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Crispr/Ncas9-Edited Cd34+ Cells Rescue Mucopolysaccharidosis Iva Fibroblasts Phenotype, Angélica María Herreno-Pachón, Andrés Felipe Leal, Shaukat Khan, Carlos Javier Alméciga-Díaz, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis (MPS) IVA is a bone-affecting lysosomal storage disease (LSD) caused by impaired degradation of the glycosaminoglycans (GAGs) keratan sulfate (KS) and chondroitin 6-sulfate (C6S) due to deficient N-acetylgalactosamine-6-sulfatase (GALNS) enzyme activity. Previously, we successfully developed and validated a CRISPR/nCas9-based gene therapy (GT) to insert an expression cassette at the AAVS1 and ROSA26 loci in human MPS IVA fibroblasts and MPS IVA mice, respectively. In this study, we have extended our approach to evaluate the effectiveness of our CRISPR/nCas9-based GT in editing human CD34+ cells to mediate cross-correction of MPS IVA fibroblasts. CD34+ cells were electroporated with the CRISPR/nCas9 system, …

Development Of Parapneumonic Effusion In A Patient Using Kratom, Emma Glover, Morgan Kiryakoza, Nader Mina

Conference Presentation Abstracts

Introduction: “Kratom” refers to both Mitragyna speciosa, a tree native to Southeast Asia, and to its products, derived from the tree’s leaves, which are marked as an herbal supplement. Kratom is an herbal supplement with both opioid and stimulant-like effects. While there are no approved uses for kratom by the U.S. Food and Drug Administration, it is frequently used by individuals to manage withdrawal symptoms and cravings (especially related to opioid use), pain, fatigue, and mental health disorders. Furthermore, because kratom is unregulated, it can contain contaminants, including heavy metals and harmful bacteria. This case details the development of parapneumonic …

A Tobacco Treatment Training Program Expands The Number Of Healthcare Providers Trained To Use Evidence-Based Practices And Methods, Alex Hurst, Maher Karam-Hage, Jennifer Cofer, Mehwish Javaid, Diane Beneventi, Janice Blalock, Tiffany Winter, Paul M. Cinciripini, Ernest Hawk

Advances in Cancer Education and Quality Improvement

Tobacco-use disorder remains a global health challenge, despite declining rates, and is a leading cause of morbidity and mortality, especially among special populations that disproportionally do not have access to comprehensive treatment services. The lack of trained providers and slow dissemination of new tobacco treatment knowledge are obstacles to accessing comprehensive evidence-based treatments. Less is known about the impact of specialized training programs on healthcare professionals' ability to effectively treat tobacco use. This paper reports on the evaluation of the tobacco treatment training program, training methodology, and the demographics of the specialists trained.

MD Anderson’s Tobacco Treatment Training Program (TTTP) …

Advancing Research On Retinitis Pigmentosa: An Investigation Of Natural History, Visual System Plasticity, And Mutation-Independent Treatment., Cecilia A. Attaway

Electronic Theses and Dissertations

Retinitis Pigmentosa (RP) is an inherited retinal disease characterized by rod and then cone photoreceptor degeneration. ~25% of cases are caused by a genetic mutation that results in autosomal dominant RP (adRP). There has been a lack of exploration of the progression of degeneration in adRP models. In Chapter Two, I examined visual acuity (VA) changes, retinal structure, and function from early to late-stage disease in a murine P23H Rho ‘knock-in’ mouse model (Rho^P23H/+), the most common form of adRP in North America. To establish a natural history, I evaluated behavioral VA, using the visual water task, …

Personalizing Intermittent Fasting: The Role Of Microbiome Diversity And Fiber Intake In Shaping Health Outcomes, Jana Gjini, Robin Moore, Venkateswar Venkataraman

Rowan-Virtua Research Day

BACKGROUND: Intermittent fasting (IF) has been linked to improved metabolic health, reduced inflammation, and increased longevity in animal models. These effects are thought to be mediated through changes in the gut microbiome. Murine studies consistently show that IF enhances microbial diversity and promotes beneficial species like Lactobacillus and Bifidobacterium, improving metabolic profiles and gut barrier function. However, human studies reveal inconsistent results, suggesting that individual-level factors such as baseline microbiome composition and fiber intake may influence response to IF.

