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Filippo Mancia, Ph.D.

Professor of Physiology & Cellular Biophysics
Co-Director of Graduate Studies, Department Physiology & Cellular Biophysics

Structural biology of integral membrane proteins.

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CURRENT RESEARCH

 

We are interested in the structure and function of membrane proteins. Proteins that reside within the plasma membrane are responsible for how a cell detects and responds to extra-cellular stimuli, of biological, chemical and physical nature. High-resolution snapshots of such molecules offer invaluaFilippo Mancia graduated in Chemistry in Pavia (Italy), and obtained a PhD at the MRC Laboratory of Molecular Biology in Cambridge, UK. His post-doctoral work was carried out in the labs of Drs. Wayne Hendrickson and Richard Axel at Columbia University.

He is a structural biologist with considerable experience in x-ray crystallography, and more recently in single particle cryo-electron microscopy, and in production and characterization of eukaryotic and prokaryotic membrane proteins for structural studies.

Dr. Mancia’s main research focus is on membrane protein – lipid interactions. Within this realm, his lab has recently determined the high-resolution structure of enzymes from three families, which process lipid substrates. (1) GtrB, a polyisoprenyl phosphate glycosyltransferase attaches glucose to a lipid carrier for membrane translocation and a glycosyl donor for subsequent reactions. This reaction represents the first step in all protein glycosylation and glycosylation of the cell wall. (2) ArnT uses sugar-charged donors produced by GtrB-like enzymes, and transfers the saccharide to lipid A on the cell surface of bacteria, altering antibiotic resistance properties. (3) The Mancia lab determined the structure of a phosphatidylinositol-phosphate (PIP) synthase – an enzyme required for inositol-lipid synthesis – with a bound CDP-diacylglycerol substrate. This enzyme is a member of the CDP-alcohol phosphotransferase family (CDP-APs), which catalyze the defining step in glycerophospholipid biosynthesis across all kingdoms of life. Retinoids (Vitamin A derivatives) are also lipids, and thus in this theme fits another project of the lab, aimed at understanding how STRA6-mediated cellular uptake of retinol occurs – fits into this research theme. The Mancia lab’s experience in structural biology, in overexpression of integral membrane proteins, in functional analyses of membrane proteins and in high-throughput techniques for membrane protein purification and selection, make it a unique environment for researchers interested in studying membrane protein-lipid substrate interactions, and in developing tools to advance this rapidly evolving field.

Dr. Mancia has also been a key member of the New York Consortium of Membrane Protein Structure (NYCOMPS), located at the New York Structural Biology Center (http://nysbc.org/) where he has played a pivotal role in the design, development, implementation and optimization of the high-throughput cloning and protein production platform for prokaryotic membrane proteins successfully functioning at the NYCOMPS center. NYCOMPS has recently transitioned to a NIH-funded biomedical technology resource center named the Center on Membrane Protein Production and Analysis (COMPPÅ, https://www.comppaa.org/; Wayne Hendrickson, PI), and he serves on the executive committee for COMPPÅ.

Selected Publications

2021

Cater, R.J., Chua, G.L., Erramilli S.K., Keener, J.E., Choy, B.C., Tokarz, P., Chin, C.F., Quek, D.Q.Y., Kloss, B., Pepe, J.G., Parisi G., Kossiakoff A.A., Khelashvili, G., Silver, D. and Mancia, F. (2021). Structural basis of omega-3 fatty acid transport across the blood-brain barrier. Nature, 595:315-319. doi: 10.1038/s41586-021- 03650-9. PMID: 34135507.

Nygaard, R., Yu, J., Kim, J., Ross, D., Parisi, G., Clarke, O.B., Virshup, D.M. and Mancia, F. (2021). Structural basis of WLS/Evi-mediated Wnt transport and secretion. Cell, 184(1):194-206.e14. doi:10.1016/j.cell.2020.11.038. PMID: 33357447.

Kim, J., Tan, Y.Z., Wicht, K.J., Erramilli, S.K., Dhingra, S.K., Okombo, J., Vendome, J., Hagenah, L.M., Giacometti, S.I., Warren, A.L., Nosol, K., Roepe, P.D., Potter, C.S., Carragher, B., Kossiakoff, A.A., Quick, M., Fidock, D.A. and Mancia, F. (2019). Structure and Drug Resistance of the Plasmodium falciparum Transporter PfCRT. Nature, doi: 10.1038/s41586-019-1795-x. PMID: 31776516.    

2019

Petrou, V.I., Herrera, C.M., Schultz, K.M., Clarke, O.B., Vendome, J., Tomasek, D., Banerjee, S., Rajashankar, K.R., Belcher Dufrisne, M., Kloss, B., Kloppmann, E., Rost, B., Klug, C.S., Trent, M.S., Shapiro, L. and Mancia, F. (2016). Structures of aminoarabinose transferase ArnT suggest a molecular basis for resistance to polymyxins. Science, 351, 608-612.

2016

Chen, Y., Clarke, O.B., Kim, J., Stowe, S., Kim, Y.K., Assur, Z., Cavalier, M., Godoy-Ruiz, R., von Alpen, D.C. Manzini, C. Blaner, W.S., Frank, J., Quadro, L., Weber, D.J., Shapiro, L., Hendrickson, W.A. and Mancia, F. (2016). Structure of the STRA6 receptor for retinol uptake. Science, 353, pii: aad8266. doi: 10.1126/science.aad8266.

RECENT HONORS AND AWARDS

Schaefer Research Scholar

Burroughs Wellcome Fund Collaborative Research Travel Award

Visiting Professor in Biochemistry, Department of Biochemistry, University of Rome
La Sapienza, Rome, Italy

Clyde and Helen Wu Assistant Professor of Physiology and Cellular Biophysics

2016

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