Medicine and Health Sciences Commons^™

Establishing Best Practices Guidelines For Collaborative Research In Global Surgery: Developing A Delphi Survey, Ramitha Eshan Ruwanpathirana, Swati Deshpande, Sophia Abdulhai, Mathilde Djeneba Billau, Sumeja Catic, Theresa L Chin, Julia N Harrison, Pratyush Kumar, Maria Cecilia T Leyson, Helen W Li, Katayoun S Madani, Arthur Serumaga, Margaret Tarpley, Grayson Wright, Nia N Zalamea, Joshua S Ng-Kamstra

Faculty, Staff and Students Publications

Background: Collaborative research in global surgery has resulted in the rapid development of the field via knowledge creation and dissemination, research capacity building, and direct improvements in the delivery of clinical care. Yet the establishment and maintenance of trans-boundary collaborations carries significant risk to health systems, clinicians, patients, and researchers, particularly if such collaborations are not developed thoughtfully and with appropriate guardrails. In recent years, there has been significant growth in the literature on the pervasiveness and impact of neocolonialism on global health research.

Methods: To harness the benefits of global surgery research collaboration while mitigating these risks, we reviewed …

Incidence And Risk Factors Of Developing A Dysrhythmia After Blunt Thoracic Trauma., Jessica Jowers, Kevin Van Derveer, Katherine Moore, Nathaniel Harshaw, Julie M Reichert, Hannah Karr, Urhum Khaliq, David J Cziperle, Lindsey L Perea

General Surgery Resident Research

Background/Objectives: The incidence of dysrhythmia after blunt thoracic trauma varies in the literature from 8-75%, and the complication rate from these dysrhythmias is not well studied. The aims of this study are to (1) identify the incidence of dysrhythmia following blunt thoracic trauma, (2) identify risk factors associated with developing a dysrhythmia, and (3) identify the incidence of cardiac intervention after developing a dysrhythmia. We hypothesize that blunt thoracic trauma may result in post-injury dysrhythmias. Methods: This is a retrospective review of trauma patients ≥ 18 years with a blunt mechanism of injury at a Level 1 Trauma …

Implementing A Training Resource For Large-Scale Genomic Data Analysis In The All Of Us Researcher Workbench, Jasmine Baker, Erik Stricker, Julie Coleman, Shamika Ketkar, Taotao Tan, Ashley M Butler, Laterrica Williams, Latanya Hammonds-Odie, Debra Murray, Brendan Lee, Kim C Worley, Elizabeth G Atkinson

Duncan NRI Faculty and Staff Publications

A lack of representation in genomic research and limited access to computational training create barriers for many researchers seeking to analyze large-scale genetic datasets. The All of Us Research Program provides an unprecedented opportunity to address these gaps by offering genomic data from a broad range of participants, but its impact depends on equipping researchers with the necessary skills to use it effectively. The All of Us Biomedical Researcher (BR) Scholars Program at Baylor College of Medicine aims to break down these barriers by providing early-career researchers with hands-on training in computational genomics through the All of Us Evenings with …

Lewy Body Dementia Promotion By Air Pollutants, Xiaodi Zhang, Haiqing Liu, Xiao Wu, Longgang Jia, Kundlik Gadhave, Lena Wang, Kevin Zhang, Hanyu Li, Rong Chen, Ramhari Kumbhar, Ning Wang, Chantelle E Terrillion, Bong Gu Kang, Bin Bai, Minhan Park, Ma Cristine Faye Denna, Shu Zhang, Wenqiang Zheng, Denghui Ye, Xiaoli Rong, Liu Yang, Lili Niu, Han Seok Ko, Weiyi Peng, Lingtao Jin, Mingyao Ying, Liana S Rosenthal, David W Nauen, Alex Pantelyat, Mahima Kaur, Kezia Irene, Liuhua Shi, Rahel Feleke, Sonia García-Ruiz, Mina Ryten, Valina L Dawson, Francesca Dominici, Rodney J Weber, Xuan Zhang, Pengfei Liu, Ted M Dawson, Shizhong Han, Xiaobo Mao

