Public Health Commons^™

Lilrb4 Regulates Circadian Disruption-Induced Mammary Tumorigenesis Via Non-Canonical Wnt Signaling Pathway, Olajumoke Ogunlusi, Mrinmoy Sarkar, Kayla Carter, Arhit Chakrabarti, Devon J Boland, Tristan Nguyen, James Sampson, Christian Nguyen, Danielle Fails, Yava Jones-Hall, Loning Fu, Gus Wright, Da Mi Kim, James J Cai, Bani Mallick, Alex C Keene, Jeff R Jones, Tapasree Roy Sarkar

Faculty, Staff and Students Publications

Epidemiological studies have shown that circadian rhythm disruption (CRD) is associated with the risk of breast cancer. However, the role of CRD in mammary gland morphology and aggressive basal mammary tumorigenesis and the molecular mechanism underlying CRD-induced carcinogenesis remain unknown. To investigate the effect of CRD on aggressive tumorigenesis, a genetically engineered mouse model of aggressive breast cancer was used. The impact of CRD on the tumor microenvironment was investigated using the tumors from LD12:12 and CRD mice via scRNA-seq, flow cytometry, multiplexing immunostaining, and realtime PCR. The effect of LILRB4-immunotherapy on CRD-induced tumorigenesis was also investigated. Here we investigated …

Frequency, Duration, And Cost Of Pulmonary Exacerbations Among Patients With Bronchiectasis, Maitreyee Mohanty, Claudia Leiras, Haiyan Sun, Reina Rau, John Fastenau, Joseph Feliciano, Sunjay R Devarajan

Faculty, Staff and Students Publications

Background: In administrative claims database studies of bronchiectasis, pulmonary exacerbations are usually defined using a fixed period for their start and end, which prevents assessment of exacerbation duration and thereby limits assessment of exacerbation characteristics. Here, we applied a novel cost-based algorithm to characterize exacerbations.

Methods: This cohort study used the Merative MarketScan Commercial Claims and Encounters database, 1-Jan-2016 to 31-Dec-2022. Patients ≥18 years with bronchiectasis (≥2 outpatient or ≥1 inpatient claim with bronchiectasis; no cystic fibrosis) had 12 months of continuous enrollment before (baseline) and ≥12 months after (follow-up) index (first bronchiectasis claim). Cost-based exacerbations were identified by compound …

Young Adults And Early-Onset Psychosis: A Grounded Theory Study Of Experiences Of Identity Development, Katherine Hayden-Lewis, Deborah Rubel

The Qualitative Report

While identity development is a crucial task for young individuals ages 15-25, current research inadequately centralizes identity development in the context of first-time psychosis related to schizophrenia spectrum disorders. This study addresses the knowledge gap by exploring the grand research question, “How does a young person experience their identity development after the first episode of psychosis?”. Constructivist grounded theory methods influenced by critical frameworks were used to collect and analyze data with seven young adults engaged in first episode psychosis programs. Participants were young adults, between the ages of 19-24, that at the time of the study were enrolled in …

Post-Release Health Insurance Utilization Among Ex-Prisoners: A Scoping Review, Icha Khaerunnisa, Megah Andriany, Luky Dwiantoro

Kesmas

The lack of health insurance coverage after prison release significantly reduces access to essential healthcare services, hindering the continuity of care during community reintegration. The evidence on studies of health insurance use following prison release is limited. This scoping review aimed to summarize research on health insurance utilization after release from prison. Literature searches were conducted across databases including ScienceDirect, PubMed, and Scopus. Relevant articles were selected through a two-stage screening process. Data were extracted from the included studies and presented in tabular and descriptive formats. The keywords used were "health insurance AND post-release" and "inmates OR prisoners." This scoping …

