The Verdin lab studies the relationship between aging and the immune system. Aging is associated with defects in the adaptive immune system and with a state of chronic activation of the innate immune system (chronic inflammation).
We study how immune aging is regulated by nutrition. We have demonstrated how changes in the relative abundance of key cellular metabolites such as NAD+, acetylcoenzyme A, and the ketone body beta-hydroxybutyrate fluctuate under different nutritional conditions (obesity, calorie restriction, fasting, time-restricted feeding, ketogenic diet) and how this influences immune responses. We are working on key enzymes regulated by these metabolites. These include sirtuins (NAD+), histone acetyltransferases (acetylcoenzyme A), and histone deacetylases (HDACs).
We utilize worm, mice, and human model systems (including stem cells and iPSCs) to define how nutrients influence immune responses during aging. We are also studying how HIV infection induces a state of chronic inflammation and immune activation and how this induces accelerated aging in patients infected with HIV.
Why it matters
We believe chronic inflammation represents a key unifying factor underpinning the development of the chronic diseases of aging, including neurodegeneration (Parkinson’s and Alzheimer’s), cancer, type 2 diabetes, and atherosclerosis (heart attack and stroke). We are intrigued by possible connections between senescence, leaky gut, and innate immune activation. A better understanding of the mechanisms leading to the chronic inflammation associated with aging should provide novel therapeutic targets and potential interventions against human aging.
Science is showing that while chronological aging is inevitable, biological aging is malleable. There's a part of it that you can fight, and we are getting closer and closer to winning that fight.
Eric Verdin, MD
Dr. Verdin is the president and chief executive officer of the Buck Institute for Research on Aging. A native of Belgium, Dr. Verdin received his Doctorate of Medicine (MD) from the University of Liege and completed additional clinical and research training at Harvard Medical School. He has held faculty positions at the University of Brussels, the National Institutes of Health (NIH), and the Picower Institute for Medical Research. Dr. Verdin is also a professor of medicine at University of California, San Francisco.
Dr. Verdin studies how metabolism, diet, and small molecules regulate the activity of HDACs and sirtuins, and thereby the aging process and its associated diseases, including Alzheimer’s. He has published more than 210 scientific papers and holds more than 15 patents. He is a highly cited scientist (top 1 percent) and has been recognized for his research with a Glenn Award for Research in Biological Mechanisms of Aging and a senior scholarship from the Ellison Medical Foundation. He is an elected member of several scientific organizations, including the American Association for the Advancement of Science, the American Society for Clinical Investigation, and the Association of American Physicians. He also serves on the advisory council of National Institute on Drug Abuse at the National Institutes of Health.
Dr. Verdin has extensive experience working with biotech companies. He is a founder of Acylin (purchased by Abbvie). He served on the scientific advisory boards of Elixir, Sirtris (purchased by GSK), Calico (Google), and Nokia, and he also served as advisor to Sofinnova Ventures. Dr. Verdin has also worked for several years as a consultant to Novartis, GSK, J&J, Altana, Roche, Pfizer, and other biotech companies.
Nicolas Andrews, PhD Senior Staff Scientist
Nicolas earned his PhD in immunology from Emory University. There, he used a model of chronic viral infection to investigate the role of initial viral dose and early inflammatory signals in shaping the quality and magnitude of virus-specific T cell responses. His subsequent research encompassed topics as diverse as cancer biology, autoimmunity, recombinant antibody technology, and the role of chromatin structure in the DNA damage response. After a brief period in academia, Nicolas joined the Verdin lab in the summer of 2019 to study mechanisms that establish and maintain HIV latency. Additionally, he will investigate mechanisms that contribute to the accelerated aging phenotype of HIV-infected patients. When not in the lab, Nicolas enjoys trail running and exploring the backroads of California from the seat of a motorcycle.
Olga Bielska, PhD Postdoctoral Research Fellow
Olga obtained her BSc and MSc degrees in Biochemistry from the Taras Shevchenko National University of Kyiv in Ukraine. Then she moved to Germany to study Regenerative Biomedicine at the DFG-Center for Regenerative Therapies Dresden (CRTD). She conducted her Master thesis work in the US at the University of Florida and worked there for a year after her graduation from TU Dresden. In Florida, she mastered laser capture microdissection technique (LCMT) and established a staining protocol suitable for RNA isolation from human pancreatic islets of patients with type 1 diabetes for microarray analysis. She moved back to Europe to pursue her PhD degree in the Iargest research unit of France - Institute of Genetics and Molecular and Cellular Biology (IGBMC) affiliated with the University of Strasbourg. There she studied the signaling pathways that regulate mitochondrial dynamics during mitotic progression. Her passion to mitochondrial biology brought her to the lab of Eric Verdin. In the Buck, she studies how mitochondrial metabolism and function affect aging process in humans and mice. She likes gardening, photography, NBA games and interior design.