Faculty, Staff and Student Publications

Evidence links air pollution to dementia, yet its role in Lewy body dementia (LBD) remains unclear. Here we showed in a cohort of 56.5 million individuals across the U.S. that PM2.5 exposure raises LBD risk. Mechanistically, we found PM2.5 exposure led to brain atrophy in wild-type mice, an effect not seen in α-synuclein (αSyn)-deficient mice. PM2.5 exposure generated a highly pathogenic αSyn strain, PM-PFF, with enhanced proteinase K-resistance and neurotoxicity, resembling αSyn LBD strains. PM2.5 samples from China, the U.S., and Europe consistently induced proteinase-resistant αSyn strains and in vivo pathology. Transcriptomic analyses revealed shared responses between PM2.5-exposed mice and …

Dissecting Microbial Communities With Single-Cell Transcriptome Analysis, Andrew W Pountain, Itai Yanai

Faculty, Staff and Student Publications

Revealing insights into the function of microbial communities requires moving beyond measuring bulk taxonomic composition to detecting interactions between subpopulations. Following the transformative impact of single-cell gene expression profiling techniques on numerous fields of human biology, recent years have seen increased application to microbes. We review progress in the development of these techniques and discuss challenges in applying them to microbial communities. We highlight applications for dissecting the microbiome in human health and disease that reveal functional heterogeneity within gut communities, antibiotic responses, and the dynamics of mobile genetic elements. As single-cell gene expression technologies continue to develop, they are …

Human Papillomavirus Integration Induces Oncogenic Host Gene Fusions In Oropharyngeal Cancers, Nusrat Khan, Keiko Akagi, Shiming Jiang, Joe Dan Dunn, Bo Jiang, Weihong Xiao, Madison P O'Hara, Li Shen, Qi Wang, Vakul Mohanty, Jing Wang, Sara Goodwin, Jamie L Hutchins, Kevin R Coombes, Jagannadha K Sastry, David E Symer, Maura L Gillison

Faculty, Staff and Student Publications

HPV integration disrupts host genomic structure and expression, but whether these alterations promote cancer development remains unclear. Multiple genomic analyses of oropharyngeal cancers identified several host fusion genes, including recurrent FGFR3-TACC3 fusions, expressed from rearranged genomic loci adjacent to HPV integration sites. Evolutionary modeling implicated integration of virus concatemers into the host genome as a common initiating event in fusion formation. Co-expression of HPV16 E6/E7 and FGFR3-TACC3, but neither alone, was sufficient for tumor development in both xenograft and syngeneic mouse models and led to unique transcriptional programs implicated in carcinogenesis. FGFR3-TACC3 expression decreased the ubiquitination and degradation of …

Detection Of Cancers Three Years Prior To Diagnosis Using Plasma Cell-Free Dna, Yuxuan Wang, Corinne E Joshu, Samuel D Curtis, Christopher Douville, Vernon A Burk, Meng Ru, Maria Popoli, Janine Ptak, Lisa Dobbyn, Natalie Silliman, Josef Coresh, Eric Boerwinkle, Anna Prizment, Chetan Bettegowda, Kenneth W Kinzler, Nickolas Papadopoulos, Elizabeth A Platz, Bert Vogelstein

Faculty, Staff and Student Publications

To explore how early can cancers be detected prior to clinical signs or symptoms, we assessed prospectively collected serial plasma samples from the Atherosclerosis Risk in Communities (ARIC) study, including 26 participants diagnosed with cancer and 26 matched controls. At the index time point, eight of these 52 participants scored positively with a multicancer early detection (MCED) test. All eight participants were diagnosed with cancer within 4 months after blood collection. In six of these 8 participants, we were able to assess an earlier plasma sample collected 3.1 to 3.5 years prior to clinical diagnosis. In four of these six …

The Causal Pivot: A Structural Approach To Genetic Heterogeneity And Variant Discovery In Complex Diseases, Chad A Shaw, C J Williams, Taotao Tan, Daniel Illera, Nicholas Di, Joshua M Shulman, John W Belmont

