Growing Stem Cell-Derived Pancreatic Islets to Improve Transplantation Therapy for Type 1 Diabetes
Sambra Redick, PhD, is a senior research scientist in the laboratory of Dr. David Harlan. She leads the development of stem cell-derived islets at the UMass Chan Diabetes Center of Excellence (DCOE) for various collaborative research projects, including efforts to genetically engineer them to evade immune detection. Transplanting stem cell-derived islets into a person with type 1 diabetes, without them requiring toxic immunosuppressive therapy, is the core focus of our research.
Since arriving at the DCOE in 2015, she helped put to rest a decades-old debate about beta cells. In collaboration with engineers at Worcester Polytechnic Institute (WPI), she developed a novel tool to improve the removal of individual islets from human pancreas slices, allowing for better investigation. Dr. Redick focuses on functional and transcriptional profiling of pancreatic islets from diabetic and non-diabetic donors. She has developed techniques to remove and study single islets from slices of human pancreas that we receive as members of the Network for Pancreatic Organ Donors with Diabetes (nPOD). Those methods allow her to obtain transcriptional profiles of single cells from within those islets.
Dr. Redick manages the Pappas Stem Cell Differentiation Core, which grows stem cell-derived islets for various collaborative research projects. The Harlan lab focuses on insulin-producing beta cells and their role in attracting the immune system's attention, leading to the autoimmune attack that causes type 1 diabetes (T1D).
Scientists from the UMass Chan DCOE, The Jackson Laboratory, Harvard Medical School, and University of Toronto comprise the Breakthrough T1D Barbara Dewey Cammett Center of Excellence in New England, led by Dr. Harlan. The group is working to genetically modify stem cell-derived islets to make them undetectable to the immune system. Those engineered cells are tested in our “humanized” mice to determine their functionality in vivo. Transplanting stem cell-derived islets into a person with type 1 diabetes, without requiring toxic immunosuppressive therapy, is the ultimate goal.
Sambra Redick, PhD
Her interest in cell biology stems from a 4th-grade science project she did on DNA replication. Sam grew up in South Carolina and became the first person in her family to finish college.
“My folks always told me I was going to college, and I decided in junior high that I wanted not just to get one degree, I wanted to get them all,” she said with a smile.
She studied genetics at the University of Georgia, then earned both her master’s and PhD in molecular biology at Princeton University, where she had planned to study virology.
Her first postdoctoral fellowship was at the University of North Carolina, where she worked in a lab that used mouse embryonic stem cells to study blood vessel development.
Sam realized early on that she didn’t aspire to run her own lab, but she enjoys performing bench research. “I like working with my hands doing the physical experiments, and I love troubleshooting,” she said.
Her second postdoc position was at Duke University, where she worked in a lab on two completely different projects. “At that point, I didn’t necessarily care what the project was,” she said. “I just wanted to investigate interesting questions and use cool tools!” She published papers about cell adhesion and anti-adhesion before transitioning to the bacterial cell division side of the lab.
Joining UMass Chan Medical School and the Diabetes Center of Excellence
She joined UMass Chan Medical School in 2003 and worked in the laboratory of Dr. Stephen Doxsey, where she focused on cell division. After 12 years in the Doxsey Lab, funding dried up, and Sam’s campus network led to a position in the Harlan Lab at the UMass DCOE.
At that time, donated pancreatic islets were obtained from deceased diabetic and non-diabetic donors and separated into single cells. Sam performed RNA-sequencing to examine the transcriptome of those cells to determine their messenger RNA molecules. The Harlan Lab was looking for differences between beta cells from the islets of people who had T1D and those who were non-diabetic. They compared gene expression in cells from people who passed away at various stages of the disease process with that in cells from people without diabetes to investigate changes in gene expression. The goal was to understand whether beta cells attract immune cells, triggering the autoimmune attack, or if they are “innocent bystanders.”
They soon determined that sorting cell groups by insulin might overlook important information, as beta cells from people with T1D didn’t produce much insulin. Sam began developing new techniques to interrogate single cells regardless of hormone expression. Today, they capture islet cells using a molecular biology process that isolates single cells and labels each cell's individual gene expression. This process continues to produce gigabytes of data, which our bioinformatician analyzes to identify cell types by their gene-expression hallmarks and to examine how individual gene-expression profiles vary.
Resolving a 30-year debate by locating beta cells in people with T1D that express important immune pathway gene products
By far the most significant genetic risk for T1D is driven by the expression of immune genes called “human leukocyte antigen class II” (HLA Class II). Yet many believed that human beta cells were incapable of expressing HLA Class II and other essential genes that support their function. Collaborative research in the Harlan Lab definitively showed that beta cells from individuals with T1D express these important gene products. Since these are immune system genes, this raises the question of whether this immune function is essential for what T cells do to trigger the autoimmune attack on beta cells.
Creating a tool to procure single islets
The Harlan lab believes that, since diabetes is a patchy disease with varying effects on islets of different sizes and cellular compositions, studying individual islets will be beneficial. Dr. Redick has developed techniques to separate single islets, including a halo of T cells around the edge of the islet, allowing them to study the importance of that ring of immune cells. They’ve developed a novel tool to punch and recover individual islets from living pancreas slices for more in-depth investigation.
Sam and her husband share their home with two cats. She enjoys growing a garden at home, especially vegetables that are unavailable locally. “I’m a southerner, so we have a big okra patch, purple top turnips with the greens on,” she said. “All the cliches of southern food.” She enjoys cooking and compares it to lab work, because you follow a protocol, except “the experiment rarely fails so badly that you can’t have dinner,” she joked.
Sam’s favorite part of living in New England is the four seasons. She enjoys fall foliage, winter sports like cross-country skiing, and spring and summer activities such as hiking, kayaking, and cycling.
Sam's Favorites
TV Shows: M.A.S.H., Star Trek Next Generation, Big Bang Theory
Movies: The Princess Pride, Harold and Maude
Restaurants: Eller’s for breakfast, Fatima’s Café, Nancy Chang’s, BT’s Smokehouse
Hobbies: Steam train enthusiast
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