Rachid Boutoual, PhD Postdoctoral Research Scholar
Dr. Boutoual grew up in Agadir, Morocco. He joined the Verdin lab in October, 2018, following his PhD in molecular and cellular biology from the University of Abdelmalek Essaadi, faculty of Sciences, Tetouan, Morocco. Rachid completed the majority of his studies for his Ph.D. work in the laboratory of Dr. Maria Eugenia Armengod at Principe Felipe Research Center, Valencia, Spain. His doctoral dissertation was focused on the understanding the molecular mechanisms of mitochondrial diseases associated with defects in the post-transcriptional modification of mitochondrial tRNAs catalyzed by the proteins TRMU, MTO1 and GTPBP3. Rachid is currently interested in the role of mitochondrial sirtuins, protein acylation and epigenetic regulation in aging. If time permits, he enjoys playing sports, especially football and swimming, long walks on the beach and of course as he is new to San Francisco, he enjoys exploring this city.
Anthony Covarrubias, PhD Postdoctoral Research Fellow
Dr. Covarrubias is currently exploring the links between inflammation and aging. He joined the Verdin lab in spring 2016 after earning his PhD in the biological sciences program at the Harvard School of Public Health. He has a particular interest in how the innate immune system utilizes nutrients. He came to the Verdin lab because it was among the first to show that endogenous changes in metabolites can affect gene function, and his project in the lab is focused on understanding how metabolites impact the innate immune system during aging. Anthony grew up in Los Angeles and got his undergraduate degree in biochemistry from UCLA. After grad school at Harvard, he is glad to be back on the West Coast. He is new to San Francisco and enjoys exploring the city, visiting breweries, and cheering for the Dodgers when they are in town!
Andrew Cruz PhD Candidate, USC-Buck Biology of Aging Program
Andrew grew up in Long Beach, California, and earned his bachelor’s degree in molecular cell biology from California State University, Long Beach. In his undergraduate lab, he probed structural aspects of Gα-interacting vesicle-associated protein, a signaling protein which plays a role in regulating cell migration and promoting cell survival. Anthony joined the Verdin lab in May 2018. He is interested in the factors that regulate nucleolus size and longevity. Outside of the lab, he enjoys reading, eating at new restaurants, and learning new songs on the ukulele.
Alessia Grozio, PhD Scientist
Alessia earned her PhD in biochemistry at the University of Genoa in Italy where she studied the role of Sirtuin 6 in pancreatic ductal cancer and the extracellular generations of NAD+ precursors by ecto-enzymes in different cancer cell lines. In 2013, she moved to Washington University School of Medicine in St.Louis, where she worked on the characterization of a novel nicotinamide mononucleotide (NMN) transporter. In November 2019, Alessia joined Dr. Verdin lab to focus on the cellular and molecular mechanisms of aging. Outside the lab, Alessia enjoys traveling and shopping at flea markets.
Vicki Hirth Lab Technician
Herb Kasler, PhD Staff Scientist, Flow Cytometry Core Director
Dr. Kasler did his undergraduate work in biology at Duke University and earned his PhD in immunology from University of California, Berkeley, working on the regulation of cell death in T-cell development in the laboratory of Dr. Astar Winoto. Since joining the Verdin lab, his main area of focus has been elucidating the immunobiology of histone deacetylase 7 (HDAC7), an epigenetic regulator with an essential role in the maintenance of immune self-tolerance. With other members of the immunology group, he is working to define the molecular mechanisms whereby the TCR-dependent nuclear export of HDAC7 mediates both negative thymic selection and the differentiation of agonist-selected innate-like T-cell populations. By understanding the important role of HDAC7 in T-cell development, he hopes to gain new insights into the regulation of immune self-tolerance and also to identify novel molecular pathways that can be targeted in autoimmune disease. When he is not pushing back the frontier of human knowledge one miniprep at a time, he likes to cook fabulous food for his friends and family, hike through the many splendid landscapes surrounding the Bay Area, and play at being a suburban farmer.
Ik-Jung Kim, PhD Postdoctoral Research Scholar
Dr. Kim is originally from South Korea. After earning an undergraduate and a master’s degree at Sogang university, he moved to the United States for a PhD training in the field of cellular microbiology. At the University of Illinois at Urbana-Champaign, he worked in Dr. Steven Blanke’s lab to study human infection with Helicobacter pylori, which he found manipulates host metabolism, resulting in a global metabolic shift from a biosynthetic to a catabolic state. As growing older, his deep interest in human metabolism stretched to aging biology and finally drew him to the Buck Institute. Since joining Verdin lab in February, 2019, he strive to understand how the levels of NAD+, a central metabolite involved in energy production and healthspan, are systemically regulated, using in vitro and in vivo models. Outside of the lab, he can be found exploring the beautiful nature in Northern California, or, pampering his hedgehog pets.
Ryan Kwok Research Associate
Oishika Panda, PhD Postdoctoral Research Fellow
Dr. Panda joined the Buck in February 2018, after her PhD in chemistry and chemical biology from Cornell University, Ithaca, New York. Having grown up in hot and humid Kolkata, India, and done her graduate studies in snowy-for-8-months-of-the-year Upstate New York, she has mixed feelings about the Bay Area weather! Dr. Panda is interested in applying her analytical chemistry skills to study the regulation of posttranslational acylations of proteins by endogenous metabolites, and their signaling functions. In her spare time, she enjoys trying out new cheesecake recipes, playing with cats and dogs, and discussing Harry Potter and Middle Earth trivia with whoever wants to listen!
