Moderated Poster Discussions - T0 Research/Science

Tuesday, April 15, 2025
2:10 pm - 3:20 pm

T0 Research/Science: Basic biomedical research, including preclinical and animal studies, not including interventions with human subjects.

MATERNAL HEMOGLOBIN A1C IS ASSOCIATED WITH NEWBORN BLOOD PRESSURE (Cardiology / Cardiovascular Disease)
Colman I. Freel, BS, University of Nebraska Medical Center
Diabetes mellitus (DM) affects over 16% of pregnancies. Infants of diabetic mothers (IDM) have an increased risk of developing cardiovascular diseases, with evidence suggesting that cardiovascular physiology, particularly blood pressure, is altered early in life. However, there is a paucity of research evaluating these changes during the neonatal period. Several forms of DM complicate pregnancies, each with distinct pathophysiology and impacts on newborn health. The varying clinical criteria and testing to diagnose DM can make it challenging to study impacts on newborns; however, there are measures of hyperglycemia that can standardize studies. Hemoglobin A1c (HbA1c) remains the gold standard for evaluating glycemic burden, reflecting the average blood glucose level over ~3 months. This method hinges on glucose modifications to cellular proteins, which affects various cell types. If unchecked, hyperglycemia-driven modifications can induce cellular dysfunction, damage, and phenotypic shifts, particularly in endothelial cells, which line blood vessels and regulate blood pressure. Given that glucose crosses the placenta, maternal hyperglycemia may impact fetal endothelial cells. Therefore, we hypothesized that higher maternal HbA1c would correlate with increased newborn blood pressure, reflecting potential impacts on neonatal endothelial cells.

DERMAL EXPOSURE TO MICROCYSTIN-LR THICKENS DERMAL LAYERS IN VIVO AND DISRUPTION OF STRUCTURAL AND IMMUNE SIGNALING IN VITRO (Dermatology)
Benjamin W. French, University of Toledo
Harmful algal blooms (HABs) are on the rise globally, including throughout the Great Lakes region.  HABs produce cyanotoxins, with microcystin-LR (MC-LR) being one of most prevalent and potent of over 300 microcystin congeners. Dermal contact is one of the most common exposure routes to HAB cyanotoxins, and dermatologic symptoms represent one of the most common complaints after HAB exposure. Diseases such as chronic kidney disease (CKD) and atopic dermatitis (AD) can disrupt the skin barrier, potentially increasing susceptibility to MC-LR. Previous work has shown that pre-existing diseases impacting the kidney increase susceptibility to MC-LR. Yet, there is limited research on the dermal route of exposure, even in healthy skin. We sought to evaluate the impact of MC-LR on the skin barrier using in vivo and in vitro models.

MARINOBUFAGENIN AS A POTENTIAL BIOMARKER FOR PREECLAMPSIA AND ITS THERAPEUTIC TARGET (Diagnosis or Treatment of a Disease Process or Clinical Syndromes)
Mehruba Zaman, BS, Virginia Commonwealth University SOM
Marinobufagenin (MBG), a cardiotonic steroid, is not only found to be elevated in preeclampsia (preE) but also may be a potential causative agent for preE. In previous studies, high levels of urinary MBG were found in patients with pre-eclampsia, which is defined as an onset of hypertension and proteinuria during pregnancy. Its pathogenesis lies in MBG causing deleterious signaling and an anti-angiogenic milieu in cytotrophoblasts (CTB) - which are normally involved in vascular remodeling during placental development. We evaluated in preE rat models the effects of anti-MBG human monoclonal antibody on cellular signaling in CTBs, as well as on prepartum blood pressure, kidney function, fetal rat birth weight along with collecting a serial measurement of MBG in human subjects during their pregnancy.