Nivolumab Plus Ipilimumab Induce Hyper-Progression In Renal Medullary Carcinoma: Results Of A Phase Ii Trial And Preclinical Evidence, Melinda Soeung, Xinmiao Yan, Ciro Zanca, Jing Qian, Menuka Karki, Fei Duan, Hania Khan, Li Zhang, David H Peng, Mariah Williams, Rong He, Ziheng Chen, Luigi Perelli, Jianfeng Chen, Rebecca S Tidwell, Pankaj K Chauhan, Courtney N Le, Truong N A Lam, Nirjar Bhattacharya, Rutvi Shah, I-Lin Ho, Jason P Gay, Caroline C Carrillo, Ningping Feng, Kang Le, Guang Gao, Teresa L Perry, Faika Mseeh, Yongying Jiang, Quanyun A Xu, Niki Marie Zacharias, Rahul A Sheth, Tharakeswara K Bathala, Priya Rao, Najat C Daw, Durga N Tripathi, Cheryl L Walker, Mohammad M Mohammad, Jianhua Zhang, Guangchun Han, Yanshuo Chu, Ruiping Wang, Minghao Dang, Enyu Dai, Fuduan Peng, Yunhe Liu, Akshaya Jadhav, Wenhua Lang, Claudio A Arrechedera, Leticia Campos Clemente, Edwin R Parra, Hsinyi Lu, Cara L Haymaker, Ignacio I Wistuba, Andrew Futreal, Andrea Viale, Michael J Soth, Philip Jones, Joseph R Marszalek, Timothy Heffernan, Giulio F Draetta, Nizar M Tannir, Jianjun Gao, Linghua Wang, Giannicola Genovese, Pavlos Msaouel

Faculty, Staff and Students Publications

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here we report the results of a phase II clinical trial (NCT03274258) of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in patients with RMC, with objective response rate as primary outcome. Enrollment was halted for futility at a prespecified interim analysis as all 10 treated patients experienced rapid disease progression. 5/10 met radiological criteria for hyperprogression and median progression-free survival (secondary outcome) was 1.38 months (95% confidence interval: 1.28, 1.60). In a post-hoc single-cell RNA sequencing analysis, data from patients with RMC before and after nivolumab plus ipilimumab treatment indicated that …

Geographic And Socioeconomic Predictors Of Early Follow-Up Loss In Patients Undergoing Pituitary Neuroendocrine Tumors (Pitnets) Resection: A Retrospective Review Of 1143 Cases, Daniel Quintana, Rithvik Ramesh, Robert C. Osorio, Wesley Shoap, Paul Mcmillan Villalobos, Philip V. Theodosopoulos, Sandeep Kunwar, Jose Gurrola, Ivan H. El Sayed, Manish K. Aghi, Ezequiel Goldschmidt

School of Medicine Faculty Publications

OBJECTIVE: Postoperative follow-up after PitNET resection is essential for monitoring tumor recurrence and endocrinological deficits. Despite advances in telehealth, loss to follow-up remains a persistent challenge across neurosurgical patients. This study aims to identify factors to identify patients are at higher risk of being lost to follow-up after surgery. METHODS: A retrospective analysis was conducted on 1,143 adult patients who underwent PitNET resection between 2012 and 2019 at a single institution. Clinical and radiological data were analyzed to assess loss to follow-up in the cohort. Multivariable logistic and negative binomial regression models were used to identify factors independently associated with …

Development And Applications Of A Health Equity Summary Score Using The Medical Expenditure Panel Survey, Ronald R. Sanchez

Dissertations and Theses

Despite sustained national efforts, disparities in healthcare delivery persist among racial and ethnic minorities, low-income individuals, and socially at-risk populations. Monitoring modifiable aspects of care delivery, such as the structures and processes that health systems can directly improve, is a key strategy for addressing these gaps. However, most measures evaluate modifiable aspects of care delivery separately, limiting understanding of how improvements in one domain reinforce the other and how their combined effect influences equitable care.

This dissertation addresses this gap by combining patient experience and clinical quality, two modifiable aspects of care that captures how patients interact with the health …

The Follow-Up Gap: Racial Disproportionality And Social Determinants Of Health In New Jersey’S Hearing Detection And Intervention Program, Maryrose Mcinerney, Wendy Zeitlin

Journal of Early Hearing Detection and Intervention

Objectives. To assess how race/ethnicity and social determinants of health are related to loss to follow-up (LTF) from NJ’s Early Hearing Detection and Intervention (EHDI) program.

Methods. All infants born in NJ between June 2015 and June 2017 referring for additional hearing healthcare after hospital discharge were considered for inclusion in this study. The sample consisted of 4,141 babies, 10.7% of which received no follow-up care. Step-wise multi-level logistic regression was used to determine how race/ethnicity, family-level, and community-level social determinants of health (SDOH) were predictive of LTF.

