My research program centers on two main areas. We have spent a number of years investigating the cellular mechanisms by which heat (hyperthermia) kills cells, because of the interest in using hyperthermia for cancer therapy. We specialize in the use of flow cytometry and cell sorting to analyze cellular effects of hyperthermia. We have studied the effects of hyperthermia on the cell cycle, intracellular pH, membranes (membrane fluidity and membrane potential), and intracellular ions such as calcium and sodium. Currently we are investigating the role of heat shock proteins, particularly hsp70, in modulating heat sensitivity and thermotolerance. We are particularly interested in the cell cycle variation in the expression of hsp70. We are also investigating how heat shock proteins may be involved in apoptosis, and the role of apoptosis in cell killing by hyperthermia and other agents. We are also currently investigating the mechanisms of cell cycle blocks induced in mammalian cells by hyperthermia, using antibodies against various cyclins, cyclin dependent kinases (CDKs), and cyclin dependent kinase inhibitors (CKIs).
Recent Publications:
He, L and Fox MH: Activation of heat shock transcription factor 1 activation in heated Chinese hamster ovary cells is dependent on the cell cycle and is inhibited by sodium vanadate. Radiation Research151: 20-29, 1999.
He L, Fox MH: Variation of heat shock protein 70 through the cell cycle in HL-60 cells and its relationship to apoptosis. Experimental Cell Research 232: 64-71, 1997.
Hang H, Fox MH: Levels of 70 kDa heat shock protein through the cell cycle in several mammalian cell lines. Cytometry 25: 367-373, 1996.
Amorino G., Fox MH: Heat-induced changes in intracellular sodium and membrane potential: Lack of a role in cell killing and thermotolerance. Radiation Research 146: 283-292, 1996.
Amorino G., Fox MH: Effects of hyperthermia on intracellular chloride. J. Membrane Biology 152: 217-222, 1996.
He L, Fox MH: Comparison of flow cytometry and Western blotting to measure hsp70. Cytometry 25: 280-286, 1996.
Wieder ED, Fox MH: The role of intracellular free calcium in the cellular response to hyperthermia. Int J Hyperthermia 11: 733-742, 1995.
Hang H, Fox MH: Cell cycle variation of hsp70 levels in HeLa cells at 37 C and after a heat shock. J Cellular Physiology 165: 367-375, 1995.
Hang H, Fox MH: Expression of HSP70 induced in CHO cells by 45.0 C hyperthermia is cell cycle associated and DNA synthesis dependent. Cytometry19: 119-125, 1995.
Amorino GP, Fox MH: Intracellular Na+ measurements using sodium green tetraacetate with flow cytometry. Cytometry 21: 248-256, 1995.
Hang H, Fox MH: Low pH suppresses synthesis of HSPs and thermotolerance. Radiation Research 140: 24-30, 1994.
LaRue SM, Fox MH, Withrow SJ, Powers BE, Straw RC, Cote‚ IM, Gillette
EL: Impact of heterogeneity in the predictive value of kinetic parameters
in canine osteosarcoma. Cancer Research 54: 3 916-3921, 1994.