Community outreach and engagement within a partnership structure is conceptualized, implemented, and evolves through relationships among partner groups, which are in turn affected by their institutional and geographic contexts. Furthermore, factors like leadership style and partner areas of expertise influence the scope and level of representation of community partners within a multi-institutional research partnership. The Meharry-Vanderbilt-TSU Cancer Partnership is the longest-standing, continuously funded Comprehensive Partnerships to Advance Cancer Health Equity (CPACHE) site. The goal of this project is to understand the role of community outreach and engagement within the MVTCP, and how it has grown and evolved over time. The MVTCP Planning & Evaluation Core conducted interviews (n=41) with MVTCP partnership members (including faculty, staff, students, and community advisory board members) between June and September 2024 as part of a broader study on partnership impact. For the sub-study proposed in this abstract, we analyzed 12 interviews with faculty and community advisory board members who played key roles in shaping and supporting community outreach and engagement of the MVTCP over time. Emerging themes include partner expectations regarding community outreach and engagement; partner definitions of community engagement; understanding how engagement practices influenced partnership behaviors; and community contributions. Findings will inform improvement processes and efforts to continue to build a sustainable partnership that addresses cancer disparities using many strategies informed by and committed to engaging community members in the research ecosystem. Calandra Whitted, Sarah Suitor, Ashmeet Oberoi, Dana Marshall, Rebecca Selove, Meredith Meadows, Karen Winkfield. Community outreach and engagement in a multi-institutional cancer partnership: Lesson from two decades of partnership and practice [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr B067.

Background Hereditary cancer syndromes cause a high lifetime risk of early, aggressive cancers. Early recognition of individuals at risk can allow risk-reducing interventions that improve morbidity and mortality. Family health history applications that gather data directly from patients could alleviate barriers to risk assessment in the clinical appointment, such as lack of provider knowledge of genetics guidelines and limited time in the clinical appointment. New approaches allow linking these applications to patient health portals and their electronic health records (EHRs), offering an end-to-end solution for patient-input family history information and risk result clinical decision support for their provider. Methods We describe the design of the first large-scale evaluation of an EHR-integrable, patient-facing family history software platform based on the Substitutable Medical Applications and Reusable Technologies on Fast Healthcare Interoperability Resources (SMART on FHIR) standard. In our study, we leverage an established implementation science framework to evaluate the success of our model to facilitate scalable, systematic risk assessment for hereditary cancers in diverse clinical environments in a large pragmatic study at two sites. We will also evaluate the success of the approach to improve the efficiency of downstream genetic counseling resulting from pre-counseling pedigree generation. Conclusions Our research study will provide evidence regarding a new care delivery model that is scalable and sustainable for a variety of medical centers and clinics. Trial registration This study was registered on ClinicalTrials.gov under NCT05079334 on 15 October 2021.

Fetuin-A, also known as alpha-2-Heremans-Schmid-glycoprotein (Ahsg), is a multifunctional molecule with diverse roles in biological processes such as mineralization, tumor growth, and inflammation. This review explores the involvement of Ahsg in various cancers, including liver, breast, prostate, colorectal, brain, osteosarcoma, and lung cancers. In many cancer types, Ahsg promotes tumor growth, invasion, and metastasis through various mechanisms, including cellular adhesion, spreading, chemotaxis, and modulation of cell-growth signaling pathways. Additionally, Ahsg has been implicated in the regulation of inflammatory cytokine production, making it a potential marker of inflammation in cancer. The complex interplay between Ahsg and cancer progression highlights its potential as a diagnostic biomarker and therapeutic target in various cancers. However, further research is needed to fully elucidate the mechanisms of action of Ahsg in cancer and to explore its clinical implications in cancer diagnosis, prognosis, and treatment.

A person's phenotypic sex (i.e., endogenous expression of primary, secondary, and endocrinological sex characteristics) can impact crucial aspects of genetic assessment and resulting clinical care recommendations. In studies with genetics components, it is critical to collect phenotypic sex, information about current organ/tissue inventory and hormonal milieu, and gender identity. If researchers do not carefully construct data models, transgender, gender diverse, and sex diverse (TGSD) individuals may be given inappropriate care recommendations and/or be subjected to misgendering, inflicting medical and psychosocial harms. The recognized need for an inclusive care experience should not be limited to clinical practice but should extend to the research setting, where researchers must build an inclusive experience for TGSD participants. Here, we review three TGSD participants in the Family History and Cancer Risk Study (FOREST) to critically evaluate sex- and gender-related survey measures and associated data models in a study seeking to identify patients at risk for hereditary cancer syndromes. Furthermore, we leverage these participants' responses to sex- and gender identity-related questions in FOREST to inform needed changes to the FOREST data model and to make recommendations for TGSD-inclusive genetics research design, data models, and processes.

