Why is aging the largest risk for developing so many apparently disparate diseases, ranging from neurodegeneration to cancer? One answer to this question lies in the evolutionarily selected, stress-responsive state termed cellular senescence. Senescent cells cease proliferation, which prevents early life cancer. They also secrete numerous molecules that promote tissue repair and regeneration. However, because senescent cells gradually accumulate with age, they eventually cause tissue degeneration, chronic inflammation, and many age-related diseases, including, ironically, late life cancer.
The Campisi lab studies the regulation and characteristics of cell states, with an emphasis on cellular senescence. We use simple and complex human and mouse cell cultures, intact human and mouse tissues, and mouse models to understand the molecular pathways that drive cellular senescence and other cell states. We also use genetic and pharmacological manipulations to understand how cell states cause both the degenerative diseases of aging as well as cancer and to design strategies to modulate or ameliorate their effects.
Why it matters
Aging is a complex, multisystem process that exacts an enormous emotional and economic toll on societies. Understanding and manipulating this process is the next big challenge in biomedical research. It is now clear that many age-related changes and pathologies are caused by cellular responses to endogenous and environmental stimuli. Understanding these responses is essential to developing safe interventions that can extend the years of healthy life in human populations.
Modern medicine has enabled us to extend lifespan - often at the expense of healthspan. My lab is focused on disrupting one of the major drivers of aging. Our goal is to enable more healthy years of life.
Judy Campisi, PhD
Dr. Campisi received a PhD in biochemistry from the State University of New York at Stony Brook and completed her postdoctoral training in cell cycle regulation at the Dana-Farber Cancer Institute and Harvard Medical School. As an assistant and associate professor at the Boston University Medical School, she studied the role of cellular senescence in suppressing cancer and soon became convinced that senescent cells also contributed to aging. She joined the Lawrence Berkeley National Laboratory as a senior scientist in 1991. In 2002, she started a second laboratory at the Buck Institute. At both institutions, Dr. Campisi established a broad program to understand the relationship between aging and age-related disease, with an emphasis on the interface between cancer and aging.
Dr. Campisi is a member of the National Academy of Sciences and a fellow of the American Association for the Advancement of Science.
She has received numerous awards for her research, including two MERIT awards from the National Institute on Aging and awards from the AlliedSignal Corporation, Gerontological Society of America, and American Federation for Aging Research. She is a recipient of the Longevity prize from the IPSEN Foundation, the Bennett Cohen award from the University of Michigan, and the Schober award from Halle University, and she is the first recipient of the international Olav Thon Foundation prize in Natural Sciences and Medicine. Dr. Campisi currently serves on advisory committees for the Alliance for Aging Research, Progeria Research Foundation, and NIA’s Intervention Testing Program. She is also an editorial board member for more than a dozen peer-reviewed journals. Dr. Campisi is a scientific founder of Unity Biotechnology, a California-based company focused on developing therapies for age-related pathologies. She has served on the scientific advisory boards of the Geron Corporation, Sierra BioScience, and Sangamo Biosciences.
Nicholas Aguirre, PhD Postdoctoral Research Fellow
Dr. Aguirre completed his bachelor’s degree at California State University, Long Beach. He received a master’s degree in exercise physiology from California States University, Fullerton, where he studied the effects of concurrent exercise order on human physiological and humoral responses. He continued his education with the completion of a PhD at University of California, Davis, working with Dr. Keith Baar to elucidate posttranslational mechanisms regulating skeletal muscle plasticity in response to mechanical loading, nutrition, and aging in mice with a skeletal muscle-specific knockout of the leucine transporter LAT1. His current work as a postdoctoral fellow in the Campisi lab is focused on the investigation of novel methods for improving mitochondrial function to combat diseases resulting from or presenting with mitochondrial dysfunction.
Fatouma Alimirah, PhD Postdoctoral Research Fellow
Dr. Alimirah received a PhD in cell and molecular biology from the Illinois Institute of Technology in Chicago, Illinois. She determined the functional role of two distinct vitamin D receptor isoforms in breast cancer during her graduate studies. In the Campisi lab, she is investigating how cellular senescence contributes to breast and skin carcinogenesis.
Serban Ciotlos PhD Candidate, USC-Buck Biology of Aging Program
Serban completed his bachelor’s degree in bioengineering at 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 models of aging and disease at the single cell/nucleus level, using both wet-lab and single-cell sequencing/bioinformatics approaches.
