Using transgenic animal modeling, Dr. Pinkert's work has illustrated the potential of modifying the immune system, enhancing growth performance and the feasibility of biopharmaceutical production ('molecular pharming'). Enabling technologies and procedures have also been developed for the genetic engineering of both nuclear and mitochondrial genes. Most recently, his laboratory has embarked on pioneering studies revolving around mitochondrial transfer techniques and the development of transmitochondrial animals.
In vertebrates, mitochondrial DNA (mtDNA) encodes 37 genes that are highly conserved across all species. In humans, mutations arising exclusively within the mitochondrial genome give rise to a class of severely debilitating and lethal disorders. Such mutations, many of which exist in a heteroplasmic state (where both normal and mutant mitochondrial genomes coexist in varying proportions), mainly affect tissues with high cellular energy requirements (e.g., brain, muscle, heart, kidney and endocrine organs). In contrast to nuclear genes, mitochondrial gene replication and function differ markedly - from exclusive matrilineal inheritance to the presence of hundreds or thousands of mitochondria within a given cell. Various human diseases have been associated with specific mtDNA mutations including diabetes mellitus, myocardiopathy and retinitis pigmentosa, as well as age-associated changes in the functional integrity of mitochondria as seen in Parkinson's, Alzheimer's and Huntington's diseases. Accordingly, the ability to manipulate and regulate the expression of mitochondrial genes provides a basis for developing innovative gene therapy paradigms. In collaborative studies, the creation of transmitochondrial mice (mice harboring introduced and species-specific mitochondrial genes) represents an initial step toward providing a greater understanding of mitochondrial dynamics while paving the way for therapeutic interventions in humans and manipulation of mitochondrial genetics in a host of species.