Wells Center Newsletter November 2024

Top News

New findings challenge decades-old standard for VUR management in children
A study conducted by investigators from the Wells Center's kidney and urology translational research group found that a common test for assessing kidney damage in children with vesicoureteral reflux (VUR) may not be the most effective. Their findings, recently published in JAMA Pediatrics, could lead to better care for children with VUR.
Find out more

Gut microbiome differences in children linked to febrile malaria development
New research from the Schmidt laboratory emphasizes the gut microbiome's significant role in febrile malaria development. The findings, recently published in Nature Communications, suggest that treatments targeting gut bacteria could offer promising strategies to decrease the risk of the disease, particularly in children.
Read more

Study uncovers first evidence of resistance to standard malaria treatment in African children with severe malaria
In collaboration with colleagues at Makerere University in Uganda, investigators from the pediatric infectious diseases and global health research group uncovered evidence of partial resistance to artemisinin derivatives, the primary treatment for malaria, in Ugandan children with severe or “complicated” malaria.
Learn about the study

Indiana helps drive global progress in Type 1 diabetes screening through TrialNet
More than 250,000 people have been screened for Type 1 diabetes risk worldwide through TrialNet, with over 10,000 screenings conducted locally by IU School of Medicine's TrialNet clinical research center at Riley Children's Health. This achievement highlights significant progress in the early detection and prevention of Type 1 diabetes.
Read about the milestone

Team Wells Updates

2024 Wells Center Retreat
The annual Wells Center Retreat took place on September 5, 2024, at the NCAA headquarters in downtown Indianapolis. Wells Center faculty, staff, students and trainees joined the full-day event to learn more about the center’s research programs and connect with colleagues. The retreat also featured a dynamic poster session, with awards going to 16 poster winners.

Scientist by day, artist and aerospace enthusiast by night
Ivana Daniels is a fourth-year PhD student working with the Wells Center’s Gaston laboratory. In a recent blog post, discover how her unique blend of interests fuels her research in respiratory syncytial virus and her dream of one day taking her work to the stars.

National CCEH meeting
Representatives from the IU Cooperative Center of Excellence in Hematology (IU-CCEH) including Wells Center researchers Reuben Kapur, Karen Pollok and Pratibha Singh gathered in Chicago on August 29 for a national CCEH meeting.

Annual Halloween celebration
The Wells Center celebrated Halloween on October 24, 2024, with a festive gathering featuring pumpkin and costume contests. Prizes were awarded to four creative pumpkins and three costumed colleagues!

Welcome to the Wells Center
Help us extend a warm welcome and congratulations to the members of Team Wells who have joined us since August 2024:

Discovery in Action

Congratulations to Grant and Award Recipients
Members of the Wells Center have received numerous grants and awards in recent months. Here are a few highlights:

Joan Cook-Mills, PhD | “Development of allergy in offspring is enhanced by maternal eicosanoids and lung microbiota composition dysbiosis.” (NIH R01 - National Institute of Allergy and Infectious Diseases)

Jamie Felton, MD | “Type I Interferons and B Cell Metabolism as Drivers of Type 1 Diabetes // Diabetes-Docs: Physician-Scientist Career Development Program (DiabDocs)” (Stanford University)

Carmella Evans-Molina, MD, PhD | “RARE and Atypical Diabetes Network (RADIANT)” (Baylor College of Medicine) / George and Frances Ball Foundation (Riley Children’s Foundation)

Bill Hagopian, MD, PhD | “Clinical and Economic Optimization Platform for Type 1 Diabetes Screening” (University of Colorado) / “Limited Competition: Continued Follow-up of Subjects and Initiation of a Second Case-control Cohort in The Environmental Determinants of Diabetes in The Young Study (TEDDY)” (University of South Florida)

Santhosh Pasupuleti, PhD | The Developmental and Hyperactive Ras Tumor (DHART) SPORE Career Enhancement Program Award

Andrew Schwaderer, MD | “A mechanistic approach to intercalated cell phagocytosis” (NIH R01 - National Institute of Diabetes and Digestive and Kidney Diseases)

Emily K. Sims, MD | “The Finding Immune Nascent Diabetes (FIND-T1D)” (Leona M. And Harry B. Helmsley Charitable Trust) 

Nathan VanDusen, PhD | “Development of tools for rapid systematic refinement of in vivo gene editing technologies” (NIH R21 - National Institute of Child Health and Human Development)

Stephanie Ware MD, PhD | “Indiana Collaborative for Undiagnosed Rare Disease” (NIH U01 - National Institute of Neurological Disorders and Stroke) / “Diagnosing the Unknown for Care and Advancing Science (DUCAS) (UDN Clinical Research Support Core)” (Washington University)

