The unexpected results, or the most puzzling findings, are always the most intriguing and exciting. It means you’re onto something new. I think that’s what draws me to science, discovering something new that no one else has been able to explain before—Kristin McCabe, scientist
A funny thing happened to Kristin McCabe, PhD after arriving at Columbia University Medical Center in 2015 to study cholesterol metabolism and atherosclerosis. Dr. McCabe, who works with a newly identified gene called Ttc39b (associated with HDL cholesterol) made a discovery so promising, she earned the coveted 2016 Russell Berrie Foundation Fellowship—which is in diabetes research.
The expansion of Dr. Kristin McCabe’s career in cardiovascular research to include obesity began in the laboratory of Dr. Alan Tall, MD, Dr. McCabe’s mentor, who conducts research on the pathogenesis of atherosclerosis, obesity and fatty liver disease. Prior to Dr. McCabe’s arrival at Columbia, Dr. Tall’s lab showed that knocking out Ttc39b (T39) in mice decreases atherosclerosis and fatty liver, a discovery published in Nature1 in 2016. Dr. McCabe joined the lab soon after and began working on experiments to test whether T39 might make a good therapeutic target for future drug development.
Next came the element of surprise that drew Dr. McCabe, 30, to science in the first place. “When I started knocking down T39 in adult mice and put them on a high-fat diet, we noticed that in addition to having lower plasma cholesterol and decreased liver triglycerides, these mice were also resistant to diet-induced obesity, with significantly lower fat storage, and were more insulin sensitive.”
Her experiments underway now are designed to determine what the role of T39 is in fat storage and what the mechanism is by which T39 acts to prevent diet-induced obesity. “T39 might turn out to be a good therapeutic target for the treatment of obesity and insulin resistance, as well as atherosclerosis and fatty liver,” said Dr. McCabe, who was born, raised and educated in Canada. “Obesity is a major risk factor for developing type 2 diabetes, an increasingly prevalent condition in the western world, for which new therapeutic options are greatly needed.”
Her Mentor, Dr. Tall had this to say about Dr. McCabe and her work: “Dr. McCabe has made the exciting and unexpected discovery that knocking down T39 expression in liver and adipose leads to major protection from the development of obesity and insulin resistance in mice fed a high-fat diet. Her work points to a novel role of T39 knockdown in promoting beiging2 of white adipose tissue. These studies have novel mechanistic and therapeutic implications. In addition to Dr. McCabe's hard work, the resources of the Russell Berrie Diabetes Foundation, Columbia’s Obesity Center, the Diabetes Education Research Center (DERC) and expert guidance from collaborators (Drs. Li Qiang, Domenico Accili and Anthony Ferrante) has made these studies possible.”
The Naomi Berrie Diabetes Center’s Russell Berrie Foundation Fellowship in Diabetes Research, now in its 19th year, is designed to support the mentored diabetes-related research activity of outstanding postdoctoral fellows for a period of up to two years. Research projects can be laboratory-based, like Dr. McCabe’s or clinical, and can relate to causes, consequences or treatments of diabetes and allied disorders such as obesity.
- Hsieh J et al. (2016) TTC39B deficiency stabilizes LXR reducing both atherosclerosis and steatohepatitis. Nature; 535:303-7
- White adipose beiging: A process by which energy-storing white fat gains some of the beneficial characteristics of energy-burning brown fat