Cao Lab

The long-term interest of this lab is to understand the impact of physical environment and mental state on physiological processes and disease pathology, and the underlying mechanisms. We have recently reported how an enriched environment not only improves brain function and resiliency, but also affects the body’s overall state of health.

Our mechanistic studies have led to the characterization of a novel brain-fat axis, the hypothalamic-sympathoneural-adipocyte axis (HSA) and the development of molecular therapy for obesity and diabetes. These findings provide insights on how one’s living condition, social contact and lifestyle can efficiently influence brain activity (cognition, stress, mood, etc.) and how these changes in the brain interact with other systems (fat, endocrine, immune systems, etc.), both at the molecular level and at the systemic level, to influence the metabolism and various diseases such as obesity, diabetes and cancer through a central mechanism.

The programmatic theme of our research is how environmental stimuli to the central nervous system shape biological processes and disease pathology, and how this knowledge can be harnessed to improve health and treat diseases. Our current research is further defining the HSA axis and pursuing therapeutic potential, including gene transfer to the hypothalamus and genetic or pharmacological modulation of adipose tissue. One major project studies the preventive and therapeutic effects of HSA axis activation in cancer and obesity. A second project attempts to understand how eustress (environmental enrichment) and distress (social isolation) trigger molecular changes in the brain that lead to differential effects on cancer. A third project seeks to understand the role of HSA axis in healthy aging to identify interventions to combat the chronic diseases of aging, many of which are associated with alterations in fat metabolism. A fourth project investigates a subset of obesity (human adenovirus type 36 infection) that is insulin sensitive and metabolically healthy, and explores the possibility of using viruses to treat metabolic syndromes and cancer.

We have also developed a novel anxiety/depression mouse model based on perception and are investigating its mechanisms.

Additional projects seek to understand how environments may program brain circuits during adolescence, leading to long-term impact on health and disease in adulthood. Several exploratory projects are studying how environment influences type 1 diabetes via modulating emotionality and the immune system; the interaction between environment and diet and its effects on obesity/cancer risk; how to manipulate brain or fat to prevent or treat cancer cachexia.

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