Baohua Zhou, PhD | “FOXP3 E2 Isoform in Asthma Severity and Persistence.” (NIH R01 - National Institute of Allergy and Infectious Diseases)

Recent Publications

• “A Novel Echocardiography Feature-Tracking Algorithm for Stabilized Frame-to-Frame Extraction of Aortic Root Diameters in the Parasternal Long Axis.” Published in Journal of the American Society of Echocardiography. Contributing IU authors: Frederick W. Damen, Dongbing Lai, Benjamin J. Landis
• “Activation of the Snail transcription factor induces Mdm2 gene expression.” Published in Journal of Biological Chemistry. Contributing IU authors: Alexander R. Mabry, James Gorman, Juan S. Delvasto, Justin H. Layer, Lindsey D. Mayo
• “Antisense Oligonucleotide Therapy for Calmodulinopathy.” Published in Circulation. Contributing IU authors: Shuai Guo, Wen-Chin Tsai, Michael Rubart
• “Beta cell extracellular vesicle PD-L1 as a novel regulator of CD8+ T cell activity and biomarker during the evolution of type 1 diabetes.” Published in Diabetologia. Contributing IU authors: Chaitra Rao, Daniel T. Cater, Saptarshi Roy, Jerry Xu, Andre G. De Oliveira, Carmella Evans-Molina, Jon D. Piganelli, Emily K. Sims
• “CDHu40: a novel marker gene set of neuroendocrine prostate cancer.” Published in Briefings in Bioinformatics. Contributing IU authors: Sheng Liu, Elnaz Pashaei, Yong Zang, Lei Yang, Xin Lu, Jun Wan
• “CRISPR-Cas9-mediated homology-directed repair for precise gene editing.” Published in Molecular Therapy Nucleic Acids. Contributing IU author: Nathan J. VanDusen
• “Decreased vascular reactivity associated with increased IL-8 in 6-month-old infants of mothers with pre-eclampsia.” Published in Pediatric Research. Contributing IU authors: Kok Lim Kua, James E. Slaven, Shanique Edwards, David M. Haas, Christina Tiller, Jeffrey Bjerregaard, Laura S. Haneline, Robert S. Tepper
• “Dendritic cell-specific deletion of PKCδ in offspring of allergic mothers prevents the predisposition for development of allergic lung inflammation in offspring.” Published in Journal of Leukocyte Biology. Contributing IU authors: Jacquelyn D. Lajiness, Jeffrey C. Bloodworth, Ross L. Blankenship, Allison E. Kosins, Joan M. Cook-Mills
• “Early ascertainment of genetic diagnoses clarifies impact on medium-term survival following neonatal congenital heart surgery.” Published in JCI. Contributing IU authors: Benjamin J. Landis, Benjamin M. Helm, Matthew D. Durbin, Lindsey R. Helvaty, Jeremy L. Herrmann, Michael Johansen, Gabrielle C. Geddes, Stephanie M. Ware
• “Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed and Refractory Juvenile Myelomonocytic Leukemia: a Report from the Children's Oncology Group.” Published in Cancer Discovery. Contributing IU authors: Steven P. Angus, Christopher Davis, Steven D. Rhodes
• “Emerging concepts and success stories in type 1 diabetes research: a roadmap for a bright future.” Published in Diabetes. Contributing IU authors: Emily Sims, Carmella Evans-Molina
• “Glomerular Filtration Rate Changes Following UTI in Children With Vesicoureteral Reflux.” Published in JAMA Pediatrics. Contributing IU authors: David S. Hains, Michelle C. Starr, Andrew L. Schwaderer
• “Glucose intolerance as a consequence of hematopoietic stem cell dysfunction in offspring of obese mice.” Published in Molecular Metabolism. Contributing IU authors: Merve Denizli, James Ropa, Lindsay Beasley, Joydeep Ghosh, Kelli DeVanna, Taylor Spice, Laura S. Haneline, Maegan Capitano, Kok Lim Kua 
• “Increased allergic inflammation and decreased lung insulin sensitivity in offspring of obese allergic mothers.” Published in Journal of Leukocyte Biology. Contributing IU authors: Christopher Luke Damron, Jeffrey C. Bloodworth, Aki Hoji, Jose Casasnovas, Kok Lim Kua, Joan M. Cook-Mills
• "Increased vascular deposition of oxidized LDL in untreated juvenile dermatomyositis.” Published in Pediatric Rheumatology. Contributing IU author: Joan M. Cook-Mills
• “Influence of maternal α-lipoic acid supplementation in Sprague Dawley rats on maternal and fetal metabolic health in pregnancies complicated by obesity.” Published in the Journal of Nutritional Biochemistry. Contributing IU author: Kok Lim Kua
• “In vivo CRISPR/Cas9-mediated screen reveals a critical function of TFDP1 and E2F4 transcription factors in hematopoiesis.” Published in Leukemia. Contributing IU author: Ngoc Tung Tran
• “Life-long functional regeneration of in vivo airway epithelium by the engraftment of airway basal stem cells.” Published in Nature Protocols. Contributing IU author: Andrew Tilston-Lünel
• “Mechanisms for initiation of food allergy by skin pre-disposed to atopic dermatitis.” Published in Immunological Reviews. Contributing IU authors: Haoran Gao, Allison E. Kosins, Joan M. Cook-Mills
• “Microparticle Mediated Delivery of Apelin Improves Heart Function in Post Myocardial Infarction Mice.” Published in Circulation Research. Contributing IU author: Michael Rubart
• “miR-146a-5p mediates inflammation-induced β cell mitochondrial dysfunction and apoptosis.” Published in Journal of Biological Chemistry. Contributing IU authors: Preethi Krishnan, Renato Chaves Souto Branco, Staci A. Weaver, Garrick Chang, Chih-Chun Lee, Farooq Syed, Carmella Evans-Molina
• “Mitochondrial DNA Copy Number Variation in Asthma Risk, Severity, and Exacerbations.” Published in the Journal of Allergy and Clinical Immunology. Contributing IU author: Benjamin Gaston
• “Non-coding cause of congenital heart defects: Abnormal RNA splicing with multiple isoforms as a mechanism for heterotaxy.” Published in HGG Advances. Contributing IU authors: John R. Wells, Maria B. Padua, Allison M. Haaning, Amanda M. Smith, Muhammad Tariq, Stephanie M.  Ware
• “R-loops facilitate AAV-mediated nuclease-free gene targeting.” Published in Molecular Therapy. Contributing IU authors: Bryan Hu, Roland W. Herzog
• “Rapidly evolving genome and epigenome editing technologies.” Published in Molecular Therapy. Contributing IU authors: Ngoc Tung Tran, Renzhi Han
• “Redundancy in Innate Immune Pathways That Promote CD8+ T-Cell Responses in AAV1 Muscle Gene Transfer.” Published in Viruses. Contributing IU authors: Ning Li, Sandeep R. P. Kumar, Di Cao, Maite Munoz-Melero, Sreevani Arisa, Bridget A. Brian, Calista M. Greenwood, Kentaro Yamada, Dongsheng Duan, Roland W. Herzog
• “Revisiting the pattern of loss of β-cell function in preclinical Type 1 Diabetes.” Published in Diabetes. Contributing IU author: Carmella Evans-Molina
• “Sodium butyrate prevents cytokine-induced β-cell dysfunction through restoration of stromal interaction molecule 1 expression and activation of store-operated calcium entry.” Published in the FASEB Journal. Contributing IU authors: Chih-Chun Lee, Tatsuyoshi Kono, Farooq Syed, Staci A. Weaver, Paul Sohn, Wenting Wu, Garrick Chang, Carmella Evans-Molina
• “Spatial transcriptomics implicates impaired BMP signaling in NF1 fracture pseudarthrosis in murine and patient tissues.” Published in JCI Insight. Contributing IU author: Simon J. Conway
• “The gut microbiome is associated with susceptibility to febrile malaria in Malian children.” Published in Nature Communications. Contributing IU authors: Kristin M. Van Den Ham, Layne K. Bower, Nathan W. Schmidt
• “Vitamin C supplementation improves placental function and alters placental gene expression in smokers.” Published in Scientific Reports. Contributing IU authors: Robert S. Tepper, David M. Haas