Results. In each model, the odds of being LTF were significantly higher …

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 …

Band-Aids And Backroads: Surviving Rural Healthcare In South-Central Mississippi, Cambry L. Craft

Honors Theses

Health is more than the absence of disease—it is the product of opportunity, trust, and access. Yet for millions living in rural areas of the United States, equitable healthcare remains out of reach. This thesis seeks to amplify the voices of rural residents in Mississippi and uncover how their experiences, beliefs, and cultural values shape their perception of their local hospital and the care that is provided there. This qualitative research study examines the experiences and opinions of a rural community in south-central Mississippi regarding their local hospital, as well as their perceptions of the most effective approach to prevent …

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 …

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: …

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 …

In Vivo Pharmacokinetic Evaluation Of A Gastro-Retentive Triple Drug Delivery System Utilizing Natural Polymers For Enhanced Helicobacter Pylori Eradication, Edukulla Satheesh Kumar, Hindustan Abdul Ahad, Thirumalesh Naik Sugali Banoth

Bulletin of Faculty of Pharmacy Cairo University

This study evaluates the in vivo pharmacokinetics of triple-drug gastro-retentive formulation (metronidazole- Plantago ovata seed mucilage/ clarithromycin- Abelmoschus esculentus fruit mucilage/enteric-coated pantoprazole) for Helicobacter pylori eradication, with a focus on pharmacokinetic parameters (e.g., relative bioavailability vs. conventional doses) as the true contribution. In a cross over study using six rabbits, plasma concentrations of metronidazole, clarithromycin, and pantoprazole sodium were measured via High Performance Liquid Chromatography technique, and pharmacokinetic parameters were determined. A single dose of the optimized formulation (C-8) produced optimal drug levels, with a mean Cmax of 24.36 ± 0.84 μg/mL and tmax at 6 hours. The other pharmacokinetic …

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 …

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.

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 …

Preclinical Efficacy Of Tasquinimod-Based Combinations In Advanced Myeloproliferative Neoplasms In Blastic Phase, Warren Fiskus, Lucia Masarova, Christopher P Mill, Christine E Birdwell, Kaberi Das, Hanxi Hou, John A Davis, Antrix Jain, Anna Malovannaya, Taghi Manshouri, Andrew Dunbar, Surbhi Sharma, Tapan M Kadia, Courtney D Dinardo, Prithviraj Bose, Naveen Pemmaraju, Sanam Loghavi, Xiaoping Su, Raajit K Rampal, Marie Törngren, Kapil N Bhalla

Faculty, Staff and Students Publications

The alarmins, S100A8 (A8) and S100A9 (A9), are low molecular weight proteins belonging to the S100 protein family. A8 and A9 are secreted into the extracellular space and plasma, in which they interact with Toll-like receptor 4, receptor for advanced glycation end products, and CD33. In these studies, we determined the preclinical efficacy of tasquinimod (TQ) against advanced myeloproliferative neoplasm (MPN) cell lines and patient-derived (PD) CD34+ blastic phase (BP; >5% blasts in the peripheral blood) MPN cells. TQ induced loss of viability in cell lines and PD MPN-BP cells, but not in normal CD34+ progenitor cells. In TQ-treated PD …

Use Of An Expert Panel For Symptomatic Patients With Grade I Degenerative Lumbar Spondylolisthesis: A Randomized Clinical Trial, Zoher Ghogawala, Tasneem Rizvi, Zhibang Lin, Adam Kanter, Praveen Mummaneni, Erica Bisson, Todd Albert, Daniel Resnick, Michael Wang, Steven Glassman, David Polly, Mohamad Bydon, Subu Magge, Luis Tumialan, Michael Fehlings, Michael Steinmetz, Robert Whitmore, Vedantam Rajshekhar, James Harrop, Roger Härtl, Elnasri Ahmed, Dom Coric, Paul Mccormick, Richard Assaker, Abdul Msaddi, Langston Holly, Yoshiharu Kawaguchi, Asdrubal Falavigna, Fred Barker, Edward Benzel

Department of Neurosurgery Faculty Papers

BACKGROUND AND OBJECTIVES: The appropriate utilization of lumbar fusion when performing laminectomy for lumbar spondylolisthesis is uncertain. The objective was to determine whether the use of a surgical expert review panel recommending fusion might improve patient selection, possibly reducing surgical failures.