Center on Aging Staff Publications

We present the Causal Pivot (CP) as a structural causal model (SCM) for analyzing genetic heterogeneity in complex diseases. The CP leverages an established causal factor or factors to detect the contribution of additional suspected causes. Specifically, polygenic risk scores (PRSs) serve as known causes, while rare variants (RVs) or RV ensembles are evaluated as candidate causes. The CP incorporates outcome-induced association by conditioning on disease status. We derive a conditional maximum-likelihood procedure for binary and quantitative traits and develop the Causal Pivot likelihood ratio test (CP-LRT) to detect causal signals. Through simulations, we demonstrate the CP-LRT’s robust power and …

Medical Students’ Perspectives On Dobbs V Jackson Women’S Health Organization, Victoria Lazarov, Cecilia Mastrogiacomo, Mikaela Koch, Kirsten Wohlars, Tova Ablove, Student Perspectives On Reproductive Rights Research Group

Cooper Rowan Medical Journal

Background: In June 2022, the Dobbs v Jackson Women’s Health Organization ruling overturned the previously upheld constitutional right to abortion. The resulting impact on medical training and student decision-making remains uncertain. This study aims to assess the nationwide impact of the Dobbs decision on medical students’ geographic residency preferences, specialty selection, and level of concern regarding civil and criminal charges for physicians providing abortion and fertility care.

Methods: An anonymous IRB-approved REDCap survey was distributed to American accredited medical schools across the United States and Israel between December 2022 and May 2023. Participants indicated specialty interests and geographic preferences for …

Investigating Bacterial Vaginosis Pathogenesis Using Peptide Nucleic Acid-Fluorescence In Situ Hybridization With A Focus On The Roles Of Gardnerella Species, Prevotella Bivia, And Fannyhessea Vaginae, Sheridan D. George, Megan H. Amerson-Brown, Lúcia G.V. Sousa, Tyler M. Carter, Alexa H. Rinehart, Ashleigh N. Riegler, Sixto M. Leal, Kristal J. Aaron, Jiaying Hao, Ashutosh Tamhane, Chaoling Dong, John W. Lammons, Jacob H. Elnaggar, Keonte J. Graves, Paweł Łaniewski, Melissa M. Herbst-Kralovetz, Christopher M. Taylor, Nuno Cerca, Christina A. Muzny

School of Graduate Studies Faculty Publications

Background. Bacterial vaginosis (BV) is a vaginal dysbiosis characterized by polymicrobial communities of BV-associated bacteria (BVAB) adhered to the vaginal epithelium. Despite decades of research, its etiology remains unknown. We aimed to investigate BV biofilm formation over time among women who developed incident BV (iBV) using peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH), focusing on 3 key BVAB (Gardnerella species, Prevotella bivia, and Fannyhessea vaginae). Methods. Heterosexual, nonpregnant women ages 18–45 with optimal vaginal microbiota were enrolled to self-collect twice-daily vaginal specimens for 60 days. iBV was defined as a Nugent score of 7–10 on ≥ 4 consecutive specimens. For …

Utilization Of The Fundamentals Of Vascular Surgery Symposium In Surgical Curricula, Priscilla Tanamal, Amit Chawla, Amanda Tullos, Claudie Sheahan, Malachi Sheahan

School of Medicine Faculty Publications

Objective: Simulation is a helpful adjunct to vascular surgery training, in which high-volume surgical experience portends better patient outcomes. Louisiana State University Health New Orleans hosts a 3-day program, the Fundamentals of Vascular Surgery (FVS) Symposium, during which vascular trainees from across the nation can participate in didactic and hands-on lessons with an emphasis on procedures less frequently performed during residency, taught by attending surgeons from various institutions. The objective of this study was to examine the effect of the FVS Symposium on participant confidence in endovascular and open procedures and evaluate any differences between junior and senior level residents. …