HYPOTHESIS: Baseline gut microbiome diversity and habitual dietary fiber intake modulate the metabolic and inflammatory benefits of intermittent fasting in humans. …

Enhancing The Eden Alternative Model With Well Standards: A Case Study Analysis, Mariah Stoner

Architecture Masters of Science Program: Theses

This thesis investigates the potential for improving the Eden Alternative Model, a person-centered approach to elder care that emphasizes creating a homelike environment and meaningful relationships, using WELL Standards, a building certification system focused on enhancing human health and well-being through improvements in environmental quality. Through a mixed-methods approach involving quantitative data analysis and qualitative case studies, this research examines how WELL Standards, which cover aspects such as air quality, water quality, lighting, and thermal comfort, can improve environmental quality and resident satisfaction within the Eden Alternative Model. This research introduces a tailored approach to elder care by combining these …

Volatile Anesthetic Exposure During Organogenesis (Weeks 6-9): Implications For Fetal Brain Development, Cheryce Daniel, Kylon Coombs

Rowan-Virtua Research Day

Organogenesis, particularly during gestational weeks 6 through 9, represent a critical window for fetal brain development. During this period, neurogenesis, neural tube closure and synaptic organization are actively occurring. Disruption of these processes, especially from exogenous agents, can result in lasting developmental consequences.

The U.S Food and Drug Administration has issued warnings regarding the use of anesthetic agents such as isoflurane, sevoflurane, and desflurane. Noting the potential risk of neurotoxic effects on the developing brain. This warning is particularly highlighted when administered drugs are present for long periods of time or during repeated procedures. The goal of this literature review …

A Better Road To Recovery- Effectiveness Of Osteopathic Manipulative Treatment Compared To Conventional Methods On Post-Concussion Patients, Joliana H. Eskandar

Rowan-Virtua Research Day

Background:

Concussion, a form of traumatic brain injury, often presents with sleep disturbances, headache, confusion, and memory impairment. Current treatment includes reduced screen time, physical activity, and increased rest. For decades, these treatment options have demonstrated improvement in symptoms. Recently, there is growing interest in whether using osteopathic manipulative treatment (OMT) to target structural dysfunctions is more effective. This review compares OMT to conventional treatment methods in post-concussion patients.

Methods:

This literature review uses data from clinical trials, randomized controlled trials, observational studies, and case reports within the past 10-15 years. It includes adolescents, adults, elderly, athletes, and non-athletes while …

Dabigatran Reduced Acute Microgliosis In A Mouse Model With Tbi, Nicholas R. Eltman, Rashmeena Abbasi, Mary C. Kosciuk, Syed Ahmed, Jose L. Pascual, Randel L. Swanson, Nimish K. Acharya

Rowan-Virtua Research Day

Objective:

The study objective was to investigate the acute anti-inflammatory effects of dabigatran in a preclinical mouse controlled cortical impact (CCI) model of severe traumatic brain injury (TBI).

Design

Mice were separated into three groups: controlled cortical impact (CCI) with dabigatran (drug treatment, n=5), CCI with saline (positive control, n=5), and sham CCI without saline or dabigatran (negative control, n=3). Dabigatran (80mg/kg) or saline was administered orally at 2, 10, 18, 26, 34, and 42 hours following experimental CCI in the drug treatment or positive control groups, respectively. Animals in the negative control group received sham CCI only. 48h following …

Accelerated Tumor Growth And Lymphatic Spread Of Transplantable Melanomas In Tumor Necrosis Factor(Tnf)-Transgenic Mice, Catherine F. Alapatt, Robert Hughes, Roger Sheffmaker, Gillian Mcguire, Daniel Deegan, Igor Kuzin, Andrea Bottaro

Rowan-Virtua Research Day

Melanoma is the fifth most common cancer among American adults, with significant morbidity and mortality at 5 years remaining >60% for patients with stage IV disease. The malignancy is due to the transformation of melanocytes, with one of the major risk factors being ultraviolet light exposure. Although as many as one in five human cancers have been linked to chronic inflammation, the role of inflammatory signals in melanoma growth and metastasis remains poorly understood.

