Digital Commons Network^™

Exploring The Acceptability Of The Kimberley Mum’S Mood Scale For Perinatal Mental Health Screening In Gove District Hospital, North-East Arnhem Land, Tom P. Atkinson, Erica P. Spry, David Atkinson, Julia V. Marley, Emma Carlin

Journal of the Australian Indigenous HealthInfoNet

Objective: Across Australia perinatal mental health challenges disproportionately impact Aboriginal women. Identifying Aboriginal women at risk of adverse mental health outcomes in the perinatal period is an important step in supporting their overall health and wellness. Current screening tools have significant limitations when used with Aboriginal women.

The Kimberley Mums Mood Scale (KMMS) is a culturally secure approach to screening for perinatal mental health disorders in Aboriginal women. It has been validated in the Kimberley region of Western Australia and may be able to improve mental health screening in other regions. In this study the KMMS was trialled at a …

Sex Differences In Cardiovascular Disease And Associatedfactors In People Living With Hiv: Evidence From All Of Us Program, Hao Zhang, Huiyi Xia, Fanghui Shi, Qingyang Li, Sharon Weissman, Xiaoming Li Ph.D., Xueying Yang

Faculty Publications

Background

People living with HIV (PLWH) face a higher risk of cardiovascular disease (CVD), with significant sex differences in outcomes. However, it is unclear whether these differences are driven by distinct risk factor profiles or by a differential impact of shared risk factors. This study aimed to identify factors associated with CVD among PLWH and to specifically assess for effect modification by sex using a large, diverse nationwide database.

Methods

We utilized data from the All of Us Research Program (AoU). The primary outcome was a composite of coronary artery disease or stroke. We used multivariable logistic regression to identify …

State Of Ohio Adversity And Resilience (Soar) Study Protocol: A Comprehensive, Multimodal, Family-Based, Longitudinal Observational Investigation Of Risk And Resilience In Mental Health And Substance Use Disorders, Chris Flask, Martha Sajatovic

Faculty Scholarship

Introduction Deaths related to drug overdose and suicide in the USA have increased 500% and 35%, respectively, over the last two decades. The human and economic costs to society associated with these - €- deaths of despair' are immense. Great efforts and substantial investments have been made in treatment and prevention, yet these efforts have not abated these increasing trajectories of deaths over time. The COVID-19 pandemic has exacerbated and highlighted these problems. Notably, some geographical areas (eg, Appalachia, farmland) and some communities (eg, low-income persons, - €- essential workers', minoritised populations) have been disproportionately affected. Risk factors have been …

Agitation In Alzheimer’S Disease: From Assessment To Therapeutics, Antonio L Teixeira, Youngran Kim, Thiago M Cordeiro, Gabriel A De Erausquin, Natalia P Rocha

Faculty, Staff and Student Publications

Agitation is a neuropsychiatric syndrome characterized by excessive motor and/or verbal behaviors, with or without aggressive behaviors. The prevalence of agitation in Alzheimer’s disease varies from 5% to over 50%. Multiple factors have been implicated in its pathophysiology, including disease stage, comorbidity with other symptoms (e.g., psychosis, anxiety/depression), and psychosocial factors. Ruling out delirium and identifying environmental triggers are fundamental steps in the management of agitation in Alzheimer’s disease. For establishing an effective therapeutic plan, it is important to define duration, severity, and potential for harm. While non-pharmacological approaches are considered the first line of intervention, pharmacological agents …

Editorial: Healthcare Technologies And Space: Therapeutic Built Environment As A Health Technology And Technologies For Improved Healthcare Settings, Evangelia Chrysikou, Fernando Loizides, Marianna Obrist, James Barlow, Paul Barach

College of Population Health Faculty Papers

No abstract provided.

What Covid-19 Taught Extension: Experiences Of Extension County Engagement Specialists Promoting Vaccinations In Meat Processing Plants In Rural Missouri., Wilson Majee, Ifeolu David, Lynelle Phillips, Rachel Buenemann, Kassandra Maturino

Journal of Extension

Extension played a significant role, in collaboration with other key community organizations, by disseminating information that debunked COVID-19 myths, and promoting vaccinations at the community level. In this article we present insights from the experiences of Extension faculty at the University of Missouri who were engaged in promoting COVID-19 vaccinations for meat processing plant workers. Findings from this quality improvement project highlight opportunities for leveraging Extension field faculty, and challenges to consider in future public health promotion efforts.

