Dietary restriction (DR), the reduction in nutrient intake without malnutrition, has been well documented as a means to extend lifespan and slow age-related diseases in many systems. We and others have previously demonstrated that lifespan extension by inhibition of the TOR pathway overlaps with the effects of DR in D. melanogaster, S. cerevisiae, and C. elegans. However, other DR response mechanisms exist that remain undiscovered. The overall goal of the Kapahi lab is to understand how an organism responds to nutrient status to influence health and disease.
We utilize worms, flies, and mice as model systems to understand how nutrients influence age-related changes in specific tissues and disease processes. We take creative approaches to develop models for various human diseases that are influenced by nutrient status using invertebrates. We study how various physiological and molecular processes, including fat metabolism, circadian clocks, advanced glycation end products, calcification, and intestinal permeability, are influenced by nutrients to impact organismal health and survival. We collaborate with multiple groups at University of California, San Francisco, and University of California, Berkeley, to undertake interdisciplinary approaches to translate our findings from multiple models to humans.
Why it matters
Our work has relevance to certain age-related human diseases, including diabetes, Alzheimer’s disease, kidney stone formation, intestinal diseases, and obesity. There is an ongoing debate about the limitation of lifespan as a measure of aging and the need to assess healthspan to find the most promising interventions for humans. Through functional measures of different tissue functions and disease models, we are also examining the relationship between healthspan and lifespan.
Our work on aging in simple animals has led to real possibilities of treating human diseases, something I never thought possible when I began my career.
Pankaj Kapahi, PhD
Dr. Kapahi received his PhD from the University of Manchester, where he worked with Tom Kirkwood. He did his postdoctoral work with Seymour Benzer at Caltech and Michael Karin at University of California, San Diego. He joined the Buck Institute as an assistant professor in 2004.
Dr. Kapahi has published more than 80 scientific papers and holds three current patents. He has been recognized for his scientific excellence with many awards, including the Eureka Award from the National Institute on Aging, a New Scholar Award from the Ellison Medical Foundation, a Glenn Award for Research in Biological Mechanisms of Aging, the Nathan Shock Young Investigator Award, and the Breakthrough in Gerontology and Julie Martin Mid-career awards from AFAR. He currently serves on the editorial board of Aging Cell, Aging, and PLOS Genetics. Dr. Kapahi also initiated the first master’s degree course in gerontology at the Buck Institute.
S. B.Sudipta Bar Postdoctoral Research Scholar
J. B.Jennifer Beck Lab Manager
Jennifer is an honors graduate of University of California, Davis, and has held positions at various institutions. At University of California, Berkeley, she studied NK cells, T-cells, lymphoma, and type 1 diabetes as well as how to control the innate immune system to better fight autoimmune diseases. At Johns Hopkins University, she studied breast cancer, polycystic kidney disease, and understanding cellular migration via 3D microenvironment and advanced microscopy techniques. At Eastern Connecticut Health Network, she analyzed clinical research regarding opioid prescriptions, physician professionalism, and antibiotic resistance. At the Buck, her studies have focused on genetic variance, circadian rhythm, kidney stones, and diabetes. She is currently researching Alzheimer's and neurodegeneration.
N. B.Neelanjan Bose, PhD Postdoctoral Research Fellow
Sanjib Kumar Guha, PhD Postdoctoral Research Fellow
Dr. Guha earned a master's degree in biological sciences from California State University, East Bay, and a PhD in neuroscience from Pompeu Fabra University (UPF) in Barcelona, Spain. He joined the Kapahi lab in 2016, where he works primarily on glyoxalase genes and their implication in Parkinson's disease and on finding novel regulators of these glyoxalases using C. elegans as the main model organism.
Tyler Hilsabeck PhD Candidate, USC-Buck Biology of Aging Program
Tyler holds a bachelor's degree in physics from Texas Tech University and a master's degree in biology from the University of Texas at San Antonio. His PhD studies in both the Kapahi and Brem labs focus on using computational and biological tools to understand the relationships between metabolites, genes, and aging-related phenotypes in Drosophila melanogaster.
Brian Hodge, PhD Postdoctoral Research Fellow
Dr. Hodge joined the Kapahi lab as a postdoctoral research fellow in the summer of 2016. He received his PhD in physiology from the University of Kentucky and completed a short postdoc at the University of Florida prior to starting at the Buck. His research is focused on understanding how environmental factors such as nutrients and light influence circadian gene expression and the processes of aging. He utilizes Drosophila genetics and bioinformatic (RNA-Seq, ChIP-Seq) and molecular genetic approaches to identify transcriptional regulators of circadian clocks and longevity. Brian also serves as vice president of the Postdoctoral Association at the Buck.
