Christina Pacak, PhD

Christina A. Pacak, Ph.D. is a molecular biologist whose research interests are focused on understanding underlying mechanisms in rare disorders that impact mitochondrial function to guide therapeutic development relevant to both rare and common disorders. Using mouse models and human patient-derived, differentiated induced pluripotent stem cells her laboratory examines cardiac, neuronal, and skeletal muscle samples in search of common effectors of mitochondrial function that can be targeted using adeno-associated virus (AAV) based delivery or other treatment strategies. The Pacak lab research program incorporates global proteomics strategies to define these mechanisms and test the efficacy of various treatment approaches.

• Cardiac – The Pacak lab recently described the downregulation of a protein called TMEM65 in Barth syndrome (a mitochondrial cardioskeletal myopathy). As TMEM65 is involved in maintenance of mtDNA copy numbers and localization of Cx43 to the polar ends of cardiomyocytes, it may represent a critical link between mitochondrial dysfunction and the development of arrhythmias. Studies to evaluate this in a variety of arrhythmogenic models are underway.
• Neuronal – Work in the Pacak lab to evaluate mitochondrial function in Cockayne syndrome (a premature aging, neurodegenerative disorder) has revealed several mechanistic parallels with Alzheimer’s disease. These include both metabolic and the unfolded/misfolded protein response pathways based upon TMT proteomics evaluations. A Cockayne syndrome gene therapy project has demonstrated our ability to correct these features of the disease in the brain and provides proof-of-concept support that this can be rectified. Studies to evaluate and eventually manipulate these pathways in patient iPSC-derived cerebral organoids have commenced.
• Skeletal Muscle – The Pacak Lab is performing comparative analyses of mitochondrial function and proteomic profiles across multiple forms of Limb Girdle Muscular Dystrophy (LGMD). Our goal is to identify alterations in mitochondrial function for LGMDs of known and unknown genotype, determine whether these alterations are unique or shared across subtypes, establish how they change with and influence LGMD progression, and reveal novel pathways for therapeutic targeting to augment precise aspects of mitochondrial function.