Qiong (Annabel) Wang Lab Research Highlights

Our laboratory’s research interest is to determine the mechanisms that regulate the plasticity and function of adipose tissue. Our long-term goal is devoted to limiting the pathogenesis of and developing treatments for chronic metabolic diseases in adult and aged populations. We are currently working on these projects: 
 
Molecular and metabolic heterogeneity of brown adipocytes. 
Thermogenesis in brown adipocytes is a well-established process since it exerts metabolically beneficial effects on whole-body energy homeostasis. Brown adipose tissue has been assumed to have a homogeneous population of brown adipocytes. The thermogenic activity of brown adipose tissue is also believed to be homogeneously regulated in all brown adipocytes. Utilizing multiple murine genetic labeling systems, single-cell RNA sequencing of primary brown adipocytes, and 3D imaging of brown adipose tissue, we recently identified two distinct brown adipocyte subpopulations with distinct molecular and metabolic features, as well as differential thermogenic activities, co-existing in the brown adipose tissue. The dynamic exchange between these two brown adipocyte subpopulations upon environmental temperature fluctuations provides new insights into the regulation of brown adipose tissue thermogenic activity. 
 
Mammary adipose tissue remodeling during female reproduction in health and obesity. 
The risk for breast cancer is transiently increased with each pregnancy, and women diagnosed with breast cancer within 5 years postpartum have a high mortality rate. Despite the intensive studies on the pathogenesis of breast cancer in general, how reproduction promotes breast cancer is still largely unknown. My lab recently showed that during lactation, mammary adipocytes undergo a process of dedifferentiation to become adipocyte precursor-like cells; during involution, these dedifferentiated cells can proliferate, and re-differentiate back into adipocytes. Thus, for the first time, we discovered that terminally differentiated mature adipocytes could dedifferentiate, go back to the cell cycle, and regain the capacity of self-renewal. Interestingly, obesity is associated with an increased risk of breast cancer. Thus, obesity-related dysfunction of mammary adipocytes may largely contribute to pregnancy-associated mammary tumor formation and progression.
 
Aging-related white adipose tissue remodeling and dysfunction. 
When people age, many of them suffer from increased white adipose tissue (WAT) accumulation, especially in the visceral (abdominal) area. Visceral adiposity accelerates aging by promoting insulin resistance, cardiovascular dysfunction, and many other chronic health conditions, significantly shortening health span and lifespan. Thus, preventing or reducing adipose tissue accumulation is critical for healthy aging. Unfortunately, the relationship between aging and adipose tissue accumulation is poorly understood. Adipocytes (fat cells) undergo hypertrophy (cell enlargement) during aging, but it remains unclear if adipose tissue also expands through adipogenesis (the generation of new adipocytes), which will grant adipose tissue with unlimited potential to grow. Right now, our lab is evaluating the contribution of adipogenesis in age-related adiposity.