Patient iPSC Research
Human iPSCs are pluripotent stem cells artificially generated by transiently expressing a set of exogenous transcription factors in somatic cells. We now realize the cells have a great value as a system to model human diseases. iPSCs can be generated from skin biopsies or blood samples of patients, and can be differentiated in vitro into cell types which are not easily accessible in patients, such as neurons and cardiomyocytes. Since iPSCs retain all the genomic information from the original patients, iPSCs can be utilized to study how genetic aberrancies in the patient manifest in target cells in vitro. Indeed, pioneering studies have demonstrated that disease-specific iPSCs are useful for understanding disease mechanisms. Moreover, iPSC-derived cells, when recapitulating some disease phenotypes in vitro, can be a fast-track screening tool for drug discovery. Further, iPSCs will also become a valuable tool to predict drug efficacy and toxicity for individuals, thus promoting personalized medicine. To this end, we established the Center for Cellular Reprogramming (http://ccr.med.ufl.edu/) in the institute and are actively promoting patient iPSC research in collaboration with many internal and external investigators.
Mammalian Mitochondrial ADP/ATP Transporters
Since we first identified the 4th member of mammalian adenine nucleotide translocase (ANT) genes about a decade ago, we have been studying function and regulation of mammalian Ant paralogs. ANTs are the most abundant proteins in mitochondria and primarily exchange the ADP/ATP through the mitochondrial inner membrane (MIM), thus they play an essential role in bioenergetics in eukaryotes. ANTs have also been implicated in regulation of the mitochondrial permeability transition pore (MPTP) and are implicated in uncoupling, and therefore may also play a role in the control of cellular survival and death. All eukaryotes have multiple ANT family genes (paralogs), and their gene expression is differentially regulated. In some cases, expression is presumably dependent on the extracellular oxygen and nutrient environment, and in other cases, expression is controlled in a tissue-specific manner. Using mouse genetics, yeast genetics and biochemical approaches, we are identifying both specific and redundant roles of ANT paralogs in mammalian development, homeostasis and disease.