Parkhitko Lab

Andrey A Parkhitko, PhD
Assistant Professor of Medicine
Division of Endocrinology and Metabolism

Our lab is interested in how age-dependent metabolic changes can be targeted to extend health- and lifespan.

Parkhitko Lab

Lab Focus

My laboratory’s interest is how metabolism is reprogrammed with aging and how age-dependent metabolic changes can be targeted to extend health- and lifespan. Using Drosophila as a model system, we demonstrated that aging is characterized by extensive reprogramming of methionine metabolism and delayed processing of SAH, a competitive inhibitor of a broad spectrum of methyltransferases. In addition, we demonstrated that tyrosine metabolism is altered with age due to the activation of the tyrosine degradation pathway. Our goal is to determine how these metabolic pathways crosstalk to regulate the activity of methyltransferases (methionine metabolism) and the production of neuromediators (tyrosine metabolism). We are also interested in whether ‘resetting’ the methionine and tyrosine metabolic pathways back to a more youthful state can be translated to delay aging of higher organisms and improve phenotypes related to Alzheimer’s disease. In addition, we would like to introduce bacterial enzymes analogous to Methioninase that can provide novel metabolic functions to eukaryotic cells, and to repurpose CRISPR/Cas9 multiplex systems for simultaneous targeting of different metabolic pathways to achieve additive/synergistic effects on lifespan.

What question I’d like to answer

How can we combine targeting of different pro-longevity pathways to achieve additive/synergistic extension of health- and lifespan and how they can be translated into human beings?
Faculty Bio

Andrey obtained his combined Bachelor, Master and Medical degree in Biochemistry and Molecular Biology at Russian State Medical University (RSMU), one of the premier medical schools in Russia. During his last year at RSMU, he was selected to work in the U.S. for one year in Dr. Henske’s laboratory at the Fox Chase Cancer Center, Philadelphia, PA. After completing his master’s thesis project, he was invited to continue his project at the Brigham and Women’s Hospital and Harvard Medical School in Boston, MA where Dr. Henske’s lab had moved. His Ph.D. thesis focused on the role of autophagy in the treatment of Tuberous Sclerosis Complex. For postdoctoral training, Andrey joined Dr. Norbert Perrimon’s lab, also at Harvard Medical School, to study how metabolism changes during aging in Drosophila, and how these changes could be targeted to extend lifespan and suppress age-dependent diseases. During his postdoctoral training, he was awarded the LAM Foundation Fellowship Award and the NIH Pathway to Independence Award (K99/R00). In 2020, Andrey was appointed to the rank of Assistant Professor at the Aging Institute at the University of Pittsburgh School of Medicine.

Read more: Department of Medicine Faculty Profile

Selected Publications

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; PMCID: PMC7744100.

Parkhitko AA, Binari R, Zhang N, Asara JM, Demontis F, Perrimon N. Tissue-specific down-regulation of S-adenosyl-homocysteine via suppression of dAhcyL1/dAhcyL2 extends health span and life span in Drosophila. Genes Dev. 2016 Jun 15;30(12):1409-22. doi: 10.1101/gad.282277.116. Epub 2016 Jun 16. PMID: 27313316; PMCID: PMC4926864.

Parkhitko AA, 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. PMID: 31460700; PMCID: PMC6826121.

Parkhitko AA, Filine E, Mohr SE, Moskalev A, Perrimon N. Targeting metabolic pathways for extension of lifespan and healthspan across multiple species. Ageing Res Rev. 2020 Dec;64:101188. doi: 10.1016/j.arr.2020.101188. Epub 2020 Oct 5. PMID: 33031925.

Parkhitko AA, Singh A, Hsieh S, Hu Y, Binari R, Lord CJ, Hannenhalli S, Ryan CJ, Perrimon N. Cross-species identification of PIP5K1-, 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. PMID: 33591981; PMCID: PMC7909629.

Current Lab Members

Farzdaq Al hammood, MB, Research Technician
Aidan Graham, Pitt Undergraduate Student
Maxwell A. Abom, Pitt Undergraduate Student
Palak S Mehta, Pitt Undergraduate Student

Research Support