The cells in our body need to respond to a number of stressor to maintain homeostasis and protect the body from invading pathogens. A key cellular homeostatic process is autophagy, a highly conserved, multi-step pathway that facilitates removal of cytosolic material by lysosomal degradation. Conversely, the deregulation of autophagy is part of the etiology of multiple diseases, including cancer and neurodegerative diseases.
In the Hansen lab, we investigate the autophagy process using a combination of the genetically tractable and short-lived model organism Caenorhabditis elegans as well as mammalian cell culture systems to understand the regulation of autophagy and its age-dependent changes to be able to reconstitute the process in older organisms and in disorders with dysregulated autophagy.
Why it matters
While aging is not only a fundamental and interesting biological process, aging and age-related diseases constitute increasingly important health issues in our society as the population of elderly people in the US is rapidly growing and will be doubled in 2030. An important avenue to help improve human health is via research on the basic mechanisms of aging, a key example being the cellular homeostatic process called autophagy.
Understanding the molecular mechanisms of aging is critical to our efforts to try and develop new therapeutic efforts towards curing age-related diseases and improving the healthy years of our lives.
Malene Hansen, PhD
Dr. Hansen was born and raised in Denmark and received her M.Sc. and Ph.D. from Copenhagen University. Starting in 2001, Dr. Hansen carried out postdoctoral studies in the laboratory of Professor Cynthia Kenyon, Ph.D., at the University of California, San Francisco. She established her laboratory at Sanford Burnham Prebys Medical Discovery Institute studying molecular mechanisms of aging in the fall of 2007, and joined the Buck Institute in February 2021 as Chief Scientific Officer and faculty member.
Dr. Hansen has been recognized for her research throughout her career, including an Ellison Medical Foundation New Scholar in Aging Award, a Glenn Award for Research in Biological Mechanisms of Aging, a Julie Martin Mid-Career Award in Aging Research and a Breakthrough in Gerontology Award supported by the Ellison Medical Foundation and American Association for Aging Research. Moreover, her lab is/has been funded by federal grants from both the National Institute on Aging and the National Institute for General Medical Sciences. Dr. Hansen serves as an ad hoc reviewer for multiple scientific journals and is currently chair of the National Institute’s of Health’s Cellular and Molecular Mechanisms of Aging study section.
Dr. Hansen has organized a number of international scientific conferences, including the Cold Spring Harbor Laboratory’s meeting on Mechanisms of Aging from 2014-2018 and the 2020 Keystone meeting on Aging, and she is a co-chair of the 2022 Gordon Research Conference on Autophagy.
Michael Broussalian Research Associate
Michael grew up in San Diego and received his B.S. in Cell Biology at UC Davis. He earned his MSc in Biological Sciences from Dominican University of California, which he completed in Dr. Gordon Lithgow's lab at the Buck Institute. His work for his masters thesis focused on characterizing pathologies of a C. elegans model of NGLY1 Deficiency, and identifying small-molecule therapeutic interventions for this disorder. In the Hansen Lab, Michael studies the role and regulation of the cellular recycling process called autophagy, and the different proteins working in this process. Outside of the lab, Michael enjoys playing board games, trying new restaurants, performing improvised theatre, solving escape rooms, and attending rock concerts.
Ling-Hsuan Sun PhD student, USC-Buck Biology of Aging Program
Ling-Hsuan was born and raised in Taiwan and received a dual bachelor’s degree in nutritional science & education and life science from National Taiwan Normal University, Taiwan. Her research experience started in 2012 as an undergraduate student in Dr. Po-Jung Tsai’s lab, and next as a research assistant in Institute of Physiology at National Yang-Ming University, Taiwan in Dr. Tzong-Shyuan Lee’s lab for one year. In 2015, she began research on aging biology in Dr. Ao-lin Allen Hsu’s lab and earned an M.Sc. degree in Biochemistry and Molecular Biology at National Yang-Ming University in 2017. In the Hansen lab, she will be exploring how the cellular recycling process called autophagy links to aging using the nematode C. elegans and mammalian cell models. Aside from research, Ling-Hsuan likes to immerse herself in Kyudo, Japanese traditional archery, which she first started doing during a foreign student exchange to Japan as an undergraduate student.
Autophagy measurements in C. elegans are published in Chapter 17:
- Chang, M. Hansen, C. Kumsta. Assessing tissue-specific autophagy flux in adult Caenorhabditis elegans. Chapter 17 in Aging Methods in Molecular Biology (2020) Editor: Sean Curran. Published: Springer Nature. PMID:32410036 [PubMed – in process]
- Hansen, DC. Rubinsztein, and DW Walker. “Autophagy as a promoter of longevity: insights from model organisms”. Nature Reviews Molecular Cell Biology (2018), Sep;19(9):579-593, doi:10.1038/s41580-018-0033-y. PMCID: PMC6424591.
- Kumsta, JT. Chang, R. Lee, EP. Tan, Y. Yang, R. Loureiro, E. Choy, SHY. Lim, I. Saez, A. Springhorn, T. Hoppe, D. Vilchez, and M. Hansen. “The autophagy receptor p62/SQST-1 promotes proteostasis and longevity in C. elegans by inducing autophagy.” Nature Communications, 2019 Dec 11;10(1):5648. doi: 10.1038/s41467-019-13540-4. PMID: 31827090.
- Chang, C. Kumsta, A. Hellman, L. Adams, and M. Hansen. “Spatiotemporal regulation of autophagy during C. elegans aging”, eLife (2017);6. doi:10.7554/eLife18459. PMCID:PMC5496740.
- Kumsta, JT. Chang, J. Schmalz, and M. Hansen. Hormetic heat stress and HSF-1 induce autophagy to improve survival and proteostasis in C. elegans, Nature Communications (2017) Feb 15;8:14337. doi: 10.1038/ncomms14337, PMID: 28198373, PMCID: PMC5316864.
- Wilkinson, JS. Jariwala, E. Anderson, K. Mitra, J. Meisenhelder, JT. Chang, T. Ideker, T. Hunter, V. Nizet, A. Dillin, M. Hansen, “Phosphorylation of LC3 by the Hippo kinases STK3/STK4 is essential for autophagy”, Molecular Cell, 2015, Jan 8;57(1):55-68. PMCID: PMC4373083.
- Lapierre, C. Daniel De Magalhaes Filho, PR. McQuary, CC. Chu, O. Visvikis, JT. Chang, S. Gelino, B. Ong, A. Davis, JE. Irazoqui, A. Dillin, and M. Hansen, “The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans”, Nature Communications (2013) Aug 8; 4:2267. PMCID: PMC3866206.
Dr. Hansen’s full publication list