Abstract PURPOSE: Family Health History (FHH) is a key factor in assessing cancer risk, yet health providers often do not have adequate time or resources to collect FHH systematically. African Americans and other medically underserved populations suffer significantly higher cancer incidence and mortality. These populations would benefit if their cancer risk were better defined. The Family History and Cancer Risk Study (FOREST) aims to implement a patient-facing web-based FHH cancer risk assessment platform called MeTree in a clinic with a high percentage of underserved patients at Meharry Medical College (MMC) and a cohort at Vanderbilt University Medical Center. METHODS: Partnering with the MMC Community Engagement Core (CEC), we conducted two virtual studios with 12 Nashville minority community members. Topics of concern were medical data privacy, potential benefits, and proper informed consent. CEC recommendations informed our pre-implementation planning. Recruitment methods consisted of a staffed table outside of and, later, presence inside the MMC Family & Community Med. Clinic waiting room. Patients could also request assistance to navigate MeTree with the study research coordinator (in person or virtually). RESULTS: Since October 2022, 76 potential participants have been invited to FOREST from MMC. 26 patients were interested, 18 were eligible, 16 patients consented, and 12 patients completed the MeTree FHH. Of note, 6 patients utilized in-person assistance from the research study coordinator. Overall, 2 of the 12 patients who completed MeTree were determined to be at high-risk for cancer. CONCLUSION: We observed a 30% enrollment rate and 43% completion rate. Also, 6 of 26 patients requested and received assistance. In-person recruitment had the highest volume of potential enrollments (16 interested), yet lower completion rates (5/16 = 31%) compared to the pamphlet QR code (5 interested with 3/5 completing = 60%). We realize that these numbers are not large enough to show statistical significance at this early stage, and we plan to implement FOREST in a higher volume clinic (Internal Medicine at Nashville General Hospital) to determine if this trend scales. Citation Format: Clasherrol Edwards, Dana R. Marshall, Leah Alexander, Justin D. Andujar, S.T. Bland, Jillian Duke, Sarah Jones, Jeffrey Leegon, Kate F. Mittendorf, Lori A. Orlando, Georgia L. Wiesner, Siddharth Pratap. Implementation of the FOREST cancer risk study at an HBCU: The family history and cancer risk study at Meharry Medical College [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A079.

From the earliest recognition of families with a high rate of cancer over 100 years ago, researchers have been focused on the genetic underpinnings of inherited cancers; however, identification remains a significant challenge due to persistent barriers across patient, provider, and health system stakeholders, despite recent advances in the development of electronic medical records (EMR) and risk prediction tools that use family health history (FHH) information. Innovations in bioinformatic technology hold great promise in overcoming many of these barriers, particularly with the development of FHH applications that collect and analyze family data and SMART-on-FHIR capabilities that can integrate third-party apps with the EMR.

Abstract Colorectal cancer (CRC) is the third most common cancer, for both incidence and mortality, in the United States 1 Although incidence and mortality are decreasing for all races and ethnicities in the U.S., African American (AA) males continue to disproportionately bear the burden of this disease. Socioeconomic status (SES) accounts for some of this disparity as AAs, like many underserved populations, are impacted by low socioeconomic status. Individuals with the lowest SES are 40% more likely to be diagnosed with CRC than those with the highest SES. However, SES doesn't account for all of this disparity. Significant differences in the transcriptomes of AA and Caucasian American (CA) CRC tumors have been reported (UNC reference). Publicly available databases house large numbers of previously analyzed and published studies that can be analyzed again on the background of accumulated knowledge of genes and pathways and provide new insights into the biology of those tumors that may reveal new targets for therapy. With this idea in mind, GSE28000, stored in the NCBI GEO database, was identified for further analysis. The transcriptomes had been characterized using the Agilent-014850 Whole Human Genome Microarray 4 × 44K G4112F platform. The transcriptomes for 24 AA males and 16 CA males were compared using the Biostatistical analysis performed using GEO2R. This resulted in the identification of 2150 differentially expressed, annotated, genes (p≤0.05). The differentially expressed genes were uploaded into Webgestalt and an over-representation analysis for diseases was performed using the OMIM database. A statistically significant (Benjamini & Hochberg FDR p≤0.05) group of four genes associated with CRC was identified. These genes, with log2 differential expression and p-value respectively, were PIK3CA (-0.36861932), FGFR3 (-0.83181818), DCC (0.32934659), and SRC (0.37958239). A positive log difference indicates higher expression in the tumors of AA patients. Although these data are intriguing, the inability to generalize these results from this single study were clear, so we sought to validate these results in other publicly available databases. These validation efforts are ongoing but the difficulty in drawing strong conclusions about this outcome is in the underrepresentation of AA patients in cohorts and clinical trials. African American males' high incidence and mortality rate in CRC and their low presence in clinical trials embellishes the lack of racial equity in clinical trials. A study by the Mayo Clinic in 2013 pointed out of 14,232 CRC trials enrolled, only 746 were African American (11,850 CA). These inequitable results press for the need of an increase in African Americans and other disproportionately affected groups through the cooperation amongst researchers, doctors, minorities, and cancer institutes. Citation Format: Darryl A. Sams, Dana R. Marshall. Gene expression levels correlation to colon cancer disparities amongst African and Caucasian American men [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-226.

