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Mary-Elizabeth Patti, M.D.

Research Summary

Type 2 diabetes is typically present for years before diagnosis, and individuals at risk for diabetes have insulin resistance and other metabolic abnormalities for years before that.  The primary focus of the Patti Laboratory is to identify the molecular and metabolic pathways which are disrupted in individuals at risk for diabetes.  We are particularly interested in mechanisms by which environmental or nutritional factors can mediate risk, potentially by altering transcriptional regulation and metabolism at a cellular level.  By understanding these mechanisms, we are hopeful that we will be able to identify new approaches to diabetes prevention and treatment. To address these key questions, scientists in the Patti Lab utilize both cellular and animal models of diabetes risk, as well as tissue samples from human volunteers with insulin resistance or established type 2 diabetes.  Current projects include analysis of metabolism and transcriptional regulation in (1)  iPS cells (skin-derived stem cells) derived from patients with diabetes or insulin resistance, and (2) mouse models of diabetes risk created by disruption of candidate genes or in response to prenatal nutritional exposures.   With these studies, we continue to identify and test new genes and pathways in the cell which are important for maintaining normal insulin response (insulin sensitivity) and blood glucose levels.   

Some of our recent findings include:

• Insulin resistance and nutrition during early life can profoundly influence disease risk in adult life and may also impact on health of subsequent generations.  We recently demonstrated (Science 2014) that prenatal nutritional exposures of a pregnant mouse confer diabetes risk not only in offspring, but also in grandoffspring mice, potentially by altering germ cell methylation and transcriptional patterns. 
• Insulin resistance and nutrition during early life can affect the metabolic function of stem cells - cells which are critical for normal development.  
• By analyzing muscle samples from human volunteers with insulin resistance and/or type 2 diabetes, we identified the STARS-SRF pathway as a novel mediator of muscle insulin resistance and regulator of systemic metabolism.  By studying the impact of this pathway in cells and mice, we hope to identify new targets for treating type 2 diabetes. 

PubMed link:

We are hopeful that understanding how transcriptional, epigenetic, and metabolic regulation is altered prior to the onset of diabetes will provide us the opportunity to identify new methods to reduce diabetes risk and also to reduce risk for subsequent generations.

In Dr. Patti’s role as an endocrinologist and director of the hypoglycemia clinic at Joslin, she cares for patients with severe hypoglycemia after bariatric or other forms of gastrointestinal surgery.   Given the severity of this condition, she is working to identify mechanisms responsible for hypoglycemia, and is investigating new therapies to reduce its frequency and severity.


Dr. Patti received her undergraduate and medical degrees through an accelerated medical school program at Jefferson Medical College, followed by internal medicine residency at the University of Pittsburgh, and training in the joint Harvard Medical School endocrinology fellowship program.  She is currently Investigator, Co-Director of the Joslin Advanced Genetics and Genomics Core, Director of the Hypoglycemia Clinic (all at Joslin Diabetes Center), and Associate Professor of Medicine, Harvard Medical School.  Dr. Patti has served on many volunteer leadership roles within the American Diabetes Association. She was elected to the American Society of Clinical Investigation in 2009 and to Fellowship in both the Obesity Society and American College of Physicians in 2014. 

Page last updated: September 19, 2019