Elizabeth R. Simons
Professor of Biochemistry
Department of Biochemistry
Boston University School of Medicine
Silvio Conte Building, K602
72 E. Concord Street
Boston, MA 02118
Phone: 617-638-4332
Fax: 617-638-5339
Email: esimons@bu.edu
Education
B.Ch.E., Cooper Union
M.S., Ph.D., Yale University, CT
Research Interest
Our interest lies in the initial immune system’s response to a foreign entity by the phagocytic cells. Signal transduction and degranulation control in phagocytic cells and their precursors in response to chemotactic and phagocytic stimuli. We are currently concentrating on stimulation by organisms which evade the normal phagocytic killing processes and therefore remain vital (e.g. mycobacteria such as M. tuberculosis). The normal process is initiated by the cell membrane’s specific receptors and involves generation of cytoplasmic cation signals, leading to motion along a chemoattractant concentration gradient to the origin of the chemoattractant where different receptors are engaged, phagocytosis occurs, leading to fusion with organelles to form a phagolysosome whose contents include bactericidal agents such as reactive oxygen species, lytic enzymes and inhibitory factors. We believe that evasion by certain organisms occurs because the organism takes over control of the cells’ responses, either at the level of signaling, at the formation of the phagocytic vacuole, at its fusion with the internal organelles and/or in the environment of the phagolysosome itself. We’ve shown this to be true for certain fungi. The laboratory’s interests hence concern the kinetics of initial responses of a secretory cell to recognition, by its membrane receptors, of a specific stimulus. We are investigating the mechanism by which these signals are transmitted and result in the cells’ eventual functional degranulation. We differentiate between the chemotactic and phagocytic pathways, using fluorescent techniques to evaluate receptor identity, occupancy and ensuant response kinetics of individual cells, measured by flow cytometry. Kinetic measurements are performed, by fluorimetry, spectrophotometry and flow cytometry. Electrophoresis, chromatography, cellular cavitation and organellar separation, enzymology, microscopy, tissue culture, immunological techniques (ELISA and Western blotting) are all used.
Representative Publications
T.S. Harrison, J. Chen, E.R. Simons and S.M. Levitz. Determination of the pH of the Cryptococcus neoformans vacuole.Medical Mycology 40: 329-332, 2002
J. Bernardo, H.J. Long, X. Yu and E.R. Simons. Immune complex stimulation of human neutrophils involves a novel Ca2+/H+ exchanger that participates in the regulation of cytoplasmic pH: Flow cytometric analysis of Ca2+/H+ responses by subpopulations. J. Leukocyte Biol. 72:1172-1179, 2002
I. Kaur, E.R. Simons, V.A. Castro, C.M.Ott and D.L.Pierson,Changes in neutrophil functions in astronauts. Brain, Behavior and Immunity 18: 443-450, 2004
J.M. Herrmann, A. Kantarci, H.J. Long, J. Bernardo, H. Hasturk, L.V. Wray, Jr., E. R. Simons, T. E. Van Dyke. Simultaneous measurements of cytoplasmic Ca2+ responses and intracellular pH in neutrophils of localized aggressive periodontitis (LAP) patients. J. Leukocyte Biol. 78:612-619, 2005
I. Kaur, E.R. Simons, V.A. Castro, C.M.Ott and D.L.Pierson,Changes in monocyte functions in astronauts, Brain, Behavior and Immunity, 19: 547-554, 2005
I. Kaur, E.R. Simons, S.L. Fonteno and D.L. Pierson. Stresses of spaceflight and the response of monocytes to LPS. Brain, Behavior and Immunity, in press 2007
J.M. Herrmann, J. Bernardo, H.J. Long, K. Seetoo, M.E. McMenamin, E.L. Batista, T.E. Van Dyke, E. R. Simons, Sequential chemotactic and phagocytic activation of human polymorphonuclear neutrophils, Infection and Immunity 75:3989-3998,. 2007