Food Insecurity, Educational Attainment, And Type 2 Diabetes In African Americans In Rural Southern Us, Dana Elaine Lowe

Walden Dissertations and Doctoral Studies

Abstract Rural African Americans experience a higher prevalence of Type 2 diabetes compared to their White counterparts, yet little research has explored the roles of food insecurity and educational attainment in this disparity. The purpose of this quantitative, correlational study was to examine whether food insecurity and educational attainment were associated with the prevalence of Type 2 diabetes among African Americans aged 18 to 65 years in rural Southern United States, using the World Health Organization’s social determinants of health framework. Data from the 2019-2022 IPUMS National Health Interview Survey (N=793) were analyzed both descriptively and using multiple logistic regression …

Be Faster Community Of Practice To Increase Rapid Initiation Of Antiretroviral Therapy In Houston, Texas: A Pre-Post Intervention Study, Naomi Sequeira, Bich N Dang, Melanie Goebel, Monisha Arya, Avishek Ghosh-Hajra, Kathryn Fergus, Shital M Patel

Faculty, Staff and Students Publications

Background: Rapid initiation of antiretroviral therapy (Rapid ART) is a key strategy of the Ending the HIV Epidemic (EHE) initiative. The Baylor College of Medicine Extension for Community Healthcare Outcomes (ECHO) Facilitating Antiretroviral Start Earlier (BE FASTER) program was developed to address this call-to-action. The program uses the ProjectECHO tele-mentoring model as an implementation tool in Harris County, a priority EHE jurisdiction. The authors present results on the acceptability and feasibility of the BE FASTER program.

Methods: Multidisciplinary health professionals from 5 Ryan White Part A funded agencies formed the community of practice. The BE FASTER program included 9 monthly …

Estimated Impact Of 2022–2023 Influenza Vaccines On Annual Hospital Burden In The United States, Kaiming Bi, Shraddha Ramdas Bandekar, Anass Bouchnita, Annalise Cramer, Spencer J Fox, Rebecca K Borchering, Matthew Biggerstaff, Lauren Ancel Meyers

Faculty, Staff and Student Publications

During the COVID-19 pandemic early years, infection prevention measures suppressed transmission of seasonal influenza and other respiratory viruses. The early onset and moderate severity of the US 2022-2023 influenza season may have resulted from reduced use of nonpharmaceutical interventions or lower population immunity after 2 y of limited influenza virus circulation. We used a mathematical model of influenza virus transmission that incorporates vaccine-derived protection against both infection and severe disease to estimate the impact of influenza vaccines on healthcare burden. Assuming reported levels of past vaccine effectiveness (VE) against infection and hospitalization, we estimate that influenza vaccines prevented 69,886 (95% …

Development Of A Low-Barrier, Reimbursable Take-Home Naloxone Program At A Regional Health System, Kory S. London, Sejal Patel, Drew Lockstein, Jamal Rashid, Dennis Goodstein, Richard Pacitti, Tareva Warrick-Stone, Frederick Randolph, Alan Cherney, Karen Alexander, Megan Reed

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

INTRODUCTION: Take-home naloxone (THN) programs in emergency departments (ED) can reduce opioid overdose deaths by providing naloxone directly to at-risk patients before discharge. However, sustainable models that integrate reimbursement and workflow alignment remain limited.

METHODS: A reimbursable ED-led THN program was developed across a large regional health system. The program used electronic health record (EHR)-integrated ordering, on-site kit dispensing, and third-party insurance billing when available. Kits were stocked in automated medication dispensing systems and supplemented by city-provided stock for uninsured patients. Pilot outcomes included kits dispensed and reimbursement rates across eight participating EDs.

RESULTS: A total of 2,520 naloxone kits …

Vitamin D Deficiency And Cardiovascular Health Disparities In High-Melanin Populations: A Scoping Review, Jalen K. Luter, Silver R. Kaylor, Michael S. Boyer

Doctoral Projects

Cardiovascular disease (CVD) remains a leading cause of mortality and disproportionately affect individuals with darker skin tones, partly due to vitamin D deficiency (Sabzmakan et al., 2014). This Doctor of Nursing Practice (DNP) project uses a scoping review methodology to examine the relationship between vitamin D deficiency and cardiovascular outcomes, with an emphasis on high-melanin populations. Guided by the Joanna Briggs Institute Framework, the review synthesizes existing evidence, identifies gaps in representation and biomarker use, and highlights social and biological contributors to disparity. Databases including PubMed, CINAHL, EMBASE, and Scopus were searched, and studies were screened using standardized inclusion criteria: …

