Poster Day 2025: Abstracts: Basic Science

Elizabeth Smith³, Jennifer Baek¹, Kimberly Curry¹, and Rui Wang ^{1, 2}

¹Department of Surgery, Case Comprehensive Cancer Center, Case Western Reserve University

²Department of Surgery, University Hospitals Cleveland Medical Center

³Alabama College of Osteopathic Medicine

Abstract:

Inflammatory bowel disease (IBD) is a group of inflammatory-driven diseases in the gastrointestinal (GI) tract that includes ulcerative colitis (UC) and Crohn’s disease (CD). IBD affects over 3 million people in the USA and puts patients at higher risk of developing colorectal cancer due to the chronic inflammation associated with IBD (data from Crohn’s & Colitis foundation, 2023). Treating the chronic inflammation remains a major challenge for treating patients with UC and lowering the risk of colorectal cancers. Several clinical studies have shown that elevated leucine rich ⍺2 glycoprotein 1 (LRG1) expression in the serum and inflamed colon mucosa of patients with IBD correlates with disease severity and the mechanism by which LRG1 promotes colonic inflammation in IBD is not fully understood^1–3. Our preliminary data shows that: (1) Systemic LRG1 knockout attenuated disease severity in male mice with DSS-induced colitis as shown through disease symptoms and histopathology. (2) LRG1 may promote colonic inflammation by promoting neutrophil extracellular trap (NET) formation. Together, our data suggest that LRG1 plays a pro-inflammatory role in inflammatory bowel disease by promoting neutrophil mediated immunity and NET formation and suggest the potential of blocking LRG1 for patients with UC. Further investigations are needed to elucidate the mechanism by which LRG1 promotes NET formation.

Lawrence LeClaire, PhD

Background:

Dysregulation of kinase signaling is a hallmark of uncontrolled growth, migration, and survival in diverse human cell types. Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), a member of the germinal center kinase (GCK) family, has emerged as a central regulator of cellular signaling pathways. Beyond its known role in breast cancer progression, where it influences cytoskeletal remodeling, invasion, and adhesion, recent studies have demonstrated MAP4K4’s involvement in a wide range of biological systems. MAP4K4 regulates inflammatory signaling in endothelial and immune cells, where its loss diminishes leukocyte adhesion and chemokine production while promoting regulatory T-cell differentiation. In metabolic tissues, such as adipocytes and hepatocytes, MAP4K4 modulates insulin sensitivity and lipid metabolism by affecting mTOR/4E-BP1 and AMPK signaling. Additionally, elevated MAP4K4 activity has been observed in pancreatic and gastric cancers, where it drives tumorigenesis via MLK3 phosphorylation and extracellular-matrix remodeling. Collectively, these findings underscore MAP4K4 as a signaling hub that integrates stress response, adhesion dynamics, and metabolic control across multiple tissues. MAP4K4 is expressed as 55 known splice variants across human tissues, suggesting tissue-specific regulatory functions that remain poorly characterized. This study aims to identify MAP4K4 isozymes enriched in metastatic versus normal epithelial cell types using an inexpensive, rapid PCR-based assay. Establishing this method provides a foundation for comparing MAP4K4 variant expression not only in breast cells but also in other cell systems where MAP4K4 plays key roles in inflammation, metabolism, and differentiation.

Methods:

Primer sets were designed to amplify coding regions corresponding to conserved and variable MAP4K4 domains. Primer Set 1: Exons 2–11 (kinase domain), Primer Set 2: Citron homology (CNH) domain, Primer Set 3: Exons 13–17 (alternatively spliced poly-proline and Arg/Lys repeats), Primer Set 4: Exons 18–20 (interdomain region). cDNA was synthesized from RNA isolated from normal (MCF-10A) and metastatic (MDA-MB-231) human breast epithelial cell lines. PCR fragments were subcloned and sequenced to identify isozyme-specific splice patterns. MAP4K4 tissues expression data were obtained from NCBI database and The Human Protein Atlas

Results:

These primer sets successfully amplified predicted MAP4K4 regions across cell types, confirming the presence of both conserved and tissue-specific splice variant that cross reference with tissues and cancer types.

Conclusion:

This PCR-based system enables detection of MAP4K4 isozyme diversity. Given the kinase’s expanding roles in metabolic regulation, inflammation, and cytoskeletal control, this assay provides a platform to explore MAP4K4 isoforms contribute to signaling specificity in cancer and non-cancer cell types.

