Medicine and Health Sciences Commons^™

Enhanced Staphylococcus Aureus Protection By Uncoupling Of The Α-Toxin-Adam10 Interaction During Murine Neonatal Vaccination, Kelly L Tomaszewski, Meagan Blanchard, Reuben Olaniyi, Hannah R Brenton, Samantha Hayes, Farheen Fatma, Gaya K Amarasinghe, Byoung-Kyu Cho, Young Ah Goo, Andrea C Dedent, Stephanie A Fritz, Juliane Bubeck Wardenburg

2020-Current year OA Pubs

Staphylococcus aureus remains a leading global cause of bacterial infection-associated mortality and has eluded prior vaccine development efforts. S. aureus α-toxin (Hla) is an essential virulence factor in disease, impairing the T cell response to infection. The anti-Hla antibody response is a correlate of human protective immunity. Here we observe that this response is limited early in human life and design a vaccine strategy to elicit immune protection against Hla in a neonatal mice. By targeted disruption of the interaction of Hla with its receptor ADAM10, we identify a vaccine antigen (Hla

Monte Carlo Simulations Of Cefepime In Children Receiving Continuous Kidney Replacement Therapy Support Continuous Infusions For Target Attainment., H Rhodes Hambrick, Nieko Punt, Kathryn Pavia, Tomoyuki Mizuno, Stuart L. Goldstein, Sonya Tang Girdwood

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Sepsis is a leading cause of acute kidney injury requiring continuous kidney replacement therapy (CKRT) and CKRT can alter drug pharmacokinetics (PK). Cefepime is used commonly in critically ill children and is cleared by CKRT, yet data regarding cefepime PK and pharmacodynamic (PD) target attainment in children receiving CKRT are scarce, so we performed Monte Carlo simulations (MCS) of cefepime dosing strategies in children receiving CKRT.

METHODS: We developed a CKRT "module" in the precision dosing software Edsim++. The module was added into a pediatric cefepime PK model. 1000-fold MCS were performed using six dosing strategies in patients aged …

The Perfect Storm: Abnormal Baseline Qt With Chronic Methadone Use And Serious Hypokalemia, Oscar J. Lopez, Diana Othon, Yilen Karen Ng-Wong, Jose Sleiman

School of Medicine Publications

Methadone, a well-known drug used for pain control and as a treatment for opioid addiction, can cause arrhythmias, including torsades de pointes (TdP), which may progress to ventricular fibrillation and sudden death. We present a case of a middle-aged woman with a long history of methadone use who presented to the emergency department after experiencing cardiac arrest at home. During her hospitalization, she experienced multiple episodes of TdP that improved with isoproterenol and potassium correction. The initial diagnosis was methadone-induced prolonged QT. However, even with discontinuation of methadone, her QTc remained prolonged. Congenital long QT syndrome was suspected, and genetic …

Hepatic Targets To Control Blood Glucose And Potentially Aid In The Treatment Of Diabetes, Rena A. Velissarios

PANDION: The Osprey Journal of Research and Ideas

Maintaining glucose homeostasis is extremely important to remain in good health and prevent disease. This homeostasis is achieved via the regulation of hepatic metabolic pathways like gluconeogenesis and glycogenesis by insulin, which is expressed during high blood glucose. Insulin is responsible for facilitating the uptake of glucose into other tissues from the blood, as well as signaling whether to stimulate or slow glucose metabolism in the liver. Hyperglycemia is one of the main effects of diabetes, a disease characterized by the body’s inability to produce or respond to insulin. Without insulin, hepatic glucose output continues and blood glucose accumulates, causing …

The Short Allele Of The Serotonin Transporter Gene (Slc6a4) Increases Predisposition To Anxiety And Negative Emotional States, Gabriella Hitti

PANDION: The Osprey Journal of Research and Ideas

Mental disorders, such as anxiety and mood disorders, have long been a focus of psychological research, and increasing evidence points to a genetic basis for their occurrence. Polymorphisms of the serotonin transporter (5-HTT) gene (SLC6A4) may predispose an individual to anxiety-related symptoms. SLC6A4 has two common alleles: the short (s) allele, which results in less 5-HTT protein production, and the long (l) allele, which results in more 5-HTT. Integrated findings from psychometric evaluations, behavioral animal models, and biological assessments establish a link between the s allele of SLC6A4 and heightened anxiety phenotypes. The allele’s influence on serotonin levels and brain …

Wmdds Bulletin Directory 2024

West Michigan District Dental Society Bulletin

In the 2024 Directory edition of the West Michigan District Dental Society Bulletin, the reader will find a comprehensive listing of WMDDS members for 2024.

