Major Research Projects

• Regulation of Mitochondrial Gene Expression

We have worked for many years on nucleus-encoded factors that are required for expression and maintenance of mtDNA, their interactions, and mechanism of action. These include the dedicated mitochondrial RNA polymerase and requisite transcription factors, proteins required for modification, processing and translation of mitochondrial RNAs, and the coupling of these processes to mitochondrial ribosomes. We also study what controls the amount of mtDNA/cell and mtDNA repair pathways.

• Mitochondrial Dysfunction and Oxidative Stress in Ataxia-Telangiectasia (A-T)

We were one of the first groups to show that mitochondrial dysfunction contributes to the pathology of the human disease Ataxia-Telangiectasia. Ongoing efforts involve the study of the mouse model of this disease and how the ATM protein is involved in mitochondrial redox sensing pathways that control nuclear gene expression.

• Mitochondrial Stress Signaling Pathways and their Role in Aging and Disease

Mitochondrial dysfunction comes in multiple physiologically relevant forms, including increased reactive oxygen species (ROS) production, deficits in energy metabolism and ATP production, and altered mitochondria dynamics (e.g., fission and fusion). We are interested in the specificity of these pathways and how they might be exploited as potential therapies for mitochondrial-based diseases. We also study how mitochondria contribute to aging using yeast and mouse models.

• Mitochondria in Cancer and the Immune System

We are studying several animal models of mitochondrial dysfunction to understand its role in tumorigenesis, metastasis and innate immune signaling.

Shadel Video Interviews

VIDEO (30 min): Mitochondria and Aging: In an interview on TSN (The Science Network), Professor Shadel describes the basics of mitochondrial function and mitochondrial interaction with aging through signaling pathways.

VIDEO (4 min): Mitochondria DNA Defects Cause Deafness: A Yale interview with Professor Gerald Shadel about a Yale study revealing the pathway by which mitochondrial DNA defects cause maternally-inherited deafness.