Michael L. Gross

Titles:

Professor, Department of Chemistry

Titles:

Professor of Immunology and Internal Medicine, Washington University School of Medicine

Office Contact Information

Degrees:

Postdoctoral Fellow, University of Pennsylvania

Degrees:

Postdoctoral Fellow, Purdue University

Degrees:

Ph.D. University of Minnesota

Degrees:

B.A. St. John's University

Office:

Cyclotron 101

Mailbox:

Campus Box 1134

Phone:

314-935-4814

Fax:

314-935-7484

Email:

mgross@wustl.edu

URL:

NIH / NCRR Mass Spectrometry Resource

Research specialization

Analytical Chemistry; Biological Chemistry; Biophysical Chemistry; FT-ICR instrument development; MALDI matrix development; Mass spectrometry for protein biochemistry and biophysics; Modified DNA and cancer; Physical organic chemistry; Protein and peptide analysis; Proteomics

Research

We are developing biophysical methods using mass spectrometry to understand protein interactions. One method is PLIMSTEX (Protein Ligand Interaction by Mass Spectrometry, Titration and H/D Exchange). The figure shows the titration of fatty acid binding protein (structure on left) with the fatty-acid ligand, potassium oleate, to give a complex (on right) that now contains the fatty-acid anion. The y-axis data are mass spectrometric molecular weight measurements, and the solid line is computed from our model that gives the equilibrium constant and protection factor for the protein-ligand interaction.

A more specific approach for footprinting is to map proteins with reactions of OH radicals. In FPOP (fast photochemical oxidation of proteins), we “paint” certain surface-accessible amino-acid residues by reacting the protein in a flow tube (see figure below) with radicals generated from H₂O₂ by a pulsed KrF laser (248 nm). With appropriate scavengers, the reaction time is remarkable short (~ 1 microsec). Certain amino acids react with the radicals to become oxidized (depicted as turning from “green” to “yellow”--see figure below). PLIMSTEX and FPOP may be useful for determining protein-protein interfaces, affinities for tiny amounts of proteins in biophysics and drug discovery.

Another goal is development of Fourier transform MS. Of interest are accurate mass measurement and new trap designs (see figure below) designed to incorporate electric field compensation. Two instruments equipped with 7-tesla magnets, and soon a 12-tesla instrument for top-down proteomics are available for fundamental and applied research.

The laboratory is an NIH National Research Resource. Under this aegis, coworkers pursue method/instrument development and/or collaborate, for example, on DNA photodamage research (J Taylor), photosynthetic bacteria (R Blankenship), bacterial cell-wall analysis (J Schaefer) and antigenic peptides in immunology (E Unanue).

Centers

NIH / NCRR Mass Spectrometry Resource

Awards & Honors:

