Sergio Grinstein, PhD
University of Toronto
The Hospital for Sick Children
Pitblado Chair in Cell Biology
Dr. Sergio Grinstein is a senior scientist in the The Hospital for Sick Children Research Institute and a professor of Biochemistry at the University of Toronto. He is internationally recognized for his research in two areas: the control of intracellular pH and the elucidation of mechanisms underlying the microbicidal response of macrophages and neutrophils.
Dr. Grinstein completed his PhD in 1976 at the Centro de Investigacion y Estudios Avanzados in Mexico City. He then spent two years as a postdoctoral fellow in Cell Biology at Sick Kids, followed by a year in the Department of Biochemistry at the Federal Institute of Technology in Zurich. He has been an International Scholar of the Howard Hughes Medical Institute and recipient of the Canadian Institutes of Health Research Distinguished Scientist Award and is a Fellow of the Royal Society of Canada.
- signal transduction
- leukocyte biology
- pH regulation
- ion transport
Two major areas are under study in my laboratory. The first one investigates the molecular mechanisms utilized by white blood cells to eliminate infectious organisms. More specifically, we are studying the processes whereby macrophages and neutrophils migrate to sites of infection, ingest microbes and destroy them, as well as the strategies used by certain microorganisms to outsmart the immune system and avoid killing.
The second area deals with the role and regulation of ion transport and pH of intracellular compartments. We have devised means of measuring the pH and ionic composition of individual organelles within intact live cells and are currently investigating the identity and properties of the molecules responsible for transport of ions and for intracellular acid/base regulation.
Future Research Interests
We anticipate to make extensive use of molecular biology and single-cell spectroscopy to pursue our studies of innate immunity and of ion transport and pH regulation.
Touret, N., Paroutis, P., Terebiznik, M., Harrison, R., Trinbetta, S., Pypaert, M., Chow, A., Jiang,A., Shaw, J., Yip, C., Moore, H-P., van der Wel Houben, D., Peters, P.J., de Chastellier, C., Mellman, I., Grinstein, S. (2005) Quantitative and dynamic assessment of the contribution of the endoplasmic reticulum to phagosome formation. Cell. 2005 Oct 7;123(1):157-70.
Yeung, T., Terebiznik, M., Yu, L., Silvius, J, Abidi, W.M., Philips, M. Levine, T. Kapus, A. and Grinstein, S. (2006) Receptor activation alters inner surface potential during phagocytosis. Science. 313: 347-351.
Yeung, T., Gilbert, G., Shi, J., Silvius, J., Kapus, A. and Grinstein, S. (2008) Membrane phosphatidylserine regulates surface charge and protein localization. Science 319: 210-213.
Alexander, R.T., Jaumouillé, V., Yeung, T., Furuya, W., Peltekova, I., Boucher, A., Zasloff, M., Orlowski, J. and Grinstein, S. (2011) Membrane surface charge dictates the structure and function of the epithelial Na/H exchanger. EMBO J. 30(4): 679.
Fairn, G.D., Hermansson, M., Somerharju, P. and Grinstein, S. (2011) Phosphatidyserine is polarized and required for proper Cdc42 localization and for development of cell polarity. Nature Cell Biol. 13(12): 1424-1430.
Heit, B. Kim, H., Cosio, G., Castaño, D. Lowell, C.A. Kain, K.C. and Grinstein, S. (2013) Multimolecular signaling complexes enable Syk-mediated signaling of CD36 internalization. Dev. Cell. 24(4): 372-383.
Canton, J., Neculai, D. and Grinstein, S. (2013) Scavenger receptors in Homeostasis and immunity. Nature Rev. Immun. 9: 621-634.
Neculai, D., Schwake, M., Ravichandran, M., Zunke, F. Collins, R.F., Peters, J., Neculai, M., Plumb, J., Loppnau, P., Pizarro, J.C., Seitova, A., Trimble, W.S., Saftig, P. Grinstein, S. and Dhe Paganon, S. (2013). Structure of LIMP-2 provides functional insights with implications for SR-BI and CD36. Nature. 504(7478): 172-176.
Jaumouillé, V., Farkash, Y., Jaqaman, K., Das, R., Lowell, C.A. and Grinstein, S. (2014) Actin cytoskeleton reorganization by the tyrosine kinase Syk regulates Fcg receptor responsiveness by increasing its lateral mobility and clustering. Dev. Cell. 29(5): 534-546.
Schlam, D., Bagshaw, R.D., Freeman, S.A., Collins, R.F., Pawson, T., Fairn, G.D., Grinstein, S. and Brumell, J.H. (2015) Phosphoinositide 3-kinase enables phagocytosis of large particles by terminating actin assembly through Rac/Cdc 42 GTPase-activating proteins. Nature Commun. 6: 8623.
Freeman, S.A., Goyette, J., Furuya, W., Woods, E.C., Bertozzi, C.R., Bergmeier, W., Hinz, B., van der Merwe, P.A., Das, R., Grinstein, S. (2016) Integrins form an expanding diffusional barrier that coordinates phagocytosis. Cell. 164(1-2): 128-140.
Johnson, D.E., Ostowski, P., Jaumouillé, V. and Grinstein, S. (2016) The position of lysosomes within the cell determines their luminal pH. J. Cell Biol. 212(6): 677-692.
Canton, J., Schlam, D., Breuer, C., Gütschow, M., Glogauer, M. and Grinstein, S. (2016) Calcium-sensing receptors signal constitutive macropinocytosis and facilitate the uptake of NOD2 ligands in macrophages. Nature Commun. 7: 11284.