Peoria Research News: Fall 2025
Alzheimer’s Disease Research Focuses on Myd88 Molecule
More than 7 million Americans currently live with Alzheimer’s disease (AD), yet the underlying causes remain largely unclear, and effective treatments or preventive measures are still lacking. Ken-Ichiro Fukuchi, MD, PhD, and Junling Yang, PhD, have conducted mainly NIH-funded research on AD for over 20 years, focusing on the cellular and molecular mechanisms of AD and developing novel immunotherapeutic strategies. They were the first to show that specific toll-like receptor (TLR) signaling pathways in the immune system modulate AD progression and brain inflammation. Using AD mouse models lacking TLR signaling molecules, they demonstrated the role of immune signaling in disease development. They also pioneered a new immune gene therapy approach, using adeno-associated virus (AAV) vectors to deliver genes that trigger antibody production against amyloid plaques in the brain, significantly reducing AD-like pathology.
Many top AD risk factors, including aging, hypertension, diabetes, obesity, hyperlipidemia, and certain infections, are linked to chronic systemic inflammation, which can promote or even initiate AD-related brain changes. However, the molecular and cellular mechanisms behind this link are still unknown. In their currently NIH-funded project, they are investigating the role of TLR signaling in both systemic and central inflammation in AD, with a focus on Myd88, a key TLR signaling molecule in microglia. To address these questions, they employ interdisciplinary approaches, including molecular biology, gene targeting, cell culture models, immunology, bone marrow stem cell transplantation, gene therapy, bioinformatics, and behavioral neuroscience. Their research explores how microglial Myd88 contributes not only to brain inflammation but also to adult neurogenesis and the integration of new neurons into existing neural circuits.
Ken-Ichiro Fukuchi, MD, PhD, is professor, and Junling Yang, PhD, is research assistant professor in the Department of Cancer Biology and Pharmacology.
Alzheimer’s Disease Research Focuses on Myd88 Molecule
Deshpande Advances Work on Novel Endotracheal Tube
Girish Deshpande, MD, has worked with 10xbeta, a New York-based company, to create a modular design of the novel endotracheal tube by Vilom Innovations, LLC. This will not only reduce the cost of each tube, which can be used short term such as in OR procedures and could be built further to integrate with its own holder for prolonged ICU use. He is currently working to get verification and validation testing performed prior to submission to FDA for regulatory approval. This tube is specially designed not only to decrease unplanned extubations at all ages but will also address several other complications associated with endotracheal intubation. Unplanned extubations are responsible for increased morbidity and mortality across all ages and are responsible for increased hospitalization cost by $41,000 in adults, about $36,000 in children and approximately $49,000 in neonates and premature babies.
Girish Deshpande, MD, is professor of Clinical Pediatrics in the Division of Critical Care Medicine of the Department of Pediatrics
Deshpande Advances Work on Novel Endotracheal Tube
HistoLogic App Helps Students Learn Histology
Medical students must learn an immense amount of knowledge during their first two years of training, so many trainees supplement their education with electronic learning resources. Memory mnemonic videos, online question banks, and medical mobile applications (apps) are a sliver of the options available to students. Jonathan Fisher, PhD, noticed that students struggled with histology, the study of cells and tissues under the microscope. Medical students must know the appearance of healthy tissue in order to recognize the changes that occur with disease. The best way to learn histology is to practice by viewing many examples so Fisher decided to turn the process into a game. Free and downloadable to any electronic mobile device, the HistoLogic app provides high-definition images of tissues and explains their roles in the body. The app also provides hundreds of histology practice questions with three difficulty levels. The randomized questions come in sets of ten, and students can track their score to see how their learning is improving. The HistoLogic prototype contained only one organ system, and Dr. Fisher has added five more since 2021. The final module should be ready by fall of 2026.
Educational apps are a new field for medical education, so Dr. Fisher’s research focuses on the ways students use HistoLogic to learn. Students can opt in to provide anonymous data such as the number of times they launch the app, total time spent on the app, and their highest scores on challenge mode. By analyzing the anonymous data, Dr. Fisher can see trends in the ways students use HistoLogic across the first two years of medical school. He is curious if there are parts of the year with higher use versus lower use. He wonders if there is a link between hours of class time and HistoLogic use. Dr. Fisher wants to know what features attract students to apps and how they use HistoLogic to study.
Jonathan Fisher is associate professor of cell biology in the Department of Health Sciences Education and Pathology
Jonathan Fisher
Building on Pediatric Oncology, Hematology Research
Pedro de Alarcon, MD, and Dr. Manu Gnanamony, PhD, are leading work that focuses on understanding the biology of childhood cancers – primarily neuroblastoma and Hodgkin lymphoma – and the understanding of disorders primarily platelet generation, thrombopoiesis, and stem cell biology with the goal of uncovering disease mechanisms and developing better treatment strategies.
