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1020 Locust Street
JAH 572K
Philadelphia, PA 19107
Our present knowledge of mitochondria highlights activities beyond energy production and into their decision-making role in many cellular processes. Our insight on the essential roles of mitochondrial signaling in disease-relevant processes such as innate immunity is rapidly expanding. However, several questions remain regarding the origin, mechanisms, and significance of such phenomena.
The Tigano Laboratory performs foundational research on mitochondrial disorders, mitochondrial DNA mutations, and mitochondrial stress signaling. With powerful genetic approaches and cutting-edge technologies, we aim to shed light on the complex signaling pathways that mitochondria use to communicate with the nucleus and other organelles about stress and damage.
In particular, we will investigate how aberrant mitochondrial signaling influences innate immunity and what pathways are conducive to mtDNA mutation. These aberrations can negatively influence the progression of several human disorders by fostering tissue degeneration. Therefore, our research harbors the potential for paving new therapeutic approaches for diseases characterized by mitochondrial dysfunction and inflammation.
Research Projects
How does mitochondrial stress govern cellular signaling?
We recently uncovered how mitochondrial stress, in the form of double stranded breaks in the organelles genetic material (mtDNA), triggers systemic innate immunity. This signaling event is engaged after mitochondrial nucleic acids relocates in the cytoplasm through mitochondrial herniation, a particular form of mitochondrial outer membrane permeabilization.
Inflammation and immunity are known to exert both positive and negative effects on the etiology and the evolution of human diseases. For example, neurodegeneration is triggered by uncontrolled inflammatory responses while the therapeutic effects of standard of care cancer treatments are boosted by systemic immune responses.
Our main interests are to understand the molecular details of herniation and explore the effects of mitochondrial driven innate immunity on the severity of human diseases.
How are different cells impacted by aberrations in mitochondrial DNA?
Mitochondria are equipped with 16.6 kb pairs of genetic information, mtDNA, present in thousands of copies per cell. The information that they code for is essential for life. Nevertheless, in patients with mitochondrial diseases or even during normal aging, deleterious aberrations can arise and be accumulated to a pathogenic threshold. The effects of surpassing this threshold are neuronal and muscular degeneration and the outcome is often fatal.
Although we discovered the first deletion in mitochondrial DNA more than 50 years ago, why aberrations in mitochondrial DNA accumulate to pathogenic threshold eludes us.
The Tigano lab uses innovative models to interrogate the cellular and tissue specific responses to mtDNA deletions with the aim to elucidate the molecular mechanisms behind their dangerous accumulation.