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Learn about research projects funded by the 2021 Clinical/Translational Research Support Awards from the Herman B Wells Center for Pediatric Research.

Wells Center recognizes three scientists with translational research awards

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The Herman B Wells Center for Pediatric Research has recognized three scientists with funding for their promising clinical/translational studies.

The Clinical/Translational Research Support Awards are distributed annually and made possible by Riley Children’s Foundation, the fundraising arm of Riley Hospital for Children at IU Health and of pediatric research at Indiana University School of Medicine. This year’s awardees each received $50,000 to fund their projects, which include research related to diabetes and leukemias.

Elizabeth Sierra Potchanant, PhD
Assistant Research Professor of Pediatrics

Project title: Targeting PLK1 as a novel synthetic lethality strategy for acute myeloid leukemias with Fanconi anemia pathway mutations

Fanconi anemia is a rare bone marrow disorder that is associated with acute myeloid leukemia (AML), the leading cause of leukemia-related mortality in children. Treatment of AML in kids with Fanconi anemia is especially difficult due to the disorder’s impairment of DNA repair activity. Because of this, children with Fanconi anemia who develop AML may receive lower doses of chemotherapy treatment compared to other AML patients, potentially under-treating the cancer.

Dr. Sierra Potchanant’s project hypothesizes that FA genes that are frequently mutated in pediatric AML could be sensitive to inhibition of an enzyme called PLK1. Previous work from Dr. Sierra Potchanant has shown that over-expression of PLK1 correlated with mutation of the Fanconi anemia pathway, suggesting that those cancer cells may have increased reliance on the enzyme.

To build on this data, Dr. Sierra Potchanant will work with the Precision Genomics team at IU Health to gather samples from AML patients at Riley Hospital for Children at IU Health. Using these, she will assess the effects of pharmacological inhibition of PLK1 in Fanconi anemia-related leukemia, and may provide a preclinical rationale for the development of precision treatments for vulnerable pediatric cancer patients with Fanconi anemia and AML.

Jamie Felton, MD
Assistant Professor of Clinical Pediatrics
Project title: Exosomal microRNA cargo facilitates islet-immune cell interaction to drive Type 1 diabetes

Type 1 diabetes is a chronic and costly autoimmune disease in which the body no longer produces the insulin hormone that regulates blood sugar levels. Each year, about 64,000 people—mostly children and adolescents--are diagnosed with Type 1 diabetes. For the rest of their lives, they will require insulin therapy to survive.

Dr. Felton’s research focuses on the interaction between beta cells, which produce insulin, and immune cells called B lymphocytes, or B cells. Specifically, she looks at how B cells and beta cells communicate with one another to initiate the destruction of beta cells and eventual onset of Type 1 diabetes.

Earlier studies from Dr. Felton and her colleagues suggested that some dysfunctional beta cells secrete a communication mechanism called exosomes that transfer a specific type of microRNA, miR-21. Their data suggest that this process could theoretically trigger an inflammatory response in B cells, resulting in the pivotal moment at which some people become at-risk for developing Type 1 diabetes.

Dr. Felton’s project will further define these communication mechanisms between beta cells and B cells while establishing previously unidentified indicators, or biomarkers, that suggest risk for Type 1 diabetes. Collectively, this work paves the way for earlier intervention and possible disease delay or even prevention for children at risk for Type 1 diabetes.

Jie Jiang, PhD
Assistant Research Professor of Pediatrics

Project title: The role of GCN2 in leukemia progression and targeting therapeutics

Cancer cells are adaptive—that’s why they’re so prolific. For patients with T-acute lymphoblastic leukemia (T-ALL), this adaptivity leads to a worse prognosis than in any other form of ALL, which is the most common type of blood cancer in children. Relapse occurs in about one-fourth of pediatric T-ALL patients, and survival after relapse is below 25%.

Dr. Jiang’s research focuses on targeting the nutrient of cancers--amino acids--for cancer treatment. However, cancer cells use a critical adaptive pathway through a kinase called GCN2, which it then exploits to supplement the nutrient to feed the cancers.

Dr. Jiang’s work has established promising data from both a novel Kras mutation-driven mouse T-ALL model and human pediatric patient samples, proving that targeting GCN2 in addition to nutrient depletion (like common chemotherapies for ALL, such as L-asparaginase) could be an effective combination therapy for T-ALL.

Importantly, this project will lay the groundwork for better understanding of the role of adaptive metabolic response in chemo-resistant T-ALL. Meanwhile, this work establishes rationale for targeting the GCN2 adaptive pathway to improve outcomes for T-ALL patients, and will shed light on applying this nutrient-depleting strategy for targeting the “undruggable” Kras mutation-driven cancers.

The views expressed in this content represent the perspective and opinions of the author and may or may not represent the position of Indiana University School of Medicine.
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Sara Buckallew

Communications Coordinator

Sara Buckallew works in the Dean's Office of Strategic Communications. As a communications coordinator, Sara supports internal and external communication needs for the Herman B Wells Center for Pediatric Research and the Center for Diabetes and Metabolic...