An Allele-Agnostic Mutant-Kras Inhibitor Suppresses Tumor Maintenance Signals And Reprograms Tumor Immunity In Pancreatic Cancer, Kathleen M Mcandrews, Francesca Paradiso, Clint A Stalnecker, Benson S Chellakkan, Fredrik I Thege, David H Peng, Barbara A Moreno Diaz, Hikaru Sugimoto, Sarah I Patel, Krishnan K Mahadevan, Michelle L Kirtley, Danielle Wills, Amari M Sockwell, Andre Luis F Fonseca, Yunhe Liu, Kimal I Rajapakshe, Nathaniel G Yee, Phuong Thao Tran, Huda Alchikh Omar, Antonio Tedeschi, Fiorella Schischlik-Siegl, Andrew S Boghossian, Matthew G Rees, Melissa M Ronan, Jennifer A Roth, Dorothea Rudolph, Martin Aichinger, Florian Ebner, Artem V Artemov, Jesse Lipp, Laura Pisarsky, Valerie Laura Herrmann, John Park, Jörg F Rippmann, Otmar Schaaf, Vanessa Chandler, Mariah Williams, Charles E Deckard, Linghua Wang, Channing J Der, Christopher Vellano, Paola A Guerrero, Timothy P Heffernan, Raghu Kalluri, Anirban Maitra

Faculty, Staff and Student Publications

KRAS is among the most frequently mutated oncogenes in cancer, and for decades, efforts at pharmacological blockade of its function in solid cancers have been unsuccessful. A notable advance in this endeavor is the recent development of small molecule KRAS inhibitors, which enable direct targeting of the mutant oncoprotein. Here, we comprehensively evaluate the pre-clinical efficacy of BI-2493 a panKRASi, a first-in-class allele agnostic mutant KRAS inhibitor, in pancreatic ductal adenocarcinoma (PDAC). We report effective tumor growth suppression across a broad range of models, including cell lines, patient-derived xenografts (PDXs), syngeneic orthotopic models, and prolonged survival in genetically engineered mouse …

Sociodemographic Determinants Of Telehealth Visits: A Comparison Of Mental Health And Substance Use Disorders With Other Services, Stanley Nkemjika, Orman Trent Hall, Jeanette Tetrault, Ayana Jordan

Department of Psychiatry and Human Behavior Faculty Papers

BACKGROUND/OBJECTIVES: Discrimination has wide-ranging implications, affecting patients' trust in healthcare professionals and their intentions to seek care. It can cause barriers that can affect access to care, especially among racial and ethnic minority groups in mental healthcare settings. Hence, we aim to examine the relationship between racial discrimination and reasons for using telehealth services.

METHOD: Using the 2022 Health Information National Trends Survey (HINTS-6), we isolated 6017 participants who reported on discrimination inquiry. The primary dependent variable in this study is self-reported discrimination in healthcare, while the main independent variable is the reason for the most recent telehealth visit, and …

An Isoform-Specific Runx1c-Btg2 Axis Governs Aml Quiescence And Chemoresistance, Cuijuan Han, Zhiping Zhang, Edie I Crosse, Sogand Sajedi, Bin Lu, Xiyue Wang, Sadik Karma, Mitch Kostich, Sakthi Harini Rajendran, Dylan B Udy, Steven Chen, Alexander Arnuk, Abimbola Eunice Lawal, Kayla R Koenig, Meryl Mckenna, Patrick K Reville, Hussein A Abbas, Omar Abdel-Wahab, Pedro Miura, Robert K Bradley, Eric Wang

Faculty, Staff and Student Publications

Aberrant levels or structures of RNA isoforms are a hallmark of many cancers, including acute myeloid leukemia (AML), yet their role in AML chemoresistance remains unclear. We conducted a paired analysis of RNA isoform changes in patients with AML before therapy and at relapse after chemotherapy and identified intragenic DNA methylation at the proximal promoter of the transcription factor RUNX1, which resulted in elevated expression of the long-isoform RUNX1C through its alternative distal promoter. The unique N-terminal region of RUNX1C orchestrated an isoform-specific transcriptional program that promoted chemoresistance, with its direct target BTG2 playing a role in chemotherapy resistance. …

Left Atrial Thrombus In Rheumatic Mitral Stenosis: A Case Of Therapeutic International Normalized Ratio Failure, Muhammad Salman Sabri, Carly Weber, Yanis Belkadi, Donald C. Haas, Yasotha Rajeswaran

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: Atrial fibrillation or flutter in rheumatic mitral stenosis (MS) increases left atrial appendage (LAA) thrombus risk despite therapeutic anticoagulation.