Tumor necrosis factor (TNF)-transgenic (TNFtg) mice are a well-established model of chronic systemic inflammation, with involvement of joints and other organ systems. To assess the effect …

Frequency Modulation Of Deep Brain Stimulation Targeting The Periaqueductal Gray: Effects On Pain Perception And Autonomic Regulation, Jack Hennen, Avneet Chawla, Jared Garfinkle, Wen Hao Luo

Rowan-Virtua Research Day

Introduction:

The periaqueductal gray (PAG) is a midbrain structure, and effective target for deep brain stimulation (DBS), involved in the modulation of a multitude of sensory and autonomic processes. It has distinct functional columnar organization, with each column playing its own role in alteration of the body’s ability to respond to pain and stressful stimuli.

Background:

Research regarding the effects of DBS on the PAG has shown the four main subregions of the PAG: the dorsomedial PAG (dmPAG), dorsolateral PAG (dlPAG), lateral PAG (lPAG), and ventrolateral PAG(vlPAG), produce various physiologic outputs when stimulated. These outputs are region and frequency dependent. …

Photodynamic Therapy Vs. 5-Fluorouracil For Field-Directed Treatment Of Actinic Keratosis: A Comparative Literature Review, Bhumik Patel

Rowan-Virtua Research Day

BACKGROUND: Actinic keratosis (AK) is a common precancerous skin condition arising from chronic UV exposure and often involves field cancerization, where visible lesions coexist with subclinical damage. Effective field-directed treatments are critical for preventing progression to squamous cell carcinoma.

HYPOTHESIS: Photodynamic Therapy (PDT) may offer superior efficacy, cosmetic outcomes, and patient adherence compared to topical 5-Fluorouracil (5-FU), despite its higher cost and clinical setting requirement.

METHODS: This literature review analyzed peer-reviewed studies from 2015–2025 comparing PDT and 5-FU for field-directed AK treatment. Outcomes assessed included lesion clearance, recurrence, tolerability, adherence, cost, and patient satisfaction.

RESULTS: PDT demonstrated high clearance rates …

Chemical Exposures In Utero: Phthalates And Congenital Heart Defects, Demi Poulathas

Rowan-Virtua Research Day

Background: Congenital heart defects (CHDs) are the most common type of birth defect. Approximately 80% of CHDs have unknown causes, and phthalates may play a contributing role. Phthalates are ubiquitous environmental chemicals used as plasticizers in a wide range of products, including cosmetics and electronic devices. After entering the body, phthalates bind to the progesterone receptor, which is necessary for fetal development. While multiple studies have explored environmental factors in CHD development, few have examined the effects of phthalates on CHDs in humans. Methods: A literature review was conducted to investigate the relationship between parental occupational phthalate exposure and the …

Mechanisms Mediating The Protective Effects Of Caffeine On Alzheimer’S Disease Progression, Jessica Ivanov, Malky Bernat, Joshua Drawbaugh, Jeremy Mehta, Namira Rahmani, Saikumar Thellapally

Rowan-Virtua Research Day

Background: This review aims to examine the molecular mechanisms through which caffeine may exert neuroprotective effects against Alzheimer’s Disease (AD).

Methods: A literature review was done across PubMed and Embase to identify studies between 2000 and 2024, exploring the mechanism behind caffeine’s effects on AD. The criteria focused on peer-reviewed articles involving human or animal models. Information was gathered on study design, participant characteristics, caffeine consumption, proposed mechanisms, and effects on cognition.

