BS University of Notre Dame, 1973
PhD University of Washington, 1978
503-494-5454I was raised in Seattle, WA and graduated summa cum laude from the University of Notre Dame. Missing the Northwest, I decided to return to the Seattle for my graduate training in the Dept. of Genetics at the University of Washington. My thesis project focused on initial attempts to understand chromosome structure using yeast as an experimental model. After finishing my Ph.D. work, my attention turned to something new and I spent four years in the laboratory of Dr. Ching Kung at the University of Wisconsin in Madison, WI as a postdoctoral fellow. My projects here focus on trying to understand the molecular basis of a variety of ion channel mutants that had been generated in the protozoan Paramecium. My first faculty position was in the Dept. of Biology at Case Western Reserve University in Cleveland, OH where I continued to work on Paramecium but became fascinated by trying to understand the nature of the protein conformational changes driven by voltage changes in ion channels. For a number of years, we modeled these changes within the context of a mitochondrial protein, exploiting the powerful genetics available in the yeast system. While at Case, I began my work on cell signaling in Drosophila, which eventually focused on the mechanisms responsible for synaptic growth. In 1986, I jumped at the chance to move back to the Northwest and was a founding member of the Vollum Institute. More recently, in collaboration with Dennis Bourdette, my lab is the using mouse genetics and mouse models of MS to try to understand the role of mitochondria in the axonal severing that results in the permanent disability accompanying this disease.
Mitochondria in multiple sclerosis – establishing the connection
The aim of this project is to define the role of mitochondrial dysfunction in neurodegenerative aspects of multiple sclerosis (MS). Classically, MS has been considered primarily an inflammatory disease. As a result, much effort has gone into developing therapies to control the pernicious immune response in MS. However, over the past decade accumulating evidence indicates that MS is more complicated than earlier believed and has established the importance of to axonal injury as primarily responsible for the irreversible disability that occurs in afflicted individuals. Although the mechanisms are incompletely understood, one reasonable scenario proposes that neurodegenerative aspects of MS stem from a cascade of ionic imbalances involving mitochondrial dysfunction, concomitant deficits in cellular energy supply, mitochondrial Ca2+ overload and corresponding increases in the generation of reactive oxygen species (ROS)
Using a mouse model of MS, our recent work has pointed to a specific mitochondrial protein controlling the mitochondrion’s ability to release Ca2+ as critically involved in the axonal degeneration occurring in this disease. This work is the first to directly implicate mitochondria, and their role in cellular Ca2+ homeostatic networks, in a key aspect of the pathogenesis associated with MS. Future work will be directed by our overall hypothesis predicting that enhancing ability of axonal mitochondria to sequester Ca2+ in response to Ca2+ overload delays mitochondrial dysfunction leading to neurodegenerative aspects of MS. Experiments evaluating this idea will rest in large part on the use of genetic strategies available in mice to test the role of proteins suspected to be involved in regulating mitochondrial Ca2+ homeostasis in pathways leading to axonal destruction in mouse models of MS. These genetic studies will be complemented by live cell imaging to establish, for example, whether mitochondria missing specific proteins can preserve function in the face of elevated Ca2+ levels which would normally lead to the mitochondrial dysfunction and release of cell death activators. In the long term, our hope is that this work will lead to the identification of novel targets for therapeutic intervention, since effective management of this disease will require treatments that slow the pathogenic inflammatory response as well as neuroprotective strategies that reduce axonal damage.
Giorgio V, Soriano ME, Basso E, Bisetto E, Lippe G, Forte MA, Bernardi P (2010) Cyclophilin D in mitochondrial pathophysiology. Biochim Biophys Acta 1797:1113-1118.
Barsukova A, Komarov A, Hajnoczky G, Bernardi P, Bourdette D* and Forte M* (2011) Activation of the mitochondrial permeability transition pore modulates Ca2+ responses to physiological stimuli in adult neurons. Eur J Neurosci 33:831-842.
Barsukova AG, Bourdette D, Forte M (2011) Mitochondrial calcium and its regulation in neurodegeneration induced by oxidative stress. Eur J Neurosci 34:437-447.
Su KG, Savino C, Marracci G, Chaudhary P, Yu X, Morris B, Galipeau D, Giorgio M, Forte M*, Bourdette D* (2012) Genetic inactivation of the p66 isoform of ShcA is neuroprotective in a murine model of multiple sclerosis. Eur J Neurosci 35:562-571.
Barsukova AG, Forte M*, Bourdette D* (2012) Focal increases of axoplasmic Ca2+, aggregation of sodium-calcium exchanger, N-type Ca2+ channel, and actin define the sites of spheroids in axons undergoing oxidative stress. J Neurosci 32:12028-12037.
Su K, Bourdette D, Forte M (2012) Genetic inactivation of mitochondria-targeted redox enzyme p66ShcA prreserves neuronal viability and mitochondrial integrity in response to oxidative challenges. Front Physiol 3:285-291.
Giorgio V, von Stockum S, Antoniel M, Fabbro A, Fogolari F, Forte M, Glick GD, Petronilli V, Zoratti M, Szabo I, Lippe G, Bernardi P (2013) Dimers of mitochondrial ATP synthase form the permeability transition pore. Proc Natl Acad Sci U S A 110:5887-5892.
Su K, Bourdette D, Forte M (2013) Mitochondrial dysfunction and neurodegeneration in multiple sclerosis. Front Physiol 4:169-179.
BA, Reed College, 2013
During my final year at Reed College I had the opportunity to work on my senior project in the Forte Lab studying the effects of mitochondrial calcium regulation in Drosophila. After receiving my B.A. in Biology I joined the lab full time, continuing my work with Drosophila, managing the mouse colony, and expanding my knowledge of molecular biology techniques.
BA, Concordia University, 1999
I graduated from Concordia University in Portland with a BA in Biology. I then spent two years in Dr. Tom Soderling’s lab working with the Drosophila homolog of Ca2+/calmodulin kinase I, and five years in Dr. Sarah Smolik’s lab working on Drosophila orthologs of CBP. In 2007, I joined Mike Forte’s lab and have spent the last few years on all aspects of mouse molecular biology, both protein and DNA. I also make sure the lab runs as smoothly as possible by managing the ordering of all supplies.
BS, Portland State University, 2003
My foray into science began in high school biology where we were encouraged to examine the biological world around us. Following high school, I attended and graduated from Portland State University. While an undergraduate, I worked in a lab investigating the affects of ethanol on thermoregulation. After Portland State, I entered the Forte Lab, dividing my time between both the Drosophila and mouse projects. I am in charge of the ever-expanding mouse colony and all mouse genetics. In addition, I have developed the skills required for light level, and confocal microscopy for the mouse project.