Congratulations to the Berrie Center’s Utpal Pajvani, MD, PhD, a recipient of the David L. Williams Lecture and Scholarship award, given annually to an early career investigator working in the general area of lipid and lipoprotein metabolism and atherosclerosis.
Young investigators must submit a recently published scientific publication in order to be considered for the David L. Williams award. Dr.Pajvani’s award is based on his 2013 paper in the journal, Nature Medicine, Inhibition of Notch uncouples Akt activation from hepatic lipid accumulation by decreasing mTorc1 stability.
Last month, Dr. Pajvani delivered an invited lecture at the 2014 Kern Lipid Conference in Vail, Co., reporting the results published in his Nature paper showing that inhibiting a protein in the liver of obese mice called Notch reduces glucose production and decreases the incidence of fat deposition in the liver. His work has implications for the treatment of three public health epidemics—obesity, type 2 diabetes and fatty liver disease. Fatty liver disease is defined by excess storage of fat in the liver, seen most often in obesity and/or type 2 diabetes, is currently the most common cause of liver disease, and the fastest growing reason for liver transplantation in the United States.
Dr. Pajvani became interested in the Notch pathway when he was an endocrine fellow in Dr. Domenico Accili’s laboratory at the Berrie Center. While Notch had been extensively studied in the context of cancer, its metabolic functions were largely unknown at the time. The investigators discovered Notch signaling in the obese mice with liver disease.
Today, says Dr. Pajvani, who has made Notch inhibitors the cornerstone of his research, “our studies show that Notch may be as important a pathway to the development of metabolic disease as it is in cancer.” Dr. Pajvani and team have already cured type 2 diabetes and fatty liver disease in obese mice, by inhibiting Notch. Surprisingly, Dr. Pajvani explained, “while inhibiting Notch did not stop the mice from overeating, it protected them from developing these two major complications of obesity, diabetes and liver disease.”
A new class of therapeutic drugs that block the Notch pathway are currently in advanced clinical trials for the treatment of leukemia, and part of Dr. Pajvani’s research approach is to, as he puts it, “exploit the existing knowledge on Notch and cancer and apply it differently.” These drugs may turn out to have important roles in treating metabolic diseases or liver disease.
Dr. Pajvani, 38, graduated from MIT and earned his MD, PhD at Albert Einstein College of Medicine. He did his residency in Internal Medicine at Columbia University where he is currently an assistant professor of Medicine in the division of Endocrinology. In addition to running a basic diabetes research laboratory, he also has a clinical diabetes practice at the Berrie Center.