Results: The studies support caffeine's potential as a therapeutic, neuromodulator against AD through six mechanisms: inhibition of adenosine A2A receptors, decreased amyloid-beta production and aggregation, promotion of amyloid …

Assessing The Efficacy Of Prolonged Doxycycline Pep Use In High-Risk Populations For Sti Prevention, Lam Doan, Pearl Joslyn, Lizann Sung, Timothy Breiner, Sarah Marotta, Shikhar Rastogi

Rowan-Virtua Research Day

First recommended in October 2022, doxycycline post-exposure prophylaxis (DoxyPEP) has been increasingly used as a treatment for multiple sexually transmitted infections (STIs). To evaluate the efficacy of prolonged DoxyPEP use in high risk populations - men who have sex with men (MSM) and transgender women - for STIs, different sources addressing various aspects of DoxyPEP, its efficacy in STI prevention, and the potential consequences of its widespread use in terms of antimicrobial resistance were examined. Across 9 studies, DoxyPEP was found to decrease the incidence of bacterial STIs, specifically, syphilis, chlamydia, and gonorrhea with varying efficacy, especially for gonorrhea. Furthermore, …

Systematic Review And Meta-Analysis Examining If Hyperplasia Occurs In Humans In Response To Resistance Exercise, Hitesh Gowda, Scott Dankel, Harshal Parmar, Nicholas Barton

Rowan-Virtua Research Day

Background: It is commonly believed that resistance exercise in humans induces muscle growth primarily via muscle hypertrophy, but there is some debate as to whether muscle hyperplasia occurs. The purpose of this meta-analysis was to quantitively assess whether the presence of muscle hyperplasia occurs in humans performing resistance training.

Methods: Medline, Scopus, and Web of Science were searched on May 17, 2024. Studies that assessed muscle fiber number pre and post resistance training were included in a three-level random effects model to assess changes in muscle fiber number.

Results: A total of 11 studies met the search criteria, with all …

Musculoskeletal Changes In Pregnancy: Implications For Long-Term Bone & Joint Health, Jaylyn Thompson, Clarence Julian Clark Ii, Nayarith Lopez, Aziza Ndaw

Rowan-Virtua Research Day

Pregnancy and lactation represent significant physiological challenges to maternal skeletal health, with substantial implications for both short and long-term musculoskeletal integrity. Research emphasizes that lactation induces notable skeletal adaptations, with up to 10% bone mineral density loss occurring in trabecular-rich regions such as the spine and hip (1,5). While most women experience substantial recovery post-weaning, the research indicates that recovery patterns vary significantly, with some women experiencing incomplete restoration of bone mass, potentially compromising long-term skeletal strength (3).

The underlying mechanisms driving these changes are primarily hormonal, with elevated parathyroid hormone-related protein (PTHrP) and decreased estrogen levels during lactation facilitating …

Case Report: Alpha Gal Syndrome, Eric Haljasmaa, David Parkes, Wayne Tamaska

Rowan-Virtua Research Day

We report a case of a 40-year-old male who presented with sensation of throat closing and shortness of breath while at work at a meat processing facility. The differential diagnosis of shortness of breath is throat closing includes, but is not limited to, allergic reactions to antibiotics in meat, allergy to food additives, Symptom triggers are useful in identifying causes and a good supporting history and exposures can help with diagnosis. In this case, the patient had a known diagnosis of Alpha-gal syndrome (AGS) which is a tick-bite associated, possibly life-threatening immunoglobin E-mediated (IgE) hypersensitivity to galactose-alpha-1,3-galactose (alpha-gal). The patient …

Natural Killer T Cell-Mediated Control Of Francisella Tularensis-Induced Cytokine Storm Syndrome, Cameron M. Torres

Open Access Theses & Dissertations

Inflammation is critical for the effective clearance of viral and bacterial challenges, while simultaneously a mechanism utilized by many highly infectious pathogens to cause disease. The bacterium Francisella tularensis, the causative agent of human tularemia, elicits a cytokine storm, wherein the immune system over-responds to the presence of the bacterium causing a dysregulated release of proinflammatory and regulatory cytokines. Without treatment, tularemia mortality can be as high as 30%, with inhalation of as few as 10 CFUs inducing respiratory tularemia. Natural Killer T (NKT) cells are innate-like T lymphocytes with a diverse array of regulatory functions. Unlike conventional T cells, …

Venlafaxine Exposure In Pregnancy And Its Association With Pre-Eclampsia Development, Jhanvi Patel