Acinetobacter baumannii is an opportunistic bacterial pathogen that causes severe infections in immunocompromised patients. The emergence of multi- and pan-drug resistant strains of A. baumannii from clinical sources has confounded treatment and enhanced morbidity and mortality associated with these infections. One way that A. baumannii circumnavigates environmental and antimicrobial challenge is by forming tertiary architectural structures of cells known as biofilms. Biofilm-inhibiting molecules could be deployed as a potential chemotherapeutic strategy to inhibit or disrupt A. baumannii biofilms and mitigate adverse outcomes due to infection. Lactoferrin is an innate immune glycoprotein produced in high concentrations in both human and bovine milk which has previously been shown to have antibacterial and antibiofilm activities. We sought to test lactoferrin against a bank of clinical isolates of A. baumannii to determine changes in bacterial growth or biofilm formation. Our results indicate that human lactoferrin has slightly more potent antibacterial activities than bovine lactoferrin against certain strains of A. baumannii and that these effects are associated with anatomical site of isolation. Additionally, we have shown that both bovine and human lactoferrin can inhibit A. baumannii biofilm formation and that these effects are associated with anatomical site of isolation and whether the strain forms robust or weak biofilms.

Background Acinetobacter baumannii is a gram-negative bacterium which causes opportunistic infections in immunocompromised hosts. Genome plasticity has given rise to a wide range of strain variation with respect to antimicrobial resistance profiles and expression of virulence factors which lead to altered phenotypes associated with pathogenesis. The purpose of this study was to analyze clinical strains of A. baumannii for phenotypic variation that might correlate with virulence phenotypes, antimicrobial resistance patterns, or strain isolation source. We hypothesized that individual strain virulence phenotypes might be associated with anatomical site of isolation or alterations in susceptibility to antimicrobial interventions. Methodology A cohort of 17 clinical isolates of A. baumannii isolated from diverse anatomical sites were evaluated to ascertain phenotypic patterns including biofilm formation, hemolysis, motility, and antimicrobial resistance. Antibiotic susceptibility/resistance to ampicillin-sulbactam, amikacin, ceftriaxone, ceftazidime, cefotaxime, ciprofloxacin, cefepime, gentamicin, levofloxacin, meropenem, piperacillin, trimethoprim-sulfamethoxazole, ticarcillin- K clavulanate, tetracyclin, and tobramycin was determined. Results Antibiotic resistance was prevalent in many strains including resistance to ampicillin-sulbactam, amikacin, ceftriaxone, ceftazidime, cefotaxime, ciprofloxacin, cefepime, gentamicin, levofloxacin, meropenem, piperacillin, trimethoprim-sulfamethoxazole, ticarcillin- K clavulanate, tetracyclin, and tobramycin. All strains tested induced hemolysis on agar plate detection assays. Wound-isolated strains of A. baumannii exhibited higher motility than strains isolated from blood, urine or Foley catheter, or sputum/bronchial wash. A. baumannii strains isolated from patient blood samples formed significantly more biofilm than isolates from wounds, sputum or bronchial wash samples. An inverse relationship between motility and biofilm formation was observed in the cohort of 17 clinical isolates of A. baumannii tested in this study. Motility was also inversely correlated with induction of hemolysis. An inverse correlation was observed between hemolysis and resistance to ticarcillin-k clavulanate, meropenem, and piperacillin. An inverse correlation was also observed between motility and resistance to ampicillin-sulbactam, ceftriaxone, ceftoxamine, ceftazidime, ciprofloxacin, or levofloxacin. Conclusions Strain dependent variations in biofilm and motility are associated with anatomical site of isolation. Biofilm and hemolysis production both have an inverse association with motility in the cohort of strains utilized in this study, and motility and hemolysis were inversely correlated with resistance to numerous antibiotics.