CASE SUMMARY: A 72-year-old woman on warfarin with moderate MS and atrial flutter presented with dyspnea. Transesophageal echocardiogram (TEE) showed a large LAA thrombus despite an international normalized ratio >2.5. Cardioversion was deferred, and the international normalized ratio target was raised to a range of 2.5 to 3.5.

TAKE-HOME MESSAGES: While cardioversion can be considered in patients with uninterrupted anticoagulation without TEE, those with rheumatic MS are at high risk of LAA and LA thrombus and should undergo TEE before …

Reliability Of T2-Weighted Mri Volumetric Measurements For Knee Effusion Assessment Following Acl Injury: An Intra-Rater And Inter-Rater Study, Reginald Chinweze, Neal Weldon, Matthew A. Tao, Melissa Manzer, Elizabeth Wellsandt

Posters and Presentations: Physical Therapy

Purpose: Knee effusion after anterior cruciate ligament (ACL) injury and reconstruction is associated with quadriceps dysfunction and may contribute to early osteoarthritis development. This study was subsequently designed to determine the intra-rater and inter-rater reliability of our method for volumetric quantitative measurements of knee effusion using T2-weighted magnetic resonance imaging (MRI) after ACL injury and reconstruction.

Methods: MRIs of 10 ACL-injured knees and 10 uninjured knees from participants aged 15-35 years old were included. Exclusion criteria included previous knee injury/surgery, inflammatory disease, BMI >30 kg/m2, and concomitant grade III ligament tears. Two independent raters analyzed effusion volumes using custom MATLAB …

Nebulization Of An Mrna-Encoded Monoclonal Antibody For Passive Immunization Of Foals Against Rhodococcus Equi, Rebecca M Legere, Jeannine A Ott, Cristina Poveda, Daryll Vanover, Karin E R Borba, Jae Yeon Joo, Cameron L Martin, Bibiana P Da Silveira, Jocelyne M Bray, Kerstin Landrock, Gus A Wright, J Chistensen Blazier, Andrew E Hillhouse, Ashley L Benham-Duret, Brandon Mistretta, Rafaela L Klein, Sarah M Thompson, Amelia R Woolums, Michael F Criscitiello, Luc R Berghman, Angela I Bordin, Philip J Santangelo, Jeroen Pollet, Noah D Cohen

Faculty, Staff and Students Publications

Inhalation of Rhodococcus equi causes severe pneumonia in humans and animals worldwide, most commonly affecting horse foals. The standard for preventing R. equi pneumonia in foals is transfusion of hyperimmune plasma, which is expensive and carries the risk of adverse effects. Our goal was to passively immunize foals against R. equi by nebulizing mRNA encoding an equine monoclonal antibody (mAb) against the virulence-associated protein A (VapA) directly into the lungs. VapA-specific memory B cells from an immunized horse were used to identify and select the sequence for an equine immunoglobulin (Ig)G1 mAb. In vitro-transcribed mRNA encoding this sequence expressed …

Amoxicillin Vs Ceftriaxone To Treat Pneumonia Caused By Amoxicillin-Non-Susceptible Streptococcus Pneumoniae, Daniel M Musher

Faculty, Staff and Students Publications

Although the article by J Càmara, I Grau, A González-Díaz, N Santos, et al. (Antimicrob Agents Chemother 69:e00237-25, 2025, https://doi.org/10.1128/aac.00237-25) suggests that ceftriaxone is greatly superior to amoxicillin in treating pneumonia due to pneumococci with an MIC > 2 mg/L, much of the difference in efficacy of the two drugs may have been due to dosage, route, and times of administration of the amoxicillin.

