KATE (CLAYCOMBE) LARSON, Ph.D.
Kate (Claycombe) Larson, Ph.D. received her doctoral degree at the University of Tennessee in Nutritional sciences where she studied transcriptional regulation of adipose gene expression and genetics of obesity. She completed a postdoctoral training in nutritional immunology at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, and served as Nutritional Science faculty at Michigan State University before joining the ARS USDA GFHNRC in August 2010. Combining her training in immunology and obesity research, she developed her research program addressing adipose tissue associated inflammation in obesity. Her research interests include obesity-associated immune dysfunction and the mechanisms by which anti-inflammatory nutrients modulate these processes. Her work has been published in highly rated journals such as PNAS, Circulation, J. of Nutr., Am. J. Physiol., Physiol. Genomics, and J Biol. Chem.
Dr. Larson's research interests focus on the role of adipose tissue inflammation and anti-inflammatory nutrients in reducing metabolic disease risks in obese humans and animals. Dr. Larson's research led to her discovery that stromal vascular fraction (SVF) cells and particularly adipose stem cells secrete the highest levels of interleukin-6 (IL-6) as well as monocyte chemotactic protein-1 (MCP-1) when compared to other cell types in the adipose tissue cells of obese animals. Dr. Larson's research team is currently investigating how inflammatory functions of SVF and adipose stem cells of obese animals are regulated by n-3 polyunsaturated fatty acids or flavonoids. Dr. Larson's current research interests also includes studying how maternal and neonatal environments affect adipose tissue cell functions in animal models of obesity.
Identified a major cellular basis for the pro-inflammatory effects of obesity: Dr. Larson's research addressed the metabolic basis for the enlargement of adipose tissue leading to pervasive proinflammatory effects in obese animal models. This involved innovative methodologies to clarify the specific roles of various distinct cell types within adipose tissue. Dr. Larson discovered that one component of adipose tissue, the stromal vascular fraction (SVF) cells, is the primary source of pro-inflammatory cytokines (IL-6) and chemokines (MCP-1) in genetically obese ob/ob mice. The high impact of the work was highlighted by its being featured on the cover of the Journal of Nutrition (J Nutr, Oct 2004) when it was first published. This body of work constituted the first demonstration of the importance of adipose SVCs in increasing the body's overall inflammatory response in obesity.
Discovered one of the key bases for adipose tissue inflammation and chemotaxis in obesity: Dr. Larson's research revealed a key role for resident adipose tissue stem cells. She discovered that adipose stem cells secrete the highest levels of chemotactic protein, monocyte chemotactic protein-1 (MCP-1), among all adipose tissue SVF cells. Her work showed that adipose tissue progenitor stem cells produce the highest level of inflammatory proteins, which cause migration of inflammatory immune cells to adipose tissue from the circulation. This work was pivotal in explaining inflammatory immune cell migration to adipose tissue in obesity - that inflammation is exacerbated by the activities of resident adipose stem cells to attract even more immune cells to already-inflamed adipose tissue. Dr. Larson's finding was published in the Am J Physiol (Aug 2007).
Discovered that leptin (an adipose tissue derived hormone regulating energy metabolism and food intake) modulates the development of bone marrow B cells (antibody secreting immune cells): Dr. Larson's research addressed the impact of obesity on antibody secreting bone marrow B cell differentiation. Her work showed that while leptin administration caused obese mice to eat less food, it doubled the number of B cells in the bone marrow of obese mice by stimulating mature B cell development from their precursor cells. Dr. Larson's work was published in Proceeding of National Academy of Science journal in February 2008.
Elucidated the molecular basis of the anti-inflammatory effects of n-3 polyunsaturated fatty acids (n3PUFAs). Dr. Larson collaborated with other leading experts in the USDA North Central Multi-State Research Group in a study of the roles of n3PUFAs in reducing adipose tissue inflammation in obesity. The collaborative research demonstrated that n3PUFAs potently suppress IL-6 gene expression, and that this occurs by a mechanism involving the down-regulation of Toll-Like Receptor-2 (TLR-2)-mediated signaling pathways in adipose stem cells. These findings open new possibilities for addressing adipose tissue inflammation, particularly as they provide a more complete mechanistic rationale for the use of dietary approaches (as sources of n3PUFAs) to reduce obesity-related metabolic disease risks.