EVALUATION OF PROTOPORPHYRIN IX FLUORESCENCE IMAGING FOR BURN DEPTH DIAGNOSIS IN PORCINE MODELS (Diagnosis or Treatment of a Disease Process or Clinical Syndromes)
Bailey Ann. Donahue, BS, University of Wisconsin School of Medicine and Public Health
Burn injuries affect nearly half a million people annually in the United States, impacting individuals of all ages and often leaving survivors with permanent scarring and adverse long-term sequelae. A key objective in modern burn management is reducing scarring for long-term wellbeing and quality of life. Achieving this goal requires acute determination of burn depth and regenerative capacity of the injured tissue. However, clinical visual assessment, the current standard for determining burn depth, is prone to errors, with inaccuracies occurring in 25-30% of cases. An objective and reliable method for burn depth diagnosis is needed to assist physicians in proper treatment planning.

NOVEL PROTEIN BINDERS: TARGETING TRANSFERRIN RECEPTOR FOR THERAPEUTIC APPLICATIONS (Diagnosis or Treatment of a Disease Process or Clinical Syndromes)
Denise Peng, Yale University
Transferrin receptor (TfR), a transmembrane protein responsible for ferric metabolism, is a key target for disorders implicated with iron dysregulation, ranging from anemia to glioblastoma. Accordingly, Huang et al. (2024) designed a protein binder (Pb) that demonstrated endocytosis and lysosomal trafficking in U-251MG glioblastoma cells. This de novo engineering of Pbs, peptides typically shorter than 65 amino acids (Cao et al., 2022), represents an innovative artificial intelligence technology that circumvents the limitations of traditional monoclonal antibodies (mAbs), namely off-target effects and low stability. In accessing sterically hindered sites while balancing shape complementarity and maximizing tautomer interaction, Pbs can achieve precise targeting of disease-associated molecules and pathways. Here, TfR is an especially promising target due to the broader implications of cellular iron uptake including mitochondrial function and DNA synthesis. Expanding these applications, targeting TfR to fine-tune iron availability can reduce oxidative stress, alleviating tissue damage in Duchenne muscular dystrophy (Alves et al., 2022). We thus hypothesize that validating current and creating novel Pb designs for uptake into muscle cells via TfR internalization can pave the way for new therapeutic delivery mechanisms.

ANTI-FIBROTIC THERAPY FOR PRIMARY SCLEROSING CHOLANGITIS (Gastroenterology / Clinical Nutrition)
Mariam Khwaja, BS, Texas A&M University School of Medicine
Primary sclerosing cholangitis (PSC) is a rare and severe condition in which chronic bile duct injury prevents bile from draining out of the liver properly and thus leads to liver fibrosis. Currently, there are no approved therapeutics for PSC, and the only definitive cure is liver transplant. Hence, an urgent need exists to find effective treatments, particularly interventions that can prevent, reduce, and potentially reverse liver fibrosis.

H2 relaxin (serelaxin) acts on the G protein-coupled receptor (GPCR) ‘Relaxin Family Peptide Receptor 1’ (RXFP1) to mediate vasodilatory and cardioprotective effects in patients with acute heart failure (AHF). However, the long-term beneficial effects of serelaxin in AHF are likely related to its strong anti-fibrotic effects that have been found in animal models of multiple diseases involving fibrosis - including in cardiac, pulmonary, renal, and hepatic organ systems. Recent data suggest that serelaxin may be a promising treatment for diseases characterized by fibrosis. Despite its enormous potential, serelaxin has a short half-life in vivo, is difficult to synthesize, and cross-reacts with the related receptor, RXFP2. In addition, the cAMP-mediated actions of serelaxin may be associated with deleterious long-term effects. To address these limitations, we have identified a novel B-chain-only peptide variant of serelaxin, B7-33, which is RXFP1-specific and ameliorates fibrosis via cell-specific effects on fibroblasts. B7-33 is less expensive to manufacture, and, being a single chain peptide, far easier to functionalize to improve in vivo stability and efficacy.

