Gaetano Montelione

Professor and Constellation Chair

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.