Acinetobacter baumannii is a serious threat to human health, per the Centers for Disease Control and Prevention's latest threat assessment. A. baumannii is a Gram-negative opportunistic bacterial pathogen that causes severe community and nosocomial infections in immunocompromised patients. Treatment of these infections is confounded by the emergence of multi- and pan-drug resistant strains of A. baumannii. A. baumannii colonizes abiotic and biotic surfaces and evades antimicrobial challenges by forming biofilms, which are three-dimensional architectural structures of cells adhered to a substrate and encased in an extracellular matrix comprised of polymeric substances such as polysaccharides, proteins, and DNA. Biofilm-inhibiting compounds have recently gained attention as a chemotherapeutic strategy to prevent or disperse A. baumannii biofilms and restore the utility of traditional antimicrobial strategies. Recent work indicates that human milk oligosaccharides (HMOs) have potent antibacterial and biofilm-inhibiting properties. We sought to test the utility of HMOs against a bank of clinical isolates of A. baumannii to ascertain changes in bacterial growth or biofilm formation. Our results indicate that out of 18 strains tested, 14 were susceptible to the antibiofilm activities of HMOs, and that the potent antibiofilm activity was observed in strains isolated from diverse anatomical sites, disease manifestations, and across antibiotic-resistant and susceptible strains.

Abstract Early detection of head and neck cancers (HNCa) correlate with improved outcomes. Salivary proteins may potentially be used for effective screening, which may result in increased survival time. This project aims to find potential biomarkers for laryngeal cancer, which ultimately could be detected by testing saliva or a swab of the back of the mouth. These simple screening methods would be of great benefit to high-risk individuals, and could potentially decrease disparities seen between minorities and white Americans. African American (AA) and white American (WA) men share similar incidences of laryngeal and tonsillar cancer, which affect men at a much higher rate than women. Among AA and WA men there is an alarming disparity, in which AA men are two to three times more likely to succumb to their disease. It is hypothesized that the salivary proteomes for tonsillar and laryngeal cancer, from AA and WA men, possess prognostic potential illustrating an association with the molecular characteristics of the tumor. MUDPIT proteomic analysis was done on four groups of pooled samples, four per group. Samples were collected with the approval of the Meharry Medical College Institutional Review Board. Inclusion criteria were males diagnosed with late stage (III or IV) laryngeal or tonsillar HNCa, active smokers, and HPV negative. Exclusion criteria were non-smokers and HPV positive. Groups were designated as AA/T, WA/T, AA/L and WA/L. A total number of 117 proteins were identified. AA/L had 111 proteins while WA/L had 116 proteins. Twenty proteins were detected from 1.6-fold to 1.62E+06 –fold greater in AA/L relative to WA/L. Eighty proteins were detected from 1.5-fold to 7.9E+07-fold greater in WA/L relative to AA/L. The resulting salivary proteomes were analyzed using WebGestalt. Pathway analysis for AA/L vs WA/L showed significant alignment with Reactome pathways. 8 proteins were found to be associated with innate immune function. There were no significant categories for enrichment category disease_Disgenet, however several proteins aligned with cancer categories at a non-significant level, such as annexin A1. Disease_GLAD4U recognized a statistically significant enrichment category of dental plaque. Represented proteins include CA6, PRH1 and MUC5B. Pathway analysis with KEGG, Panther and Reactome, were used for proteins greater in WA/L, and revealed overrepresentation of proteins associated with metabolic activity, hypoxia and the innate immune system. In addition, disease_disgenet showed proteins mapping to mouth neoplasms, SCC of esophagus, and cancer invasion. Finally, GLAD4U showed significance with periodontal diseases, ischemia and inflammation. A limitation of this research is the small sample size, nevertheless the potential differences between racial groups promotes further investigation. Exploration of these specific proteins or protein signatures can give insight into varying physiological responses to disease and can be used to create a more personalized therapeutic approach. Citation Format: Derek Wagner, Hannah Trew, Billy Ballard, Victor Paramov, Sid Pratap, Dana Marshall. The salivary proteome of African American and white American males diagnosed with laryngeal cancer [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D129.