Rosalba Perrone, PhD Postdoctoral Research Fellow
Dr. Perrone joined the Verdin lab in January 2017. She earned her PhD in biomedicine at the University of Padua in Italy, studying innovative therapeutic targets at the HIV proviral level. In the Verdin lab, her original interest in HIV biology meets her new and exciting interest in aging. She’s working to investigate and elucidate mechanisms that link HIV infection and aging, since increasing evidence supports accelerated aging in HIV-positive patients. Science is not her only big passion. Rosalba loves to express herself through creative arts, primarily with belly dancing. She also loves everything that comes from her home country of Italy — especially the good food and music. Her first goal in life is to always be passionate, curious, and happy. Her motto is, “Resolve to be the sun!”
Rebeccah Riley Senior Research Association (Acting Lab Manager)
Elena Silva Staff Scientist
Daria Timonina PhD Candidate, USC-Buck Biology of Aging Program
Daria received her undergraduate degree in biochemistry from the University of Arizona. Her thesis focused on G-Quadruplexes, a naturally occurring secondary structure in DNA. After graduating, she worked as a laboratory technician at Massachusetts General Hospital, using patient samples to study potential lung cancer treatments. In her free time she enjoys snowboarding, climbing, and painting.
Marius Walter, PhD Postdoctoral Research Fellow
Dr. Walter grew up in the south of France and received a master’s degree from the Ecole Polytechnique in Paris. His PhD work at the Institut Curie in Paris focused on transposable element regulation during embryonic development. Marius joined the Verdin lab in September 2016 and has been working on using CRISPR genetic screens to uncover new mechanisms that regulate the establishment of HIV latency. He is also developing new therapeutic strategies against herpes viruses and has been particularly interested in cytomegalovirus. When not in the lab, Marius can be found climbing, skiing, biking, or backpacking in various parts of California. His diet consists almost exclusively of avocado, Pringles, and clementines.
Ran Zhang, PhD Postdoctoral Research Fellow
Dr. Zhang grew up in Tongling, China, and joined the Verdin lab in September 2017. He holds a bachelor’s degree in clinical medicine and a PhD in biochemistry and molecular biology from the Chinese Academy of Medical Sciences and Peking Union Medical College. He is currently interested in epigenetic regulation of metabolism and aging. Ran enjoys hiking and cooking.
- Verdin, E. (2015 Dec 4). NAD⁺ in aging, metabolism, and neurodegeneration. Science, 350(6265), 1208–13. DOI: 10.1126/science.aac4854. Review. PubMed PMID: 26785480.
- Verdin, E., Ott, M. (2015 Apr). 50 years of protein acetylation: From gene regulation to epigenetics, metabolism and beyond. Nat Rev Mol Cell Biol, 16(4), 258–64. DOI: 10.1038/nrm3931. PubMed PMID: 25549891.
- Gut, P., Verdin, E. (2013 Oct 24). The nexus of chromatin regulation and intermediary metabolism. Nature, 502(7472), 489–98. DOI: 10.1038/nature12752. Review. PubMed PMID: 24153302.
- Shimazu, T., Hirschey, M. D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C. A., Lim, H., Saunders, L. R., Stevens, R. D., Newgard, C. B., Farese, R. V. Jr, de Cabo, R., Ulrich, S., Akassoglou, K., Verdin, E. (2013 Jan 11). Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science, 339(6116), 211–4. DOI: 10.1126/science.1227166. PubMed PMID: 23223453. PubMed Central PMCID: PMC3735349.
- Hirschey, M. D., Shimazu, T., Jing, E., Grueter, C. A., Collins, A. M., Aouizerat, B., Stančáková, A., Goetzman, E., Lam, M. M., Schwer, B., Stevens, R. D., Muehlbauer, M. J., Kakar, S., Bass, N. M., Kuusisto, J., Laakso, M., Alt, F. W., Newgard, C. B., Farese, R. V. Jr, Kahn, C. R., Verdin, E. (2011 Oct 21). SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome. Mol Cell, 44(2), 177–90. DOI: 10.1016/j.molcel.2011.07.019. PubMed PMID: 21856199. PubMed Central PMCID: PMC3563434.
- Hirschey, M. D., Shimazu, T., Goetzman, E., Jing, E., Schwer, B., Lombard, D. B., Grueter, C. A., Harris, C., Biddinger, S., Ilkayeva, O. R., Stevens, R. D., Li ,Y., Saha, A. K., Ruderman, N. B., Bain, J. R., Newgard, C. B., Farese, R. V. Jr, Alt, F. W., Kahn, C. R., Verdin, E. (2010 Mar 4). SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature, 464(7285), 121–5. DOI: 10.1038/nature08778. PubMed PMID: 20203611. PubMed Central PMCID: PMC2841477.