Metabolism Clnical Exercise Sleep Data Science Aging, Alzheimer's Disease, and Cancer Neuroscience

Metabolism

Metabolism

Our studies focus on how circadian regulation of metabolism can be influenced by nutritional timing, disease, and diet. Time-restricted feeding (TRF), is a feeding paradigm in which mice are fed only during their active phase. We use this as a model to study the influence of the timing of food intake and circadian rhythms on metabolic homeostasis. Read more »

Clnical

Clinical

The clinical arm of the lab studies how lifestyle interventions (alone or in combination with medication) can improve age-related diseases in humans, including from pre-diabetes, diabetes, cardiovascular disease, and/or cancer in humans. We use a combination of cutting-edge technology, including wearable devices (ex. continuous glucose monitors and actigraphy) and a smartphone app our lab created (myCircadianClock), to implement and monitor clinical interventions in participants living in the real world.  Our research is focused on using personalized circadian interventions, such as time-restricted eating, to help treat diseases, such as prediabetes/type 2 diabetes, metabolic syndrome, and affective disorders, as well as to help offset the burden of shift work. Read more »

Exercise

As part of the Wu-Tsai Human Performance Alliance, our group is dedicated to unraveling the molecular regulation that underpins physical performance, injury prevention, healing, and recovery. Recognizing the significance of comprehending the biological principles of exercise, we aim to optimize human performance and health outcomes across all medical fields. While most of medicine’s understanding of health is derived from studying disease, we are focusing on the optimal state of health and performance. Currently, we are investigating how sleep disruption, meal timings, and various exercise modalities impact molecular pathways, metabolism, and exercise adaptation on a systemic, multi-organ level, employing state-of-the-art experimental techniques. Read more »

Sleep

Sleep is a foundational pillar of health and the intricate dance of circadian behaviors plays a crucial role in determining the quality of our sleep, which in turn, significantly impacts our physiological performance. We are fascinated by the dynamic interplay between these elements. We use behavioral mouse models to delve into topics such as the influence of sleep on immune functions and metabolic processes as well as the effects of dietary timing on sleep quality.

Data Science

Our lab, along with valued collaborators, generates vast multi-omics datasets spanning DNA-Seq, RNA-Seq, proteomics, metabolomics, phenotypes, and clinical trial data. To manage this wealth of information, we have developed scalable data processing pipelines that ensure uniform analysis across high-performance computing clusters and cloud-based systems. We integrate these multi-omics datasets using advanced statistical models to answer critical research questions. Being committed to open data principles, we also create user-friendly data accessioning and visualization web applications to enhance accessibility.

Aging, Alzheimer's Disease, and Cancer

Age is the major risk factor for many diseases, including cancer and neurodegeneration. Alzheimer’s disease (AD) is a progressive neurodegenerative disease. It usually starts with mild memory loss, progresses through cognition difficulty, and ends up with a complete loss of perception and response to environmental stimuli. In 2023, there were 6.7 million Americans age 65 or older living with AD. To better our understanding of AD pathology, its impact on circadian rhythms, the underlying molecular basis, and also to explore the potential benefits of time-restricted feeding (TRF) on AD, we are currently conducting experiments in different animal models of AD. We utilize a variety of research tools, including genetic, behavioral, molecular, immunohistological, electrophysiological, and biochemical methods, to investigate AD progression in animals. Our ultimate goal is to find ways to slow down AD progression and improve the quality of life in AD patients.  For cancer, circadian disruption is linked to increased risk. Cell and animal models have been established to elucidate the intricate molecular interactions between circadian rhythm regulation and the development of cancer, as well as the potential implications for cancer therapy.

Neuroscience

Our laboratory studies the neuroscientific aspects of the regulation by light of circadian rhythms in mammals and in health and disease.  Using a combination of fluorescent and electron microscopy imaging, we characterize the morphology of retinal cells and brain regions receiving direct input from the retina. We are particularly interested in the non-visual opsins and the suprachiasmatic nucleus (SCN).  We use state-of-the-art electron microscopy to elucidate the connectomics of our regions of interest. We established the retinal network involving the melanopsin-expressing cells, characterized the local specialization of their axon terminals, and revealed the subregion specificity and integration of retinal input of the SCN. Finally, we correlate our morphological and connectomics findings with functional assays, in and ex vivo. These assays include evaluating the electrical response to light of retinal photoreceptor cells, the effect of lighting conditions on locomotor activity, and sleep regulation.