When Dr. Utpal Pajvani, an Assistant Professor of Medicine at Columbia University, is not seeing patients at the Naomi Berrie Diabetes Center—or teaching endocrine fellows, medical residents and students—the MD/PhD conducts an active research program at the Berrie Center looking for new therapeutics for both type 1 diabetes and type 2 diabetes. His findings—on the promising role of a new class of medications for type 2 diabetes, known as Notch inhibitors—were first published nearly two years ago in the journal Nature Medicine. Notch inhibitors continue to be the cornerstone of Dr. Pajvani's research.
The Notch developmental pathway was discovered nearly 100 years ago by geneticists who were studying naturally occurring mutations in fruit flies —in the form of tiny notches in their wings. More recently researchers have found that inappropriately active Notch signaling causes leukemia and other cancers. As a result, pharmaceutical companies have developed inhibitors to the Notch pathway that are currently in advanced clinical trials (Phase 2/3) for cancer.
“Our studies show that the Notch pathway is as important in the development of type 2 diabetes as in cancer,” said Dr. Pajvani. “So the approach I’m taking is to not reinvent the wheel. It is to take drugs that already exist and test them first in mice and then in people. If we can harness or use the machinery and knowledge that already exists, we can save hundreds of millions of research dollars that have been expended for the use in cancer patients. For many years now, we just haven’t been paying close enough attention to what our cancer colleagues have been studying. But we are now beginning to realize that there’s a lot of intersection between researchers in metabolism and researchers in cancer development. The same pathways are involved. I’m just hoping to exploit the existing knowledge and apply it differently.”
Dr. Pajvani became interested in the Notch pathway in 2007 while working as an Endocrine fellow in the laboratory of Dr. Domenico Accili, whose interest and research in another pathway, FOXO1, were already legendary to the budding diabetes researcher. Since then, he has become a world authority on the use of Notch inhibitors in type 2 diabetes through his studies on obese, insulin resistant mice. “We can already cure type 2 diabetes in mice with Notch inhibitors,” Dr. Pajvani said enthusiastically. “Surprisingly, Notch inhibitors do not promote weight loss or stop the mice from overeating, but still can protect obese mice from developing complications from their obesity — diabetes and fatty liver disease.” Next step: Testing Notch inhibitors in people with type 2 diabetes.
Dr. Pajvani recently moved to Leonia, New Jersey with his wife Christina, a woman with similar scientific gifts, and their children Kai, 2 and Anya, 3 months.
Listen to a podcast of Dr. Pajvani discussing the Notch pathway, Notch inhibitors and their promise for people with diabetes.
To read more about Dr. Pajvani, click here.
To support comprehensive diabetes research and care at the Berrie Center, click here.