Abstract Historically, and currently, black males have the highest mortality rates of any demographic group defined by race plus gender. Even though incidence has dropped for all demographic groups, and survival has improved as well, black males still bare a disproportionate burden of mortality. It has been reported that even when controlling for variables associated with prognosis, including socioeconomic status, black males still die at higher rates than white males. The question is whether this is true when one focuses on patients in lower socioeconomic groups where baseline health is poor for both blacks and whites. We hypothesized that patients in the lowest socioeconomic tertile would have a life expectancy that was significantly reduced compared to those of higher socioeconomic tertiles regardless of race, tumor grade, age at diagnosis, insurance status, anatomic subsite of the cancer and HPV status (all factors associated with prognosis). Towards answering this question, we analyzed de-identified data from a customized head and neck cancer dataset with HPV status, additional cancer treatment fields and census tract SES subset recode, from the Surveillance, Epidemiology and End Results (SEER) database that tracked patients diagnosed with HNSCC from 2010-2016. This retrospective cohort multivariate analysis utilized survival analysis methods such as Kaplan-Meier survival, hazard curves, regression, and the hypertabastic survival method, to analyze the survival time of our patients. Cross-tabulation between the registry SES tertile and race shows significance (p<0.001) with the majority of blacks (58%) in the lowest socioeconomic tertile compared to 21.9% of whites. Blacks significantly differ from whites for categories age at diagnosis (p<4.8E-16), subsite hypopharynx (p<2.6E-4), subsite oropharynx (p<1.5E-7), subsite tongue (p<4.5E-4), HPV status (p<3.4E-28), and presence in uninsured insurance category (p<4.2E-7). Individuals in the lowest SES tertile and the uninsured groups died at higher rates than their wealthier insured peers. Proportional hazards regression reveals that across all insurance groups (Insured, Uninsured, Medicaid, and Unknown), blacks had significantly shorter survival than whites. So, regardless of whether we used SES tertile rank or insurance status as proxies for SES, and despite the idea that low SES would level the mortality playing field for black and white HNSCC patients, this preliminary analysis showed otherwise. Additionally, the association of black race with additional variables associated with poor prognosis continues to confound the interpretation of these outcomes. Determining that the racial mortality disparity exists regardless of socioeconomic tertile or insurance status can guide future research to focus on biological factors that may impact survival outcome. Citation Format: Dana R. Marshall, Joycemary Amponsem, Billy R. Ballard, Mohammed A. El Kadmiri, Young J. Kim, Derek Wilus, Mohammad A. Tabatabai. Insurance status and racial disparities in mortality for black and white head and neck cancer patients in the United States [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1177.

Abstract Head and Neck Squamous Cell Carcinoma (HNSCC) is one the types of Cancer in The United States with inequality in the mortality rate among Black patients when compared to White patients. Patients of European dissent (Whites) are more likely to be diagnosed with any type of HNSCC but patients of African dissents (Blacks) are more likely to die from ant type of HNSCC when all patients are HPV negative. The difference in survival based on race and ethnicity prompted the need for a better and early diagnostic marker for HNSCC among Blacks and other groups with poor prognosis of HNSCC. The present research seeks to identify a specific and safe salivary proteome marker for the early diagnosis of HNSCC. The hypothesis of this article is that there is a significant difference in the salivary proteome of AA patients with HNSCC when compared to WA patients which is specific to cancer site. Eight patient samples with confirmed diagnosis of Laryngeal cancer at Nashville General hospital (IRB Protocol Number 14-03-172) were collected with appropriate informed consent. Patient samples were pooled together and analyzed using IHC for the presence of shared protein expression. Each protein sample was later analyzed individually using IHC in order to obtain specific proteins expressed by each patient’s salivary proteome. A Multidimensional Protein Identification Technology (MUDPIT) was used to analyze salivary samples to increase resolution for identifying proteins and peptides. MUDPIT was used to increase resolution of analyzed proteins and was compared with other proteins associated with LaCa using a known online protein database called WebGestalt. The most highly expressed proteins in each of the samples were further analyzed using The Human Protein Atlas in order to study the location of the salivary proteome and its function when expressed. 20 unique protein genes obtained from Label Free Quantification (LFQ) analysis was further analyzed for the function of the genes and gene co-localization in the body using an online database known as GeneMANIA. Finally, PEAKS was used to ascertain the effect of proteins. Result shows differences in the salivary proteome of AA patients compared to WA’s. Specifically, proteins involved in transcriptional mis-regulation were over- represented in AA>WA patients which included some proteins associated with metastasis (JUP), dis-functional immune cells (CD14), over-expressed tumor- suppressor proteins (DMBT1 and DRB2) and elevated level of antimicrobial innate immunity (His 1 & 3) are all higher than the normal values in healthy patients without LaCa both among AA and WA. Future research is required to expand on these identified proteins to help provide a safe and specific biomarker for the diagnosis of LaCa among AA patients. Future research can also provide direction as to where therapeutics can be directed and how they can be safely administered to generate the most effective treatment that can improve the prognosis of the disease among AA patients and others with groups with poor prognosis. Citation Format: Oyinloye A. Jose, Oladipupo Anibire, Derek Wagner, Dana Marshall, Billy Ballard, Siddharth Pratap, Victor Paramov. Profiling of salivary proteome specific for the diagnosis of head and neck cancer among African Americans [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-089.