Corrections to this year's directory can be found in the Fall 2024 issue of the WMDDS Bulletin.

Barriers To Cardiac Rehabilitation Enrolment And Secondary Prevention Adherence In Patients With Coronary Heart Disease Following Percutaneous Coronary Intervention: A Cross-Sectional Survey, Ahmed Mohammed Almoghairi, Jane O’Brien, Anna Doubrovsky, Jed Duff

Journal of the Saudi Heart Association

Objectives: This study aimed to evaluate adherence to secondary prevention measures and to identify barriers to cardiac rehabilitation enrolment among patients with coronary heart disease after percutaneous coronary intervention.

Methods: An observational cross-sectional survey was conducted through computer-assisted telephone interviews to assess recently treated percutaneous coronary intervention patients at the Prince Sultan Cardiac Center in Saudi Arabia.

Results: Out of 104 surveyed patients with coronary heart disease, 85 (82%) were male, with an average age of 59.5 years. The obesity rate was 28% (n = 29), with a high prevalence of comorbidities: 82 (79%), 63 (61%), and 62 (60%) …

Teach Me How To Love: The Love Ethic As A Foundation For Liberatory Counseling Education, R. Danielle Scott

The Journal of Advancing Education Practice

Centering social justice within the university classroom is essential for fostering an inclusive and equitable learning environment and empowering students toward an orientation for social change. This article explores how interdisciplinary learning, grounded in bell hooks’ concept of the “love ethic” from All About Love, can enhance counseling education within the field of Speech, Language, and Hearing Sciences (SLHS). The study focuses on a flexible-synchronous course designed for upper-level undergraduate students as an elective in the Communication Sciences and Disorders department at a predominantly White Midwestern public university. By integrating decolonized course content and a critical, inclusive pedagogical approach, the …

A Rare Case Of Large Nonvalvular Papillary Fibroelastoma Manifesting As Vertigo And Exertional Dyspnea, Mohaddeseh Behjati, Mohsen Mirmohammadsadeghi, Ehsan Abadi, Mohammad Hossein Paknahad, Parisa Adib-Hajbagheri

Journal of the Saudi Heart Association

Papillary fibroelastoma of the heart is an uncommon benign tumor that usually originates on the heart's valve structures. Instances of nonvalvular papillary fibroelastomas are exceptionally scarce. In this Case Presentation we reported a 46- year old woman presented with positional vertigo and exertional dyspnea. Transthoracic echocardiography revealed a mobile oval shape mass in left ventricle at the site of antrolateral papillary muscle and According to Cardiac magnetic resonance a benign avascular intracavity left ventricle mass is noted highly suggestive for a large papillary fibroelastoma. The tumor was completely resected and the pathological diagnosis was papillary fibroelastoma.

Ada News - 10/07/2024, American Dental Association, Publishing Division

ADA News

Established in 1970 as the official newspaper of the American Dental Association, the ADA News serves practicing dentists and others allied to the dental profession in the U.S. and internationally. It is the No. 1 source of news and information about the many benefits and services the ADA delivers to members daily as well as timely information on scientific, social, political and economic developments affecting dentistry and health care.

Be At Your Best- Provider Wellbeing, Trisha Williams, Tobie O'Brien, Kristin Ray

Advanced Practice Perspectives Podcast: For Nursing Contact Hours

In this episode, nursing director Kristin Ray leads a discussion focusing on provider well-being, how to cope with stress and avoid burnout, and some practices that can be helpful to help alleviate these feelings.

Click here to stream the podcast episode.

Clinical, Diagnostic, And Metabolic Characteristics Associated With Nephrolithiasis In The Black Women's Health Study, Maria D'Amico, Richard K. Babayan, David S. Wang, Shaun Wason, Yvette C. Cozier

Jefferson Hospital Staff Papers and Presentations

Background/Objectives: Nephrolithiasis (kidney stones) is a frequently occurring urologic condition resulting in significant patient morbidity and healthcare costs. Despite the higher prevalence of metabolic risk factors for nephrolithiasis among Black women, there have been few epidemiologic studies of kidney stones focusing on this group.

