We want to understand how inter-tissue communication, specifically the long-range secreted signals called neuropeptides, influence behavior and aging. Neuropeptides transmit messages within the brain and across the nervous system to control vital physiologic processes like energy homeostasis, as well as motivational and emotional states including sleep, arousal, pain, stress, and mood. We are developing new methods to monitor and manipulate neuropeptide signaling in living animals, and also identifying the fundamental enzymes that regulate neuropeptide communication. We are also working to elucidate the complex interactions between the ovary and brain during middle-age and to identify the neuronal factors that lead to the onset of reproductive decline in females. We employ advanced imaging, genetic, and biochemical approaches to investigate these questions using both worm and mouse model systems. Our goal is to discover how age-related changes in neuropeptide signaling systems in the brain can influence whole organism healthspan and longevity, and to discover strategies to prevent or delay ovarian aging.
Why it matters
As animals age they exhibit correlated, recognizable and predictable changes to their physiology. These changes occur across multiple tissues; alterations in neuropeptide signaling that lead to disruption of organismal homeostasis may be one mechanism by which these concerted changes occur during aging. Understanding how neuropeptide signaling systems are regulated in the brain, how they mediate inter-tissue communication, and how they change over time is essential for the design of appropriate interventions to delay ovarian aging, to modulate age-related chronic and degenerative conditions, and to treat disorders characterized by behavioral dysfunction.
For more information: http://garrisonlab.com
We want to understand how a breakdown in homeostatic circuits in the brain drive systemic aging.
Jennifer Garrison, PhD
Jennifer Garrison is an assistant professor at the Buck Institute for Research on Aging and also holds appointments in the Department of Cellular and Molecular Pharmacology at University of California, San Francisco (UCSF) and the Davis School of Gerontology at the University of Southern California. During her doctoral studies at UCSF with Jack Taunton, she discovered the molecular target of a natural product and elucidated a novel mechanism by which small molecules can regulate protein biogenesis. As a postdoctoral fellow in Cori Bargmann's lab at Rockefeller University, she found that the nematode C. elegans produces a neuropeptide that is an evolutionary precursor of the mammalian peptides vasopressin and oxytocin, and she mapped a neural circuit by which this molecule, nematocin, modulates mating behavior. As an independent investigator, Dr. Garrison was named an Alfred P. Sloan Foundation Neuroscience Research Fellow and an Allen Institute for Brain Science Next Generation Leader. She also received a Maximizing Investigators' Research Award (MIRA) for Early Stage Investigators from the National Institutes of Health, a Glenn Award for Research in Biological Mechanisms of Aging, and a Junior Faculty grant from the American Federation of Aging Research.
Katelyn Adam PhD Candidate, USC-Buck Biology of Aging Program
Katelyn received her B.S. from UC Berkeley in molecular environmental biology. As an undergraduate she worked in Dr. Caroline Williams lab studying physiological ecology. Katelyn joined the Garrison lab as a Research Associate to study the role of neuropeptides in aging and reproductive longevity. She continues her work as a PhD candidate in the USC-Buck PhD program.
Courtney Hudson PhD Candidate, USC-Buck Biology of Aging Program
Courtney received her bachelor’s degree in biopsychology from UC Santa Barbara in 2015. She worked in the laboratory of Dr. Karen Szumlinski examining cellular changes in brain produced by chronic exposure to drugs of abuse. She completed an honors thesis on the role of glutamate within the nucleus accumbens in methamphetamine addiction. She joined the Garrison Lab in 2015 and is currently a PhD candidate in the Buck-USC PhD program. The goal of her research is to understand the role of neuropeptide signaling in behavior and how it changes with age.
Heeun Jang, PhD Postdoctoral Research Scholar
Heeun Jang received her B.S. in biology from Pohang University of Science and Technology in South Korea. During her Ph.D at The Rockefeller University, she studied with Dr. Cori Bargmann to dissect a neural circuit for social behavior in C. elegans. She demonstrated circuit modulation by neuronal state and sexual dimorphism to elicit a range of behavioral responses to social and environmental stimuli. After finishing her degree, Heeun extended her studies in Dr. Bargmann’s lab/HHMI by developing a powerful genetic tool based on stomatin-like proteins to interrogate electrical coupling between neurons, and used this tool to elucidate gap junction-based neural circuits for social behavior in C. elegans. In the Garrison lab, Heeun studies how the neural circuits change in the brain of aging mice.
Jacqueline Lo, PhD Postdoctoral Research Fellow
Jacqueline Lo obtained her B.S. in Molecular and Cell Biology at UC Berkeley before joining Molecular Biology Ph.D. program at the University of Southern California. As a graduate student, Jackie studied the role of the ubiquitin ligase complex WDR23-DDB1-CUL4 in the regulation of cytoprotective pathways in Dr. Sean Curran’s lab at USC. She discovered that the WDR23 complex negatively regulates NRF2, a transcription factor that responds to cellular stress. Jackie is currently a postdoc in the Garrison lab and is interested in how neuropeptide signaling is regulated and how these pathways are altered with age.
Wil Loveless Lab Technician
Wil Loveless received his B.A. in biology from Sonoma State University in 2018. Upon graduating, he began working as an intern in the Garrison Lab, which led to him becoming a Lab Technician.
Andrew Rodriguez PhD Candidate, USC-Buck Biology of Aging Program
Wenke Wang, PhD Postdoctoral Research Scholar
Wenke received his PhD in biochemistry, molecular and cellular biology fromCornell University. During graduate school, he characterized the role of two highly homologous protein SET-9 and SET-26 in C. elegans. He is now a joint postdoc in Garrison and Brem lab. He is interested in studying the genetic basis for phenotypic differences between wild isolated worm strains.
- Garrison, J. L., Knight, Z. A. (2017 Nov 10). Linking smell to metabolism and aging. Science, 358(6364), 718–19.
- Garrison, J. L., Macoscko, E. Z., Bernstein, S., Pokala, N., Albrecht, D. R., Bargmann, C. I. (2012 Oct 26). Oxytocin/vasopressin-related peptides have an ancient role in reproductive behavior. Science, 338(6106), 540–3.
- Knight, Z. A., Tan, K., Birsoy, K., Schmidt, S., Garrison, J. L., Wysocki, R. W., Emiliano, A., Ekstrand, M. I., Friedman, J. M. (2012 Nov 21). Molecular profiling of activated neurons by phosphorylated ribosome capture. Cell, 151(5), 1126–37.
- McGrath, P T., Xu, Y., Ailion, M., Garrison, J. L., Butcher, R. A., Bargmann, C. I. (2011 Aug 17). Parallel evolution of domesticated Caenorhabditis species targets pheromone receptor genes. Nature, 477(7364), 321–5.
- Bautista, D. M., Sigal, Y. M., Milstein, A. D., Garrison, J. L., Zorn, J. A., Tsuruda, P. R., Nicoll, R. A., Julius, D. (2008 Jul). Pungent agents from Szechuan peppers excite sensory neurons by inhibiting two-pore potassium channels. Nature Neuroscience, 11(7), 772–9.
- Garrison, J. L., Kunkel, E. J., Hegde, R. S., Taunton, J. (2005 Jul 14). A substrate-specific inhibitor of protein translocation into the endoplasmic reticulum. Nature, 436(7048), 285–9.
Dr. Garrison’s Pubmed link