Gaetano Montelione

About

The unique strengths of our laboratory involve development of NMR methods and software for analysis of protein structures and dynamics, and in applying these methods in structure-function studies. As Director of the NIGMS-funded Northeast Structural Genomics Consortium (NESG) for 16 years (2000 - 2016), we lead a team that determined more than 1,200 3D structures by X-ray crystallography and NMR methods. Over the course of this project we developed expertise in protein expression and crystallization, and in reconstitution and structure determination of soluble proteins and membrane-associated lipoproteins. We also developed extensive experience in software development, creating a cost-efficient pipeline for protein sample and structure production, achieving the NIGMS project goal of total cost per structure deposited in the PDB of ~$50,000.
Our laboratory research program revolves around the themes of new technology development for protein sample production and computational analysis. Based on our experience as a central node for protein sample production and structure determination by NMR in the NIGMS PSI program, rigorous structure and dynamic analysis of small (20 kDa), more challenging systems, including integral membrane proteins and protein complexes. The group's biomedical focus areas include structure-function studies of proteins and complexes involved in cancer biology, and both influenza and SARS CoV2 virus infection. These projects require hybrid approaches, combining NMR data with X-ray crystallography, SAXS, paramagnetic NMR and EPR, and other biophysical methods, along with advanced computational modeling and structural bioinformatics.
In order to ensure rigor in applying this broad range of methods, we collaborate intensively with internationally-recognized experts in these domains. For example, we work with experts to explore the impact of Evolutionary Coupling (C. Sander, D. Marks), Rosetta (D. Baker), and CHARMM (W. Im) modeling methods for determining 3D structures of larger proteins for which only sparse, incomplete experimental data is available, including integral membrane proteins. We rely on our collaborators for SAXS (J. Tainer), fluorescence spectroscopy (C. Royer), and cryoEM (J. Hunt, K. Das) data, and to provide expertise in these critical experimental methods. We also lead the structural biology components of several biomedical collaborations, including projects on viral-host protein/RNA interactions of murine leukemia (with M. Roth, Rutgers) and influenza (with S. Patel, Rutgers) viruses, SARS-CoV2 antiviral drug development (with A. Garcia-Sastre, Mt. Sinai), DNA damage repair (with S. Bunting, Rutgers), and de novo protein design (with D. Baker, U Wash.). We also collaborate with the Critical Assessment of Protein Structure Prediction (CASP) program to organize efforts in sparse-NMR-guided structure prediction across the CASP community, and with the wwPDB to develop robust and rigorous methods of protein and nucleic acid structure quality assessment. All of these collaborations are aimed at ensuring the highest rigor and quality control, and in addressing important biomedical questions.
Our laboratory has trained more than 45 graduate students and postdocs, and more than 100 undergraduate students. Many of these have gone on to leading positions in industry and academics. Several are professors at research universities. Others have scientist or management positions at pharmaceutical and biotechnology companies. A list of laboratory alumni, and their current positions, is available on our lab home page.https://montelionelab.chem.rpi.edu/about/alumni.htm
Montelione is recipient of numerous awards and honors including the Damon Runyon-Walter Winchell Cancer Research Fellow; Searle Scholar Award; Johnson & Johnson Research Discovery Award; American Cyanamid Award in Physical and Analytical Chemistry; National Science Foundation Young Investigator Award; Proctor and Gamble Young Investigator Award; Camille Dreyfus Teacher-Scholar Award; Rutgers University Board of Trustees Award for Scholarly Excellence; Biophysical Society Michael and Kate Bárány Award for Young Investigators; Elected Fellow of the American Association for the Advancement of Science (AAAS) ; Inaugural Jerome and Lorraine Aresty Endowed Chair, Rutgers University; and Endowed Constellation Chair in Structural Bioinformatics, Rensselaer Polytechnic Institute. He has published > 350 peer-reviewed papers, with > 20,000 citations and an impact H-index of 77.
With Prof. G. Wagner (Michigan), Montelione carried out pioneering work on NMR pulse sequence development, including the design and implementation of the first triple-resonance protein NMR experiments, as well as the high-impact ZZ-exchange and J1-resolved E_COSY experiments. At Rutgers, he followed up this work by development of the HCCNH-TOCSY, HCCcoNH-TOCSY, and related widely-adopted triple-resonance NMR experiments. Montelione has made key contributions in computational NMR methods development, including the development of software for automated analysis of protein resonance assignments, automated analysis of 3D structures, and for protein NMR model quality assessment. Work with R. Krug on the influenza A non-structural protein 1 (NS1) has provided the basis for creation of attenuated virus vaccines, that are now in clinical trials.