A Diagnostic Dilemma Due To A Large Chiari Network, Kyle Admire, Xian Qiao

Cardiovascular Research Symposium

INTRODUCTION: Chiari networks are reticulated networks of fibers that result from incomplete reabsorption of the right valve of the sinus venosus. While the true clinical significance of these is currently unknown, there are associations with dysrhythmias, paradoxical emboli, and thrombi formation. Here, we describe a large, incidentally found Chiari network which encompasses most of the right atrium.

CASE: A 42-year-old female with a past medical history of obesity (BMI 58) and well-controlled asthma presented to the emergency department in respiratory distress with hypercapnia and hypoxemia. Computed tomography (CT) with angiography of the chest was performed and did not show a …

Challenging Case: Acute Type A Aortic Dissection With Multi-Organ Malperfusion, Rishab Agarwal, Allebelle Bradshaw Md, Jennifer S. Lawton Md

Cardiovascular Research Symposium

Description of case: A 57-year-old male with hypertension and obesity presented with acute, severe chest pain. He developed a cold, numb right leg with motor deficits. He was hypotensive with a lactate of 7.4. CT imaging revealed an acute Type A aortic dissection (TAAD) with malperfusion involving the right internal carotid, right subclavian, and right coronary arteries, as well as the superior mesenteric artery, and right iliac artery (Fig 1A/B). He was transferred to our tertiary center for emergent surgery.

Five hours after presentation, he underwent emergent ascending aortic replacement, deep hypothermic circulatory arrest, and retrograde cerebral perfusion. The …

Association Between Cardiovascular Risk And Kidney Function In A Real-World Peruvian Cohort, Juan Munoz-Moreno, Gina Sanchez, Johanna Contreras

Cardiovascular Research Symposium

Background: Cardiovascular risk and kidney function are interrelated, with variations by sex and age. Middle-aged women often have slightly lower kidney function than men, increasing susceptibility to early renal effects of elevated cardiovascular risk, but data from Latin America remain limited.

Methods: Cross-sectional study of adults aged 40-79 years evaluated at a tertiary hospital in Peru between January and June 2024. We excluded individuals with established cardiovascular disease, statin use, LDL >190 mg/dL, or incomplete ASCVD risk data. Ten-year ASCVD risk was estimated using the 2013 Pooled Cohort Equations with race set as “Other” and classified as low, borderline, intermediate, …

Six-Year Survival Following Liver Transplant In Val30met Hereditary Transthyretin Amyloidosis, Juan Munoz-Moreno, Johanna Contreras

Cardiovascular Research Symposium

Background: Hereditary transthyretin amyloidosis (ATTRv) is a progressive, multisystem disorder caused by pathogenic TTR mutations affecting the heart and peripheral nerves. While disease-modifying agents such as tafamidis are available, liver transplantation (LTx) remains an option in selected genotypes, with over 50% of Val30Met carriers surviving up to 20 years post-transplant.

Case: A 53-year-old male with a permanent pacemaker for complete atrioventricular block presented with NYHA class II dyspnea, syncope, and lower extremity paresthesias. ECG showed atrial fibrillation. Transthoracic echocardiography revealed preserved ejection fraction, biventricular wall thickening with granular appearance, moderate left atrial dilation, and moderate mitral regurgitation. Speckle-tracking echocardiography demonstrated …

Mechanical Circulatory Support As A Bridge To Early Recovery Of Left Ventricular Function In Fulminant Myocarditis, Juan Munoz-Moreno, Gina Sanchez, Johanna Contreras

Cardiovascular Research Symposium

Background: Fulminant myocarditis (FM) is a rare cause of acute heart failure that can lead to a rapid left ventricular ejection fraction (LVEF) decline within four weeks. With in-hospital mortality up to 18.2%, timely mechanical circulatory support (MCS) is essential to stabilize hemodynamics and bridge to recovery or transplantation.

