Malene Hansen, Ph.D.
Malene Hansen's Research Focus
Aging is a fundamental biological reality that is familiar to all of us. But how do organisms age at the molecular level? Several genes and processes have been identified that affect the rate of aging, many of which play important roles in highly conserved signaling pathways with relevance to age-related diseases like cancer and neurodegeneration. However, how these processes and conserved genes affect aging at the cellular and molecular level to influence organismal aging is not fully understood. The Hansen lab's research is directed toward understanding the molecular mechanisms that affect the process of aging.
Using a combination of genetic, cytological and biochemical approaches in the genetically tractable model organism C. elegans as well as in mammalian cell culture, we focus on unraveling how several evolutionarily conserved signaling pathways and processes modulate organismal aging.
A particular focus of the lab is to understand the role of autophagy, a basic cellular process by which cytosolic components are being degraded and recycled, in organismal aging. Autophagy has been linked to many age-related diseases as well as aging, and new molecular insights on how autophagy functions in aging may facilitate future treatments of age-linked disorders, including cancer and neurodegenerative diseases.
Malene Hansen's Research Report
A conserved modulaTOR of aging
A key interest of our lab is the nutrient sensor and kinase TOR (Target Of Rapamycin). TOR is emerging as a key regulator of lifespan and healthspan, and the mechanism(s) by which TOR operates to affect organismal aging is currently under intense investigation. TOR regulates several important biological processes that may modulate aging in a conserved fashion, these include protein synthesis and the cellular recycling process autophagy. In our lab, we are investigating how TOR and TOR-regulated processes contribute to the aging process in C. elegans. You will find a couple of these interesting projects outlined below!
An important focus of the lab is to elucidate the role and regulation of autophagy in aging. Autophagy is a cellular process by which the cell can degrade and recycle cytoplasmic material (Figure 1), and we and others have shown that autophagy is important for the longevity effects of at least some long-lived C. elegans strains, including animals subjected to dietary restriction. Nutrient limitation is a potent environmental method of health- and lifespan improvement observed in a multitude of different model organisms, including monkeys. We have observed that dietary-restriction triggers autophagy, and genes with functions in this process are required for dietary-restricted animals to live long (Hansen et al., PLoS Genetics, 2008). However, the mechanisms by which autophagy modulates longevity are not yet understood. To address this critical question, we are using a combination of genetic and molecular approaches to understand how and where in the organism the autophagy process functions to modulate longevity. We are also investigating the mechanisms by which the cytoplasmic material/cargo, yet to be characterized as non-specific or selective in nature, is degraded during the aging process.
We also use mammalian cell culture to characterize conserved regulators of the autophagy process. Autophagy has been linked to many age-related diseases as well as aging, and new molecular insights on how autophagy functions in aging may facilitate future treatments of age-linked disorders, including cancer and neurodegenerative diseases.
Our lab also studies the TOR-regulated process of mRNA translation. We and others have found that inhibition of the translational machinery or of regulators of protein synthesis, including the ribosomal S6 kinase (S6K) and translation initiation factors (eIFs), can extend lifespan and improve healthspan (Hansen et al., Aging Cell, 2007), possibly in a conserved fashion. We are using biochemical and genomic approaches to elucidate the mechanisms by which key translational regulators of protein synthesis affect aging and age-related diseases.
Malene Hansen's Bio
Malene Hansen received her early training at the University of Copenhagen in Denmark. She received a Master’s degree in Biochemistry in 1998 and a Ph.D. degree in Molecular Biology in 2001. During this time, Dr. Hansen worked as a trainee in several labs in the US, including the University of North Carolina in Chapel Hill, and The Scripps Research Institute, La Jolla. After her Ph.D, Dr. Hansen trained as a postdoctoral fellow in molecular genetics at the University of California in San Francisco. Dr. Hansen received postdoctoral funding from the Danish National Research Councils as well as an Ellison/American Federation of Aging Research Senior Postdoctoral Fellowship. Dr. Hansen was recruited to Sanford-Burnham Medical Research Institute in September 2007.