Research

Other Focus Areas

structural bioinformatics, host - pathogen interactions, protein structure, dynamics, and function, biomolecular NMR spectroscopy, molecular biophysics, integral membrane proteins

Publications

The following is a selection of recent publications in Scopus. Gaetano Montelione has 383 indexed publications in the subjects of Biochemistry, Genetics and Molecular Biology, Chemistry, and Chemical Engineering.

Roberto Tejero, Yuanpeng Janet Huang, Theresa A. Ramelot, Gaetano T. Montelione
Frontiers in Molecular Biosciences
, 9
, 2022
.
Yaohui Li, Rongzhen Zhang, Chi Wang, Farhad Forouhar, Oliver B. Clarke, Sergey Vorobiev, Shikha Singh, Gaetano T. Montelione, Thomas Szyperski, Yan Xu, John F. Hunt
EMBO Journal
, 41
, 2022
.
Kaifeng Hu, Woonghee Lee, Gaetano T. Montelione, Nikolaos G. Sgourakis, Beat Vögeli
Frontiers in Molecular Biosciences
, 9
, 2022
.
Gaurav Bhardwaj, Jacob O'Connor, Stephen Rettie, Yen Hua Huang, Theresa A. Ramelot, Vikram Khipple Mulligan, Gizem Gokce Alpkilic, Jonathan Palmer, Asim K. Bera, Matthew J. Bick, Maddalena Di Piazza, Xinting Li, Parisa Hosseinzadeh, Timothy W. Craven, Roberto Tejero, Anna Lauko, Ryan Choi, Calina Glynn, Linlin Dong, Robert Griffin, Wesley C. van Voorhis, Jose Rodriguez, Lance Stewart, Gaetano T. Montelione, David Craik, David Baker
Cell
, 185
, 2022
, pp.3520-3532.e26
.
Daniel R. Colman, Gilles Labesse, Gurla V.T. Swapna, Johanna Stefanakis, Gaetano T. Montelione, Eric S. Boyd, Catherine A. Royer
Proteins: Structure, Function and Bioinformatics
, 90
, 2022
, pp.1331-1345
.
Keith J. Fraga, Yuanpeng J. Huang, Theresa A. Ramelot, G. V.T. Swapna, Arwin Lashawn Anak Kendary, Ethan Li, Ian Korf, Gaetano T. Montelione
Journal of Magnetic Resonance
, 342
, 2022
.
Khushboo Bafna, Christopher L. Cioffi, Robert M. Krug, Gaetano T. Montelione
Frontiers in Chemistry
, 10
, 2022
.
Yuan Wang, Bochao Liu, Huimei Lu, Jingmei Liu, Peter J. Romanienko, Gaetano T. Montelione, Zhiyuan Shen
Cell Reports
, 39
, 2022
.
Ivan Anishchenko, Samuel J. Pellock, Tamuka M. Chidyausiku, Theresa A. Ramelot, Sergey Ovchinnikov, Jingzhou Hao, Khushboo Bafna, Christoffer Norn, Alex Kang, Asim K. Bera, Frank DiMaio, Lauren Carter, Cameron M. Chow, Gaetano T. Montelione, David Baker
Nature
, 600
, 2021
, pp.547-552
.
Yuanpeng Janet Huang, Ning Zhang, Beate Bersch, Krzysztof Fidelis, Masayori Inouye, Yojiro Ishida, Andriy Kryshtafovych, Naohiro Kobayashi, Yutaka Kuroda, Gaohua Liu, Andy LiWang, G. V.T. Swapna, Nan Wu, Toshio Yamazaki, Gaetano T. Montelione
Proteins: Structure, Function and Bioinformatics
, 89
, 2021
, pp.1959-1976
.

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