Case: A 49-year-old Japanese man with hypertension and diabetes presented with two weeks of dyspnea and angina after a flu-like illness. On admission, he developed ventricular fibrillation requiring advanced CPR. Physical exam revealed pulmonary congestion. ECG showed repolarization abnormalities. TTE demonstrated severe biventricular dysfunction (LVEF 9%, RVFAC 9%). Labs showed elevated …

Inferior Vena Cava Thrombosis In Nephrotic Syndrome: Two Cases Managed With Endovascular Thrombectomy, Rishab Agarwal, Benjamin Samberg, David Dexter Md

Cardiovascular Research Symposium

Background: Nephrotic syndrome (NS) confers a hypercoagulable state that can precipitate venous thromboembolism (VTE), rarely involving the inferior vena cava (IVC).

Cases: We describe two patients with NS who developed IVC thrombosis. One underwent mechanical thrombectomy using the ClotTriever®/Protrieve™ system (Inari Medical, Irvine, CA, USA); the other underwent aspiration thrombectomy using the AngioVac® system (AngioDynamics, Latham, NY, USA), with adjunct balloon maneuvers for renal vein thrombus.

Outcomes: Both patients achieved immediate IVC recanalization with symptom improvement and patent IVC on short‑term duplex follow‑up.

Conclusions: In NS‑associated IVC thrombosis, device‑based endovascular thrombectomy can be performed safely with restoration of caval patency. …

How Life-Cycle Real-World Evidence Can Bridge Evidentiary Gaps In Precision Oncology, Emanuel Krebs, Deirdre Weymann, Tania M. Bubela, Dean A. Regier

Office of the Provost

Precision oncology uses omics-based diagnostic technologies to inform histology-agnostic cancer treatment. To date, health system implementation remains limited owing to high uncertainty in regulatory and reimbursement evidence submissions. In this perspective, we describe a life-cycle approach to the evaluation of precision oncology technologies that addresses evidentiary uncertainty and is grounded in real-world evidence (RWE) derived using data routinely collected by healthcare systems. We consider the role for RWE in international regulatory and reimbursement decision-making, review common biases for observational precision oncology evaluations, make specific recommendations for RWE study design and analysis, and specify healthcare system requirements for data collection. We …

Subtype-Specific Her3 Enrichment In Basal-Like Breast Cancer Is Regulated Via The Gata2/Gata3–Foxa1 Axis, Congcong Tan, Hui Lyu, Sanbao Ruan, Yakun Wu, Margaret E. Larsen, Shou Ching Tang, Bolin Liu

School of Medicine Faculty Publications

Basal-like breast cancer (BLBC) is a major subtype of triple-negative breast cancer (TNBC), characterized by aggressive behavior, limited treatment options, and poor prognosis. While HER3 overexpression is frequently observed in TNBC and associated with poor outcomes, its subtype-specific expression and therapeutic potential remain unclear. Here, we demonstrated that HER3 signaling is selectively hyperactivated in BLBC compared to claudin-low breast cancer (CLBC) using transcriptomic profiling. Histone deacetylase inhibitors (HDACi), Romidepsin and Panobinostat, exerted potent antitumor effects on BLBC by selectively downregulating HER3 expression. HER3 levels were positively correlated with FOXA1, a key transcriptional activator. Mechanistically, we identified GATA2 and GATA3 as …

Periprocedural Results And Right Ventricular Outcomes Of Computer Assisted Vacuum Thrombectomy Treatment Of Acute Pulmonary Embolism: Interim Analysis Of 300 Patients From The Strike-Pe Study, John M. Moriarty, Brian J. Schiro, Suhail Y. Dohad, Houman Tamaddon, Hugh C. Davis, David M. Shavelle, George S. Chrysant, Elias A. Iliadis, David J. Dexter, Juan J. Ciampi Dopazo, Andrew Holden, Frances M. West, Brent Keeling, Andrew S. P. Sharp, Ido Weinberg

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

BACKGROUND: Pulmonary embolism (PE) can be a life-threatening condition. Endovascular treatment is emerging as a promising treatment to restore hemodynamic stability and reverse right ventricular (RV) dysfunction in PE; however, more studies are needed to elucidate the effects on the right ventricle after endovascular treatment. This analysis reports the effects of computer assisted vacuum thrombectomy on RV function.