Geoff Meyerhof Dominican University Master's Student
Geoff joined the Kapahi lab as a Dominican University master's student in the fall of 2017. He completed his undergraduate studies at the University of Colorado Boulder, where he majored in molecular, cellular, and developmental biology. His current research uses Drosophila melanogaster to study the relationship among diet, circadian rhythms, and neurodegenerative disease.
Harshani Peiris, PhD Postdoctoral Research Fellow
Harshani Peiris received her Bachelor’s degree from Ramapo College of NJ in biology and bioinformatics, the post baccalaureate degree from University of Pennsylvania and PhD in quantitative systems biology from University of California, Merced. She joined Buck Institute as a postdoctoral scientist in 2015 and is a Hillblom post-doctoral fellow grantee since 2017. She is a molecular biologist trained in in-vitro cell culture model systems and in- vivo vertebrate (mouse, rat) and invertebrate (planarian/ Schmidtea mediterranea, C. elegans) systems. Her goal is to understand how different systems maintain systemic homeostasis and how disruption of the systemic balance leads towards aging and pathologies. Further, Harshani is investigating how signaling pathways govern metabolic and proliferative homeostasis, and how we can tune these pathways to achieve homeostasis and longevity.
Amit Sharma, PhD Postdoctoral Research Fellow
Dr. Sharma holds a bachelor’s degree in microbiology and a master’s degree in biomedical sciences from Delhi University, India. He earned his PhD in biotechnology from the University of Pune, India, where he identified posttranscriptional regulation of cytokine IL-10 and its effect on allergic airway inflammation. His postdoctoral work focuses on cellular senescence and investigating novel molecular regulatory pathways involved in mitigating genotoxic stress using Drosophila melanogaster and human cell culture model.
Kenneth Wilson PhD Candidate, USC-Buck Biology of Aging Program
Kenneth received his bachelor’s degree in molecular and cell biology from University of California Berkeley and his master’s degree in biological sciences from Dominican University of California. His current research focuses on understanding how natural genetic variation can influence response to diet to affect longevity and health.
- Zee, T., Bose, N., Stoller, M., Kapahi, P. Alpha-lipoic acid ameliorates stone formation in a mouse model of cystinuria. (Accepted at Nature Medicine).
- Luis, N. M., Wang, L., Ortega, M., Deng, H., Katewa, S. D., Li, P. W., Karpac, J., Jasper, H., Kapahi, P. Intestinal IRE1 is required for increased triglyceride metabolism and longer lifespan under dietary restriction. Cell Rep, 25, 17(5), 1207–1216.
- Chaudhuri, J., Bose, N., Gong, J., Hall, D., Rifkind, A., Bhaumik, D., Peiris, T. H., Chamoli, M., Le, C. H., Liu, J., Lithgow, G. J., Ramanathan, A., Xu, X. Z., Kapahi, P. (2016 Nov 21). A Caenorhabditis elegans model elucidates a conserved role for TRPA1-Nrf signaling in reactive α-Dicarbonyl detoxification. Curr Biol, 26(22), 3014–25.
- 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 Jan 12). Peripheral clocks modulate lifespan and fat metabolism upon dietary restriction. Cell Metab, 23(1), 143-54. doi: 10.1016/j.cmet.2015.10.014. Epub 2015 Nov 25.
- Chen, D., Li, P. W., Goldstein, B. A., Cai, W., Thomas, E. L., Chen, F., Hubbard, A. E., Melov, S., Kapahi, P. (2013). Germline signaling mediates the synergistically prolonged longevity produced by double mutations in daf-2 and rsks-1 in C. elegans. Cell Rep, 5, 1600–10.
- Katewa, D., Demontis, F., Kolipinski, M., Hubbard, A., Gill, M., Perrimon, N., Melov, S., Kapahi, P. (2012). Intra-myocellular triglyceride turnover plays a critical role in mediating responses to dietary restriction in Drosophila melanogaster. Cell Metab, 16, 97–103.
- Zid, B. M., Rogers, A. N., Katewa, S. D., Vargas M. A., Kolipinski, M. C., Lu, T. A., Kapahi, P. (2009). 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila. Cell, 139, 149–60.
- Pan, K. Z., Palter, J. E., Rogers, A. N., Olsen, A., Chen, D., Lithgow, G. J., Kapahi, P. Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans. Aging Cell, 6(1), 111–9. PMID: 17266680.
- Kapahi, P., Zid, B. M., Harper, T., Koslover, D., Sapin, V., Benzer, S. Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol, 14, 885–90.
- Rossi, A., Kapahi, P., Natoli, G., Takahashi, T., Chen, Y., Karin, M. (2000). Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IkappaB kinase. Nature, 403(6765), 103–8.