Wells Center Newsletter | August 2024

Top News

Acute myeloid leukemia discovery tackles drug-resistant gene mutations
Researchers from the Kapur lab and their collaborators unveiled insights expected to enhance treatment options for acute myeloid leukemia (AML). With a new chemical compound engineered to overcome drug-resistant gene mutations not targeted by current treatments, the researchers aim to provide a new alternative with longer-lasting effects and improve outcomes for future patients battling this aggressive disease. 
Read more about this research.

New gene therapy approach shows promise for Duchenne muscular dystrophy
Researchers in our gene and cell therapy program have made a significant breakthrough in developing a new gene therapy approach that restores full-length dystrophin protein, which could lead to new treatments for people with Duchenne muscular dystrophy. In a recent study published in Nature Communications led by Renzhi Han, PhD, the team demonstrated the effectiveness of this novel gene therapy technology in improving muscle tissue and overall strength in mice models of Duchenne muscular dystrophy. 
Read more about this research.

Summer internships empower future physicians and scientists 
More than 40 high school and undergraduate students participated in the Wells Center Summer Internship, the Medical Physician Engineers, Scientists and Clinicians Preparatory (MPESC-Prep) program and the Cooperative Center of Excellence in Hematology (CCEH) program from June to July. The students learned from experts at IU while conducting their own research to present at the end of their programs.
Meet some of the interns.

New research explores the urea cycle’s strong connection to fatty liver disease
Brian DeBosch, MD, PhD, joined us in July 2024 to lead the Wells Center’s newly established nutrition and molecular metabolism research program. DeBosch is making strides in understanding the molecular origins of fatty liver disease, a leading cause of liver failure in the United States. In a study recently published in Cell Metabolism, DeBosch and his research collaborators uncovered a critical link between defects in the urea cycle and the development of fatty liver disease.
Learn more. 

Team Wells Updates

Indianapolis welcomes international breath research experts for 2024 Breath Summit
In June, more than 100 breath research specialists traveled to Indianapolis for the 2024 Breath Summit. This year the Wells Center hosted the event in collaboration with the International Association of Breath Research (IABR). This conference offers attendees an engaging opportunity to hear about the latest breakthroughs and emerging topics in breath research, network and establish new connections with peers. 

2024 IU-CCEH Workshop
The annual IU Cooperative Center of Excellence in Hematology (CCEH) workshop took place June 25-27. The program welcomed 18 students from the CCEH, MPESC-Prep, Wells Center Summer Internship, and MOSIAC Crispus Attucks High School programs to learn about the latest hematology techniques and research from experts at IU. 

2024 Cardiac Retreat 
The cardiac developmental biology research group hosted their annual retreat in Bloomington, Indiana on July 13. The retreat consisted of internal guests with nine external world-class speakers including Dr. Marco Osterwalder from the University of Bern, Dr. Felix Engel from the University of Erlangen, Dr. Benoit Bruneau from the Gladstone Institutes, Dr. Sean M. Wu from Stanford University, Dr. Guo Huang from the University of California, San Francisco, Dr. Rajan Jain from the University of Pennsylvania, Dr. Xingbo Xu from University Medical Center of Goettingen and Dr. Jose Luis de la Pompa from the Spanish National Center for Cardiovascular Research.

2024 Gaston PPG Scientific Meeting
In July, members from the pediatric translational research group's Gaston lab and their collaborators held their 2024 PPG scientific meeting at Case Western Reserve University in Cleveland. They recapped their grant's research progress and planned for the year ahead.

Support from Strides for Sarcoma
On August 6, Gabriella and Nicholas Conjelko, the twin founders of Strides for Sarcoma, visited the Wells Center with the Riley Children’s Foundation to present the Pollok lab with a $7,500 donation to fuel sarcoma research following their inaugural fundraising event in July. The Conjelkos started the organization in support of their two cousins who were diagnosed with sarcoma.

2024 Barth Syndrome Conference
Simon Conway, PhD, was a speaker at the 2024 Barth Syndrome Foundation Biennial International Scientific, Medical, and Family Conference that brings together families, scientists and clinicians affected by Barth Syndrome to learn from one another and to hear about the latest therapeutic approaches and discoveries within the field. He presented a talk on his new patient-tailored Barth Syndrome mouse model.

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

Discovery in Action

Congratulations to Grant and Award Recipients
Wells Center members have received a vast number of grants and awards in recent months. A select few are highlighted below.

