Why do we age? Despite more than 30 years of research in the genetics of aging and a much longer history interrogating the process more generally, we still don’t know the answer to this basic question. There has been some success in manipulating the lifespan of simple laboratory organisms and, to a lesser extent, mammalian systems such as the laboratory mouse. However, true insight into the mechanisms which modulate longevity elude us at present. Otherwise we would be able to make our favorite model systems with lifespans of a few weeks live for not just a month or two but potentially decades, all while remaining youthful and healthy.
The Melov lab takes a multidisciplinary geroscience approach to better understand the core mechanisms that drive aging. This includes a heavy reliance on multiple model systems, including invertebrate models, mammalian models (the laboratory mouse), human cell lines and tissues, and state-of-the-art genomic technologies that rely on heavy computational methods to better understand how cells and tissues change with age and/or pharmacological intervention.
Why it matters
We must constantly question our own models and data to gain genuine insights into the mechanisms that drive the degenerative changes arising from intrinsic aging processes. A key philosophy of the lab is that it is not enough to enhance healthspan through simple dietary or lifestyle interventions. We argue that such approaches merely fine-tune an organism to survive in its current environment. While worthwhile for generally improving health, such paradigms will do little to uncover the key drivers that limit lifespan. In contrast, we hope to develop novel multidisciplinary approaches in geroscience to develop therapeutics that are effective in reducing or ameliorating the cellular damage arising from endogenous aging processes. Such an approach will pay massive dividends to improve the health and longevity of a rapidly aging world.
Efforts to extend healthspan by delaying the aging process are moving from ‘impossible’ to ‘inevitable.’ The Buck Institute is uniquely positioned to play a pivotal role in this new area of medicine.
Simon Melov, PhD
Dr. Melov was the third faculty hire at the Buck Institute when it opened its doors in 1999 and currently serves as co-director of the Institute’s Mouse Phenotyping and Single-Cell Biology cores. An Australian, Dr. Melov obtained his bachelor’s degree in human genetics from the University of New South Wales in Sydney, Australia, and then completed his PhD in biochemistry at Imperial College London in the United Kingdom. He carried out postdoctoral studies on the genetics of aging at the University of Colorado, Boulder, and on mitochondrial disease at Emory University in the Department of Molecular Medicine. He also holds adjunct appointments at the Andrus College of Gerontology, University of Southern California, and Dominican University of California in San Rafael.
Dr. Melov is facile in multiple aspects of aging biology, which is now termed geroscience. He has published more than 100 papers and has twice received the Glenn Award for Research in Biological Mechanisms of Aging. He was the first faculty member at the Buck Institute to receive a senior scholarship from the Ellison Medical Foundation. He was one of the founding editors of the highly respected journal Aging Cell and served as the inaugural and founding chair of the Gordon Research Conference on Oxidative Stress and Disease.
Dr. Melov has extensive experience in working with biotech and pharma, having received numerous competitive awards from this sector and accumulated broad experience serving as a consultant. He has also served on more than 30 study sections for the National Institutes of Health.
Jubilee Ajiboye Research Associate
Jubilee completed her B.Sc in Biology and Chemistry at Campbell University, North Carolina in 2016. She went on to work as a research intern at the World Health Organization field office, Nigeria where her research focused on epidemic disease surveillance and response. From 2018-2019, she worked in the Mouse Metabolic Phenotyping Core at The Jackson Laboratory, Bar Harbor ME. Her current focus involves managing day to day affairs of the Buck Mouse Phenotyping Core, expanding research capabilities, and equipping scientists with cutting-edge tools for phenotyping laboratory mice.
Serban Ciotlos Graduate Student
Serban completed his B.S. in Bioengineering at the University of California, Santa Cruz, in 2011. From 2012 to 2013, he worked in systems and software engineering at Roche Molecular Systems, and from 2013 to 2017, he worked in bioinformatics at Complete Genomics. His research focuses on investigating the role of senescence in cardiovascular disease, using single cell profiling techniques.
Sofiya Galkina Staff Scientist
Sofiya Galkina is an MD from Donetsk, Ukraine. Before joining the Buck she worked at Gladstone Institute and UCSF's Department of Experimental Medicine. She was focusing on preclinical HIV studies and antiviral drug research, using a humanized mouse model. Her current role is to assist scientists with all kinds of tools available in the Mouse Phenotyping Core.
Chandani Limbad, PhD Research Scientist
Chandani pursued an MS in Biomedical Engineering from NYU and a PhD in Comparative Biochemistry from UC Berkeley in conjunction with the Buck Institute. During her PhD she identified how senescence-driven damages in astrocytes lead to neuronal dysfunction. Her current research focus is to identify novel therapeutic targets for side effects of chemotherapy.
Nicolas Martin, PhD Postdoctoral Fellow
Nicolas Martin is a comparative biologist with a background on lipidomics and mitochondrial metabolism. Nicolas completed his Ph.D. at the University of Wollongong, NSW in 2019. His doctoral research focused on the influence of dietary lipids on lifespan of female honey bees. Over the last few years, Nicolas' research has been targeting to experimentally test mechanisms that could explain the difference in lifespan between short-lived workers and long-lived queens. Workers live for 4-6 weeks while queens can live for years! Throughout his post-doctoral research at the Buck, Nicolas will investigate epigenetic regulations in female honey bees. We will use state of the art technology to explore how female honey bees can regulate the same genome to produce two distinct phenotypes. The honey bee represents a unique system that can provide a conceptual framework for understanding how environmental changes could influence epigenomic modifications and how those modifications affect transcriptional modulation.