METHODS: Eligible patients for the single-arm, prospective, international, multicenter STRIKE-PE (A Prospective, Multicenter Study of the Indigo Aspiration System Seeking to Evaluate the Long-Term Safety and Outcomes of Treating Pulmonary Embolism) cohort study are adults with acute PE with symptoms for ≤14 …

Targeting Aldh16a1 Mediated Thioredoxin Lysosomal Degradation To Enhance Ferroptosis Susceptibility In Smarca4-Deficient Nsclc, Guoshu Bi, Jiaqi Liang, Yunyi Bian, Guangyao Shan, Shencheng Ren, Haochun Shi, Xiaolong Huang, Junkan Zhu, Qun Wang, Wei Jiang, Boyi Gan, Cheng Zhan

Faculty, Staff and Student Publications

Ferroptosis, an iron-dependent form of cell death, holds promise for cancer therapy. However, the intricate link between ferroptosis and oncogenic mutations remains unclear. Here we show that SMARCA4, a well-established tumour suppressor whose deficiency is associated with poor prognosis and resistance to treatments, sensitizes non-small cell lung cancer (NSCLC) cells to ferroptosis. Mechanistically, SMARCA4 promotes chromatin accessibility and expression of ALDH16A1. Surprisingly, ALDH16A1 lacks ALDH enzymatic activity, but binds to the anti-ferroptotic oxidoreductase thioredoxin (TXN), facilitating its translocation to the lysosome and subsequent degradation. Meanwhile, ALDH16A1 directly inhibits TXN's oxidoreductase function by occluding its active site. We also show that …

Inhibition Of Mcl-1 And Mek Overcomes Mek Inhibitor Resistance In Triple-Negative And Inflammatory Breast Cancers, Mohd Mughees, Moises Tacam, Alex W Tan, Mary Kathryn Pitner, Lakesla R Iles, Xiaoding Hu, Emilly S Villodre, Bisrat G Debeb, Takahiro Kogawa, Bora Lim, Rachel M Layman, Wendy A Woodward, Naoto T Ueno, Debu Tripathy, Savitri Krishnamurthy, Yuan Qi, Lajos Pusztai, Jian Wang, Varsha Gandhi, Geoffrey Bartholomeusz, Chandra Bartholomeusz

Faculty, Staff and Student Publications

The MAPK pathway can drive resistance in highly aggressive breast cancers. Our previous work showed that the MEK inhibitor (MEKi) AZD6244 (selumetinib) prevented lung metastasis in a breast cancer xenograft model. In clinical studies, MEKis as single agents have had only modest activity against solid tumors due to the onset of resistance. Using synthetic lethality siRNA screening, we identified myeloid cell leukemia-1 (MCL-1) as a potential contributor to AZD6244 resistance. We hypothesized that MCL-1 promotes MEKi resistance in highly aggressive breast cancers and that MCL-1 inhibition overcomes AZD6244 resistance. We established two AZD6244-resistant cell lines: MDA-MB-231-R (triple-negative breast cancer) and …

Trends In Radiation Use From 2004 To 2020 Among Adolescents And Young Adults With Hodgkin Lymphoma, Kelsey L Corrigan, Amy M Berkman, Jillian Gunther, Clark R Andersen, Susan Wu, Amber Gibson, Branko Cuglievan, Miriam B Garcia, Gohar Manzar, Penny Fang, Brian De, Sairah Ahmed, Cesar Nunez, Michelle A T Hildebrandt, David C Mccall, Susan K Parsons, Michael E Roth

Faculty, Staff and Student Publications

Background: Hodgkin lymphoma has excellent survival rates in adolescents and young adults (AYA, diagnosed between ages 15 and 39 years). However, survivors are at risk of treatment-related late effects. Whereas radiotherapy (RT) de-escalation/omission has emerged as an approach to minimize late effects, no prior studies have evaluated RT use over time in AYAs with Hodgkin lymphoma.

Methods: Using the National Cancer Database, we identified 40,717 AYAs diagnosed with Hodgkin lymphoma between 2004 and 2020. Differences in sociodemographic and clinical variables were assessed using a two-sample two-sided t test or χ2 test. RT use was summarized per year by frequency with …