2008, Bruker Daltonics Lectureship, University of Konstanz, Germany
2008, Freiser Lectureship, Purdue University
2006, J.J. Thomson Medal for Service to Int'l MS, Foundation for International Mass Spectrometry
2005, Excellence in Mentoring Award, Washington University Graduate Student Senate
2005, New Jersey Distinguished Lectureship, NJ Section ACS Mass Spectrometry Discussion Group
2004, Outstanding Mentor Award, Washington University Graduate Student Senate
2002, Midwest Award for Achievements in Chemistry, American Chemical Society
2002, Excellence in Mentoring Award, Washington University Graduate Student Senate
2001, Watkins Visiting Professor, Witchita State University
2001, Outstanding Mentor Award, Washington University Graduate Student Senate
2000, Frontiers in Chemistry Lectureship, Wayne State University
2000, Plenary Lecture, Vienna Mass Spectrometry Colloquium
2000, Plenary Lecture, EnviroAnalysis 2000
1999, Field and Franklin Award, American Chemical Society
1998, Plenary Lecture, Assoc. Official Anal. Chemists' Int'l Meeting
1998, Plenary Lecture, HPLC International Symposium
1997, Plenary Lecture, Colloquium Spectroscopicum Internationale
1997, Plenary Lecture, Igler MS Tage, Innsbruck
1996, Guest Faculty, NATO School on Biol. Mass Spectrometry
1995, Pioneers in Chemistry Series, Texas A&M University
1995, Plenary Lecture, Western Biotechnology Conference, San Diego
1995, Plenary Lecture, FDA Mass Spectrom. Symposium, Washington DC
1994, Plenary Lecture, Australia/New Zealand MS Conference, Melbourne
1993, Guest Professor, NATO Adv. Study Inst. Biol. MS, Ischia, Italy
1993, Plenary Lecture, Colloquium Spectroscopium Internationale
1993, Plenary Lecture, Taiwan Int'l Chemistry Conference
1993, Plenary Lecture, Indian Society for Mass Spectrometry
1993, Lifetime Member, Indian Society for Mass Spectrometry
1993, Kraft Lectureship, Indiana University
1992, Plenary Lecture, European Tandem Mass Spectrom. Conf.
1992, Recognized as 50 Most Cited Chemists, Institute for Scientific Information, 1984-1991
1991, Plenary Lecture, Australian Symposium on Analytical Chem.
1991, Plenary Lecture, Elsevier Anal. Advances for the 90s Symposium
1990, Van't Hoff Visiting Professor, Int'l Graduate School, University of Amsterdam
1990, Guest Pfrofessor, NATO Adv. Study Inst. in Biol. Mass Spectrometry
1988, Albright & Wilson Visiting Professor, University of Warwick
1988, Plenary Lecture, American Society for Mass Spectrometry
1987, Pioneer Award, Commonwealth of Mass "In Search for the Health Consequences of Dioxin in Our Environment."
1987, Hertel Lectureship, University of Tennessee
1987, Alan Maccoll Plenary Lectureship, British Royal Society for Mass Spectrometry
1987, Plenary Lecture, British Royal Society "Spectroscopy Across Spectrum"
1986, J.C. Karcher Lectureship, University of Oklahoma
1986, Plenary Lectureship, Versailles International Workshop on Ion-Molecule Rxs.
1984, Distinguished Lecture Series, Indiana University
1984, Plenary Lecture, Swiss/French Mass Spectrometry Conference
1984, Third Cycle Lectures, Eidegenössische Technische Hochschule Lausanne
1978, Foundation Medal for Distinguished Teaching, University of Nebraska

Appointments

1994-present Professor, Department of Chemistry, Department of Immunology, School of Medicine, Washington University in St. Loius
1994-present, Principal Investigator, NIH Research Resource in Mass Spectrometry
1983-1994, Distinguished Professor, Chemistry, University of Nebraska-Lincoln
1978-1983, Professor, Chemistry, University of Nebraska-Lincoln
1978-1994, Director, NSF Center for Mass Spectrometry, University of Nebraska
1972-1978, Associate Professor, Chemistry, University of Nebraska
1968-1972, Assistant Professor, Chemistry, University of Nebraska

Publications

"Radical cation/radical reactions: A Fourier transform ion cyclotron resonance study of allyl radical reacting with aromatic radical cations", A. Russell, H. Rohrs, D. Read, D.E. Giblin, P.P. Gaspar, M.L. Gross, International Journal of Mass Spectrometry (2009), 287, 8-15.

"An endogenous peptide positively selects and augments the activation and survival of peripheral CD4+ T cells", W-L Lo, N.J. Felix, J.J. Walters, H. Rohrs, M.L. Gross, P.M. Allen, Nature Immunology, in press

"The Gramicidin Dimer Shows Both EX1 and EX2 Mechanisms of H/D Exchange", R.K. Chitta, D.L. Rempel, and M.L. Gross, Journal of the American Society for Mass Spectrometry (2009), 20, 1813-1820.

"Photocrosslinking of human telomeric G-quadruplex loops by anti cyclobutane thymine dimer formation", D.G.T. Su, H. Fang, M.L. Gross, J.-S.A.Taylor, Proceedings of the National Academy of Sciences of the United States of America (2009), 106, 12861-12866

"Miniaturizing sample spots for matrix-assisted laser desorption/ionization mass spectrometry", T. Tu, Tingting, M.L. Gross, Trends in Analytical Chemistry (2009), 28, 833-841

"Cold Chemical Oxidation of Proteins", D.M. Hambly, M.L. Gross, Analytical Chemistry (2009), 81, 7235-7242.