Julia McGirr MSc Research Associate
Julia received her B.Sc. from Brown University in Molecular Biology, Pharmacology & Physiology before pursuing a M.Sc. degree from the University of Copenhagen in Molecular Biomedicine. Her thesis work was in the role of dopaminergic signaling in ADHD and in validating a novel mouse model for the study of the disorder. Now, her project is in the Melov-Campisi labs working on the validation of novel therapeutics to mitigate deleterious side effects of chemotherapy.
Kevin Perez Bioinformatics Research Fellow
Kevin received his MS in Computer Science from New York Univesity, and his MS in Biomedical Sciences from Paris V Descartes University. He has held software engineer positions in tech companies (IBM) and startups. Before joining the Buck, Kevin was a computational biologist at Hopital Saint-Louis in Paris, and at the Broad Institute of MIT and Harvard, working on Inflammatory Bowel Disease. His current research focus is on aging and senescent cells.
Deepthi Raghu, PhD Postdoctoral Research Fellow
Deepthi Raghu received her PhD from The University of Memphis, Memphis, TN in 2019. During her PhD, she focused on the post-translational regulation of epithelial-mesenchymal transition in both development and cancer. She identified a molecular mechanism controlling the epithelial state maintenance that is conserved in mouse blastocyst trophectoderm, trophoblast stem (TS) cells, and human mammary epithelium. Her work led to the discovery of a novel O-glycosyltransferase, GALNT3, in promoting the cell surface localization of E-cadherin. In Melov’s lab, she is currently working on investigating the impact of cellular senescence in human endothelial cells.
Leyla Teos, PhD Senior Staff Scientist
Leyla Teos received her Ph.D. from Howard University in Washington D.C. in Physiology and Biophysics. Upon completion of her Ph.D., she joined the Molecular Cardiology lab of Dr. Jonathan Lederer at the University of Maryland in the Center for Biomedical Engineering & Technology; where she completed 3 years of postdoctoral training examining calcium signaling in compromised heart tissue. She was awarded a second postdoctoral fellowship and promoted to Molecular Biologist at the National Institute of Dental and Craniofacial Research (NIDCR) at the National Institute of Health. Her work at NIDCR led to the identification of the defect in calcium signaling at the IP3R3/E.R. calcium release level in patients with primary Sjogren’s Syndrome. She is currently working on the vulnerability of senescence on the cardiovascular system.
- Melov, S. (2016 Apr 29). Geroscience approaches to increase healthspan and slow aging. F1000Res, 5(F1000 Faculty Rev), 785. DOI: 10.12688/f1000research.7583.1. PubMed PMID: 27158475.
- Brand, M. D., Goncalves, R. L., Orr, A. L., Vargas, L., Gerencser, A. A., Borch Jensen, M., Wang, Y. T., Melov, S., Turk, C. N., Matzen, J. T., Dardov, V. J., Petrassi, H. M., Meeusen, S. L., Perevoshchikova, I. V., Jasper, H., Brookes, P. S., Ainscow, E. K. (2016 Oct 11). Suppressors of superoxide-H2O2 production at site IQ of mitochondrial complex I protect against stem cell hyperplasia and ischemia-reperfusion injury. Cell Metab, 24(4), 582–592. DOI: 10.1016/j.cmet.2016.08.012. PubMed PMID: 27667666.
- Fontana, L., Kennedy, B. K., Longo, V. D., Seals, D., Melov, S. (2014 Jul 24). Medical research: Treat ageing. Nature, 511(7510), 405–7. DOI: 10.1038/511405a. PubMed PMID: 25056047.
- Zykovich, A., Hubbard, A., Flynn, J. M., Tarnopolsky, M., Fraga, M. F., Kerksick, C., Ogborn, D., MacNeil, L., Mooney, S. D., Melov, S. (2014 Apr). Genome-wide DNA methylation changes with age in disease-free human skeletal muscle. Aging Cell, 13(2), 360–6. DOI: 10.1111/acel.12180. PubMed PMID: 24304487.
- Flynn, J. M., O’Leary, M. N., Zambataro, C. A., Academia, E. C., Presley, M. P., Garrett, B. J., Zykovich, A., Mooney, S. D., Strong, R., Rosen, C. J., Kapahi, P., Nelson, M. D., Kennedy, B. K., Melov, S. (2013 Oct). Late-life rapamycin treatment reverses age-related heart dysfunction. Aging Cell, 12(5), 851–62. DOI: 10.1111/acel.12109. PubMed PMID: 23734717.
- Kirkwood, T. B., Melov, S. (2011 Sep 27). On the programmed/non-programmed nature of ageing within the life history. Curr Biol, 21(18), R701–7. DOI: 10.1016/j.cub.2011.07.020. PubMed PMID: 21959160.
- Flynn, J. M., Choi, S. W., Day, N. U., Gerencser, A. A., Hubbard, A., Melov, S. (2011 Apr 1). Impaired spare respiratory capacity in cortical synaptosomes from Sod2 null mice. Free Radic Biol Med, 50(7), 866–73. DOI: 10.1016/j.freeradbiomed.2010.12.030. PubMed PMID: 21215798.