Melissa Fishel, PhD, Mark Kelley, PhD, Silpa Gampala, PhD & Steven Rhodes, MD, PhD | “Investigation of redox signaling as a therapeutic target in MPNST” (Department of Defense - Neurofibromatosis Research Program)

Renzhi Han, PhD | Gap Fund award (IU Innovation and Commercialization Office)

Santhosh Pasupuleti, PhD | “Targeting IL1RAP and CCN1 in Juvenile Myelomonocytic Leukemia” (2024 Ralph W. and Grace M. Showalter Research Award) / "Targeting PTX3 and IL-15RA in Juvenile Myelomonocytic Leukemia" (Leukemia Research Foundation)

Karen Pollok, PhD, Pankita Pandya, PhD & Reza Saadatzadeh, PhD | “Mitigating Therapy Resistance by Combination CDK4/6 and PI3K/mTOR Inhibition in Pediatric & AYA Osteosarcoma” (Department of Defense) | “Development of Therapeutic Strategies for Targeting BET Proteins and ALK in Rare Models of Embryonal Rhabdomyosarcoma with Aggressive Variants” (Department of Defense)

Emily K. Sims, MD | “Robust Mass Spectrometric Protein/Peptide Assays for Type 1 Diabetes Clinical Applications” (Pacific Northwest National Laboratory)

