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Translational Geroproteomics Unit

Nathan Basisty, Ph.D., InvestigatorNathan Basisty
Tenure Track Investigator
Head, Translational Geroproteomics Unit
Translational Gerontology Branch

 

 

The Translational Geroproteomics Unit (TGU) studies the molecular underpinnings of aging at the proteomic and multi-omic levels to guide the development of clinically relevant biomarkers and therapeutic targets for the pathologies of aging. We leverage modern mass spectrometry based proteomic technologies and computational tools in preclinical aging models and human cohorts such as the Baltimore Longitudinal Study of Aging (BLSA) with the ultimate goals of discovering protein- and PTM-based biomarkers of aging, enabling the development of senotherapeutics, improving healthspan, and understanding mechanisms of aging at the cellular and molecular levels. The TGU focuses on three hallmarks of aging: cellular senescence, altered protein turnover, and accumulation of post-translational modifications.

Cellular senescence and the senescence associated secretory phenotype (SASP) are drivers of aging as well as promising therapeutic targets for treating aging and multiple pathologies of aging such as metabolic syndrome. The TGU harnesses modern proteomic approaches to identify cell-surface and secreted biomarkers of diverse populations of senescent cells. Ultimately, this information will inform the translation of senescence-targeted therapies into humans by enabling the classification of senescent cells that emerge during normal human aging versus age-related diseases (ie metabolic syndrome). In addition, the development of such biomarkers of cellular senescence will provide fundamental insights into the biology of senescent cells in humans in vivo and lead to new biomarkers panels to assess the role of senescent cell subtypes (‘senotypes’) in epidemiological studies of aging, age-related diseases, and obesity.

Altered protein homeostasis and the accumulation of post-translational modifications are hallmarks of the aging proteome that are often overlooked in biomarker studies. Layering additional information, such as PTM-status and turnover rates, into protein biomarkers and biomarker panels will likely increase the accuracy and precision of the next generation of proteomic biomarkers of aging, chronic diseases, multi-morbidity, and frailty. The TGU aims to exploit the latest advances in proteomics to measure proteoform specific and temporal protein changes to develop increasingly specific and accurate biomarkers of health, aging, and age-related diseases.

The TGU is hiring postdoctoral fellows. Apply here.

Portfolio/Research Areas

  • Aging biomarkers and therapeutic targets
  • Classifying, quantifying, and targeting senescent cells
  • Proteostasis and protein turnover in aging
  • Post-translational modifications
  • Mass spectrometry method development

Selected Publications

  1. Tanaka T, Basisty N, Fantoni G, Candia J, Moore AZ, Biancotto A, Schilling B, Bandinelli S, Ferrucci L. Plasma proteomic biomarker signature of age predicts health and life span. eLife. Nov 19, 2020.
  2. Moaddel R, Ubaida-Mohien C, Tanaka T, Lyashkov A, Basisty N, Schilling B, Semba RD, Franceschi C, Gorospe M, Ferrucci L. Proteomics in aging research: a roadmap to clinical, translational research. Aging Cell. 2021.
  3. Basisty N, Kale A, Jeon OH, et al. A Proteomic Atlas of Senescence-Associated Secretomes for Aging Biomarker Development. PLoS Biol. 2020;18(1):e3000599. Published 2020 Jan 16. doi:10.1371/journal.pbio.3000599
  4. Basisty N, Kale A, Patel S, Campisi J, Schilling B. The Power of Proteomics to Monitor Senescence- Associated Secretory Phenotypes and Beyond: Toward Clinical Applications. Expert Rev Proteomics. 2020;17(4):297-308. doi:10.1080/14789450.2020.1766976
  5. Basisty N, Meyer JG, Wei L, Schilling B. Simultaneous Quantification of the Acetylome and Succinylome by 'One-Pot' Affinity Enrichment. Proteomics. 2018;18(17):e1800123. doi:10.1002/pmic.201800123
  6. Basisty N, Meyer JG, Schilling B. Protein Turnover in Aging and Longevity. Proteomics. 2018;18(5-6):e1700108. doi:10.1002/pmic.201700108
  7. Basisty NB, Liu Y, Reynolds J, et al. Stable Isotope Labeling Reveals Novel Insights Into Ubiquitin-Mediated Protein Aggregation With Age, Calorie Restriction, and Rapamycin Treatment. J Gerontol A Biol Sci Med Sci. 2018;73(5):561-570. doi:10.1093/gerona/glx047
  8. Basisty N, Dai DF, Gagnidze A, Gitari L, Fredrickson J, Maina Y, Beyer RP, Emond MJ, Hsieh EJ, MacCoss MJ, Martin GM, Rabinovitch PS. Mitochondrial-targeted catalase is good for the old mouse proteome, but not for the young: 'reverse' antagonistic pleiotropy? Aging Cell. 2016 Aug;15(4):634-45. doi:10.1111/acel.12472.