Timothy Thompson, OMS-III; Annelise S. Howick, OMS-III; Will Craun, OMS-III; Amanda Kettman, OMS-III; Huda Faiz, OMS-II; James Nolin, FNP-C

Background:

Previous research on Standardized Patients (SPs) demonstrated a positive impact on their healthcare interactions. We sought to explore whether this was truly a result of the experience of being an SP or simply due to working at a medical school. This study compares SPs with other medical school employees to identify the specific factors that influence changes in their perspectives on multiple dimensions of healthcare since being hired. The primary purpose is to describe the impact of being an SP on health consciousness personally and with relationships to others. We hypothesized that SP’s experiences would enhance their health consciousness.

Methods:

A survey was emailed to SPs and other medical school employees, measuring perspectives on their personal health, family health, and physicians, since working at the school. Answers involved a Likert scale with values ranging from strongly disagree to strongly agree. T-tests were used to analyze the mean difference between answers across both groups.

Results:

From 96 responses, results indicated a positive trend toward increased health consciousness among SPs in comparison to other medical school employees. T-test analyses revealed that SPs have a statistically significant increase in understanding of what a patient doctor relationship should look like (p = .003), comprehending their treatment (p = .001), and having more confidence asking their PCP about their health (p = .004). SPs were also more likely to increase their time exercising daily (p = .03), go to doctors just for OMM (p = .04), and have more empathy for people with chronic (p = .008) and psychiatric illnesses (p = .02). Lastly, SPs were more cognizant of the quality of their physical exam (p = .003), had more trust with their physician (p = .04), and gained more respect for physicians (p = .0007) through being a part of the standardized patient program.

Conclusion:

The study's findings identify positive impacts of working as a Standardized Patient, as opposed to a general medical school employee, on health consciousness. Time and experience in standardized medical encounters may improve SP’s understanding of physicians, treatment, and making healthy choices.

Deven Lackraj, Elaine Hapa, Priyanka Kundu, Caroline Lewis, Abby Tavallai

Introduction:

The number of Americans who are living with at least one major chronic health condition was estimated to be near 129 million, nearly 38% of the country’s population in 2024. The out-of-pocket cost of medication in America has been rising over the past decade and a half, with a reported increase of 41% between 2009 and 2019. Much of these increased costs can be attributed to prescription drug costs among chronic conditions. The purpose for this study was to evaluate the average annual out-of-pocket spending per person on prescription medications among adults in America.

Methods:

Using published journal articles and publicly available information from government websites, articles were identified pertaining to the topic of interest. Using the gathered information, a secondary data analysis was conducted to evaluate the variation in average annual out-of-pocket spending on prescription medications among U.S. adults ages 18 and older with chronic conditions. Chronic conditions examined were: obesity, hypertension, high cholesterol, coronary heart disease, COPD, asthma, chronic kidney disease, diabetes, cancer (excluding skin cancer), and depression. Demographic characteristics such as type of insurance coverage, Medicare/Medicaid beneficiary status, and geographic region.

Results:

In 2022, the average annual cost of out-of-pocket medical spending per county ranged from $1,010 or less per person to over $1,200. It was found that there was overlap among the counties with the highest out-of-pocket costs and counties that contained the highest burden of chronic disease. The burden of health related to chronic conditions was highest in the Southeastern United States. A person’s insurance type influenced the estimated out-of-pocket costs an insurer would have to pay. It was found that patients on Medicare Part D paid nearly 2.5 times the amount ($4500 vs. $1800) for ultra-expensive drugs when compared to persons with a commercial insurance plan. For persons with five chronic conditions, the out-of-pocket costs were above the average annual cost at nearly $2000; and in those with eight chronic conditions, the costs were estimated to be above $3600 annually. Prescription drugs for cardiovascular disease, diabetes, and cancer accounted for the majority of the annual healthcare costs.

Conclusion:

Out-of-pocket prescription spending remains a significant burden for adults with chronic conditions in the United States. Costs are highest among individuals with multiple chronic diseases, patients covered by Medicare Part D or high deductible plans, and those living in regions with greater disease prevalence. These patterns highlight the need for policy efforts aimed at reducing financial barriers to essential medications and promoting the management and prevention of chronic conditions in vulnerable populations. Additionally, it is equally important to consider the nature and severity of disease, as the number of concurrent chronic conditions is not solely sufficient for evaluation of healthcare expenses. Future studies could be aimed at evaluating health policy in regions with high burdens of chronic conditions that also have an increased out-of-pocket costs. Another future study could examine the effects of the Inflation Reduction Act’s impact on prescription medication and out-of-pocket healthcare costs following implementation of the legislation. Furthermore, future studies can examine the impact of expected changes to the Medicare out-of-pocket cap in 2025 and future price negotiations starting in 2026.