From Urban Models To Rural Realities: Adapting Hepatitis C (Hcv) Care For Underserved Communities, Caitlin A. Mccain

2025 Fall Honors Capstones Projects - Archive

This literature review examines how Hepatitis C (HCV) screening and care programs can better serve underserved populations, particularly Spanish-speaking rural communities in border states. The research supports the Hep C- Colonias Advancing & Restoring Esperanza (C.A.R.E) program’s mission by incorporating recent findings from 32 studies gathered through PubMed, Medline and Google Scholar. Hep C C.A.R.E expanded from the HepVISTA expansion project provides HCV screening, education, vaccination and linkage to care for uninsured patients at partner sites in Laredo and Maverick County. Results indicate that while HCV elimination is feasible, significant gaps persist among rural uninsured and minority populations. Effective strategies …

Does Preoperative Arthritis Affect The Outcomes Of Superior Capsular Reconstruction? A Systematic Review, Tae-Hoon Park, Hyungsuk Kim, Sukil Kim, Jongin Lee, Gerald R. Williams, Hyun Seok Song

Rothman Institute Papers

BACKGROUND: The optimal indications for superior capsular reconstruction (SCR) in cases of massive irreparable rotator cuff tears (RCTs) accompanied by degenerative arthritis remain controversial.

METHODS: A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Embase (Elsevier), and Google Scholar. Studies were included if they documented Hamada grade and reported clinical and radiographic outcomes after SCR for irreparable RCTs. American Shoulder and Elbow Surgeons (ASES) score, visual analog scale for pain (pVAS), active range of motion, and acromiohumeral distance (AHD) were analyzed.

RESULTS: In all 7 studies, there was no consistent …

Application Of Freezetb, A Targeted Nanopore Sequencing Assay, For Identification Of Drug Resistance And Lineages Among Pulmonary Tuberculosis Cases In Alaska, Bryce Inman, Jeremy Butler, Soren George-Nichol, Ganna Kovalenko, Theresa Savidge, Yvette Vergnetti, Catherine Pongratz, Elizabeth Bee, Andrew R Dinardo, Alexander Kay, Anna Mandalakas, Eric Bortz, Tara E Ness

Faculty, Staff and Students Publications

Alaska has the highest incidence of tuberculosis (TB) in the United States, with 8% mortality while undergoing TB treatment. With a quarter of TB cases lacking sputum culture to enable drug resistance testing, FreezeTB aimed to develop tools tailored to meet the challenges in Alaska while being translatable to other settings. We designed a rapid and cost-effective laboratory workflow and software to identify drug-resistant mutations in Mycobacterium tuberculosis using targeted next-generation sequencing (tNGS). FreezeTB, a Fast, Reliable, Economical Evaluation tool to Zap Endemic Tuberculosis, amplifies 22 gene loci associated with resistance to 16 anti-tuberculosis drugs. M. tuberculosis isolates from Alaska …

Characterizing The Metabolites Of The Tyrosine-Kinase Inhibitor Pexidartinib In Mouse Feces, Urine, Plasma, And Liver, Xuan Qin, Si Chen, John M Hakenjos, Jian Wang, Lei Guo, Ashish Dogra, Zhaoyong Hu, Kevin R Mackenzie, Feng Li

Faculty, Staff and Students Publications

Pexidartinib (PEX, TURALIO®), a tyrosine kinase inhibitor, is approved for treating tenosynovial giant cell tumor in adults. However, its potential to cause fatal liver injury has prompted the U.S. FDA to issue a black box warning, and the mechanisms underlying its hepatotoxicity remain largely unknown. As biotransformation may contribute to PEX-induced hepatotoxicity, understanding its metabolism is essential. Our previous research indicated that PEX forms reactive metabolites in human and mouse liver microsomes and in human hepatocytes. We investigated PEX metabolism and liver distribution in mice with a focus on metabolite characterization. Our data shows that PEX is mainly excreted into …

Effects Of Residual Pah Exposure From Firefighters’ Skin And Turnout Gear On Biospecimen Microrna Expression, Jooyeon Hwang, Jenny R Gipson, Chao Xu, Timothy Vanwagoner, Xin Xu, Robert J Agnew, Willard M Freeman

