The Forte laboratory currently focuses on the role played by mitochondria in cellular Ca2+ homeostasis and cell death. For these studies the lab uses genetic, biochemical and pharmacological analysis in mammalian systems. Most of these studies focus on the physiological role of a specific mitochondrial Ca2+ efflux pathway known as the mitochondrial permeability transition pore (PTP). By generating specific lines of mutant mice, the lab has demonstrated that the repression of PTP opening confers stunning resistance to cell death in mouse models of some of the most therapeutically challenging human diseases.

In a complimentary set of studies, a battery of potent small molecule inhibitors of the mitochondrial Ca2+ efflux have been identified. The current studies center on the use of these inhibitors as tools to identify yet unresolved biochemical components of the PTP, and on their use as therapies for a variety of devastating human diseases in which altered mitochondrial Ca2+ handling have been implicated.


Shutting down the Pore

The permeability transition pore (PTP) opening promotes cell death.Prolonged opening of the mitochondrial permeability transition pore (PTP) causes mitochondrial dysfunction and promotes cell death. It is implicated in a variety of the most therapeutically challenging human diseases and is a target of interest for novel therapeutics.