Posters

Venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI), is widely used to manage depression and anxiety, including in pregnant women. However, its known hypertensive side effects raise concerns about a potential link to pre-eclampsia, a serious pregnancy complication characterized by new-onset hypertension and proteinuria. Pregnant women with psychiatric disorders already have an increased risk of hypertensive disorders, and while untreated depression can lead to adverse outcomes such as preterm birth and fetal cortisol elevation, the safety of venlafaxine remains uncertain. Current research lacks wellcontrolled studies assessing its association with hypertensive complications in pregnancy. This systematic review aims to evaluate whether venlafaxine use …

From Trauma To Treatment: Chronic Neurobehavioral Consequences And Emerging Treatments, Moriah E. Mcguier

Dartmouth College Ph.D Dissertations

Severe trauma exposure related to traumatic brain injury (TBI) or psychiatric disorders like post-traumatic stress disorder (PTSD) leads to neurobehavioral and physiological impairments that reduce the quality of life of individuals and remain difficult to treat with current therapeutic options. Further, these conditions are highly comorbid, notably in PTSD with blast-traumatic brain injury (bTBI) commonly experienced by military members via explosive forces, leading to complex and heterogenous outcomes. To address this, preclinical models have been developed to recapitulate aspects of TBI and PTSD. This thesis utilizes two such models in rats, bTBI and the single prolonged stress (SPS) model for …

Fc Gamma Receptors Facilitate Antigenic Modulation Of Lilrb4 And Function As Predictive Biomarkers In Acute Monocytic Leukemia, Joshua Morse

Dissertations and Theses (Open Access)

Acute monocytic leukemia (monocytic AML) is a subtype of AML marked by a proliferation of abnormal monoblasts. This subtype represents approximately 10% of AML cases. The prognosis of monocytic AML is poor, with a 5-year survival of ~30%. Most patients are diagnosed at an age when they are unlikely to survive first-line non-targeted cytotoxic chemotherapy as a bridge to hematopoietic stem cell transplant (HSCT). Even patients who achieve remission commonly relapse. This population of patients would greatly benefit from precision-targeted therapies but currently there are none approved for monocytic AML.

Leukocyte immunoglobulin-like receptor B4 (LILRB4) is an immune checkpoint expressed …

Novel Application Of Orthopedic Suture Tape For Sternal Closure After Upper Hemisternotomy, Vishal N. Shah, Joshua R. Chen, Konstadinos A. Plestis

Department of Surgery Faculty Papers

The FiberTape (FT) System (Arthrex, Naples, FL, USA), initially developed for orthopedic surgery, is a new, nonmetallic, suture-based alternative to standard stainless-steel wires for sternal reapproximation. Publications on FT use after cardiothoracic surgery are limited. The FT System has not been used in upper hemisternotomy (UHS) closure. Consequently, we report the use of the FT System for sternal closure in a 70-year-old man after UHS aortic valve replacement and discuss several advantages of its application.

Targeting Bard1 Suppresses A Myc-Dependent Transcriptional Program And Tumor Growth In Pancreatic Ductal Adenocarcinoma, Sohum Patel, Eleanor Jenkins, Rutuj P. Kusurkar, Sherry Lee, Wei Jiang, Avinoam Nevler, Matthew Mccoy, Michael J. Pishvaian, Rosalie C. Sears, Jonathan R. Brody, Charles J. Yeo, Aditi Jain

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers demanding better and more effective therapies. BARD1 or BRCA1-Associated -Ring Domain-1 plays a pivotal role in homologous recombination repair (HRR). However, its function and the underlying molecular mechanisms in PDAC are still not fully elucidated. Here, we demonstrate that BARD1 is overexpressed in PDAC and its genetic inhibition suppresses c-Myc and disrupts c-Myc dependent transcriptional program. Mechanistically, BARD1 stabilizes c-Myc through ubiquitin-proteasome system by regulating FBXW7. Importantly, targeting BARD1 using either siRNAs or CRISPR/Cas9 deletion blocks PDAC growth in vitro and in vivo, without any signs of toxicity to mice. …