TARGETING MUTATED HISTONE H3.3 WITH HDAC INHIBITORS: ENHANCING CHROMATIN ACCESSIBILITY TO SUPPRESS DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) PROGRESSION (Genetic and Molecular Medicine)
Rimla Khan, MS, Stanford University
Diffuse Intrinsic Pontine Glioma (DIPG) is a rare and highly aggressive pediatric brain tumor, primarily affecting children between the ages of 5 and 10. Located in the pons, a region crucial for essential functions such as breathing, heart rate regulation, and motor control, DIPG is characterized by its infiltrative nature, which makes surgical removal impossible. The prognosis remains grim, with a median survival of approximately 11 months post-diagnosis. The tumor's rapid progression leads to devastating neurological symptoms, including difficulty walking, talking, swallowing, and, ultimately, respiratory failure.

At the molecular level, DIPG is strongly associated with mutations in the H3F3A gene, leading to the H3.3K27M mutation, a lysine-to-methionine substitution at position 27 of histone H3.3. This mutation disrupts normal epigenetic regulation by altering chromatin structure, silencing tumor suppressor genes, and activating oncogenic pathways, which contribute to uncontrolled tumor proliferation. Additionally, DIPG cells acquire stem-cell-like properties, making them highly resistant to conventional therapies such as chemotherapy and radiation. Histone acetylation, a key regulatory mechanism for gene expression, is also affected in DIPG, further promoting malignancy by allowing the upregulation of oncogenes and silencing of tumor suppressors.

Due to its location, infiltrative growth pattern, and resistance to standard treatments, DIPG remains one of the most challenging pediatric malignancies. Current treatment strategies focus on symptom management and radiation therapy to temporarily slow progression. However, emerging research into targeted molecular therapies, immunotherapy, and epigenetic modifications aims to develop more effective treatments for this devastating disease. Understanding the role of histone mutations and the dysregulation of chromatin modifications is critical in advancing DIPG research and improving patient outcomes.

INVESTIGATING THE INTERACTIONS BETWEEN TREM2 AND COMPLEMENT C1Q PROTEIN THAT ARE IMPORTANT IN NEURODEGENERATIVE DISEASES (Immunology / Allergy)
Cynthia Zhi, Washington University in St. Louis School of Medicine
TREM2 is a signaling receptor expressed on microglia that has emerged as an important drug target for Alzheimer’s disease and other neurodegenerative diseases. While a number of TREM2 ligands have been identified, little is known regarding the structural details of how they engage. The complement cascade initiating protein C1q was recently identified as a ligand for TREM2. The complement pathway is involved in pruning excess synapses, which becomes abnormally activated in Alzheimer’s disease, contributing to neurodegeneration. C1q binding to TREM2 prevents activation of the complement pathway and subsequent synapse pruning. Due to the potential importance in Alzheimer’s diseases, we are interested in studying the interactions between TREM2 and complement C1q protein.

IDENTIFYING AQUAPORIN 3 (AQP3) BINDING PARTNERS IN KAPOSI SARCOMA HERPES VIRUS (KSHV) LATENTLY INFECTED CELLS (Infectious Disease / Immunization)
Christopher N. Kywe, BS, Rosalind Franklin University
Kaposi Sarcoma Herpes Virus (KSHV) is responsible for causing Kaposi Sarcoma, primary effusion lymphoma, Castleman’s disease, and other cancers. It has a two-part lifecycle involving latent and lytic phases. Although the functions of all viral proteins encoded by the KSHV genome are known, there are currently no specific treatments to prevent KSHV infection.

RENAL ISCHEMIA ALTERS EXPRESSION OF APELIN SIGNALING PATHWAY GENES IN SWINE SCATTERED TUBULAR-LIKE CELLS (Nephrology)
Kumar Shivam, MBBS, Mayo Clinic
CD24+/CD133+ scattered tubular-like cells (STCs) are surviving renal cells that acquire progenitor-like characteristics to repair other damaged kidney cells. We have shown that renal artery stenosis (RAS) impairs the reparative capacity of STCs, but the underlying mechanisms remain elusive. Apelin is an endogenous physiological regulator with important cell protective properties, but whether RAS modulates apelin signaling in STCs is unknown.

