The aim of our research program is to elucidate the molecular mechanisms that explain the biological function of membrane proteins, as well as the physico-chemical principles that govern their structure and organization. We are particularly interested in processes of transmembrane transport and signaling, and in the relationship between protein structure and mechanism and the morphology and lipid composition of the membrane.
Membrane proteins mediate numerous essential processes in living cells, such as the import and metabolism of nutrients and the transmission of chemical signals between and within cells. They also contribute to define the morphology of the membranes where they reside, which is crucial for normal cellular activity. It is for these reasons that numerous human health disorders, from heart disease to neurodegeneration, are associated with the malfunction of membrane-associated systems. Membrane transport proteins are also crucial for the survival of multidrug-resistant pathogenic bacteria and cancer cells, and are therefore promising pharmaceutical targets. The premise of our research is that a detailed understanding of the molecular mechanisms of these fascinating systems will ultimately foster the discovery of more effective pharmacological approaches. We also believe that a better understanding of how the activity of biological systems emerges from their structure, dynamics and environment is the necessary foundation for future innovations in biomedicine and biotechnology, through rational design.
Our investigations rely primarily on computationally-intensive, physics-based molecular simulations and related theoretical methods. This approach enables us to formulate novel mechanistic hypotheses and interpretations of existing empirical data, which in turn guide the design of new experimental work. Our theoretical studies are often carried out in synergy with experimental collaborators, both at NIH and elsewhere, particularly in the areas of structural biology, biochemistry, and molecular biophysics. On the methodological front, we are actively involved in the development and implementation of novel approaches to evaluate the energetics of molecular processes, through so-called enhanced-sampling methods; we are also interested in computer-simulation methodologies specifically designed to facilitate the interpretation of experimental information.
José Faraldo-Gómez studied Physics at the Universidad Autónoma in Madrid, graduating in 1999. He went on to pursue postgraduate studies in the Laboratory of Molecular Biophysics at the University of Oxford, with fellowships from La Caixa Foundation, the British Council, and the UK Engineering & Physical Sciences Research Council. He obtained his doctoral degree in 2002, based on his research work in the laboratory of Prof. Mark Sansom. He then moved to United States, and acquired postdoctoral training in the laboratory of Prof. Benoit Roux, first at the Medical College of Cornell University in New York City, and subsequently at the University of Chicago. His pre- and post-doctoral work was focused on membrane proteins and, in later years, also on signalling enzymes, studied through computer simulations and other theoretical methods.
In late 2007 Dr. Faraldo-Gómez established the Theoretical Molecular Biophysics Laboratory at the Max Planck Institute of Biophysics in Frankfurt, Germany, where he remained until mid 2013. During this time he was also appointed Adjunct Investigator of the German Research Foundation (DFG) Cluster of Excellence Macromolecular Complexes, and Associate Investigaor of the DFG Collaborative Center Transport & Communication across Biological Membranes.
In 2013 Dr. Faraldo-Gómez relocated his laboratory to the National Institutes of Health (NIH), in Bethesda, Maryland, joining the Biochemistry & Biophysics Center of the National Heart, Lung and Blood Institute (NHLBI) as a Tenure-Track Investigator. He became a tenured Senior Investigator in 2016. Dr. Faraldo-Gómez has an extensive record of academic service and advocacy. As a trainee, he co-founded the first Postdoctoral Association at Weill-Cornell Medical College and was the first postdoctoral representative in its General Faculty Council. He served as Editor of Biophysical Journal from 2011 to 2017, and as Associate Editor of the Journal of General Physiology from 2016 to 2019. In 2019 he became a Senior Editor at eLife, after 3 years serving as a Reviewing Editor.
Dr. Faraldo-Gómez has chaired or co-chaired several international scientific events, including the 2018 Annual Symposium of the Society of General Physiologists, in Woods Hole, MA. He was elected to serve as the 2018 Chair of the Membrane Biophysics Subgroup of the Biophysical Society, becoming the first computational biophysicist to do so, and in that capacity he was a member of selection committee for the prestigious Kenneth S. Cole Award for 2017, 2018 and 2019. At NIH, he has served in the Earl Stadtman Investigator Search Committee for Computational Biology, both as a member (2014-2015) and chair (2018-2019). He is currently a member of the Promotion & Tenure Committee at NHLBI.
- Oh S, Marinelli F, Zhou W, Lee J, Choi HJ, Kim M, Faraldo-Gómez JD, Hite RK. Differential ion dehydration energetics explains selectivity in the non-canonical lysosomal K+ channel TMEM175. Elife. 2022;11.
- Tan XF, Bae C, Stix R, Fernández-Mariño AI, Huffer K, Chang TH, Jiang J, Faraldo-Gómez JD, Swartz KJ. Structure of the Shaker Kv channel and mechanism of slow C-type inactivation. Sci Adv. 2022;8(11):eabm7814.
- Lee CJ, Stix R, Rana MS, Shikwana F, Murphy RE, Ghirlando R, Faraldo-Gómez JD, Banerjee A. Bivalent recognition of fatty acyl-CoA by a human integral membrane palmitoyltransferase. Proc Natl Acad Sci U S A. 2022;119(7).
- Chadda R, Bernhardt N, Kelley EG, Teixeira SC, Griffith K, Gil-Ley A, Öztürk TN, Hughes LE, Forsythe A, Krishnamani V, Faraldo-Gómez JD, Robertson JL. Membrane transporter dimerization driven by differential lipid solvation energetics of dissociated and associated states. Elife. 2021;10.
- Marinelli F, Faraldo-Gómez JD. Force-Correction Analysis Method for Derivation of Multidimensional Free-Energy Landscapes from Adaptively Biased Replica Simulations. J Chem Theory Comput. 2021;17(11):6775-6788.
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This page was last updated on Thursday, February 9, 2023