Methods: We describe demographic and health characteristics, diagnostics, and metabolic profiles of US Black women with self-reported kidney stones. The women were participants in the Black Women’s Health Study (BWHS), a large prospective cohort of US Black women (median age 38 years) begun in 1995.

Results: Among the 2750 BWHS participants who completed an online supplemental …

Does Hospital–Physician Integration Improve Hospital Performance? Results From A Usa Longitudinal Study, Soumya Upadhyay, Randyl A. Cochran, William Opoku-Agyeman

Healthcare Administration and Policy Faculty Research

In a dynamic healthcare industry, aligning the goals and objectives of hospitals and physicians through integration has been suggested to influence performance. Physicians’ leadership and active involvement in governance can direct resource usage, Electronic Health Record (EHR) implementation, price negotiation, better coordination, and continuity of services for patients, thus affecting performance. This study aimed to examine the relationship between physician integration and hospital performance, investigating both financial and quality outcomes. We used a longitudinal study design. Our sample was hospital-level data from 2014 to 2019, which contained 6000 U.S. hospital-year observations. The dependent variables were quality outcomes (readmission rates) and …

Human Epidemiology And Response To Sars-Cov-2 (Heros): Objectives, Design, And Enrollment Results Of A 12-City Remote Observational Surveillance Study Of Households With Children, Using Direct-To-Participant Methods, Patricia C Fulkerson, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

The Human Epidemiology and Response to SARS-CoV-2 (HEROS) Study is a prospective, multicity, 6-month incidence study conducted from May 2020 to February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other National Institutes of Health-funded pediatric …

Variation In Air Sac Morphology And Postcranial Skeletal Pneumatization Patterns In The African Grey Parrot, Adam B. Lawson, Aracely Martinez, Brandon P. Hedrick, M. Scott Echols, Emma R. Schachner

School of Graduate Studies Faculty Publications

The anatomy of the avian lower respiratory system includes a complex interaction between air-filled pulmonary tissues, pulmonary air sacs, and much of the postcranial skeleton. Hypotheses related to the function and phylogenetic provenance of these respiratory structures have been posed based on extensive interspecific descriptions for an array of taxa. By contrast, intraspecific descriptions of anatomical variation for these features are much more limited, particularly for skeletal pneumatization, and are essential to establish a baseline for evaluating interspecific variation. To address this issue, we collected micro-computed tomography (μCT) scans of live and deceased African grey parrots (Psittacus erithacus) to assess …

Xenotransplanted Human Organoids Identify Transepithelial Zinc Transport As A Key Mediator Of Intestinal Adaptation, Maame Efua S Sampah, Vered Gazit, Deborah C Rubin, Et Al.

2020-Current year OA Pubs

Short bowel syndrome (SBS) leads to severe morbidity and mortality. Intestinal adaptation is crucial in improving outcomes. To understand the human gene pathways associated with adaptation, we perform single-cell transcriptomic analysis of human small intestinal organoids explanted from mice with experimental SBS. We show that transmembrane ion pathways, specifically the transepithelial zinc transport pathway genes SLC39A4 and SLC39A5, are upregulated in SBS. This discovery is corroborated by an external dataset, bulk RT-qPCR, and Western blots. Oral zinc supplementation is shown to improve survival and weight gain of SBS mice and increase the proliferation of intestinal crypt cells in vitro. Finally, …

An Iron-Rich Subset Of Macrophages Promotes Tumor Growth Through A Bach1-Ednrb Axis, Ian W Folkert, Mai T Dang, Et Al.

2020-Current year OA Pubs

We define a subset of macrophages in the tumor microenvironment characterized by high intracellular iron and enrichment of heme and iron metabolism genes. These iron-rich tumor-associated macrophages (iTAMs) supported angiogenesis and immunosuppression in the tumor microenvironment and were conserved between mice and humans. iTAMs comprise two additional subsets based on gene expression profile and location-perivascular (pviTAM) and stromal (stiTAM). We identified the endothelin receptor type B (Ednrb) as a specific marker of iTAMs and found myeloid-specific deletion of Ednrb to reduce tumor growth and vascular density. Further studies identified the transcription factor Bach1 as a repressor of the iTAM transcriptional …