Albert Davalos, PhD Staff Scientist
Dr. Davalos investigates the role of cellular senescence in distinct aging pathologies. He was involved in discovering that a nuclear protein called high mobility group box 1 (HMGB1) is the earliest marker of senescence. When secreted by senescent cells, HMGB1 acts as a damage-associated molecular pattern (DAMP) molecule. In contrast to the senescence-associated secretory phenotype (SASP), DAMPs exhibit a distinct biological profile. He is investigating their role as markers of senescence and their contribution to the cellular senescence response. In parallel, he collaborates with various research groups to examine how cellular senescence drives various cancers and may act in aging pathologies in patients administered long-term treatment of anti-retroviral therapy. Dr. Davalos received his BS from California State University, East Bay, and obtained his PhD at the University of Texas.
Karen Davis , MD Visiting scientist
Dr. Davis had a career as an anesthesiologist and general medicine practitioner in the community. At present, she is interested in mechanisms of inflammation and aging. She has a particular interest in the degenerative disease sporadic inclusion body myositis as well as sarcopenia associated with aging.
Okhee Jeon, PhD Glenn Center Postdoctoral Research Fellow
Dr. Jeon received her undergraduate degree in biomedical engineering at the Yonsei University of South Korea in 2009 and completed her PhD in biomedical engineering at Johns Hopkins University in 2017. Her current work at the Buck focuses on secondary senescence and its role in the aging process.
Abhijit Kale, PhD Postdoctoral Research Fellow
Originally from Pune, India, Dr. Kale did his undergraduate studies in microbiology at the University of Pune. He started his research career at Tata Institute of Fundamental Research in Mumbai, India, where he studied endocytosis in metazoans under the guidance of Dr. K. S. Krishnan. He received his master’s and PhD degrees from the Albert Einstein College of Medicine in New York, where he studied the role of cell competition during development of an organism in the lab of Dr. Nick Baker. He is currently a SENS postdoctoral fellow in the Campisi lab, where he is studying the interaction of senescent cells with immune cells. In his free time, he likes to hike and travel.
Dong Eun (Clare) Kim, PhD Postdoctoral Research Fellow
Dr. Kim is originally from South Korea. After finishing her undergraduate and graduate studies at Seoul National University, South Korea, she obtained her master’s degree at the University of Pittsburgh and completed her PhD at the University of Lausanne, Switzerland. Her current research interest is understanding the role of cellular senescence in DNA damage responses and aging using prematurely aging mice driven by a defect in DNA damage repair.
Chisaka Kuehnemann PhD Candidate, USC-Buck Biology of Aging Program
Chisaka is a PhD candidate in the Buck-USC graduate program, where she is studying cellular senescence, a basic aging process. Prior to joining the Buck, she did oncology drug discovery at Human Genome Sciences. She received a bachelor’s degree from the University of Maryland Baltimore County and a master’s degree from Johns Hopkins University. Her particular research focus is in understanding how certain drugs, such as those used in anti-retroviral therapies, might promote aging by inducing cellular senescence, especially since these drugs have been shown to accelerate aging in human patients. Outside of the lab, she reads science fiction, designs costumes, and is an avid cook.
Jose Alberto Lopez-Dominguez, PhD Postdoctoral Research Scholar
Originally from Spain, Dr. Lopez-Dominguez received his PhD from the University of Córdoba and continued his research as a postdoc at University of California, Davis, working on how calorie restriction and low-carbohydrate diets can influence longevity. He then moved to the Campisi lab to investigate the role of cellular senescence on obesity, diabetes, and metabolic syndrome.
Christopher Wiley, PhD Postdoctoral Research Fellow
Dr. Wiley’s research focuses on the study of aging in the context of cellular metabolism, particularly as it pertains to the process known as cellular senescence. Cellular senescence is a stress response by which cells adopt a state of permanent mitotic arrest. More than simple arrest, the senescent phenotype is complex and includes a senescence-associated secretory phenotype (SASP) that leads to secretion of multiple biologically active molecules, including proinflammatory cytokines, matrix metalloproteinases, and growth factors, that can have potent effects on the tissue microenvironment. Recently, a series of advancements have placed both senescence and the SASP at center stage with regard to variegated maladies associated with aging. Despite these advancements, senescence is still studied largely in the context of replicative exhaustion, genotoxic stress, or oncogene activation, all of which result in highly similar senescent phenotypes.