METHODS: Randomized clinical trial of patients with symptomatic degenerative lumbar stenosis with spondylolisthesis enrolled from 14 North American hospitals was conducted with patients randomized to receive an expert panel review of their case or not. Spinal expert review consisted of 10 to 15 surgeons' review of patient images and clinical data with voting on the appropriateness of fusion. Primary …

Mutant P53 Variants Differentially Impact Replication Initiation And Activate Cgas-Sting To Affect Immune Checkpoint Inhibition, Kang Liu, Lidija A Wilhelms Garan, Fang-Tsyr Lin, Weei-Chin Lin

Faculty, Staff and Students Publications

Prior research shows that Akt-dependent phosphorylation of TopBP1 in S phase results in the switch of TopBP1/Treslin binding to TopBP1/E2F1 binding, which is important to prevent replication re-initiation in late S and G2 phases. Here, we demonstrate that contact, but not conformational, mutant p53 can override this switch by binding to both TopBP1 and Treslin, thereby facilitating persistent TopBP1/Treslin interaction in late S and G2 phases, which ultimately leads to over-firing of replication initiation. This increases micronuclei formation, which is further enhanced by genotoxic stressors such as doxorubicin, PARP inhibitors, or ATR inhibitors. Consequently, contact mutant p53 increases the sensitivity …

Design Considerations For Conversational Agents To Assess The Social-Emotional Well-Being Of Young Children In Low-Income South African Communities, Lucretia A. Williams, Elizabeth A. Ankrah, Catherine E. Draper, Caylee J. Cook, Franceli L. Cibrian, Jesus A. Beltran, Kimberley D. Lakes, Gillian R. Hayes

Engineering Faculty Articles and Research

A variety of digital technologies have been used to support early childhood development (ECD) programs in low-income South African communities. Even though technology has provided opportunities to increase access to health interventions, the lack of trust and socio-economic constraints under which these tools would need to work pose complex challenges. We examine home visitors’ work processes, experiences, and preferences of a conversational agent to support their work of administering social-emotional well-being assessments to young children ages 0-5. Analysis of the results of focus groups with 51 home visitors indicates the need for designing conversational agents that support ECD in the …

Disparate Leukemia Mutations Converge On Nuclear Phase-Separated Condensates, Gandhar K Datar, Elmira Khabusheva, Archish Anand, Joshua Beale, Marwa Sadek, Chun-Wei Chen, Evdokiia Potolitsyna, Nayara Alcantara-Contessoto, Guangyuan Liu, Josephine De La Fuente, Christina Dollinger, Anna Guzman, Alejandra Martell, Katharina Wohlan, Abhishek Maiti, Nicholas J Short, S Stephen Yi, Vibeke Andresen, Bjørn Tore Gjertsen, Brunangelo Falini, Rachel E Rau, Lorenzo Brunetti, Nidhi Sahni, Margaret A Goodell, Joshua A Riback

Faculty, Staff and Students Publications

During cancer development, mutations promote changes in gene expression that cause transformation. Leukemia associated with aberrant HOXA expression is driven by translocations of nucleoporin genes or KMT2A as well as mutations in NPM1. The mechanistic convergence of these disparate mutations remains elusive. Here, we demonstrate that mutant nucleophosmin 1 (NPM1c) forms nuclear condensates in human cell lines, mouse models, and primary patient samples. We show NPM1c phase separation is necessary and sufficient to recruit NUP98 and KMT2A to condensates. Through extensive mutagenesis and pharmacological destabilization of phase separation, we find that NPM1c condensates are necessary for regulating gene expression, promoting …

Serum Response Factor Is Essential For Endometrial Function And Prevention Of Inflammatory Fibrosis, Ryan M Marquardt, Sara A Grimm, San-Pin Wu, Peter F Lais, Shu-Yun Li, Xin Xu, Erin Smithberger, David Cunefare, Charan Ganta, David Olson, Eunhee M Jeong, Jae-Wook Jeong, Bruce A Lessey, John P Lydon, Francesco J Demayo

Faculty, Staff and Students Publications

Pregnancy requires a supportive uterine environment facilitated by steroid hormone–regulated differentiation of endometrial stromal fibroblasts into decidual cells and tight control of inflammation. Serum response factor (SRF) is a widely expressed transcription factor essential for mesenchymal cell growth and differentiation with noted roles in hormonal regulation of muscle tissues but little characterization in reproductive organs. Here, we reveal that endometrial SRF is dysregulated in human endometriosis and is critical for female reproductive success in mice through regulation of endometrial stromal and epithelial cells. Immunohistochemical analysis identified decreased endometrial SRF expression in infertile endometriosis patient tissues. RNAi-based SRF knockdown in human …

