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Genetically Engineering & Testing Human Insulin-Producing Cells as a Potential Therapy or Cure for Type 1 Diabetes

Five UMass DCOE scientists are collaborating to create a stem cell-derived beta cell replacement therapy that would be invisible to the immune system, and provide insulin independence for people living with T1D

Michael Brehm Type 1 Diabetes Research

In above video Drs. Harlan & Brehm describe the JDRF Center of Excellence in New England research collaborative

Five scientists from the UMass Chan Medical School’s Diabetes Center of Excellence (DCOE) are among a team of New England researchers in a newly funded JDRF research collaboration. The goal is to create a cell replacement therapy to evade the immune system and provide insulin independence for people living with type 1 diabetes (T1D). 

David Harlan, MD, is leading a clinical study with diabetes patients from UMass Memorial Health, who have agreed to voluntarily donate their blood.


Douglas Melton, PhD, of the Harvard Stem Cell Institute, uses that blood to produce stem cell-derived pancreatic beta cells. Those insulin-producing cells are being genetically engineered by a team led by Dr. Melton, to not be recognized as immune targets by the body. They’re being modified using CRISPR and other gene editing methods to protect them from being attacked by immune cells in people with T1D. 

“For nearly 40 years, I've been helping patients manage diabetes, while focusing my research on the cure,” said Dr. Harlan, the William and Doris Krupp Professor of Medicine and Co-Director of the UMass Diabetes Center of Excellence. “In 2006, while Chief of Intramural Diabetes Research for the NIDDK/NIH, I heard Dr. Melton describe his stem cell plans, with the goal to recreate type 1 diabetes in the humanized mice being developed between UMass Medical School and The Jackson Laboratories. It inspired my move to UMass in 2009 to join Dr. Dale Greiner in co-directing our research efforts.”

The UMass DCOE laboratories of Dale Greiner, PhD and Michael Brehm, PhD, are transplanting Dr. Melton’s genetically modified stem cell-derived beta cells into their novel “humanized” mouse models of type 1 diabetes, to determine if they’re invisible to the immune system as intended. The Brehm and Greiner labs are studying the relationship between the donors’ insulin producing cells and their immune cells in various situations and stages of the disease process. Various experiments are being conducted to observe how the cells interact and to determine where and how the rejection occurs. 


“When Lenny [Dr. Shultz at The Jackson Laboratory and Professor of Medicine at UMass Chan Medical School] and I were developing the first ‘humanized’ mice in the 1980s, we only dreamed that one day they’d be optimized to where we have them now,” said Dr. Greiner, the Eileen L. Berman and Stanley I. Berman Foundation Chair in Biomedical Research, Professor of Molecular Medicine and Co-Director of the UMass Diabetes Center of Excellence. “Transplanting stem cell-derived pancreatic cells that have been genetically modified to become ‘invisible’ to the immune system, into our humanized mice, allows us to understand T1D like never before.”

This cutting-edge research is more than just a job for Dr. Brehm, Associate Professor of Molecular Medicine and Co-Director of the Humanized Mouse Core Facility at UMass Chan Medical School. “As someone who lives with type 1 diabetes, I’m invested both personally and professionally to finding a cure,” he said.  “This is an incredible group of scientists from five New England institutions collaborating to bring us one step closer to a potential cure.”


The Kent and Maehr labs in the UMass DCOE are examining the cells, both before transplantation into the humanized mice, and again after being removed following the various experiments.

“Our group is analyzing how the immune system recognizes or doesn’t recognize the modified stem cell-derived islets” said Sally Kent, PhD, The George F. and Sybil H. Fuller Term Chair in Diabetes, Associate Professor of Medicine. “Immune cells recovered from engrafted islets will be studied to determine how their function and characteristics have changed.”

The Maehr lab is helping to develop new assays to examine the cells on both a functional level, but also looking at RNA transcripts and protein markers following interaction within the humanized models. “My lab combines immunology, stem cell biology, developmental biology and functional genomics,” said René Maehr, PhD, Associate Professor of Molecular Medicine. “We’re investigating how immunological tolerance is established and recreating that process using stem cells. We believe this could leveraged to patient-specific insights and eventually treatment strategies.”

Drs. Kent and Maehr are collaborating with Jason Gaglia, MD, at Harvard Medical School. Dr. Gaglia began his career as a clinical research fellow on the islet transplant team in Dr. Harlan’s lab at the National Institutes of Health in 2000. Together, the three scientists are determining how the phenotype and observable characteristics of the cells have changed. New assays are being utilized to examine the cells on a functional level, but also looking at RNA transcripts and protein markers following interaction within the humanized mice. The process must be measured and proven to be safe before proceeding towards clinical trials.

“This is a group that enjoys collaborative science, and is less concerned with individual credit, but instead is focused on the end product,” said Dr. Melton.

The seed funder of this JDRF initiative is a member of the UMass DCOE Visiting Advocacy Committee, John Cammett. “My own desire to find a cure is inspired by my mom living with T1D for almost 60 years. We have supported several of these researchers individually before. But the JDRF Center of Excellence in New England gives me tremendous optimism because it brings together the brightest minds, with a laser-sharp focus on developing cures."


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