Faculty, Staff and Student Publications

Firefighters are routinely exposed to polycyclic aromatic hydrocarbons (PAHs) during fire suppression activities, molecular biomarkers reflecting such exposure remain underexplored. Thus, we explored an integrated exposure assessment framework linking PAH contamination on turnout gear and skin to changes in microRNA (miRNA) expression in skin and blood biospecimens. Our goals are to evaluate the relationship between fire-related PAH exposure and miRNA expression profiles in firefighters, and to identify candidate miRNA biomarkers of occupational exposure. This prospective study enrolled 25 firefighters. PAHs on turnout gear and skin were quantified post-fire using gas chromatography/mass spectrometry. Concurrently, skin tape strips and blood were collected …

Editorial: Migration And Health: A Human Rights Perspective - Conference Insights And Beyond, Noemi Rodriguez, Mira Goral, Justine Mcgovern, Allison Squires, María Isabel Roldos

Publications and Research

No abstract provided.

Vitamin D Is Glucoprotective In Aging Males But Not Females, Olivia Z B Ginnard, Maria Morales, Ji Youn Youn, Yong Xu, Stephanie R Sisley

Faculty, Staff and Students Publications

Vitamin D supplementation is linked to many beneficial health outcomes in the geriatric population, such as decreased mortality, epigenetic aging, and fracture risk. Conversely, type 2 diabetes is strongly linked to vitamin D deficiency in older adults. However, there is a discrepancy between clinical trials in adults on the efficacy of vitamin D treatment in prediabetes and diabetes. In addition, human data indicates there may be sexual dimorphism in the effect of vitamin D deficiency on dysglycemia that is more pronounced in men. These incongruities may be due to our limited understanding of the underlying mechanisms of vitamin D in …

Mapping Respiratory Health Digital Interventions In South And Southeast Asia: A Scoping Review, Laura Evans, Jay Evans, Paul Barach, Adina Abdullah, Zakiuddin Ahmed, Respire Collaboration

College of Population Health Faculty Papers

BACKGROUND: The growing burden of respiratory disease, particularly in Asia, where mortality is higher and awareness and policy engagement lag, could be mitigated through rapidly advancing digital health tools that offer opportunities for improved management, prevention, and personal health empowerment. We aimed to map the existing evidence, technologies, opportunities, and gaps related to respiratory digital health interventions in South and Southeast Asia and propose relevant recommendations.

METHODS: We used a scoping review methodology, where we searched MEDLINE, Embase, CINAHL, PsycINFO, Cochrane Library, Web of Science, PakMediNet, and MyMedR along with grey literature databases (ProQuest Thesis and Dissertations, Digital Health Atlas, …

Culture-Independent Meta-Pangenomics Enabled By Long-Read Metagenomics Reveals Associations With Pediatric Undernutrition, Jeremiah J Minich, Nicholas Allsing, M Omar Din, Michael J Tisza, Kenneth Maleta, Daniel Mcdonald, Nolan Hartwick, Allen Mamerto, Caitriona Brennan, Lauren Hansen, Justin Shaffer, Emily R Murray, Tiffany Duong, Rob Knight, Kevin Stephenson, Mark J Manary, Todd P Michael

Faculty, Staff and Students Publications

The human gut microbiome is linked to child malnutrition, yet traditional microbiome approaches lack resolution. We hypothesized that complete metagenome-assembled genomes (cMAGs), recovered through long-read (LR) DNA sequencing, would enable pangenome and microbial genome-wide association study (GWAS) analyses to identify microbial genetic associations with child linear growth. LR methods produced 44-64× more cMAGs per gigabase pair (Gbp) than short-read methods, with PacBio (PB) yielding the most accurate and cost-effective assemblies. In a Malawian longitudinal pediatric cohort, we generated 986 cMAGs (839 circular) from 47 samples and applied this database to an expanded set of 210 samples. Machine learning identified species …

A Practical Primer On How To Detect And Treat Depression In Ckd, L Parker Gregg, Lynnel Goodman, Ella Q Carroll, S Susan Hedayati

Faculty, Staff and Students Publications

Detection and management of depression have special considerations in people with kidney disease. Screening should be done every 6-12 months using a self-reported questionnaire. Clinicians should rule out symptoms from medical conditions such as dialysis inadequacy or hypothyroidism and confirm the presence of sadness or anhedonia. Sertraline has shown limited efficacy and an increased risk for adverse effects such as gastrointestinal symptoms, so cautious, gradual dose titration is warranted. Cognitive behavioral therapy has potential benefit for depressive symptoms in people with kidney disease. Current trials are evaluating behavioral activation therapy. Physical activity has many benefits and likely improves depression.

