Chironian Magazine 2020

ALUMNI PROFILE

Anton Bennett, Ph.D. ’93

Unlocking the Power of PTPs to Regulate Cell Behavior

BY KRISTIN BAIRD RATTINI

How do protein-tyrosine phosphatases (PTPs) regulate cell signaling pathways and lead to the development of disease? Those questions drive the work of Anton Bennett, Ph.D. ’93, the Dorys McConnell Duberg Professor of Pharmacology and Professor of Comparative Medicine at the Yale School of Medicine.

Throughout his tenure at Yale, Dr. Bennett has unlocked just how crucial of a role that PTPs play in cell function. “PTPs are a very highly regulated family of enzymes involved in modifying proteins,” he explains. “Those modifications allow enzymes in our body to be either switched off or switched on, and so PTPs control the ability of a cell to work properly. Understanding how PTPs are involved in switching enzymes on and off can lead us to knowledge about basic cellular functions, but it has also led us to uncover pathways in which these enzymes when dysfunctional can cause human disease. And what we’ve been able to do is connect those altered PTP functions to a variety of different human diseases such as obesity, diabetes and cardiovascular disease.”

For example, he discovered that a particular PTP known as MAPK phosphatase 1 is overexpressed in individuals with obesity and type 2 diabetes. Using genetic knockout models in mice, Dr. Bennett eliminated the expression of MAPK phosphatase 1 and then fed the mice a high-fat diet. The mice no longer gained weight and their ability to respond to insulin improved significantly. “We’re now researching how we can target MAPK phosphatase 1 pharmacologically to come up with new therapeutic strategies for obesity and/or type 2 diabetes.”

He also discovered that mutations in a PTP known as SHP-2 lead to the activation of pathways in the heart that cause a congenital heart disease called hypertrophic cardiomyopathy, or enlargement of the heart. “By identifying targets that SHP-2 interacts with, we can work out how to disable SHP-2 aberrant activity during development,” Dr. Bennett says.

During his decade as co-director of the Integrative Cell Signaling and Neurobiology of Metabolism Program at Yale, he has assembled a team of 12 faculty investigators from varied backgrounds to work toward a common goal: to understand the underpinnings of metabolism in health and disease. “We’re able to answer questions in unique ways based upon our faculty members’ different perspectives,” he says.

In 2017, he won the Blavatnik Innovation Award, created to promote high-risk, high-reward projects. “That was a very proud moment,” he says. He is using his grant to develop new tools and compounds against MAPK phosphatases for the treatment of diseases, such as fibrosis. “Fibrotic tissue disease accounts for up to 40 percent of deaths worldwide,” he says. “But there aren’t many good treatments because it hits so many different types of tissue. So, this research is extremely high risk, but the impact could be huge if we are successful.”

Dr. Bennett also serves as director of Minority Affairs for the Graduate Program in Biological Biomedical Sciences at Yale. During his tenure, the program has doubled the number of underrepresented groups who enter the program and maintain an impressive retention rate of 90 percent. That role, as well as his recent recognition as NYMC’s first Graduate School of Basic Medical Sciences Distinguished Alumni Award honoree, reinforce for him the vital importance of graduate education. “NYMC has done a really good job in training its graduate students,” he says. “By supporting the efforts of graduate education in the future, it can continue its excellence in biomedical research.” ■