Alyssa H. Hasty, Ph.D.

Cornelius Vanderbilt Chair in Molecular Physiology and Biophysics
Associate Dean for Faculty Development of the Basic Sciences
Research Health Scientist, Tennessee Valley Healthcare System
US Department of Veterans Affairs

813 Light Hall, VUMC
23rd Ave South at Pierce
Nashville
Tennessee
37232
Lab Phone
(615) 322-5972
(615) 322-5177

Mechanisms by which obesity increases risk for disease

Dr. Alyssa Hasty earned her Ph.D. at Vanderbilt University in the laboratory of Dr. Sergio Fazio and then completed a postdoctoral fellowship at Tokyo University in the laboratory of Dr. Hitoshi Shimano. She was recruited back to Vanderbilt as a faculty member in the Department of Molecular Physiology and Biophysics (MPB), and is now a Full-Professor. Dr. Hasty is particularly interested in graduate education and as such, serves as the Director of Graduate Studies for the MPB Department. Dr. Hasty is a leader in the field of immunometabolism, primarily studying the role of macrophages in obesity and metabolic disease. She developed one of the first mouse models to study obesity-related hyperlipidemia and atherosclerosis. She is also interested in the nutritional aspects of metabolic disease including a focus on the impact of various dietary fatty acids on metabolism. Her current work focuses on adipose tissue macrophage apoptosis and iron handling. Dr. Hasty has received funding from the Veteran's Administration, American Heart Association, American Diabetes Association, and National Institutes of Health. She has published over 80 original papers and review/book chapters.

Research Description

The growing worldwide obesity epidemic is frequently linked to hyperlipidemia, inflammation, and insulin resistance leading to increased risk of diabetes and cardiovascular disease. The long-term goal of my laboratory is to determine mechanisms by which obesity increases risk for and pathophysiological consequences of these devastating diseases. Macrophages are part of the innate immune system that infiltrate white adipose tissue in obese rodents and humans, and produce most of the inflammatory cytokines and chemokines secreted from AT. In addition, their presence has been shown to be temporally associated with the development of insulin resistance. My current research focus is to determine mechanisms by which macrophages are attracted to adipose tissue and what happens to them once they arrive. Some of the current projects in my laboratory are:

Macrophage Cell Death: The macrophages in adipose tissue are exposed to high levels of fatty acids that are released from the adipocytes either due to uncontrolled lipolysis or adipocyte cell death. We have evidence in vitro, that exposure of macrophages to saturated fatty acids induced inflammation, ER stress and apoptosis. However, it has not been determined whether ATMs undergo apoptosis. In addition, apoptotic cells are normally phagocytosed by other macrophages in a process called a??efferocytosisa??. It is also now known whether efferocytosis can occur in AT in vivo. We are interested in whether efferocytosis occurs in AT and whether this can contribute to resolution of the inflammation.

Turnover of Adipose Tissue Macrophages: We have growing evidence that even in lean adipose tissue the macrophages undergo apoptotic cell death. We would like to understand how the natural turnover of macrophages contributes to the overall numbers of cells in lean and obese adipose tissue. We hypothesize that this turnover may be impaired in obesity and contribute to the accumulation of macrophages in obese adipose tissue.

Macrophage Emigration: In addition to studying mechanisms by which macrophages enter adipose tissue, we are also performing experiments to determine how their numbers decline during weight loss. This may be via increased turnover or apoptosis as described above. However, an alternative would be that they could emigrate out of adipose tissue. We have a mouse model where leukocyte emigration from tissue to nearby lymph nodes is impaired. We would like to study adipose tissue macrophage emigration in this model.

Publications on PubMed.gov