The Herman B Wells Center for Pediatric Research has recognized several researchers with awards as part of the Center's spring 2023 round of funding to support five promising projects focused on emerging therapies and clinical and translational pediatric research.
With these annual awards made possible by the Riley Children’s Foundation, Wells Center scientists at Indiana University School of Medicine are empowered to conduct innovative research that benefits children in Indiana and across the world.
Project title & summary: Predicting Long-term Outcomes Using Patient-Derived Nasal Epithelial Cell Models in Individuals with Cystic Fibrosis
Cystic fibrosis is a genetic disorder treated with cystic fibrosis transmembrane conductance regulator (CFTR) modulators, but patient responses vary. Nasal Epithelial Cell (NEC) models are used to predict short-term outcomes. Huang’s study aims to uncover molecular mechanisms of CFTR functional changes during NECs differentiation in vitro and test their potential for predicting long-term outcomes on CFTR modulators.
Project title & summary: Zinc for Infection Prevention in Sickle cell anemia –2 (ZIPS2)
John’s study aims to follow up on a prior study of zinc for infection prevention in Ugandan children with sickle cell anemia that found that zinc at 10 mg per day did not prevent infection but did reduce the risk of death or stroke. In the ZIPS2 study, a higher 20 mg dose of zinc, which has been safe to give in other studies of zinc in children, will be given daily for 6 months and compared to giving a placebo pill in terms of effectiveness in preventing infection and reducing stroke risk. If the ZIPS2 study finds a reduction or strong trend toward reduction in infection in children given zinc, this will provide the data needed for a large phase 3 trial of zinc at 20 mg daily to reduce infection and risk of stroke in children in Africa with sickle cell anemia.
Project title & summary: Targeting NLRP3 inflammasome in juvenile myelomonocytic leukemia
The overall goal of this project is to find new therapies for treating juvenile myelomonocytic leukemia (JMML), a rare pediatric leukemia for which no therapies exist other than bone marrow transplantation. Unfortunately, 50% of JMML patients who undergo bone marrow transplantation relapse, which is the highest rate of relapse for any known leukemia. Thus, there is an urgent need to develop new therapies to treat this debilitating cancer. Pasupuleti and Kapur have preliminary evidence to suggest that inflammation is a major driver of JMML, and they have identified two possible therapeutic targets they believe are major drivers of inflammation in these patients. The increased presence of these markers in leukemia patients is associated with poor over survival. This project seeks to use two drugs that inhibit the function of these molecules, one of which is an FDA approved drug to treat arthritis, to assess if the drugs will kill JMML leukemic cells from the patient as well as using a pre-clinical model of JMML that mimics all the cardinal features of the human disease.
Project title & summary: A safe, non-invasive drug that strengthens the intestinal barrier can reverse the negative impact of gut microbiota on severe malaria model
The gut microbiota can make rodent malaria worse by damaging the intestinal barrier. Polidoro’s research team repurposed a celiac-disease drug to counter the malaria-induced gut damage and are now studying the effects of this treatment using human-relevant biomarkers of severity, improvement of immunity and resistance to secondary bacterial infections.
Project title & summary: The role of hypoxia-induced metabolic reprogramming in HSC functionality
In this collaborative project, Zhang and Kapur will explore the signaling and metabolic pathways that are altered by low-oxygen environments to promote the function of hematopoietic stem cells (HSCs). The project’s ultimate goal is to develop strategies to manipulate cellular signaling or nutrient availability to promote HSC function in treating hematopoietic diseases via bone marrow transplantation or gene therapy.
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.
Jackie supports the Herman B Wells Center for Pediatric Research at IU School of Medicine. As communications generalist, Jackie helps spread the word about the Wells Center's commitment to improving the health of children in Indiana and beyond through basic and translational research. She has several years of experience in non-profit and academic marketing and communications.