A key underlying cause of aging is the loss of metabolic homeostasis, which is related to dysfunction in pathways that regulate the sensing, breakdown, and import of nutrients. Skeletal muscle has emerged as a major player in regulating physiology, and dysfunction in this tissue is associated with aging and the development of age-related disease. Conversely, increased skeletal muscle function and health is associated with favorable outcomes in metabolic disease and healthspan.
The Ramanathan lab is working to understand the metabolic rewiring associated with skeletal muscle atrophy, injury, and metabolic disease. These questions are being studied in conjunction with the development of two enabling technology platforms: (1) mass spectrometry–based discovery and targeted metabolomics/metabolomic flux-analysis, and (2) 3D printed human skeletal muscle organoids. Another focus of the lab is understanding the role of carbon metabolism in the brain, on aging, and in protein aggregation using cell culture and Drosophila models. Applying these platforms and collaborating closely with colleagues at the Buck Institute on metabolism and aging-related problems are major activities of the lab.
Why it matters
Nutrients and their metabolism have emerged as important driving forces in maintaining tissue homeostasis and are major targets in aging-related skeletal muscle dysfunction. They are also rapidly emerging as a target for neurological diseases such as Alzheimer’s. Developing technologies that can comprehensively measure metabolism in vivo and in vitro (metabolomics) and in 3D human organoid models will enable the understanding of metabolic dysfunction in disease and the testing of interventions in therapeutically relevant models.
Our research is aimed at getting at the root of sarcopenia – the age-related loss of muscle mass which leads to frailty. We hope our work leads to therapies that would preserve and improve muscle function across the lifespan.
Arvind Ramanathan, PhD
Dr. Ramanathan received his PhD from the Department of Chemistry at New York University. During his PhD studies, he received additional research training at the Biotechnology Center of University of Wisconsin, Madison. He received his postdoctoral training in chemical biology and mass spectrometry at Harvard University and the Broad Institute.
Dr. Ramanathan is the director of metabolomics at the Buck Institute and is an investigator or co-investigator on numerous NIH grants. He received the Hillblom startup grant to start his lab at the Buck Institute. He has extensive experience working with biotech companies and medical centers and foundations across the country, including the Maple Syrup Urine Disease Foundation.
Therese Payne Research Associate
Therese Payne graduated from Mount Saint Mary College (Los Angeles, CA) and has 19 years of experience in analytical chemistry. She has joined the Buck Institute Proteomics Core in 2017 and is a specialist in sample preparation, cell culture and general maintenance. Mrs. Payne often develops novel protocols focused on Proteomics Workflows, and routinely interacts directly with collaborators.
Andrew Rosko Research Associate
Andy graduated with a MS in Computational Biology and Bioinformatics from Duke University in 2018. He has experience with metabolic flux modeling and other methods of biological pathway simulation. In the Ramanathan lab, he is helping to develop workflows for analysis and visualization of metabolite labeling data from LC-MS.
Rishi Sharma, PhD Postdoctoral Research Fellow
Rishi graduated with PhD in Medicinal Chemistry and Drug Development from Northeastern University, Boston in 2011. Thereafter, he worked as an ADME/ DMPK scientist for Microconstants Inc., Axcella Health and DART Neurosciences before joining BUCK Institute in 2018. Rishi has an extensive experience in drug design, analog synthesis and preclinical evaluation towards the selection of a lead clinical candidate. At BUCK he is utilizing the HPLC-MS/MS based platforms for global measurement of metabolites and fluxes in Drosophila fly dosed with 13C-Glucose.
- Zee, T., Bose, N., Zee, J., Beck, J., Yang, S., Parihar, J., Yang, M., Damodar, S., Hall, D., O’Leary, M., Ramanathan, A., Gerona, R., Killilea, D. W., Chi, T., Tischfield, J., Sahota, A., Kahn, A., Stoller, M., Kapahi, P. (2017 Mar). α-lipoic acid treatment prevents cystine urolithiasis in a mouse model of cystinuria. Nat Medicine, 23(3), 288–290.
- Wiley, C. D., Velarde, M. C., Lecot, P., Liu, S., Sarnoski, E. A., Freund, A., Shirakawa, K., Lim, H. W., Davis, S. S., Ramanathan, A., Gerencser, A. A., Verdin, E., Campisi, J. (2016). Mitochondrial dysfunction induces senescence with a distinct secretory phenotype. Cell Metab, 23(2), 303–14.
- Mark, K. A., Dumas, K. J., Bhaumik, D., Schilling, B., Davis, S., Oron, T. R., Sorensen, D. J., Lucanic, M., Brem, R. B., Melov, S., Ramanathan, A., Gibson, B. W., Lithgow, G. J. (2016). Vitamin D promotes protein homeostasis and longevity via the stress response pathway genes skn-1, ire-1, and xbp-1. Cell Rep, 2016, 17(5), 1227–37.
- Katewa, S. D., Akagi, K., Bose, N., Rakshit, K., Camarella, T., Zheng, X., Hall, D., Davis, S., Nelson, C. S., Brem, R. B., Ramanathan, A., Sehgal, A., Giebultowicz, J. M., Kapahi, P. (2016). Peripheral circadian clocks mediate dietary restriction-dependent changes in lifespan and fat metabolism in Drosophila. Cell Metab, 23(1), 143–54.
- Gutierrez, M. A., Davis, S. S., Rosko, A., Nguyen, S. M., Mitchell, K. P., Mateen, S., Neves, J., Garcia, T. Y., Mooney, S., Perdew, G. H., Hubbard, T. D., Lamba, D. A., Ramanathan, A. (2016). A novel AhR ligand, 2AI, protects the retina from environmental stress. Sci Rep, 6, 29025.
- Davis, S., O’Leary, M., Gutierrez, M., Nguyen, S. M., Mateen, S., Hsu, Y., Mitchell, K. P., Lopez, A. J., Vockley, J., Kennedy, B. K., Ramanathan, A. (2016). Metformin inhibits branched chain amino acid (BCAA) derived ketoacidosis and promotes metabolic homeostasis in MSUD. Sci Rep, 6, 28775.