Prevalence Of Potentially Inappropriate Medications In People Living With Hiv: A Systematic Review And Meta-Analysis, Mustapha Muhammed Abubakar, Abdulmuminu Isah, Ruth Jeminiwa, Ibraheem Abioye, Ismaeel Yunusa, Mohammed Abba-Aji, Osagie Kenneth Cole, Jamila Sani, Mukhtar Ijaiya, Chukwuemeka Nwachuya, Yusuf Ibrahim, Mustapha Usman, Duke Daniels, Oluwaseun Samuel Ilugbuhi, Blessing Onyinye Ukoha-Kalu

College of Pharmacy Faculty Papers

BACKGROUND: Potentially inappropriate medications (PIM) are associated with adverse health outcomes. The use of PIM among persons living with HIV (PLHIV) could be more problematic due to peculiarities such as antiretroviral toxicity and drug-disease interactions. However, PIM among PLHIV continues to receive little attention. Therefore, we aimed to systematically review and estimate the prevalence of PIM among PLHIV.

METHODS: We searched the PubMed, Scopus, and Web of Science databases to identify relevant studies from 1 January 2014 to 30 June 2024. Studies included were peer-reviewed articles that determined PIM prevalence using validated explicit or implicit tools and provided statistical information …

Efficacy Of Medical-Legal Partnerships To Address Health-Harming Legal Needs: A Systematic Review Of Experimental Studies In The Field, Jemima John, Thomas Murphy, Emily Zientek, Winston Liaw, Odinakachukwu Dimgba, Thien-An Nguyen, Catherine Burnett, Mary Aitken, Shreela Sharma

Faculty, Staff and Student Publications

Background: Despite the documented success of medical-legal partnerships (MLPs), there is a dearth of robust experimental-based research on their efficacy. This review synthesizes the findings of MLP interventions and identifies opportunities for MLP expansion in vulnerable communities.

Methods: Articles were eligible if they tested the experimental effects of an MLP intervention on health-harming legal needs (HHLNs) and had full text for review. Two reviewers independently screened articles for inclusion and assessed the quality (risk of bias) of each study.

Results: Seven studies were eligible. Populations were largely women, of color, and of lower socioeconomic status. All studies demonstrated positive effects …

What Are The Barriers And Facilitators To The Acceptance Of Information And Communication Technology-Based Interventions For Improving Resilience And Mental Health Of Healthcare Workers: A Scoping Review Protocol, Elisabete Alves, Ricardo Rodrigues, César Fonseca, Manuel Lopes, Inês Faria, Nina Dalkner, Paul Barach, Frans Folkvord, Jim Ingebretsen Carlson, Eva Reininghaus, Michele Wessa, Yvonne Prinzellner, Vanessa Leung, Eva Turk, Lara Guedes De Pinho

College of Population Health Faculty Papers

INTRODUCTION: Healthcare workers (HCWs) report overwhelming demands and experience crisis levels of burnout and unique challenges that further impair their mental health. Promotion of mental health among HCWs using information and communication technology (ICT) has received little empirical research attention and interventions for improving mental health resilience in HCWs are not well established.

DESIGN: Scoping review to map existing evidence and identify gaps for future research regarding the main barriers and facilitators of the acceptance of ICT-based interventions for improving resilience and mental health among HCWs working in all healthcare settings.

METHODS AND ANALYSIS: This protocol was developed in accordance …

State-Level Progress And Setbacks In Influenza Vaccination Among Adults ≥65: A Fifteen-Season Analysis From 2009/10 To 2023/24, Luigi Russo, Sara Farina, Raffaele Angelo Macri, William Alan Pentecost, Alessandra Maio, Leonardo Villani, Vittorio Maio, Stefania Boccia, Walter Ricciardi

College of Population Health Faculty Papers

INTRODUCTION: Influenza is a contagious respiratory infection with substantial health and economic consequences worldwide. Annual vaccination is the most effective preventive strategy; however, coverage among older adults remains suboptimal and varies considerably across the United States. This study aimed to examine state-level trends in influenza vaccination coverage among adults aged ≥65 years across fifteen influenza seasons (2009/10-2023/24).

