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.
Sudipta Bar Postdoctoral Research Scholar
Dr. Bar joined the Kapahi lab as a postdoctoral research fellow in July 2018. He received his Ph.D. in Biological Sciences from Indian Institute of Science Education and Research Kolkata, India where he studied lysosomal storage disorders using Drosophila and cell culture. At Buck, he utilizes Drosophila genetics, molecular biology, and bioinformatics tools to understand the environmental and genetic factors responsible for neurodegeneration in Alzheimer’s and related diseases. He recently received the Larry L. Hillblom postdoctoral fellowship grant (2019).
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.
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.
Pinky Kain Visiting Scientist
Dr. Kain joined the Kapahi lab last August 2018 as a Visiting Scientist. She is a recipient of prestigious Wellcome trust DBT grant in India. She received her PhD in Genetics and Neurobiology from National Centre for Biological Sciences (NCBS-TIFR), Bangalore, India. Later she moved to Institute of Neurobiology Muenster in Germany to do a short postdoc and University of California Riverside for her second postdoc. Now, she runs her own lab in India at Regional Centre for Biotechnology. The focus of her lab is to understand chemosensory behaviour especially neurobiology of taste and its modulation under various metabolic conditions, raging and disease state. Her lab is also investigating intrinsic and extreme factors that modulate taste behaviours. She utilizes Drosophila genetics, neurobiology, high end imaging, behaviour and molecular genetic approaches to dissect the taste neural circuits that convey taste information to the brain and are involved in simple feeding behaviors like acceptance or rejection of food. At buck she is investigating the molecular and behavioural changes to reprogram disturbed circadian clocks to combat neurodegeneration in Alzheimer's disease using Drosophila as a model system.
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.
Kristeen Pareja, PhD Postdoctoral Research Scholar
Dr. Pareja is originally from Los Baños Laguna, Philippines. She earned her BS degree in Biochemistry and Molecular Biology from UC Davis and her PhD in Pharmacology from Cornell University. Prior to attending graduate school, she worked in several labs including Lawrence Berkeley National Laboratory, Novozymes and Touro University. As a graduate student in the Sevier lab, she studied chaperone proteins involved in ER oxidative stress signaling. She joined the Kapahi lab in July 2018 where she is currently investigating the role of advanced glycation end products in aging and neurodegenerative diseases.
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.
- Jyotiska Chaudhuri, Yasmin Bains, Sanjib Guha, Arnold Kahn,David Hall, Neelanjan Bose, Alejandro Gugliucci, Pankaj Kapahi, The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality, Cell Metabolism, Volume 28, Issue 3, 4 September 2018, Pages 337-352
- 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.