A Neuroimmune Circuit Mediates Chemo Brain Pathology, Daniel Ahmadi

McKelvey School of Engineering Graduate Student Theses & Dissertations

Chemotherapeutic agents, while effective in targeting malignant tumors, often reduce the patients’ quality of life by inducing fatigue, pain, and motivational deficits. These symptoms are collectively referred to as “chemo brain.” The mechanisms underlying these adverse effects, and specifically whether fatigue and motivational impairments share a common etiology, remain poorly understood. The neural–immune substrates of these symptoms remain obscure, in part because standard preclinical regimens either bypass key systemic signals or introduce local toxicity confounds. Here, I establish and validate a three‑day, low‑dose intravenous cisplatin protocol that avoids peritoneal inflammation and severe renal injury yet produces robust, reversible fatigue and …

Cross-Tissue Coordination Between Slc Nucleoside Transporters Regulates Reproduction In Caenorhabditis Elegans, Youchen Guan, Yong Yu, Shihong M Gao, Lang Ding, Qian Zhao, Meng C Wang

Faculty, Staff and Students Publications

Metabolism is fundamental to organism physiology and pathology. From the intricate network of metabolic reactions, diverse chemical molecules, collectively termed metabolites, are produced. In multicellular organisms, metabolite communication between different tissues is vital for maintaining homeostasis and adaptation. However, the molecular mechanisms mediating these metabolite communications remain poorly understood. Here, we focus on nucleosides and nucleotides, essential metabolites involved in multiple cellular processes, and report the pivotal role of the SLC29A family of transporters in mediating nucleoside coordination between the soma and the germline. Through genetic analysis, we discovered that two Caenorhabditis elegans homologs of SLC29A transporters, Equilibrative Nucleoside Transporter …

Pediatric Predictive Artificial Intelligence Implemented In Clinical Practice From 2010 To 2021: A Systematic Review, Swaminathan Kandaswamy, Lindsey A Knake, Adam C Dziorny, Sean M Hernandez, Allison B Mccoy, Lauren M Hess, Evan Orenstein, Mia S White, Eric S Kirkendall, Matthew J Molloy, Philip A Hagedorn, Naveen Muthu, Avinash Murugan, Jonathan M Beus, Mark Mai, Brooke Luo, Juan D Chaparro

Faculty, Staff and Students Publications

To review pediatric artificial intelligence (AI) implementation studies from 2010 to 2021 and analyze reported performance measures.We searched PubMed/Medline, Embase CINHAL, Cochrane Library CENTRAL, IEEE, and Web of Science with controlled vocabulary. Inclusion criteria: AI intervention in a pediatric clinical setting that learns from data (i.e., data-driven, as opposed to rule-based) and takes actions to make patient-specific recommendations; published between 01/2010 and 10/2021; must have agency (AI must provide guidance that affects clinical care, not merely running in the background). We extracted study characteristics, target users, implementation setting, time span, and performance measures.Of 126 articles reviewed as full text, 17 …

Exercise As An Intervention For Postpartum Depression (Ppd), Kylie P. Mistretta

Honors Scholar Theses

Objective: To illustrate the applications of exercise for preventing the development of postpartum depression (PPD) and addressing associated risk factors identified in the literature. Data Sources: PubMed and EBSCO: Academic Search Premier were accessed using the search terms exercise OR physical activity OR yoga AND postpartum depression OR postnatal depression. A secondary search of PubMed was conducted using the search terms exercise AND pregnancy AND depression OR gestational diabetes OR weight gain OR sleep quality.

Study Selection: Studies selected for inclusion were peer-reviewed, published after January 2012, written in English, and relevant to the PPD risk factors examined. Only clinical …

Therapeutic Applications Of A Novel Humanized Monoclonal Antibody Targeting Chemokine Receptor Ccr9 In Pancreatic Cancer, Hannah G. Mcdonald, Anna M. Reagan, Charles J. Bailey, Mei Gao, Muqiang Gao, Angelica L. Solomon, Michael J. Cavnar, Prakash Pandalai, Mautin Barry-Hundeyin, Megan Harper, Justin A. Rueckert, Ángela Turrero, Araceli Tobio, Anxo Vidal, