Summary
Aging and sleep are fundamental biological processes that are highly conserved across species. Disruptions or deficiencies in these processes have been linked to a wide range of diseases, including obesity, diabetes, and cancer. Investigating the biology of sleep and aging not only enhances our understanding of their core functions and underlying mechanisms but also sheds light on how these processes interact with other health conditions. By studying molecular components and neural circuits in a simple model organism like Caenorhabditis elegans—which has a fully mapped genome and nervous system, along with tools to manipulate gene and brain function—we can directly explore the processes of sleep and aging. This approach offers valuable insights into fundamental questions such as why do we sleep? and how can we extend healthy lifespan?
The roundworm Caenorhabditis elegans is an ideal model for studying aging and sleep due to its behavioral similarities to humans, including clear sleep-like states and distinct physiological changes between sleep and wakefulness. Many of the anatomical and functional changes observed in human aging are also present in C. elegans. Its short lifespan of around three weeks, combined with a rapid 2-3 day life cycle and small size, makes it highly amenable to genetic manipulation and high-throughput screening for mutations that affect sleep and aging. Additionally, C. elegans genes share strong homology with their human counterparts, especially those involved in the regulation of sleep and aging. The model has already led to key discoveries, such as RNA interference and the genetic regulation of programmed cell death, and continues to be a powerful tool for advancing research in sleep and aging.
Sleep and metabolic processes are deeply interconnected, with significant clinical implications. For instance, insufficient sleep is linked to obesity and type 2 diabetes. We are exploring the genes and neurons that regulate these sleep-metabolic interactions. Our recent research has revealed that the conserved salt-inducible kinase 3 (SIK3) pathway plays a crucial role in the metabolic regulation of various sleep states in C. elegans, including developmentally-timed sleep (similar to circadian sleep) and stress-induced sleep (comparable to sickness sleep). The SIK3 proteins and their targets are highly conserved across C. elegans, mice, and humans. Currently, we are investigating how SIK3 coordinates the interaction between sleep and metabolism through genetic and neural approaches, as well as high-throughput behavioral analyses, to better understand why this pathway is critical for maintaining health.
Our lab is also focused on understanding organismal aging, which may involve the gradual accumulation of harmful molecular changes that contribute to age-related decline and disease. We are particularly interested in a newly recognized class of non-coding endogenous RNAs called circular RNAs (circRNAs), which are primarily produced through back-splicing events from known protein-coding genes. Our recent research has shown that circRNAs accumulate progressively and in large quantities during aging, at a genome-wide level, in C. elegans. However, the functions of these age-accumulated circRNAs, as well as those of most of the thousands of circRNAs discovered, remain unclear. Currently, we are using next-generation sequencing, genome-editing techniques, and behavioral analysis to explore the regulatory mechanisms and functions of circRNAs in aging, as well as their potential role in age-related diseases.
Finally, our lab is broadly focused on understanding how environmental and internal signals influence behavior and gene expression. We have published several studies on the dynamic changes in olfactory gene expression in response to the feeding state of the free-living nematode C. elegans. These findings may provide valuable insights into how parasitic nematodes and disease-carrying insects navigate their hosts based on their nutritional status.
Courses taught
- BIOL 190: Introduction to Cell and Molecular Biology
- BIOL 395: Genetics and Cell Biology Lab
- BIOL 475/675: Neurobiology
- BIOL 476/676: Clocks, Rhythms and Disease
- BIOL 477/677: Genes, Brain and Behavior
Education
- Ph.D., Biology, Hubrecht Institute, University of Utrecht, The Netherlands, 2003
- M.Sc., Molecular Biology, University of Leiden, The Netherlands, 1999
- B.Sc., Biochemistry, Poly Technical College of Delft, The Netherlands, 1996
- B.Sc., Microbiology, Van Leeuwenhoek Institute, The Netherlands, 1993
Experience
- 2024-present, Associate Dean, College of Science, Professor, 性爱五色天, Reno, NV
- 2022-2024, Chair, Professor, 性爱五色天, Reno, NV
- 2022, Associate Chair, Associate Professor, 性爱五色天, Reno, NV
- 2016-present, Director, Cellular and Molecular Imaging Core, COBRE Integrative Neuroscience
- 2016-2022, Associate Professor, 性爱五色天, Reno, NV
- 2009-2016, Assistant Professor, 性爱五色天, Reno, NV
- 2003-2009, Postdoctoral Fellow, Brandeis University, Waltham, MA
Selected publications
Please find a complete list of published work on .