Abstract This study set out to observe and better understand the differences, if any, in staining patterns for the oxidative stress response transcription factor Nrf2 in HNSCC patients who were HPV+ non- tobacco and alcohol users vs. HPV- tobacco and alcohol users. Increased Nrf2 activity is associated with resistance to therapy and poor outcomes. Tissues samples were obtained from the head and neck cancer repository of Nashville General Hospital at Meharry and Meharry Medical College. Nashville General Hospital at Meharry is a safety net hospital that serves the under- and uninsured citizens of Davidson County TN. FFPE sections were stained with anti- human Nrf2 antibody (Abcam 31163) and scored using a semi-quantitative evaluation gradient scale from 0-3 with 0 indicating no stain and 3 indicating strong positive Nrf2 staining. This study made use of 5 HPV+ and 2 HPV- patients. The results show that all HNSCC in the HPV+ and HPV- samples revealed positive staining for Nrf2 that ranged from weak to intense. We observed that the poorly differentiated HNSCC had a strong positive nuclear stain for Nrf2 when compared to lower tumor grades. Irrespective of whether the patient was in the HPV+ nonsmoker-nondrinker or HPV- smoker-drinker group, histological data indicates there was a positive correlation between increased Nrf2 staining and worsening tumor grade. These preliminary data suggest that potential use of Nrf2 as a prognostic biomarker for HNSCC will need to be evaluated differently for HPV+ and HPV- tumors, as HPV+ tumors are generally more responsive to therapy. Developing therapy that specifically targets Nrf2 could potentially play an immense role in managing HNSCC. Some of the limitations encountered in this study includes limited sample size. Citation Format: Oladipupo O. Anibire, Oyinloye Jose, Kenyada Williams, Billy R. Ballard, Michael G. Izban, Dana Marshall. HPV+ and HPV- HNSCC show similar nrf2 nuclear and cytoplasmic staining patterns [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-233.

Abstract Upper Aerodigestive tract (UADT) cancers are primarily squamous cell carcinomas that affect the oral cavity (hard palate, front 2/3 of tongue, gums, mucosal lining of lips and cheeks, and the floor of the mouth), oropharynx (base of the tongue, soft palate, and tonsils), hypopharynx, larynx (epiglottis and vocal cords), and the upper third of the esophagus with a five-year survival rate of 65.3% for oral cavity and pharyngeal cancers. If the cancer is detected during the localized stage, the survival rate improves to 84.4% (SEER 18 2009-2015).There have been several risk factors implicated in the pathogenesis of UADT cancers such as, male gender, smoking, alcohol use, and infection with human papilloma virus (HPV) for oropharyngeal cancers. The current literature suggests that regardless of stage people of African descent have a lower incidence of UADT cancers, but higher mortality rates compared to Caucasians. There are many proposed explanations for this paradoxical trend seen in African Americans. However, there is a paucity of research addressing this problem. We seek to understand if socioeconomic status is the underlying factor driving this disparity. We analyzed de-identified data collected from the Surveillance, Epidemiology, and End Results (SEER) program for 114,510 UADT cancer patients diagnosed from 2007-2016. We hypothesized that people who were uninsured or on Medicaid would have a life expectancy that was significantly reduced compared to those that had private insurance or Medicare regardless of race, tumor grade, gender or site of the cancer. Our study design is retrospective cohort. Our multivariate analysis model utilizes survival analysis techniques such as Kaplan-Meier survival, hazard curves and proportional hazards regression to analyze the survival time of our patients as a function of demographic and clinical variables. Survival months ranged from 0 to 119 months, with 25,122 patients experiencing death due to UADT cancers. The proportional hazards regression revealed that across all insurance groups (Insured, Uninsured, Medicaid, and Unknown) the survival time for Non-Hispanic Black People was significantly reduced compared to the other race/ethnicities (Asians, Caucasians, Hispanics (all races)) with Non-Hispanic Caucasians having the highest survival rate. Determining that the racial disparity exists regardless of insurance status, tumor grade, gender, and site of cancer can guide future researchers to focus on biological differences or other factors such as lack of access to care that underlie disease survival for UADT cancers. Citation Format: Joycemary G Amponsem, Dana Marshall, Derek Wilus, Mohammad Tabatabai. Does insurance status explain the racial disparity in survival outcome seen in upper aerodigestive tract cancers in the United States? [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B129.

