Hansen Lab

Malene Hansen, PhD

Chief Scientific Officer and Professor

Investigating the role and regulation of autophagy in aging and age-related diseases

HANSEN LAB

Lab focus

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 (Greek, ‘self-digestion’), a highly conserved, multi-step pathway that is known to facilitate removal of cytosolic material by lysosomal degradation. A number of autophagy-related proteins also serve additional functions outside of the canonical autophagy process, e.g., in endocytosis and secretion. Conversely, the deregulation of autophagy as well as mutation in many autophagy genes are key to the etiology of multiple diseases, including cancer and neurodegenerative diseases.

In the Hansen lab, we investigate the autophagy process using a combination of genetic, cytological, biochemical and pharmacological approaches in both the short-lived, microscopic nematode Caenorhabditis elegans as well as in human cell culture systems to understand the regulation of autophagy and its age-dependent changes to ultimately reconstitute the process in older organisms and in age-related diseases.

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

LAB DETAILS

The Hansen lab is pleased to acknowledge the generous support of the following major funders:

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 in 2007 at Sanford Burnham Prebys Medical Discovery Institute in La Jolla, CA, studying molecular mechanisms of aging, and joined the Buck Institute in 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 (AFAR). In 2021, she received the Irving Wright Award of Distinction from AFAR. Moreover, her lab has been funded by federal grants from 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 a past chair of the National Institute 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. She also co-organized the 2020/2022 Gordon Research Conference on Autophagy.

Michael Broussalian Associate Scientist
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.

MBroussalian@buckinstitute.org
Saam Doroodian Research Associate
Saam was born and raised in San Francisco, CA and received his B.S. from the Microbiology and Immunology program at UC Merced. His previous work focused on understanding the microbial content and symbiosis in the sea anemone, Exaptasia Pallida. In the Hansen Lab, Saam is researching how the basic cellular recycling process called autophagy is regulated during aging, using the nematode C. elegans and mammalian cell culture systems. Outside of the lab, Saam enjoys going to the beach with his girlfriend and dogs, playing billiards, and playing backgammon.

SDoroodian@buckinstitute.org
Hiroshi Ebata, PhD Postdoctoral Research Fellow
Hiroshi was born and raised in Tokyo, Japan and received his M.Sc. and Ph.D. in cell biology from the University of Tokyo. His work for his dissertation focused on apoptosis regulation by mitochondrial telomerase reverse transcriptase in mammalian cells. In the Hansen lab, he will be exploring how the cellular recycling process called autophagy links to aging using the nematode C. elegans and human cell culture models. Outside of the lab, Hiroshi enjoys weight training, going to art exhibitions, and reading philosophy books.

HEbata@buckinstitute.org
Bijoya Sen, PhD Postdoctoral Research Fellow
Bijoya is from India where she got her bachelor’s and master’s degree in Biotechnology. Aging biology was introduced to her when she joined the lab of Gayatri Ramakrishna in Institute of Liver and Biliary Sciences, New Delhi. There she studied the role of senescence-associated pathways in the progression of liver cirrhosis to hepatocellular carcinoma and received her PhD degree in 2019. Then she joined the Brand lab at Buck as a Glenn postdoctoral fellow. Her area of research was to explore mechanisms by which mitochondrial reactive oxygen species (ROS) acts as a signaling molecule to abrogate various pathways using hypoxia/HIF as a model. She recently joined the Hansen lab where she plans to delve into the cellular recycling process named autophagy and how it affects aging using mammalian cell culture and C. elegans as a model system. Outside of the lab, she enjoys a challenging hike and experimenting with recipes.

BSen@buckinstitute.org
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.

LSun@buckinstitute.org

Malene Hansen, PhD
Professor and Chief Scientific Officer
MHansen@buckinstitute.org
Phone: 415-209-2251

Alyssa West
Executive / Educational Administrator
AWest@buckinstitute.org
Phone: 415-209-2020

C. K.

Caroline Kumsta, PhD Visiting Scientist
Assistant Professor, Sanford Burnham Prebys Medical Discovery Institute (May 2022)
B. K.

Brennen Keuchel Intern
Undergraduate Student, Vanderbilt University (May - Aug. 2022)

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]

We are always excited to hear from researchers interested in joining our lab!

We are looking for highly independent scientists who will be fun to work with and who will have fun working with us.

We are especially interested in prospective postdocs who have research interests aligned with ours, but we will also consider candidates with independently thought up projects as long as they are broadly related to aging and age-related diseases.

Those interested in a postdoctoral position, please apply here.

We also encourage undergraduate who are interesting in doing independent study projects.

LAB GALLERY

Selected Publications

J. L. Nieto-Torres, S-L. Shanahan, R. Chassefeyre, T. Chaiamarit, S. Zaretski, S. Landeras-Bueno, A. Verhelle, S. E. Encalada, M. Hansen, LC3B phosphorylation regulates FYCO1 binding and directional transport of autophagosomes. Current Biology, 2021, Jun 15;S0960-9822(21)00750-8. PMID: 34146484.
J.L. Nieto-Torres, M. Hansen. Macroautophagy and aging: The impact of cellular recycling on health and longevity. Mol Aspects Med, 2021 Sep 7:101020. doi: 10.1016/j.mam.2021.101020. Online ahead of print. PMID: 34507801
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.
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.
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.