Christopher’s work has focused on two areas. First, he identified compromised mitochondrial function as a potentially important inducer of senescence. Unlike other inducers of senescence, mitochondrial dysfunction drives senescence with a distinct SASP. This new paradigm for senescence highlights the plasticity of the senescent phenotype and reveals an unexplored vector by which mitochondrial dysfunction can drive aging phenotypes such as lipodystrophy, thinning skin, and cancer. Second, he found that senescent cells secrete several eicosanoids, which are signaling lipids that promote inflammation, fever, hair loss, parturition, asthma, fibrosis, and other conditions. This senescence-associated eicosanoid biosynthesis acts to promote the SASP, reinforce mitotic arrest, and promote pulmonary fibrosis. Together, his findings reveal new insights regarding the nature of cellular senescence and offer alternative avenues for intervention for associated disorders such as aging.
- Dimri, G., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens ,M., Rubelj, I., Pereira-Smith, O., Peacocke, M., Campisi, J. (1195 Sep 26). A novel biomarker identifies senescent human cells in culture and aging skin in vivo. Proc Natl Acad Sci USA, 92(20), 9363–67.
- Krtolica, A., Parrinello, S., Lockett, S., Desprez, P., Campisi, J. (2001 Oct 9). Senescent fibroblasts promote epithelial cell growth and tumorigenesis: A link between cancer and aging. Proc Natl Acad Sci USA, 98(21), 12072–77.
- Coppe, J. P., Patil, C. K., Rodier, F., Sun, Y., Munoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P. Y., Campisi, J. (2008). Senescence-associated secretory phenotypes reveal cell non-autonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol, 6(12), 2853–68.
- Rodier, F., Coppe, J. P., Patil, C. K., Hoeijmakers, W. A. M., Munoz, D. P., Raza, S. R., Freund, A., Campeau, E., Davalos, A. R., Campisi, J. (2009 Aug). Persistent DNA damage signaling triggers senescence-associated inflammatory cytokine secretion. Nature Cell Biol, 11(8), 973–79.
- Demaria, M., Ohtani, N., Youssef, S. A., Rodier, F., Toussaint, W., Mitchell, J. R., Laberge, R. M., Vijg, J., van Steeg, H., Dolle, M. E., Hoeijmakers, J. H., de Bruin, A., Hara, E., Campisi, J. (2014 Dec 22). An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev Cell, 31(6), 722–33.
- Laberge, R. M., Sun, Y., Orjalo, A. V., Patil, P. K., Freund, A., Zhou L., Curran, S. C., Davalos, A. R., Wilson-Edell, K. A., Liu, S., Limbad, C., Demaria, M., Li P., Hubbard, G. B., Ikeno, Y., Javors, M., Desprez, P. Y., Benz, C. C., Kapahi, P., Nelson, P. S., Campisi, J. (2015 Aug). mTOR regulates the tumor-promoting senescence secretory phenotype by promoting IL-1 translation. Nature Cell Biol, 17(8), 1049–61.
- Velarde, M. C., Demaria, M., Melov, S., Campisi, J. (2015 Aug 18). Pleiotropic age-dependent effects of mitochondrial dysfunction on epidermal stem cells. Proc Natl Acad Sci USA, 112(33), 10407–12.
- Wiley, C. D., Velarde, M. C., Lecot, P., Liu, S., Sarnoski, E. A., Shirakawa, K., Lim, H., Davis, S., Ramanathan, A., Gerencser, A. A., Verdin, E., Campisi, J. (2015 Dec 10). Mitochondrial dysfunction induces senescence with a distinct secretory phenotype. Cell Metab, 23(2), 303–14.
- Demaria, M., O’Leary,, M. N., Chang J., Shao, L., Liu, S., Alimirah, F., Koenig, K., Le, C., Mitin, N., Deal, A. M., Alston, S., Academia, E. C., Kilmarx, S., Valdovinos, A., Wang, B., de Bruin, A., Kennedy, B. K., Melov, S., Zhou, D., Sharpless, N. E., Muss, H., Campisi, J. (2017 Feb). Cellular senescence promotes adverse effects of chemotherapy and cancer relapse. Cancer Discov, 7(2), 165–176.