METHODS: State-level vaccination coverage data for adults aged ≥65 years were obtained from the CDC FluVaxView platform, which reports annual estimates by influenza season. The analysis covered the 2009/10 through 2023/24 influenza seasons. Joinpoint regression was used to assess temporal trends and estimate …

Virtual Nurse Discharge: Improving Patient And Nurse Experience, Dina Flihan, Christine Odell, Stacey Davis, Carolyn Oates, Fay Wright

Patient Experience Journal

This case study reviews the virtual discharge nurse (VDN) process and its impact on patient experience and nursing workflow as an exemplar of an effective telehealth innovation at a community hospital 23-bed Short Stay Unit (SSU). At the SSU, the daily turnover rate of more than 50% of the unit census challenged the nurses’ ability to provide comprehensive individualized discharge education. SSU patient experience scores measured by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) reflected opportunities to improve the discharge process. Therefore, the direct care nurses on SSU suggested a trial innovation of a VDN to improve …

A Systematic Review Of The Literature On The Validity, Reliability, And Utility Of The Nhs Friends And Family Test As A Method For Gathering Feedback On And Improving The Experiences Of Patients, Miss Jenny King, Catherine Davidson, Miss Hannah Wade, Chris Graham

Patient Experience Journal

The NHS Friends and Family Test (FFT) is widely used across the National Health Service to collect patient feedback on care experiences. Given its scale and cost, there is strong public and organisational interest in the validity, reliability, and utility of the FFT. This study aimed to systematically review the literature on the validity, reliability, and utility of the FFT as a method for gathering feedback on and improving patient experiences. PubMed and ProQuest databases were searched in September 2024. Studies were included if they met the inclusion criteria. Information extracted included study information (e.g., title, authors, publication year, research …

Communicating Effectively When Engaging People With Lived Experience In Mental Health And Substance Use Health Research: A Qualitative Descriptive Study, Lisa D. Hawke, Wuraola Dada-Phillips, Charlotte Munro, Shoshana Hauer, Claudia Sendanyoye, Yona Lunsky, Gillian Strudwick, Tanya Halsall, Natasha Y. Sheikhan

Patient Experience Journal

Background. People with lived experience of mental health and/or substance use challenges and families (PWLE/F) are increasingly engaged in research, providing positive impacts. However, effective engagement can be challenging, including ensuring effective communication. This qualitative study sought to understand the communication preferences of PWLE/F who are engaged in mental health and substance use health research. Method. A total of 18 participants (aged 19 to 79) took part in one of four focus group discussions. A semi-structured interview guide was used to facilitate the discussions. Focus group transcripts were analyzed using codebook thematic analysis. PWLE/F were engaged in all stages of …

Patients’ Experiences Of Triage And Waiting In Emergency Departments: A Cross-Sectional Survey, Carrie Janerka, Leslie D Gavin, Fenella J Gill, Pcc Ed Triage Group

Patient Experience Journal

Objective: Patient experience is a core aspect of care quality. Patient experiences of emergency departments (EDs) have been examined, but there has been less focus on ED triage and waiting areas, often patients’ initial point of contact with a health service. This study aimed to understand patients’ experiences of ED triage and waiting room. Methods: A cross-sectional survey was conducted across five Australian EDs to understand experiences of patients 14 years and over before, during and after triage. Quantitative data were analysed descriptively and explored for correlations. Qualitative responses for suggested improvements were analysed using a conventional content analysis approach. …

Discovery Of A Novel Small Molecule Degrader Of Wild Type And Mutant Estrogen Receptors Using Dna Encoded Libraries, Anil Kumar Devakrishnan, Chandrashekhar Madasu, Yong Wang, Ramkumar Modukuri, Kurt M Bohren, Kevin R Mackenzie, Damian W Young, Suzanne A W Fuqua, Martin M Matzuk, Murugesan Palaniappan

Faculty, Staff and Students Publications

Estrogen receptor α (ERα) variants with mutations in the ligand binding domain (LBD) are less sensitive than wild type to standard-of-care drugs that bind ERα directly. To identify novel small-molecule drugs that target ERα mutants, we screened our multibillion-compound DNA-encoded libraries against ERα LBD variants. CDD-1274, which was highly enriched with all three variants, blocked spontaneous coactivator peptide recruitment to mutant ERα LBDs and inhibited estradiol-driven proliferative markers in several ER-positive breast cancer cell lines, but not in ER-negative breast cancer cells. We demonstrated that CDD-1274 induced proteasomal degradation of ERα variants in breast cancer cell lines and caused Y537S …