Recent Publications

• “A Barth Syndrome Patient-Derived D75H Point Mutation in TAFAZZIN Drives Progressive Cardiomyopathy in Mice.” Published in International Journal of Molecular Sciences. Contributing IU authors: Paige L. Snider, Elizabeth A. Sierra Potchanant, Zejin Sun, Donna M. Edwards, Ka-Kui Chan, Catalina Matias, Aditya Sheth, P. Melanie Pride, R. Mark Payne, Michael Rubart, Jeffrey J. Brault, Grzegorz Nalepa, Simon J. Conway
• “Alkynyl nicotinamides show antileukemic activity in drug-resistant acute myeloid leukemia.” Published in Journal of Clinical Investigation. Contributing IU authors: Baskar Ramdas, Ruchi Pandey, Rahul Kanumuri, Santhosh Kumar Pasupuleti, Sheng Liu, Jun Wan, Laura S. Haneline, Reuben Kapur
• “5-HTP inhibits eosinophilia via intracellular endothelial 5-HTRs; SNPs in 5-HTRs associate with asthmatic lung function.” Published in Frontiers in Allergy. Contributing IU authors: Jeffrey C. Bloodworth, Samantha L. McCarty, Samantha H. Averill, Joan M. Cook-Mills
• “A Golden Hour and Golden Opportunity for β-Cell Preservation.” Published in Diabetes. Contributing IU author: Carmella Evans-Molina 
• “Cardiomyopathy in Duchenne Muscular Dystrophy and the Potential for Mitochondrial Therapeutics to Improve Treatment Response.” Published in Cells. Contributing IU author: Renzhi Han
• “Chopping down antibodies for a good cause.” Published in Molecular Therapy. Contributing IU authors: Moanaro Biswas, Roland W. Herzog
• “Clinical Decision Analysis of Genetic Evaluation and Testing in 1013 Intensive Care Unit Infants with Congenital Heart Defects Supports Universal Genetic Testing.” Published in Genes. Contributing IU authors: Benjamin M. Helm, Stephanie M. Ware
• “Clinical Genetic and Genomic Testing in Congenital Heart Disease and Cardiomyopathy.” Published in Journal of Clinical Medicine. Contributing IU authors: Mahati Pidaparti, Gabrielle C. Geddes, Matthew D. Durbin
• “Comparisons of Metabolic Measures to Predict T1D vs Detect a Preventive Treatment Effect in High-Risk Individuals.” Published in the Journal of Clinical Endocrinology & Metabolism. Contributing IU authors: Emily K. Sims, Heba M. Ismail
• “Consensus Guidance for Monitoring Individuals With Islet Autoantibody-Positive Pre-Stage 3 Type 1 Diabetes.” Published in Diabetes Care. Contributing IU authors: Heba Ismail, Emily K. Sims, Linda A. DiMeglio
• “Critical Organ Dysfunction and Preoperative Mortality in Newborns with Hypoplastic Left Heart Syndrome.” Published in American Journal of Perinatology. Contributing IU authors: Matthew D. Durbin , Paulomi Chaudhry , Alyx Posorske , Ellen Voskoboynik 
• “Development and Validation of a Novel Placental DNA Methylation Biomarker of Maternal Smoking during Pregnancy in the ECHO Program.” Published in Environmental Health Perspectives. Contributing IU authors: Robert S. Tepper
• “Effect of estrogen receptor α on cardiopulmonary adaptation to chronic developmental hypoxia in a rat model.” Published in American Journal of Physiology-Lung Cellular and Molecular Physiology. Contributing IU authors: Patricia Esparza, Huanling Gao, Elizabeth A. Mickler, Marjorie E. Albrecht, Amanda J. Fisher, Bahktiyor Yakubov, Todd G. Cook, James E. Slaven, Robert S. Tepper
• “Efficacy of supplemental oxygen in reducing the need for laser or intravitreal bevacizumab in preterm infants with stage 2 retinopathy of prematurity.” Published in BMC Ophthalmology. Contributing IU authors: Robert Minturn, Kelly Hartigan, Sravanthi Vegunta, Charline Boente, Lilian Golzarri-Arroyo, Elizabeth Hynes, Elleen Laughlin, Kathryn Haider & Kok Lim Kua
• “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, Xiaoling Xuei
• “Fibroblast Smad7 Induction Protects the Remodeling Pressure-Overloaded Heart.” Published in Circulation Research. Contributing IU authors: Claudio Humeres, Arti V. Shinde, Izabela Tuleta, Silvia C. Hernandez, Anis Hanna, Shuaibo Huang, Harikrishnan Venugopal, Simon J. Conway, Nikolaos G. Frangogiannis
• “Genetic Testing Resources and Practice Patterns Among Pediatric Cardiomyopathy Programs.” Published in Pediatric Cardiology. Contributing IU author: Stephanie M. Ware
• “HPV Vaccine Awareness, Past Behaviors, and Future Intentions Among a Diverse Sample of Fathers Aged 27 to 45 Years: A National Survey.” Published in American Journal of Men's Health. Contributing IU authors: Kevin M. Quist, Gregory Zimet
• “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
• “Induction of the Mdm2 gene and protein by kinase signaling pathways is repressed by the pVHL tumor suppressor.” Published in PNAS. Contributing IU authors: Alexander R. Mabry, Arnima Singh, Brianna Mulrooney, James Gorman, Abigail R. Thielbar, Eric R. Wolf, Lindsey D. Mayo
• “Innate Immune Sensing of Adeno-Associated Virus Vectors.” Published in Human Gene Therapy. Contributing IU authors: Di Cao, Roland W Herzog, Sandeep R. P. Kumar
• “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
• “Isopentyl-Deoxynboquinone Induces Mitochondrial Dysfunction and G2/M Phase Cell Cycle Arrest to Selectively Kill NQO1-Positive Pancreatic Cancer Cells.” Published in Antioxidants & Redox Signaling. Contributing IU authors: Lingxiang Jiang, Yingchun Liu, Soumya Tumbath, Jiangwei Wang, Xiaolin Su, Kashif Rafiq Zahid, Katherine Li, Yaomin Chen, Kai Yang, Xiumei Huang
• “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
• “Neratinib, a pan ERBB/HER inhibitor, restores sensitivity of PTEN-null, BRAFV600E melanoma to BRAF/MEK inhibition.” Published in Frontiers in Oncology. Contributing IU authors: Dana K. Mitchell, Shelley A. H. Dixon, Steven D. Rhodes, Steven P. Angus
• “Noncanonical Microprotein Regulation of Immunity.” Published in Molecular Therapy. Contributing IU authors: Cydney Nichols, Van Anh Do-Thi, Daniel C. Peltier
• “Novel Echocardiogram Analysis Of Cardiac Dysfunction Is Associated With Mortality In Pediatric Sepsis.” Published in Shock. Contributing IU authors: Daniel T. Cater, Roberto F. Machado, Courtney M. Rowan, Benjamin Gaston
• “Oxygen tension-dependent variability in the cancer cell kinome impacts signaling pathways and response to targeted therapies.” Published in iScience. Contributing IU authors: Adedeji K. Adebayo, Poornima Bhat-Nakshatri, Christopher Davis, Steven P. Angus, Cihat Erdogan, Hongyu Gao, Nick Green, Brijesh Kumar, Yunlong Liu, Harikrishna Nakshatri
• “Prenatal Inflammatory Exposure Predisposes Offspring to Chronic Kidney Diseases Via the Activation of the eIF2α-ATF4 Pathway.” Published in Inflammation. Contributing IU authors: Ying Liu, Weinian Shou
• “Role of FoxP3+ Regulatory T Cells in Modulating Immune Responses to Adeno-Associated Virus Gene Therapy.” Published in Human Gene Therapy. Contributing IU authors: Maite Muñoz-Melero, Moanaro Biswas
• “SARS-CoV-2 Selectively Induces the Expression of Unproductive Splicing Isoforms of Interferon, Class I MHC, and Splicing Machinery Genes.” Published in International Journal of Molecular Sciences. Contributing IU author: Rafael Polidoro
• “SERCA2a overexpression improves muscle function in a canine Duchenne muscular dystrophy model.” Published in Molecular Therapy Methods & Clinical Development. Contributing IU author: Roland W. Herzog
• “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
• “Systemic delivery of full-length dystrophin in Duchenne muscular dystrophy mice.” Published in Nature Communications. Contributing IU authors: Yuan Zhou , Chen Zhang, Weidong Xiao, Roland W. Herzog, Renzhi Han
• “Targeting miR-25 to alleviate DMD-related muscle dysfunction.” Published in Molecular Therapy Nucleic Acids. Contributing IU authors: Shuang Li, Renzhi Han
• “The SWI/SNF chromatin remodelling complex regulates pancreatic endocrine cell expansion and differentiation in mice in vivo.” Published in Diabetologia. Contributing IU authors: Rebecca K. Davidson, Wenting Wu, Sukrati Kanojia, Rajani M. George, Kayla Huter, Kassandra Sandoval, Meredith Osmulski, Nolan Casey, Jason M. Spaeth
• “Viral Vector Based Immunotherapy for Peanut Allergy.” Published in Viruses. Contributing IU authors: Miguel Gonzalez-Visiedo, Roland W. Herzog, Maite Munoz-Melero, Sophia A. Blessinger, Joan M. Cook-Mills