In the area of oncology research, neuroblastoma is the most common cancer diagnosed in infants under one year old. Low-risk neuroblastoma is curable but high-risk neuroblastoma, particularly aggressive neuroblastoma subtypes with aberrant expression of MYCN/MYC grow quickly, resist treatment and have poor survival. Their laboratory recently reported that an immunotherapy drug, directed against a protein present in neuroblastoma cells, can directly kill cancer cells, independent of the immune system. This represents an unexpected and powerful additional mode of action that justifies greater use of this drug. Their current focus is on finding ways to make even the most aggressive drug-resistant neuroblastoma models vulnerable to this immunotherapy. At the same time, they are involved in identifying new compounds and repurposing existing drugs that target MYCN, a critical driver of tumor aggressiveness, with the goal of unlocking new avenues for effective treatment.
Hodgkin lymphoma is one of the most common cancers diagnosed in adolescents and young adults. It is highly curable but at the expense of high rate of long-range complications. In low and intermediate-income countries it is more frequent and has an extra peak incidence in childhood. Studying its biology would help generate therapies with less long-rage side effects. Understanding the disease has been challenging because the malignant Reed-Sternberg (HRS) cells make up less than 1% of the tumor, with the rest consisting of supportive microenvironment cells. The research of de Alarcon and Gnanamony, in collaboration with Dr. Küppers’ laboratory, in Essen, Germany, use laser capture microdissection to isolate HRS cells and compare DNA mutations across age groups and regions. Insights from these studies may help improve therapies and outcomes for children worldwide.
Platelets are tiny blood cells that help form clots and stop bleeding. In the realm of hematology research, de Alarcon and Gnanamony have come to understand that platelets have a broader function beyond clotting. They are involved in inflammation, immune response and cancer metastasis. Normally, the body makes platelets through a well-known pathway controlled by a protein (hormone) called thrombopoietin (TPO). However, during times of hematological stress, like iron deficiency, anemia, cancer or infections, the body produces increased number of platelets through additional mechanisms as of yet poorly understood. Their studies in rat models of iron deficiency showed that iron deficiency anemia did not increase the levels of TPO but increased the levels of certain molecules that can both stimulate blood vessel growth and may also accelerate the formation of megakaryocytes, the cells that give rise to platelets. By studying these adaptive mechanisms, they aim to uncover how the body responds to challenges and how such processes might be harnessed for future therapies.
Pedro de Alarcon, MD, is professor of pediatrics emeritus and William H. Albers Professor Emeritus, in the Department of Pediatrics.
Manu Gnanamony, PhD, is research assistant professor in the Department of Pediatrics.
Dr. Pedro de Alarcon and Dr. Manu Gnanamony
Tripathi’s Research Seeks to Improve Care of Critical Pediatric Patients
As a pediatric intensivist, Sandeep Tripathi, MD, focuses his primary research on improving care of the critically sick patient. Currently, he is involved in two NIH-funded clinical trials. The Stress Hydrocortisone in Pediatric Septic Shock (SHIPSS) trial is focused on answering whether steroids in patients with severe septic shock improve outcomes. In this trial, patients with septic shock are randomly assigned to receive hydrocortisone or a placebo and are followed to assess its impact on morbidity and mortality from septic shock. The Pediatric ICECAP trial is a Bayesian adaptive clinical trial that is trying to answer the complex question of whether therapeutic hypothermia after pediatric out-of-hospital cardiac arrest is beneficial, and if so, what duration of hypothermia can impact outcomes. In this trial, patients who had an out-of-hospital cardiac arrest were assigned to various durations of hypothermia ranging from 12 to 96 hours and assess the impact on their neurodevelopmental outcomes.
Tripathi’s group is also involved in predictive modeling from healthcare data. His group recently completed an analysis of over 10,000 emergency department admissions and developed an online calculator (Bayesian Assessment of Infection [BRAIN]) to calculate the probability of bacterial infection, incorporating clinical gestalt in ways that are not available in traditional models. The calculator is available at Bayesian Prediction for Positive Culture. An abstract submitted by medical student Jessica Haas from this work was awarded Best Abstract at the Society of Critical Care Medicine Midwest Chapter conference in Indianapolis. In collaboration with investigators from UCLA, Tripathi has co-authored a machine learning-based prediction model (DONATE) to predict whether a pediatric patient would die within one hour of terminal extubation (withdrawal of invasive life support). This DONATE model was recently published as a feature article in Pediatric Critical Care Medicine. This model has important applications for end-of-life counseling and resource utilization when families wish to donate organs after cardiac death. DONATE
Another initiative of Tripathi is gaining insights from retrospective patient registry and hospital medical records. His group continues to gain insights into the impact of COVID-19 in children through the Society of Critical Care Medicine VIRUS registry. They have recently validated the updated pediatric sepsis criteria (Phoenix criteria) in children hospitalized with COVID-19 and MIS-C, with results published in Hospital Pediatrics. This study provided external validation of the Phoenix sepsis criteria on an untested population and can be used for further epidemiological studies on sepsis in children hospitalized with COVID-19. COVID-19.