10.07.2024 Orsp Connect, Liz Williamson

ORED Newsletter

Lunch and Learn

Update Employee Directory

NIH Updates RPPR Instruction Guide

Genetically Conditioned Interaction Among Microrna-155, Alpha-Klotho, And Intra-Renal Ras In Male Rats: Link To Ckd Progression, Lisa M. Harrison-Bernard, L. Raij, R. X. Tian, E. A. Jaimes

School of Graduate Studies Faculty Publications

Incident chronic kidney disease (CKD) varies in populations with hypertension of similar severity. Proteinuria promotes CKD progression in part due to activation of plasminogen to plasmin in the podocytes, resulting in oxidative stress-mediated injury. Additional mechanisms include deficiency of renal alpha-klotho, that inhibits Wnt/beta-catenin, an up regulator of intra-renal renin angiotensin system (RAS) genes. Alpha-klotho deficiency therefore results in upregulation of the intra-renal RAS via Wnt/beta-catenin. In hypertensive, Dahl salt sensitive (DS) and spontaneously hypertensive rats (SHR), we investigated renal and vascular injury, miR-155, AT1R, alpha-klotho, and TNF-α. Hypertensive high salt DS (DS-HS), but not SHR developed proteinuria, plasminuria, and …

Exploration Of Epileptic Networks In Temporal Lobe Encephaloceles With Stereotactic Eeg: Electroclinical Characteristics And Surgical Outcomes, Michael D. Staudt

Faculty Scholarship

Objective: Temporal lobe encephaloceles (TLEN) have been implicated as a cause of temporal lobe epilepsy (TLE), the treatment which is primarily surgical; however, there is no clear consensus on the optimal surgical approach, because it is unclear whether TLE related to TLEN can be addressed by a restricted encephalocele resection or if a more extensive resection is required. The aim of the current article is to report the clinical and electrophysiological profile of patients with TLE secondary to TLEN who underwent stereotactic electroencephalography (SEEG) implantation to identify the epileptogenic network. Methods: A retrospective review was performed of patients with TLE …

Immunologic Signatures Of Response And Resistance To Nivolumab With Ipilimumab In Advanced Metastatic Cancer, Apostolia M Tsimberidou, Farah A Alayli, Kwame Okrah, Alexandra Drakaki, Danny N Khalil, Shivaani Kummar, Saad A Khan, F Stephen Hodi, David Y Oh, Christopher R Cabanski, Shikha Gautam, Stefanie L Meier, Meelad Amouzgar, Shannon M Pfeiffer, Robin Kageyama, Enjun Yang, Marko Spasic, Michael T Tetzlaff, Wai Chin Foo, Travis J Hollmann, Yanyun Li, Matthew Adamow, Phillip Wong, Jonni S Moore, Sharlene Velichko, Richard O Chen, Dinesh Kumar, Samantha Bucktrout, Ramy Ibrahim, Ute Dugan, Lisa Salvador, Vanessa M Hubbard-Lucey, Jill O'Donnell-Tormey, Sandra Santulli-Marotto, Lisa H Butterfield, Diane M Da Silva, Justin Fairchild, Theresa M Lavallee, Lacey J Padrón, Padmanee Sharma

Faculty, Staff and Student Publications

Identifying pan-tumor biomarkers that predict responses to immune checkpoint inhibitors (ICI) is critically needed. In the AMADEUS clinical trial (NCT03651271), patients with various advanced solid tumors were assessed for changes in intratumoral CD8 percentages and their response to ICI. Patients were grouped based on tumoral CD8 levels: those with CD8 <15% (CD8-low) received nivolumab (anti-PD-1) plus ipilimumab (anti-CTLA4) and those with CD8 ≥15% (CD8-high) received nivolumab monotherapy. 79 patients (72 CD8-low and 7 CD8-high) were treated. The disease control rate was 25.0% (18/72; 95% CI: 15.8–35.2) in CD8-low and 14.3% (1/7; 95% CI: 1.1–43.8) in CD8-high. Tumors from 35.9% (14/39; 95% CI: 21.8–51.4) of patients converted from CD8 <15% pretreatment to ≥15% after treatment. Multiomic analyses showed that CD8-low responders had an inflammatory tumor microenvironment pretreatment, enhanced by an influx of CD8 T cells, CD4 T cells, B cells, and macrophages upon treatment. These findings reveal crucial pan-cancer immunological features for ICI response in patients with metastatic disease.