Kudos and Recognition 

• Alissa Muncy from the Linnemann lab presented her thesis defense on September 27, 2024.
• In celebration of Riley Children’s Health marking a century of caring for kids, the organization created a video showcasing the Wells Center’s role in groundbreaking pediatric discoveries, including major advancements in diabetes and NF1 research.
• The 2023-24 annual report from Riley Children’s Health highlights the research and contributions of several Wells Center faculty.
• Melissa Fishel, PhD, was recently named the Myles Brand Scholar in Cancer Research by the IU Melvin and Bren Simon Comprehensive Cancer Center.
• Chandy John, MD, was interviewed by NPR to discuss his study showing evidence of partial resistance to artemisinin derivatives, the primary treatment for malaria, in Ugandan children with severe malaria.
• Rachel Katzenellenbogen, MD, was featured in a TIME article exploring the complexities of HPV diagnosis in women. 
• Mark Kelley, PhD, was featured in a Drug Target Review article about his research on APE1/Ref-1 as a promising target for cancer therapy and preclinical data indicating that other diseases could be addressed.
• Mark Kelley, PhD, has been formally invited by the DePauw University Board of Trustees to join DePauw’s College of Liberal Arts and Sciences Advisory Board. 

Learn more about the Herman B Wells Center for Pediatric Research
Read the August 2024 Newsletter
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