The threat of antibiotic resistance has increasingly become a global issue because of the gradual emergence of multi‐drug resistant (MDR) pathogens. Identifying mechanisms of resistance as well as characterization of attributes deemed beneficial for the survival of the pathogen is vital in contributing to the development of new therapeutics. Acinetobacter baumannii is a gram‐negative opportunistic, nosocomial MDR pathogen that primarily targets immunocompromised patients in medical care facilities around the world. From an assembled bank of clinical isolates of A. baumannii , there is a diverse spectrum of antibiotic resistance patterns, cell motility and biofilm formation represented. Initial RNA sequencing studies implicated the importance of the Gcn5‐related N‐acetyltransferases (GNATs) in facilitating A baumannii resistance to the aminoglycoside class of antibiotics. We aim to determine the role of GNAT proteins to antibiotic resistance in A. baumannii as well as identify which physiological processes are associated with antibiotic resistance. GNATs belong to a superfamily of enzymes that are found in all domains of life and are involved various functions including acetylation of a broad spectrum of substrates and, often times, conferring resistance to antibiotics. We performed structural and functional experiments to understand the mechanisms causing the resistant nature of A. baumannii . Preliminary crystallization studies of the enzyme GNAT 2199 yielded 4 initial conditions suitable for optimal crystal growth. We also conducted a series of enzyme activity assays which revealed that GNATs acetylate various clinically used aminoglycosides. seeking to reveal the natural aminoglycoside substrate for GNAT 2199. Furthermore, cell motility and biofilm assays were used to determine the physiological processes attributed to antibiotic resistance of A. baumannii isolates. Future work entails optimization of the crystallization conditions to produce samples suitable for X‐ray diffraction studies. This will allow us to develop GNAT superfamily structure‐function relationships as well as identify physiological processes of A. baumannii that contribute to antibiotic resistance. In total, this information will be useful for initiating new strategies to control the spread of this bacteria as well as developing new therapeutics to effectively combat this MDR pathogen. Support or Funding Information NSF No. HRD‐1547757 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Acinetobacter baumannii is an opportunistic gram‐negative human pathogen. Underscoring the threat to global health is the observation of isolates of A. baumannii that are resistant to all known antibiotics. Multidrug resistant A. baumannii is a leading cause of nosocomial infections and can lead to increased mortality and length of stay. To address this public health problem, there is a need to develop new therapeutics. Our approach is to identify potential drug targets by characterizing molecular mechanisms that contribute to the antibiotic resistance of A. baumannii. To achieve this, we leverage a collated bank of 247 isolates (72% are multi‐drug resistant) of A. baumannii from patients at Nashville General Hospital. Isolate MMC4 (Meharry Medical College Isolate 4) is resistant to >25 antibiotics and hence represents an ideal system for dissecting the molecular origins of antibiotic resistance. Here we report the identification of superoxide dismutase B (SodB) as an important antibiotic resistance factor along with its biochemical characterization and high‐resolution crystal structure. Isolate MMC4 was subjected to proteomic analysis in the presence and absence of antibiotic challenge using multidimensional protein identification technology. SodB showed the greatest differential protein expression, a greater than 40 fold increase in response to antibiotic challenge. SodB is an enzyme that protects bacteria from oxidative stress by dismutating highly reactive superoxide radicals. While the superoxide dismutase family has been extensively studied, little is known about A. baumannii SodB. We expressed SodB recombinantly from E. coli and purified it to >95% homogeneity. We evaluated the activity of SodB using a tetrazolium salt assay and established it is an iron dependent enzyme using inductively coupled plasma – optical emission spectrometry. We also determined the structure of SodB with iron bound to 1.45 angstroms resolution. The crystal belonged to the C121 monoclinic space group with unit cell sides (angstroms) and angles (degrees) 97.28, 40.74, 76.63 and 90, 123, 90, respectively. In total, these data establish the importance of protection from oxidative stress in antibiotic resistant A. baumannii and provide the first steps for a structure‐based drug design approach to target inhibition of SodB as a therapeutic strategy.Support or Funding InformationThis work was funded by National Science Foundation HRD1547757, National Institutes of Health R25MD010396 and R01HD090061, and Office of Medical Research, Department of Veterans Affairs IK2BX001701.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The American Cancer Society estimates that 1,688,780 new cases of cancer will be diagnosed in 2017 and that 600,920 people will die from their disease. The burden of cancer is disproportionately borne by the poor and underserved. Underrepresented minority physician scientists and clinician researchers are uniquely qualified to address these disparities as they have frequently experienced them in their own families and communities. As some portion of health disparities is rooted in socioeconomic status and lesser education, economically deprived and first generation college students of all races and ethnicities also experience these disparities. Unfortunately, the number of physicians who do research has been declining so the need for programs that educate students in the art and science of research is increasing. The Meharry Medical College Summer Program in Integrative Science and Cancer Research (MMC-SPiISCR) has provided Meharry medical students with the opportunity to participate in short-term cancer research experiences for eleven years. The program is unique in combining weekly half-day workshops at MMC, an historically black college or university, with a research experience supported by faculty mentors at the Vanderbilt University School of Medicine (VUSM),an institution that includes the Vanderbilt Ingram Cancer Center, one of only 69 NCI-Designated Cancer Centers in the United States and District of Columbia. The workshops include topics emphasizing bioethics and responsible conduct of research as well as presentations by Meharry faculty on their cancer research, cancer disparities, cancer and big data and more. The overarching goal of this program is to inspire Meharry medical students to aspire to medical careers in academic medicine and/or careers that will ultimately include cancer research. To date, 73 MMC students have started and completed the program and 94% are from underrepresented minority groups. The male to female ratio reflects the male to female ratio of the class. Over half of the participants presented their work at meetings outside of the program including AACR National Meeting, AACR Science of Cancer Disparities, Society of Black Academic Surgeons, Student National Medical Association, American Medical Association Research Symposium, American Society for Clinical Oncology, KBRIN Bioinformatics Summit and the Meharry-Vanderbilt-TSU Cancer Partnership Annual Retreat. The students are authors on 27 manuscripts and these numbers are still growing as is the interest of program participants in doing a year of research. Surveys of both mentors and program participant mentees overwhelmingly support the strength of this program and participation in the future. This comprehensive program will go far towards fueling the physician-scientist pipeline with researchers whose life experiences mirror those of minority and underserved patients. Citation Format: Dana R. Marshall, Carol Freund-Taylor, Philip Lammers, Leon Dent, Samuel Adunyah, Billy Ballard. Meharry Medical College medical student summer program in integrative science and cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5286.