Disclosure Patterns Of Opioid Use Disorders In Perinatal Care During The Opioid Epidemic On X From 2019 To 2021: Thematic Analysis, Dezhi Wu, Minnie Ng, Saborny Sen Gupta, Phyllis Raynor Phd, Aprn, Pmhnp-Bc, Youyou Tao, Yang Ren, Peiyin Hung, Shan Qiao, Jiajia Zhang, Jennifer Fillo, Xiaoming Li, Constance Guille, Kacey Eichelberger, Bankole Olatosi

Publications

BACKGROUND: In 2021, the United States experienced a 14% rise in fatal drug overdoses totaling 106,699 deaths, driven by harmful opioid use, particularly among individuals in the perinatal period who face increased risks associated with opioid use disorders (OUDs). Increased concerns about the impacts of escalating harmful opioid use among pregnant and postpartum persons are rising. Most of the current limited perinatal OUD studies were conducted using traditional methods, such as interviews and randomized controlled trials to understand OUD treatment, risk factors, and associated adverse effects. However, little is known about how social media data, such as X, formerly known …

Assessing The Usability Of Iprepared: An Application-Based, Non-Pharmacological Delirium Prevention Intervention, Luke S. Sztajnkrycer, Ian Ward Maia, Heidi Lindroth, Kayla P. Carpenter, Derek Vanmeter, Samantha Gracia, Grace Herbeck, Aidan Mullan, Molly M. Jeffery, Fernanda Bellolio

Journal of Geriatric Emergency Medicine

Introduction: Non-pharmacologic prevention measures reduce incident delirium by up to 30-40%% in inpatient and ED settings, but consistent application is often difficult. A mobile health application, titled iPREPARED (Improve Prevention and Recovery by Engaging Patients and FAmily-Caregivers to End Delirium) was co-developed with patients and their care partners to prepare them for delirium and empower them to use non-pharmacological prevention measures. This study assessed the feasibility, acceptability, and usability of iPREPARED in the emergency department (ED).

Methods: An IRB-approved prospective study enrolled a convenience sample of ED patients over age 60 and/or their care partners. Participants were provided a tablet …

Dna Methylation Near Mad1l1, Kdm2b, And Socs3 Mediates The Effect Of Socioeconomic Status On Elevated Body Mass Index In African American Adults, Láshauntá Glover, Adam G Lilly, Anne E Justice, Annie Green Howard, Brooke S Staley, Yujie Wang, Helen M Kamens, Kendra Ferrier, Jan Bressler, Laura Loehr, Laura M Raffield, Mario Sims, Kari E North, Lindsay Fernández-Rhodes

Faculty, Staff and Student Publications

Obesity and poverty disproportionally affect African American persons. Epigenetic mechanisms could partially explain the association between socioeconomic disadvantage and body mass index (BMI). We examined the extent to which epigenetic mechanisms mediate the effect of socioeconomic status (SES) on BMI. Using data from African American adults from the Atherosclerosis Risk in Communities (ARIC) Study (n = 2664, mean age = 57 years), education, income, and occupation were used to create a composite SES score at visit 1 (1987-1989). We conducted two methylation-wide association analyses to identify associations between SES (visit 1), BMI and cytosine-phosphate-guanine (CpG) sites measured at a subsequent …

Digital Assessments For Children And Adolescents With Adhd: A Scoping Review, Franceli L. Cibrian, Elissa M. Monteiro, Kimberley D. Lakes

Engineering Faculty Articles and Research

Introduction: In spite of rapid advances in evidence-based treatments for attention deficit hyperactivity disorder (ADHD), community access to rigorous gold-standard diagnostic assessments has lagged far behind due to barriers such as the costs and limited availability of comprehensive diagnostic evaluations. Digital assessment of attention and behavior has the potential to lead to scalable approaches that could be used to screen large numbers of children and/or increase access to high-quality, scalable diagnostic evaluations, especially if designed using user-centered participatory and ability-based frameworks. Current research on assessment has begun to take a user-centered approach by actively involving participants to ensure the development …

M3t-Lm: A Multi-Modal Multi-Task Learning Model For Jointly Predicting Patient Length Of Stay And Mortality, Junde Chen, Qing Li, Feng Liu, Yuxin Wen