Orphan Nuclear Receptor 4a1 (Nr4a1) And Nr4a2 Are Endogenous Regulators Of Cd71 And Their Ligands Induce Ferroptosis In Breast Cancer, Arafat Rahman Oany, Srijana Upadhyay, Wai Ning Tiffany Tsui, Amanuel Hailemariam, Sarah Latka, John D Landua, Sandra D Scherer, Alana L Welm, Hugo Villanueva, Michael T Lewis, Stephen Safe

Faculty, Staff and Students Publications

Ferroptosis is an iron-dependent cell death pathway that involves multiple genes, including the transferrin receptor (TFRC/CD71), glutathione peroxidase 4 (GPX4) and cystine-glutamate antiporter (SLC7A11). This study is based on the hypothesis that orphan nuclear receptor 4A1 (NR4A1) and NR4A2 maintain low levels of ferroptosis in triple negative breast cancer (TNBC) cells and bis-indole derived (CDIM) compounds act as NR4A1/2 ligands that induce ferroptosis by enhancing CD71 expression. 1,1-Bis(3'-indolyl)-1-(3,5-disubstitutedphenyl)methane (DIM-3,5) analogs were investigated for their cytotoxicity and effects on NR4A1 and NR4A2 regulated genes and induction of ferroptosis. Several assays also determined enhanced lipoperoxidation, reactive oxygen species and malondialdehyde formation in …

Burden Of Central Nervous System Cancer In The United States, 1990-2021, Hyun Jin Han, Yun Seo Kim, Seoyeon Park, Jae Il Shin, Min Seo Kim, Ju Hyung Moon, Yong Bae Kim, Hazim S Ababneh, Ahmed Abu-Zaid, Demelash Areda, Santhosh Arul, Ahmed Y Azzam, Mainak Bardhan, Mohammad Amin Bayat Tork, Babak Behnam, Gokce Belge Bilgin, Prarthna V Bhardwaj, Soumitra S Bhuyan, Nima Broomand Lomer, Meng Xuan Chen, Suma Sri Chennapragada, Xiaochen Dai, Frances E Dean, Sindhura Deekonda, Xueting Ding, Ojas Prakashbhai Doshi, Abdel Rahman E'Mar, Muhammed Elhadi, Jawad Fares, Patrick Fazeli, James L Fisher, Maryam Fotouhi, Ali Gholamrezanezhad, Fidelia Ida, Chidozie Declan Iwu, Mohamed Jalloh, Chinmay T Jani, Rizwan Kalani, Samuel Berchi Kankam, Foad Kazemi, Ariz Keshwani, Atulya Aman Khosla, Stephen S Lim, Riffat Mehboob, Tomislav Mestrovic, Ali H Mokdad, Christopher J L Murray, Gurudatta Naik, Zuhair S Natto, Dang Nguyen, Fred Nugen, Atakan Orscelik, Romil R Parikh, Louise Penberthy, Richard G Pestell, Disha Prabhu, Jagadeesh Puvvula, Shakthi Kumaran Ramasamy, Cameron John Sabet, Austin E Schumacher, Yigit Can Senol, Sunder Sham, Samendra P Sherchan, Gizeaddis Lamesgin Simegn, Jasvinder A Singh, Ranjan Solanki, Bahadar S Srichawla, Jabeen Taiba, Manoj Tanwar, Mike Tuffour Amirikah, Anjul Verma, Ismaeel Yunusa, David X Zheng, Dong Keon Yon, Keun Young Park

Faculty, Staff and Students Publications

Importance: Primary brain and central nervous system cancer (collectively referred to as CNS cancer) comprises 2% of all human cancers and poses significant health and economic challenges in the United States.

Objective: To analyze CNS cancer burden in the US, stratified by time, location (state and division), sex, age group, and Sociodemographic Index (SDI).

Design, setting, and participants: This cross-sectional study involved a repeated analysis of Global Burden of Disease Study (GBD) 2021 data in 2024. Using data from 183 sources, CNS cancer metrics in the US were estimated across states and years. US CNS cancer metrics across all sexes …

A Multiomics Recovery Factor Predicts Long Covid In The Impacc Study, Gisela Gabernet, Jessica Maciuch, Jeremy P Gygi, John F Moore, Annmarie Hoch, Caitlin Syphurs, Tianyi Chu, Naresh Doni Jayavelu, David B Corry, Farrah Kheradmand, Lindsey R Baden, Rafick-Pierre Sekaly, Grace A Mccomsey, Elias K Haddad, Charles B Cairns, Nadine Rouphael, Ana Fernandez-Sesma, Viviana Simon, Jordan P Metcalf, Nelson I Agudelo Higuita, Catherine L Hough, William B Messer, Mark M Davis, Kari C Nadeau, Bali Pulendran, Monica Kraft, Chris Bime, Elaine F Reed, Joanna Schaenman, David J Erle, Carolyn S Calfee, Mark A Atkinson, Scott C Brakenridge, Esther Melamed, Albert C Shaw, David A Hafler, Alison D Augustine, Patrice M Becker, Al Ozonoff, Steven E Bosinger, Walter Eckalbar, Holden T Maecker, Seunghee Kim-Schulze, Hanno Steen, Florian Krammer, Kerstin Westendorf, Bjoern Peters, Slim Fourati, Matthew C Altman, Ofer Levy, Kinga K Smolen, Ruth R Montgomery, Joann Diray-Arce, Steven H Kleinstein, Leying Guan, Lauren Ir Ehrlich

Faculty, Staff and Students Publications

Background: Following SARS-CoV-2 infection, approximately 10%–35% of patients with COVID-19 experience long COVID (LC), in which debilitating symptoms persist for at least 3 months. Elucidating the biologic underpinnings of LC could identify therapeutic opportunities.

Methods: We utilized machine learning methods on biologic analytes provided over 12 months after hospital discharge from more than 500 patients with COVID-19 in the IMPACC cohort to identify a multiomics “recovery factor,” trained on patient-reported physical function survey scores. Immune profiling data included PBMC transcriptomics, serum O-link and plasma proteomics, plasma metabolomics, and blood mass cytometry by time of flight (CyTOF) protein levels. Recovery factor …

Integrative Proteogenomics And Forward Genetics Reveal A Novel Mitotic Vulnerability In Triple-Negative Breast Cancer, Nicholas J Neill, Shankha Satpathy, Karsten Krug, Jitendra K Meena, Nivetha Ramesh Babu, Cheyenne Calderon, Desmon Reed, Marcus J Weber, Lacey E Dobrolecki, Alaina Lewis, Christina Sallas, Meenakshi Anurag, Kimberly R Holloway, Chen Huang, Suhas Vasaikar, Maria F Cardenas, Beom-Jun Kim, Doug W Chan, Shayan C Avanessian, Siddhartha Tyagi, Mayra Orellana, Sufeng Mao, Heyuan Li, Fade Gong, Sarah J Kurley, Kristen L Meerbrey, Calla M Olson, Amritha Nair, Tingting Sun, Hsiang-Ching Chung, Elizabeth A Bowling, Jarey H Wang, Pengju Zhang, Peng Xiao, Duxiao Yang, Fabio Stossi, Mei-Yin C Polley, Alexander B Saltzman, Filip Mundt, D R Mani, Michael A Gillette, Susan G Hilsenbeck, George Miles, Carolina Gutierrez, C Kent Osborne, Charles Y Lin, Nathanael S Gray, Jinpeng Sun, David A Wheeler, Charles M Perou, Anna Malovannaya, Michael T Lewis, Bing Zhang, Matthew J Ellis, Steven A Carr, Thomas F Westbrook

Faculty, Staff and Students Publications

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with few effective targeted therapies. Taxanes and other microtubule-targeting agents (MTAs) are frontline chemotherapies for TNBC; however, the molecular pathways that cause TNBC taxane sensitivity are largely unknown, preventing selection of taxane-responsive patients and development of more selective therapeutic strategies. In this study, we identified tumor-selective vulnerabilities in TNBC harboring inactivation of the tumor suppressor PTPN12 by integrating proteogenomic characterization and synthetic lethality screening. We discovered that PTPN12 inactivation drives mitotic defects through aberrant hyperactivation of the ubiquitin ligase complex APCFZR1, a critical regulator of the cell cycle. Consistent …