RADIATION-INDUCED LUNG INJURY IS MEDIATED BY ENDOTHELIAL CELL INTEGRIN BETA 4 (Pulmonary / Critical Care)
Weiguo Chen, MD, University of Illinois Chicago
Radiation-induced lung injury (RILI), a common complication in patients administered thoracic radiotherapy, is characterized by increased lung endothelial cell (EC) inflammation and permeability, and is associated with significant morbidity and mortality. Although the etiology of RILI is poorly understood, a potential molecule of interest in this context is integrin beta 4 (ITGB4) which we have previously identified as a mediator of EC permeability and lung inflammatory responses in acute lung injury. Accordingly, we hypothesized that ITGB4 also mediates lung injury induced by radiation.

HEMIN AND HIGH FLOW UNIQUELY CONTRIBUTE TO ENDOTHELIAL DYSFUNCTION IN THE PATHOGENESIS OF PULMONARY HYPERTENSION IN SICKLE CELL DISEASE (Pulmonary / Critical Care)
Taylor Ramsaroop, MD, University of Illinois Chicago
Pulmonary hypertension (PH) is a severe complication of sickle cell disease (SCD) and is an independent predictor of mortality. Increased flow, pathologic shear stress, and hemolysis have each been shown to influence mediators of endothelial dysfunction, yet the unique interplay of these conditions in SCD-PH is unknown. We have previously shown that hemin, a product of hemolysis, causes endothelial dysfunction under static conditions.

MRSA DYSREGULATES THE AUTOPHAGY-LYSOSOMAL PATHWAY IN LUNG ENDOTHELIAL CELLS (Pulmonary / Critical Care)
Eleftheria Letsiou, PhD, University of Illinois Chicago
Acute lung injury (ALI) caused by methicillin-resistant Staph. aureus (MRSA) is characterized by lung endothelial cell (EC) dysfunction. Previous studies have demonstrated an important role for autophagy in ALI pathophysiology, and bacteria such as MRSA can disrupt this important cellular process. During autophagy, autophagosomes fuse with lysosomes to degrade their content. Disruptions in normal lysosomal functions lead to autophagy inhibition and accumulation of autophagosomes, which are hallmark features of various diseases. Whether this critical autophagy/lysosomal axis is dysregulated in lung EC in MRSA-induced ALI is unexplored.

CHARACTERIZING A TWO-HIT MURINE PULMONARY HYPERTENSION MODEL OF PHENYLHYDRAZINE-INDUCED HEMOLYSIS AND HYPOXIA, ECHOCARDIOGRAPHIC FINDINGS AND MARKERS OF ENDOTHELIAL DYSFUNCTION (Pulmonary / Critical Care)
Nathaniel H. Schwartz, MD, University of Illinois Chicago
Pulmonary hypertension (PH) is a severe complication of sickle cell disease (SCD) with limited therapeutic options, and experimental animal models of SCD-PH are lacking. Hemolytic byproducts are known to be toxic to the pulmonary endothelium, while hypoxia has strong effects on vascular smooth muscle. We have previously shown preliminary data to support a novel murine model of PH using the toxin phenylhydrazine (PHZ) to induce hemolytic anemia and combining this with hypoxia.

CITRULLIATED AND MALONDIALDEHYDE-ACETALDEHYDE MODIFIED FIBRINOGEN PROMOTES MACROPHAGE ACTIVATION IN RHEUMATOID ARTHRITIS (Rheumatology)
Wenxian Zhou, BS, University of Nebraska Medical Center
Rheumatoid arthritis (RA) is characterized by persistent synovial inflammation, leading to progressive joint destruction, disability, and premature mortality.(1) Additionally, patients with RA are at increased risk of extra-articular complications, such as interstitial lung disease and cardiovascular disease.(2) However, mechanisms underlying these pro-inflammatory and pro-fibrotic complications remain incompletely understood. Recent studies have demonstrated that citrullinated (CIT) and malondialdehyde-acetaldehyde (MAA) modified proteins are enriched in joint and lung tissues of RA patients.(3,4) These CIT-MAA co-modified proteins directly activate macrophages, triggering pro-inflammatory and pro-fibrotic responses.(5) However, the specific macrophage intracellular signaling pathways and cytokines released that drive these cellular responses remain unknown (Figure 1).