Browsing by Author "Kirienko, Natasha V."

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    Caenorhabditis elegans as a tool for high-throughput screening and gene network analysis
    (2021-12-01) Anderson, Quinton Levi; Kirienko, Natasha V.; Wagner, Daniel
    Often, we think of mitochondria as simply as the powerhouse of the cell, but we have come to understand that they are crucial to multiple facets of cellular health. Mitochondria are involved in the production of ROS (reactive oxygen species), fatty acid metabolism, and calcium storage. Mitochondria are also extremely dynamic organelles that undergo fusion, fission, and biogenesis. While mitochondria are often involved in the health of the cell, mitochondrial dysfunction has been linked to serval pathologies from cancer to neurodegenerative diseases such as Parkinson’s and Alzheimer’s. In order to understand the genetic bias of these diseases, high throughput screening assays needs to be used. In my thesis I will discuss the development of a high throughput assay that can be utilized to understand interactions in a host-pathogen system, or an activation of the fluorescent reporter. This assay may allow us to understand the genetics that leads to observable phenotypes. These observations can be catalogued and placed into a pipeline that becomes a predictive model to treat human diseases. This advent will allow for a more personalized form of treatment options for patients.
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    Targeting Mitochondria Metabolisms for Novel AML Therapy Development
    (2021-12-03) Pei, Jingqi; Kirienko, Natasha V.; Carson, Daniel
    Mitochondrial dysfunction contributes to a wide variety of pathologies, including neurodegenerative diseases, cancer, metabolic diseases, and aging. As a consequence, oncogenesis and tumor progression heavily depends on the mitochondrial metabolism. I investigated the potential of using mitochondrial targeting drugs to selectively remove leukemia, a type of cancer that has been previously identified to be sensitive to mitochondria-targeting drugs. I optimized Hoeschst/PI dual-staining assay for quick, high-throughput screening of leukemia cell’ viability under mitochondria-targeting drugs treatments. Through combination of mitochondria-targeting drugs and anti-cancer chemotherapeutic agents, I observed high synergistic effect in the removal of leukemia in these combinations. I characterized several changes in mitochondria bioenergetic parameters that are correlated with the sensitivity of mitochondria-targeting drug to leukemia. These observations also applied to primary AML samples extracted from patients. Mitochondria health is actively surveilled by several different systems to ensure the preservation of cellular viability. Mitophagy is a conservative process that removes superfluous or damaged mitochondria. I identified 8 compounds with mitophagy activation effect that can stabilize PINK-1/PINK1 in C. elegans with my colleague Dr. Elissa Tjahjono. I observed these compounds induced selective removal of leukemia alone or in combination with other anti-cancer chemotherapeutic agents. Furthermore, these compounds reduced paralysis level in C. elegans model of neurodegenerative diseases. Taken together, activation of mitophagy using these compounds may be a novel method to develop selective therapy for leukemia and neurodegenerative diseases.