Research Interests
The main area of my research is to contribute to understanding of the metabolic mechanisms of aging and age-related diseases. The goal is to understand basic mechanisms of age-dependent metabolic reprogramming and to translate these insights into a mammalian system and ultimately into humans. To achieve this goal, my lab primarily uses Drosophila as a model system because it offers exceptional genetic tools, has a relatively short lifespan, and includes established models for age-dependent diseases. We previously identified novel members of the methionine metabolism pathway and the tyrosine degradation pathway as important regulators of health- and lifespan. Methionine and tyrosine metabolism pathways can be both targeted with FDA-approved drugs or drugs that are under current investigation for human application. This creates a strong rationale for translating these treatments to mammalian systems as anti-aging interventions or for the potential treatment of various age-related diseases. My lab is currently testing whether targeting methionine or tyrosine metabolism can delay different age-dependent manifestations in aged mice. In addition, I also developed a novel Drosophila cancer model and identified a set of synthetic lethal targets for RB1-deficient cancer cells that can be targeted therapeutically. We found that low activity of the identified synthetic lethal genes in human tumors, when combined with low levels of RB1, was associated with improved patient survival. We are currently working on translating these findings into mammalian tumor models.
Selected Publications
- Parkhitko AA, Binari R, Zhang N, Asara JM, Demontis F, Perrimon N. (2016). Tissue-specific down-regulation of S-adenosyl-homocysteine via suppression of dAhcyL1/dAhcyL2 extends health span and life span in Drosophila. Genes Dev. 30(12), 1409-22. PMID: 27313316
- Parkhitko A, Jouandin P, Mohr SE, Perrimon N. Methionine metabolism and methyltransferases in the regulation of aging and lifespan extension across species. Aging Cell. 2019 Dec;18(6):e13034. doi: 10.1111/acel.13034. Epub 2019 Aug 28. Review. PMID: 31460700
- Parkhitko AA, Ramesh D, Wang L, Leshchiner D, Filine E, Binari R, Olsen AL, Asara JM, Cracan V, Rabinowitz JD, Brockmann A, Perrimon N. Downregulation of the tyrosine degradation pathway extends Drosophila lifespan. eLife 2020 Dec 15;9:e58053. doi: 10.7554/eLife.58053. PMID: 33319750
- Parkhitko A, Filine E, Mohr SE, Moskalev A, Perrimon N. Targeting metabolic pathways for extension of lifespan and healthspan across multiple species. Ageing Res Rev. 2020 Oct 5;101188. doi: 10.1016/j.arr.2020.101188. Review. PMID: 33031925
- Parkhitko A, Singh A, Hsieh S, Hu Y, Binari R, Lord CJ, Hannenhalli S, Ryan CJ, Perrimon N. Cross-species identification of PIP5K1C-, splicing- and ubiquitin-related pathways as potential targets for RB1-deficient cells. PLoS Genet. 2021 Feb 16;17(2):e1009354. doi: 10.1371/journal.pgen.1009354. eCollection 2021 Feb. PMID: 33591981