SOLVE etc.); Vector NTI; Modeller, Swiss-Model (homology modeling); Threader, Rosetta (threading and protein design); Autodock (ligand docking); standard office and graphics software
