Protein homeostasis and aging
Old age is the major risk factor for the development of neurodegenerative diseases such as Alzheimer’s disease and a series of other ailments. The Hetzer lab is studying the impact of cumulative changes during adulthood on health and the development of disease, focusing on cell maintenance and repair mechanisms. They are particularly interested in understanding how non-dividing cells such as neurons function over the course of a lifetime and how cells lose control over the quality and integrity of proteins and important cell structures during aging. The ultimate goal is to utilize these mechanisms to delay age-related decline of organs with limited cell renewal such as the brain, pancreas and heart.
The group applies genomics, proteomics and advanced imaging techniques to pose questions about how adult tissues are maintained and repaired and why long-lived cells fail to work properly as a cell ages. Recent studies have shown that mammalian tissues are mosaics composed of cell populations with vastly different life spans ranging from days to years. The Hetzer laboratory discovered long-lived proteins (LLPs) in the nucleus, which exhibit no or very little protein turnover in the adult brain. The functional decline of LLPs could be a major contributor to age-related changes in the survival of nerve cells. A focus of his lab is to understand what allows LLPs to stay intact throughout an organism’s entire life span. In people with neurodegenerative diseases, it appears that LLPs in older cells lead to the decline of the nucleus. Understanding why this happens is the first step to potentially prevent and treat disorders like Alzheimer’s disease.
On this site:
Cho UH, Hetzer M. 2023. Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress. eLife. 12, RP89066. View
Kaneshiro JM, Capitanio JS, Hetzer M. 2023. Lamin B1 overexpression alters chromatin organization and gene expression. Nucleus. 14(1), 2202548. View
Hetzer received his PhD in biochemistry and genetics from the University of Vienna (Austria), and completed postdoctoral work at the European Molecular Biology Laboratory (EMBL; Heidelberg, Germany). He joined the faculty at the Salk Institute in 2004 and became a full professor in 2011. He has received numerous awards, including a Pew Scholar Award, an Early Life Scientist Award from the American Society of Cell Biology, a Senior Scholar Award for Aging from the Ellison Medical Foundation, a Senior Scholar Award from the American Cancer Society, a Royal Society Research Merit Award and the Glenn Award for Research in Biological Mechanisms of Aging.
2015 Keck Foundation Research Award
2015 National Institutes of Health (NIH) Transformative Research Award
2013 Glenn Award for Research in Biological Mechanisms of Aging
2009-2013 American Cancer Society Research Scholar
2009 Ellison Medical Foundation Senior Scholar in Aging
2009 Early Career Life Scientist Award, American Society of Cell Biology
2009 ASCINA Award (Austrian Scientists and Scholars in North America)
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