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Michael Forte is a senior scientist at the Vollum Institute and a professor in the Departments of Molecular and Medical Genetics, Cell and Developmental Biology, and Physiology and Pharmacology in the School of Medicine. After being awarded his B.S. from the University of Notre Dame in 1973, Forte earned his Ph.D. in Genetics from the University of Washington in 1978. He then went to the University of Wisconsin for four years of postdoctoral research in Molecular Biology. In 1982, Forte became an assistant professor at Case Western Reserve University, where he remained until his appointment to the Vollum in 1986.

Research Interests

The Forte laboratory is engaged in two projects. The first focuses on receptor pathways that couple to an intermediate protein, or G protein, to advance the signal within the cell. Although receptors in this class are important pharmacological targets, their involvement in developmental processes is poorly understood. The G_s class of heterotrimeric G proteins couple extracellular receptors to the critical intracellular second messenger, cAMP. Using the fruit fly Drosophila as an experimental system, Forte and his colleagues have found that G_s-coupled pathways are involved in mediating important decisions during the formation of the nervous system. For example, mutations eliminating G_s signaling result in a failure of neuronal processes to branch and form functional synapses. In addition, inappropriate activation of this pathway at specific times during development can lead to profound changes in a variety of cell types. The lab is now focused on determining how this signal transduction pathway interacts with and modulates other transmembrane signaling pathways within the cell and is attempting to elucidate the nature of the downstream components that lead to cell-type specific responses.

In a second project, the lab is investigating the role of mitochondria in the overall regulation of cellular calcium (Ca²⁺). Ca²⁺ ions probably represent the most ubiquitous signaling pathway in all cells and changes in cytosolic Ca²⁺ concentration mediate most of the short-term events that define changes in cell function. Mitochondria are now recognized as initiators and transducers of a range of cell signals, participating in neuronal functions like synaptic plasticity and processes central to activation and amplification of programmed cell death. Moreover, as the main source of cellular ATP, mitochondria must respond to fluctuating energy demands of the cell. As local and global fluctuations in Ca²⁺ concentration are ubiquitous in eukaryotic cells and are the common factor in a wide array of intra- and inter-cellular signaling cascades, the relationships between mitochondrial function and Ca²⁺ transients is currently a subject of intense scrutiny. Many lines of evidence now point to the fact that mitochondria act as local Ca²⁺ buffers, thus shaping spatiotemporal aspects of cytosolic Ca²⁺ signals. For example, the mitochondrial Ca²⁺ pool oscillates rapidly in synchrony with cytosolic Ca²⁺ and thus, mitochondria have the ability to shape cytosolic Ca²⁺ transients. Furthermore, proteins in the BCL2 family, central coordinating points in cell death processes, may function by modulating the exchange of Ca²⁺ from the ER to mitochondria. Mitochondria also respond to Ca²⁺ uptake by upregulating energy production, thus integrating metabolism with local Ca²⁺ signaling. The Forte lab is interested in the reciprocal effects of Ca²⁺ on mitochondria and mitochondria on the Ca²⁺ signals. Using genetic approaches in mice, the goal is to understand the response of mitochondria to Ca²⁺, the pathways by which Ca²⁺ accumulates into mitochondria, and the role of mitochondrial Ca²⁺ uptake in regulating cell death processes.

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Selected Publications

Forte, M. (2004) VDAC function in a cellular context. Topics in Current Genetics 8:251-266.

Wolfgang, W., Clay, C., Parker, J., Kidokoro, Y., Labarca, P., and Forte, M. (2004) G_sα signaling is required for synaptic growth in Drosophila. Dev. Biol. 268:295-311.

Polcic, P. and Forte, M. (2003) Quantitative assessment of the response of yeast to the expression of BCL2 family members. Biochem. J. 372:393-402.

Hou, D., Suzuki, K., Wolfgang, W., Clay, C., Forte, M., and Kidokoro, Y. (2003) Presynaptic impairment of synaptic transmission in Drosophila embryos lacking G_sα. J. Neurosci. 23:5897-5905.

Bernardi, P., DiLisa, F., Petronilli, V., and Forte, M. (2001) A mitochondrial perspective on cell death. Trends in Biochem. Sciences 26:112-117.

Wolfgang, W., Roberts, I., Hoskote, A., Jackson, S., and Forte, M. (2001) Genetic analysis of the Drosophila G_sα gene. Genetics 158:1189-1201.

Schaefer, M., Petronczki, M., Dorner, D., Forte, M., and Knoblich, J. (2001) Heterotrimeric G proteins direct two modes of asymmetric cell division in the Drosophila nervous system. Cell 107:183-194.

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