Oral tongue squamous cell carcinoma (OTSCC) has a median age at diagnosis of 62 years. The incidence of OTSCC in young adults has been increasing, and the reason is unclear. The present study describes a case, and molecular analysis, of OTSCC in a 21-year-old female. Clinical and pathological information were collected from medical records. Formalin-fixed paraffin-embedded biopsy tissue from the patient was reassessed using standard hematoxylin & eosin staining, and immunohistochemistry was used to assess the expression of cellular p16, MutL homolog (MLH)1, MLH2, MutS homolog 6 (MSH6) and PMS1 homolog 2 (PMS2). The human papilloma virus (HPV) genome was detected by PCR analysis of the extracted DNA. The young age of the patient with OTSCC was unusual. The original pathology report indicated koilocytotic atypia, a cellular abnormality associated with HPV. Although HPV-positive oral cancer tends to occur in 'younger' individuals, 21 years is unusual. The confirmation of biologically active HPV in the tumor was obtained via the observation of strong positive staining for cellular p16. The patient described a maternal family cluster of rare cancer types, thus the possibility that this rapidly growing cancer resulted from HPV infection combined with an underlying genetic mutation causing decreased DNA-mismatch repair was explored. However, MSH1, MSH2, MSH6 and PSM2, proteins that are associated with Lynch Syndrome, were expressed at normal levels. A rapidly growing OTSCC of a 21-year-old female was determined to be HPV-positive. The patient underwent combination chemotherapy and radiation and has experienced long-term survival without recurrence. The reason this tumor grew so quickly in such a young individual remains unknown. These types of cases warrant additional genomic and proteomic studies to improve understanding of this phenomenon.