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, holder of the Pitblado Chair in Cell Biology at The Hospital for Sick Children (SickKids), 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 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 PJ, 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.
Alexander RT, Furuya W, Szaszi K, Orlowski J, Grinstein S. (2005) Rho GTPases dictate the mobility of the Na/H exchanger NHE3 in epithelia. role in apical retention and targeting. Proc. Nat. Acad. Sci. 102(34):12253-8
Scott CC, Dobson W, Botelho RJ, Coady-Osberg N, Chavrier P, Knetch DA, Heath C, Stahl P, Grinstein S. (2005) sphatidylinositol-4,5 bisphosphate hydrolysis directs actin remodeling during phagocytosis. Cell Biol. 169:139-149.
Jabado N, Cuellar-Mata P, Grinstein S, Gros P. (2003) Iron chelators modulate the fusogenic properties of salmonella containing phagosomes. Proc. Nat. Acad. Sci. 100:6127-6132.
Touret N, Furuya W, Forbes J, Gros P, Grinstein, S. (2003) Dynamic traffic through the recycling compartment couples the metal transporter Nramp2 (DMT1) with the transferrin receptor. J. Biol. Chem. 278:25548-25557.
Vieira OT, Bucci C, Harrison RE, Trimble WS, Lanzetti L, Gruenberg J, Schreiber AD, Stahl PD, Grinstein S. (2003) Modulation of Rab5 and Rab7 recruitment to phagosomes by phosphatidylinositol 3-kinase. Mol Cell Biol. 7:2501-14.
Harrison RE, Bucci C, Vieira OV, Schroer TA, Grinstein S. (2003) Phagosomes fuse with lysosomes by extension of membrane protrusions along microtubules: role of Rab7 and RILP. Mol. Cell Biol 18:6494-6506.
Brumell JH, Grinstein S. (2003) Role of lipid-mediated signal transduction in bacterial internalization. Cell. Microbiol. 5:287-297.
Scott CC, Botelho RJ, Grinstein S. (2003) Phagosome maturation: a few bugs in the system. J. Memb. Biol. 193:137-152.
Tse SML, Furuya W, Gold E, Schreiber AD, Sandvig K, Inman RD, Grinstein S. (2003) Differential role of actin, clathrin and dynamin in Fcγ receptor-mediated endocytosis and phagocytosis. J. Biol. Chem. 278:3331-3338.
Szaszi K, Paulsen A, Szabo E, Numata M, Grinstein S, Orlowski J. (2002) Clathrin-mediated endocytosis and recycling of the neural-specific Na+/H+ exchanger NHE5 isoform: regulation by phosphatidylinositol 3'-kinase and the actin cytoskeleton. J. Biol. Chem. 277:42623-42632.
Touret N, Grinstein S. (2002) Voltage-gated proton "channels": a spectator's viewpoint. J. Gen. Physiol. 120:767-771.
Scott CC, Cuellar-Mata P, Matsuo T, Davidson HW, Grinstein S. (2002) Role of 3'-phosphoinositides in the maturation of Salmonella-containing vacuoles within host cells. J. Biol. Chem. 277:12770-12776.
Hayashi H, Szaszi K, Coady-Osberg N, Orlowski J, Kinsella JL, Grinstein S. (2002) A slow pH-dependent conformational transition underlies a novel mode of activation of the epithelial Na+/H+ exchanger NHE3 isoform. J. Biol. Chem. 277:11090-11096.
Terebiznik M, Vieira OV, Marcus S, Trimble WS, Meyer T, Finlay B, Grinstein S. (2002) Elimination of host cell PI(4,5)P2 by the bacterial phosphatase SopB/SigD promotes membrane fission during invasion by Salmonella. Nature Cell Biology 10:766-773.
Harrison RE, Touret N, Grinstein S. (2002) Microbial killing: oxidants, proteases dispatch and ions. Curr. Biol. 10:R357-359.
Booth JW, Kim M-K, Jankowski A, Schreiber A, Grinstein S. (2002) Contrasting requirements for ubiquitination during FcΥRIIA internalization by endocytosis versus phagocytosis. EMBO J. 21:251-258.