Research Focus Areas
The Mitochondrial Care Research Center has several research focus areas in which investigators lead research on topics related to a broad spectrum of mitochondrial diseases and conditions.
Gene and cellular therapies
This research focus area brings together Mayo Clinic investigators from multiple disciplines whose goal is to develop new therapies based on gene delivery, gene editing and cellular reprogramming. This focus area promotes research to develop novel therapeutics by restoring the function of nuclear and mitochondrial encoded genes that harbor pathogenic variants leading to mitochondrial disease.
Stem cell biology
Researchers working in this focus area endeavor to understand how mitochondrial function and energy metabolism regulate stem cell fate, function and regenerative capacity.
Specifically, this multidisciplinary team addresses fundamental questions in the emerging field of stem cell metabolism, including the molecular mechanisms by which metabolic pathways support stage-specific stem cell function, how plasticity in energy metabolism regulates cell fate decisions, and the impact of aging and disease on stem cell metabolism and tissue regenerative capacity.
The long-term goal of this research is to apply metabolism-based regenerative strategies to enhance stem cell-based repair, improve innate tissue regenerative capacity and delay aging-associated degeneration.
Bioenergetics of resilience
As leader of this focus area, Dr. Kozicz is pursuing the scientific understanding of genes and brain circuits associated with or altered by the stress response and how defects in biochemical and metabolic processes impact resilience mechanisms throughout the body.
By bridging basic and clinical research, Dr. Kozicz aims to gain a deeper understanding of deficits in behavior, learning and memory in terms of systemic bioenergetics and mitochondrial quantitative genetics, with special attention to mechanisms of sex differences.
Molecular nutrition and metabolism
Metabolism and nutrition are crucial modifiable factors that can impact mitochondrial biology. In this focus area, Dr. Chini investigates NAD metabolism and NAD-boosting interventions using molecular, cellular, animal and human studies to understand these processes.
Dr. Chini, who is also director of the Metabolism, Nutrition and Aging Program of the Robert and Arlene Kogod Center on Aging at Mayo Clinic, fosters a coordinated bench-to-bedside approach to understanding the role of metabolism and nutrition in the health span and aging process that provides tools to help improve the lives of patients with primary and secondary mitochondrial diseases.
Damaged, worn-out or superfluous mitochondria are removed from cells through a process called autophagy. While several independent mechanisms exist, the most significant and best-established pathway is orchestrated by PINK1 and PRKN, two genes that are found mutated in early-onset Parkinson's disease and certain types of cancer. Upon stress, the two encoded enzymes cooperate to identify, selectively label and target damaged mitochondria for degradation in order to protect the mitochondrial pool and thus overall health of the cell.
Similar to other selective forms of autophagy, mitophagy has attracted significant attention in the field and promises enormous potential for disease-modifying strategies. Given the importance of the PINK1-PRKN pathway for various tissues, ongoing research will likely have far-reaching implications for various primary mitochondrial disorders and age-related neurodegenerative diseases and perhaps the aging process itself.
In this focus area, Dr. Springer's goal is to delineate the genetic architecture of mitophagy and to unravel the underlying molecular mechanisms. Capitalizing on this knowledge, our research team is developing novel biomarkers and performing rationalized drug design to target the cytoprotective capacity of mitophagy.
For more information, visit Dr. Springer's Translational Cell Biology of Parkinson's Disease Laboratory.
Early alterations in mitochondrial dynamics, function and turnover are shared across the pathogenesis of many if not all neurodegenerative diseases. While the exact dysfunction and the extent may vary between different diseases, affected brain regions, or during progression of the disease, subtle mitochondrial impairments are detectable long before the accumulation of misfolded proteins, neurodegeneration or the onset of clinical symptoms. These include, but are not limited to, changes in mitochondrial ATP production, axonal transport and morphology, biogenesis, and degradation.
Investigators in this focus area use a multidisciplinary approach employing in vitro and in vivo models of neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's disease, and chronological aging, along with cells, tissues and biofluids from patients to translate basic science discoveries into novel therapies.
Current efforts focus on the development of novel biomarkers and small molecule therapeutics to target specific aspects of mitochondrial biology, such as adaptive stress response and selective degradation, that hold great promise for neuroprotection.
For more information, visit Dr. Trushina's Mitochondrial Neurobiology and Therapeutics Laboratory and Dr. Springer's Translational Cell Biology of Parkinson's Disease Laboratory.
Applied physiology and mechanistic studies of human energy metabolism
In this focus area, Dr. Lanza is leading efforts to understand molecular and cellular adaptations to exercise in the context of aging and metabolic disease.
Our investigators use a variety of analytical chemistry tools, such as mass spectrometry and nuclear magnetic resonance spectroscopy, paired with in vivo delivery of isotope-labeled tracers to monitor amino acid, protein, glucose and lipid metabolism in humans. These techniques are combined with comprehensive mitochondrial phenotyping tools, gene-expression measurements, proteomics, imaging and conventional measures of physical function to gain new insights into the processes that potentiate or attenuate adaptive responses to physical activity.
For more information, visit Dr. Lanza's Muscle Physiology and Metabolism Laboratory.
Mitochondrial disease diagnostic biomarkers
In this focus area, investigators aim to address crucial unmet needs in human mitochondrial DNA (mtDNA) disease by studying exemplary mitochondrial conditions, such as mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes. There are major gaps in the understanding of mitochondrial disorders and in the ability to diagnose these conditions.
Research steps forward are progressing toward two key goals: 1) Discovering and validating novel biomarkers for mtDNA disease, and 2) establishing diagnostic assays for clinical use at Mayo Clinic Laboratories. This focus area uses a multisite collaboration to established prospective cohorts of patients and to deep-phenotype individual participants' specimens using metabolomic, proteomic and molecular methods.
Outcomes of this research include translational analytical methods for laboratory diagnostics and potential therapeutic monitoring.
Mitochondrial dysfunction during aging
Dr. Passos brings to this focus area his experience as a cell and molecular biologist with long-standing expertise in the field of the biology of aging, having made impactful contributions to understanding the role of mitochondria and telomere dysfunction during cellular senescence.
In his research, Dr. Passos investigates molecular mechanisms of aging and potential interventions. His research has shown that mitochondria become dysfunctional with age and are key regulators of the proinflammatory phenotype characteristic of senescent cells — a major contributor to age-related diseases. His research team is investigating the molecular mechanisms by which mitochondria contribute to cellular senescence, with the hope of finding new therapies to increase health span during aging. The team uses a combination of state-of-the-art cell and mouse models to investigate mitochondria during aging and potential interventions.
For more information, visit Dr. Passos' Cell and Molecular Aging Laboratory.