"Fast Photochemical Oxidation of Protein Footprints Faster than Protein Unfolding", B.C. Gau, J.S. Sharp, D.L. Rempel, M.L. Gross, Analytical Chemistry (2009), 81, 6563-6571

"Organization of Lower Rim O-Alkylated p-Phosphonic Acid Calix[4]arenes", T.E. Clark, M. Makha, A.N. Sobolev, D. Su, H. Rohrs, M.L. Gross, C.L. Raston, Crystal Growth & Design (2009), 9, 3575-3580.

"Membrane orientation of the FMO antenna protein from Chlorobaculum tepidum as determined by mass spectrometry-based footprinting", J. Wen, H. Zhang, M.L. Gross, R.E. Blankenship, Proceedings of the National Academy of Sciences of the United States of America, (2009), 106, 6134-6139.

"2-Nitrophenyl aryl sulfides undergo both intramolecular and electrospray-induced intermolecular oxidation of sulfur: An experimental and theoretical case study", J.T. Moolayil, M. George,D. Giblin, M.L. Gross, International Journal of Mass Spectrometry (2009), 283, 222-228.

"Gas-Phase Nazarov Cyclization of Protonated 2-Methoxy and 2-Hydroxychalcone: An Example of Intramolecular Proton-Transport Catalysis", M. George, V.S. Sebastian, P.N. Reddy, R. Srinivas, D. Giblin, and M.L. Gross, Journal of the American Society for Mass Spectrometry (2009), 20, 805-818.

"Method Revealing Bacterial Cell-Wall Architecture by Time-Dependent Isotope Labeling and Quantitative Liquid Chromatography/Mass Spectrometry", G.J. Patti, J. Chen, M.L. Gross, Analytical Chemistry (2009), 81, 2437-2445.

"Isolation and identification of two novel SDS-resistant secreted chitinases from Aeromonas schubertii", C-L. Liu, C-R. Shen, F-F. Hsu, J-K. Chen, P-T. Wu, S-H. Guo, W-C. Lee, F-W. Yu, Z.Mackey, Zachary B.; J. Turk, M.L. Gross, Biotechnology Progress (2009), 25, 124-131.

"Balance of Beneficial and Deleterious Health Effects of Quinones: A Case Study of the Chemical Properties of Genistein and Estrone Quinones", Q. Zhang, T. Tu, D.A. d'Avignon, M.L. Gross, Journal of the American Chemical Society (2009), 131, 1067-1076.

"Microsecond time-scale hydroxyl radical profiling of solvent accessible protein residues", D.M. Hambly, M.L. Gross, in J. Whitelegge, Ed. Comprehensive Analytical Chemistry (2009), 52, 151-177.

"Combined Charged Residue-Field Emission Model of Macromolecular Electrospray Ionization", C.J. Hogan, J.A. Carroll, H.W. Rohrs, P. Biswas, and M.L. Gross, Analytical Chemistry (2009), 81, 369-377.

"A Mass Spectrometric Approach to the Study of DNA-Binding Proteins: Interaction of Human TRF2 with Telomeric DNA." Justin B. Sperry, Xiangguo Shi, Don L. Rempel, Yoshifumi Nishimura, Satoko Akashi, and Michael L. Gross, Biochemistry, 47, 179-1807 (2008).

"First Signature of Islet B-Cell-Derived Naturally Processed Peptides Selected by Diabetogenic Class II MHC Molecules." Anish Suri, James J. Walters, Henry W. Rohrs, Michael L. Gross, and Emil R. Unanue, Journal of Immunology, 180: 3849-3856 (2008).

"Method of Measuring Oligonucleotide-Metal Affinities: Interactions of Thrombin Binding Aptamer with K+ and Sr2+," J. Micah Wilcox, Don L. Rempel, and Michael L. Gross, Anal. Chem., 80, 2365-2371 (2008).