Kudos and Recognition 

• Congratulations to the following Wells Center graduate students on their recent thesis defenses!
  • Nayela Chowdhury from the Fishel lab presented on May 23, 2024.
  • Sukrati Kanojia from the Spaeth lab presented on June 6, 2024.
• Congrats to the following Wells Center faculty members on their recent promotions! 
  • Andrea Conroy, PhD - Associate Professor 
  • Melissa Fishel, PhD - Associate Professor 
  • Karen Pollok, PhD - Professor
  • Baskar Ramdas, PhD - Associate Research Professor
  • Kai Yang, PhD - Associate Professor 
  • Ji Zhang, PhD - Associate Professor
• Olivia Bednarski, an MSTP student working with the Wells Center’s infectious diseases and global health program, spent two months in Uganda to conduct a project focused on establishing a point-of-care test for myoglobin levels, aiming to discern the role of rhabdomyolysis in acute kidney injury during severe malaria infections.
• Ivana Daniels, a PhD student in the Gaston lab, was named a 2024-2025 Indiana Space Grant Consortium Doctoral Fellow. 
• Ben Gaston, MD, and Mike Davis, PhD, RRT, were featured in a story by Riley Children's Health highlighting the Wells Center’s pediatric translational research group’s innovative use of high-speed video microscopy and immunofluorescence microscopy in diagnosing primary ciliary dyskinesia.
• Carmella Evans-Molina, MD, PhD and Linda DiMeglio, MD, are recognized as 2024 Women Inspiring and Elevating Leadership in Diabetes (WIELD) Trailblazers. They were nominated by their peers for their critical impact on research and care in the fields of diabetes, obesity and metabolism, and join an esteemed group of 50 women experts from around the world.
• Radek Kaczmarek, PhD, was recently interviewed by the Video Journal of Hematology & Hematological Oncology to discuss current and emerging gene therapies for hemophilia.
• Radek Kaczmarek, PhD, was also a panelist on a recent episode of the Global Hemophilia Report podcast to discuss FVIII inhibitors in Hemophilia A.
• Renzhi Han, PhD, was awarded a $25,000 grant from the IU Innovation and Commercialization Office to support his triple-adeno-associated virus vector system, a type of technology that can be engineered for gene therapy applications involving extra-large genes. Dr. Han joins two other IU faculty who recently received Gap Funds, which supports projects and enhances the commercialization of faculty innovations.
• 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. He will present a talk about the same topic at the American Association of Pharmaceutical Scientists conference in October.
• Eyram Kpenu, an MD/PhD candidate in Dr. Mark Kelley’s lab, is a 2024 Deutsch Scholarship awardee.
• Rafael Polidoro, PhD, was a guest on a recent MicrobeTV podcast to discuss his career and research on the gut microbiome. 
• Rachel Ramos is a research technician in the Felton lab who was Miss South Bend 2024 and competed in Miss Indiana 2024.

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