Associate Professor of Pathology and Genetics

B.S. Chemistry, University of Nevada, Las Vegas, 1986
Ph.D. Biochemistry, Texas A&M University. 1991
Postdoctoral Fellow, Stanford University

Research Interests:

Mitochondrial Genetics and Biogenesis
Mitochondrial Dysfunction in Human Disease and Aging
Mechanisms of mtDNA Transcription and Mitochondrial Translation
Signaling Pathways that Sense and Control Mitochondrial Function

Honors:

* Amgen Outstanding Investigator Award, American Association for Investigative Pathology (ASIP), 2007
* Glenn AFAR, Breakthroughs in Gerontology (BIG) Award, 2006
* Damon Runyon-Walter Winchell Postdoctoral Fellow, 1992-1995

Current Research:

In humans, as in most animal cells, genetic information is housed not only in the nucleus, but also in mitochondria. Mitochondrial DNA (mtDNA) encodes thirteen essential proteins of the oxidative phosphorylation complexes as well as 22 tRNAs and 2 rRNAs required to translate these thirteen mRNAs in the mitochondrial matrix. Mutations in mtDNA cause maternally inherited neuromuscular disorders due to declines in cellular energy metabolism. In addition, mtDNA mutations accumulate in normal aging tissues, certain tumors, and have been implicated in late-onset diseases such a Alzheimer's, Parkinson's, and diabetes, indicating that the pathology of dysfunctional mitochondria is only beginning to be unraveled. The research in my laboratory is directed toward understanding the mechanism of gene expression in human mitochondria and its impact on human aging and disease. The ultimate goal is to understand the full impact of dysfunctional mitochondrial gene expression on human health and use this information to design specific interventions to treat mitochondria-based disease and age-related pathology.

Specifically, my lab focuses on nucleus-encoded factors that are imported into the organelle to regulate transcription, translation, replication, and maintenance of mtDNA. We are also concerned with signaling pathways that connect the nuclear and mitochondrial genomes to coordinate gene expression patterns in both compartments. We use multiple approaches to this problem including the employment of mouse and budding yeast (S. cerevisiae) genetic model systems, biochemical characterization of mitochondrial transcription events and interactions, and in vivo approaches in cultured mammalian cells.

Contact Information:

Lab website: Shadel Lab
Pathology faculty website and publications