Mitochondrial Physiology Laboratory

Ophthalmic Mitochondrial Bioenergetics Center

Contact Us

Investigator / Contact Person Anh Pham, M.D., Ph.D.

Office 305-482-5988

Email ahp79@miami.edu

Research

The primary aim of the Mitochondrial Physiology Laboratory revolves around enhancing the understanding and enhancement of mitochondrial well-being in optic neuropathy models through a diverse range of methods. Our research involves the creation of murine models tailored for detailed imaging studies, allowing precise assessment of mitochondrial dynamics and clearance in various biological settings including primary tissues, organotypic cultures, and retinal explants. Furthermore, we are actively investigating novel approaches utilizing CRISPR-based technology for the manipulation of mitochondrial DNA.

Experimental models for high-resolution imaging of mitochondria

Mitochondrial network in Purkinje neurons within organotypic culture

Mitochondria are essential organelles that perform multiple functions inside the cell including ATP synthesis, regulation of apoptosis, maintaining calcium homeostasis, and viral defense. These organelles undergo constant remodeling through membrane fusion and division as well as selective clearance and biogenesis. To facilitate high-resolution analysis of mitochondrial dynamics, we have developed inducible experimental models carrying fluorescent reporter genes imported into the mitochondria. These reporter lines enable cell-specific monitoring of individual mitochondrion.
Mitochondrial physiology in glaucoma models

Long interconnected mitochondria (red) and mtDNA (green puncta) in human trabecular meshwork cells.

Glaucoma is the leading cause of irreversible blindness worldwide, affecting more than 80 million people globally. The trabecular meshwork is the bottleneck for aqueous outflow in the eye and a key site for surgical, medical, and laser intervention. Primary trabecular meshwork cultures obtained from corneoscleral rim donors are excellent in vitro and ex vivo models for evaluating mitochondrial health during glaucoma progression. We utilize a multi-modal approach for assessing mitochondrial physiology using cell biology techniques, genomic analysis, and mullti-omic profiling to identify metabolic disturbances in the pathogenesis of glaucoma.
Gene therapy for mitochondrial DNA

CRISPR-based targeting of mutant mtDNA

Mitochondria are unique organelles that carry genomic content in the form of a circular plasmid DNA that encodes essential subunits of the electron transport chain for the Kreb cycle. Mutations in mitochondrial DNA (mtDNA) cause devastating ocular and metabolic diseases during infancy and childhood. There is no curative treatment for mtDNA disorders at this time. Our laboratory is exploring a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) based technology for targeting mtDNA mutations that has potential for rescuing these phenotypes.

Research

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Mitochondrial Physiology Laboratory