A priority of Tripathi’s research includes Identifying and addressing health care disparities. Recent work has focused on the study of racial and ethnic disparities in Central line-associated bloodstream infection (CLABSI) in 23,000 hospitalized patients over five years from 15 hospitals. This study, published in Infection Control and Hospital Epidemiology, showed that after adjusting for risk factors, Hispanic patients had slightly higher CLABSI rates than non-Hispanic whites. Health care Disparities
Sandeep Tripathi, MD, is professor of clinical pediatrics in the Department of Pediatrics.
Sandeep Tripathi
Research Explores Impact of Loneliness, Social Isolation
Loneliness and social isolation are significant health issues. They have been associated with numerous cardiovascular disease risk factors such as high blood pressure and cholesterol level, smoking, obesity, physical inactivity, and poor diet. Not only adults and the elderly are at higher risk for loneliness and social isolation but also the adolescents and young adults have experienced increased social isolation and feelings of loneliness, especially in the COVID era. Adolescence is a critical developmental stage and a vulnerable period to a variety of stressors, including loneliness and social isolation, a major source of psychosocial stress. The burden of cardiovascular disease in adolescents and young adults can result in a loss of lifetime productivity and an increase in lifetime healthcare costs. Although the impact of loneliness/social isolation on depression-like behavior has been reported, it is unknown whether loneliness/social isolation affects blood pressure in adolescents, and if so, whether these changes are sex dependent.
Researchers in the UICOMP’s Cancer Biology and Pharmacology department (Krishna Kumar Veeravalli, PhD; Sergey Malchenko, MD, PhD; and Marcelo Bento Soares, PhD) conducted collaborative research and discovered that 8-weeks of social isolation is good enough to significantly increase systolic, diastolic, and mean arterial blood pressure in females and elevated heart rate in both sexes of young mice. They also found that body weight gain was dramatically increased in socially isolated females but tended to decrease in socially isolated males. In addition, their research revealed that social isolation decreased gut microbiota diversity and resulted in more compositional fluctuations (changes previously associated with immunity, metabolism, and neurodevelopment). These discoveries from their collaborative efforts were published recently in peer-reviewed scientific journals, including Chronic Stress and Physiology & Behavior.
(Krishna Kumar Veeravalli, PhD; Sergey Malchenko, MD, PhD; and Marcelo Bento Soares, PhD)
Kelly’s Work Focuses on Pediatric Mental Health, Public Health
Sara Kelly, PhD, MPH, is leading impactful research at the intersection of youth mental health, substance use, and public health. Her recent collaborative studies with researchers in Chicago have been published in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP) and JAACAP Open, offering a nationwide analysis of pediatric substance use and mental health encounters before, during, and after the COVID-19 pandemic. These findings are also being shared at major national conferences, including the American Public Health Association (APHA) and the American Academy of Child and Adolescent Psychiatry (AACAP) annual meetings.
Kelly’s research portfolio continues to grow, with several manuscripts under review that explore emerging youth health concerns such as cannabinoid hyperemesis syndrome and climate change anxiety. She leverages large-scale datasets, including electronic health records and public health surveillance systems, to better understand and address these issues. As co-investigator on a multi-site NIH-funded study of long COVID, her work has contributed to publications in JAMA, JAMA Network Open, BMC Public Health, and PLOS ONE, with ongoing efforts to identify populations at higher risk, including members of rural communities who may experience more severe or prolonged impacts of the condition. She also is the PI of the CONNECT study, a mixed methods pilot funded by the UICOMP Center 4 Health Research in partnership with the JOLT Foundation to assess healthcare barriers and improve engagement among vulnerable populations in Central Illinois. In addition, Kelly heads the data team for the Partnership For A Healthy Community, producing regional health reports that inform local strategies and interventions. Through her research, national presentations, and community engagement, Kelly remains committed to translating data into actionable solutions that improve health outcomes for youth and underserved populations.
Sarah Kelly is research assistant professor in the Department of Pediatrics.