"Structural Features Responsible for the Biological Stability of Histoplasma's Virulence Factor CBP." Moriah R. Beck, Gregory T. DeKoster, David M. Hambly, Michael L. Gross, David P. Cistola, and William E. Goldman, Biochemistry, 47, 4427-4438 (2008).

"Strong Anion Exchange for Studying Protein-DNA Interactions by H/D Exchange Mass Spectrometry." Justin B. Sperry, J. Micah Wilcox, and Michael L. Gross, J. Am. Soc. Mass Spectrom., 19, 887-890 (2008).

"Charge Carrier Field Emission Determines the Number of Charges on Native State Proteins in Electrospray Ionization." Christopher J. Hogan, Jr., James A. Carroll, Henry W. Rohrs, Pratim Biswas, and Michael L. Gross, J. Am. Chem. Soc., 130, 6926-6927 (2008).

"Efficient Synthesis, Liquid-Chromatography Purification, and Tandem Mass Spectrometric Characterization of Estrogen-Modified DNA Bases." Qiang Zang and Michael L. Gross, Chem. Res. Toxicol., 21, 1244-1252 (2008).

"Structure Determination of an Interstrand-Type Cis-Anti Cyclobutane Thymine Dimer Produced in High Yield by UVB Light in an Oligodeoxynucleotide at Acidic pH." Dian G. T. Su, Jeffrey L.-F. Kao, Michael L. Gross, and John-Stephen A. Taylor, J. Am. Chem. Soc., 130, 11328-11337 (2008).

"Improving the Signal Intensity and Sensitivity of MALDI Mass Spectrometry by Using Nanoliter Spots Deposited by Induction-Based Fluidics," Tingting Tu, Andrew D. Sauter Jr, Andrew D. Sauter 3rd, and Michael L. Gross, J. Am. Soc. Mass Spectrom., 19, 1086-1090 (2008).

"An Electrically Compensated Trap Designed to Eighth Order for FT-ICR Mass Spectrometry." Adam M. Brustkern, Don L. Rempel, and Michael L. Gross, J. Am. Soc. Mass Spectrom., 19, 1281-1285 (2008).

"Microsecond Time-Scale Hydroxyl Radical Profiling of Solvent-Accessible Protein Residues." David M. Hambly and Michael L. Gross, chapter in Compehensive Analytical Chemistry, Volume 52, 151-177 (2008).

"Characterization of Structural Variations in the Peptidoglycan of Vancomycin-Susceptible Enterococcus faecium: Understanding Glycopeptide-Antibiotic Binding Sites Using Mass Spectrometry." Gary J. Patti, Jiawei Chen, Jacob Schaefer, and Michael L. Gross, J. Am. Soc. Mass Spectrom, 19, 1467-1475 (2008).

"Self-Organised Nano-Arrays of p-Phosphonic Acid Functionalised Higher Order Calixarenes." Thomas E. Clark, Mohamed Makha, Alexandre N. Sobolev, Dian Su, Henry Rohrs, Michael L. Gross, Jerry L. Atwood, and Colin L. Raston, New Journal of Chemistry, 32, 1478-1483 (2008).

"Estrogen Carcinogenesis: Specific Identification of Estrogen-Modified Nucleobase in Breast Tissue from Women." Qiang Zhang, Rebecca L. Aft and Michael L. Gross, Chem. Res. Toxicol., 21, 1509-1513 (2008).

"Two Approaches to Mass Spectrometric Protein Foot Printing: PLIMSTEX and FPOP." Michael L. Gross, Mei M. Zhu, and David M. Hambly, in Mass Spectrometry Analysis for Protein-Protein Interactions and Dynamics, Chance, M., ed, Wiley, 243-270, 2008.

Courses Taught

List courses:

Chemistry 112, General Chemistry
Chemistry 152, General Chemistry Laboratory
Chemistry 550, Advanced Topics in Mass Spectrometry

Curriculum Vitae:

CV Gross 2008-complete.pdf