Engineering Faculty Articles and Research

Ensuring accurate predictions of inpatient length of stay (LoS) and mortality rates is essential for enhancing hospital service efficiency, particularly in light of the constraints posed by limited healthcare resources. Integrative analysis of heterogeneous clinic record data from different sources can hold great promise for improving the prognosis and diagnosis level of LoS and mortality. Currently, most existing studies solely focus on single data modality or tend to single-task learning, i.e., training LoS and mortality tasks separately. This limits the utilization of available multi-modal data and prevents the sharing of feature representations that could capture correlations between different tasks, ultimately …

Association Between Particulate Matter And Copd Among Adults In Alaska, Adeyemi Samuel Alimi

Walden Dissertations and Doctoral Studies

Exposure to high levels of fine particulate matter (PM2.5) is emerging as a crucial risk factor for chronic obstructive pulmonary disease (COPD), a deadly lung disease with a significant public health burden. The Fairbanks North Star Borough (FNSB) in Alaska has one of the worst PM2.5 issues in the United States. The PM2.5 issues in the area are associated with increased wood-burning and temperature inversions in the winter and wildfires in the summer. Given these prevailing PM2.5 issues, this quantitative study was conducted using Alaska BRFSS datasets and a chi-square test to compare the COPD prevalence in the FNSB with …

Hybrid Quantification Of Absolute Perfusion Requires Accurate Measurement Of Myocardial Mass, Nils P Johnson, K Lance Gould

Faculty, Staff and Student Publications

No abstract provided.

An Iron-Rich Subset Of Macrophages Promotes Tumor Growth Through A Bach1-Ednrb Axis, Ian W Folkert, William A Molina Arocho, Tsun Ki Jerrick To, Samir Devalaraja, Irene S Molina, Jason Shoush, Hesham Mohei, Li Zhai, Md Naushad Akhtar, Veena Kochat, Emre Arslan, Alexander J Lazar, Khalida Wani, William P Israel, Zhan Zhang, Venkata S Chaluvadi, Robert J Norgard, Ying Liu, Ashley M Fuller, Mai T Dang, Robert E Roses, Giorgos C Karakousis, John T Miura, Douglas L Fraker, T S Karin Eisinger-Mathason, M Celeste Simon, Kristy Weber, Kai Tan, Yi Fan, Kunal Rai, Malay Haldar

Faculty, Staff and Student Publications

We define a subset of macrophages in the tumor microenvironment characterized by high intracellular iron and enrichment of heme and iron metabolism genes. These iron-rich tumor-associated macrophages (iTAMs) supported angiogenesis and immunosuppression in the tumor microenvironment and were conserved between mice and humans. iTAMs comprise two additional subsets based on gene expression profile and location-perivascular (pviTAM) and stromal (stiTAM). We identified the endothelin receptor type B (Ednrb) as a specific marker of iTAMs and found myeloid-specific deletion of Ednrb to reduce tumor growth and vascular density. Further studies identified the transcription factor Bach1 as a repressor of the iTAM transcriptional …

Longitudinal Single-Cell Profiling Reveals Molecular Heterogeneity And Tumor-Immune Evolution In Refractory Mantle Cell Lymphoma, Shaojun Zhang, Vivian Changying Jiang, Guangchun Han, Dapeng Hao, Junwei Lian, Yang Liu, Qingsong Cai, Rongjia Zhang, Joseph Mcintosh, Ruiping Wang, Minghao Dang, Enyu Dai, Yuanxin Wang, David Santos, Maria Badillo, Angela Leeming, Zhihong Chen, Kimberly Hartig, John Bigcal, Jia Zhou, Rashmi Kanagal-Shamanna, Chi Young Ok, Hun Lee, Raphael E Steiner, Jianhua Zhang, Xingzhi Song, Ranjit Nair, Sairah Ahmed, Alma Rodriquez, Selvi Thirumurthi, Preetesh Jain, Nicolaus Wagner-Bartak, Holly Hill, Krystle Nomie, Christopher Flowers, Andrew Futreal, Linghua Wang, Michael Wang

Faculty, Staff and Student Publications

The mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Multi-platform validation is performed at genomic and cellular levels in PDX models and larger patient cohorts. We demonstrate that due to 17q gain, BIRC5/survivin expression is upregulated in resistant MCL tumor cells and …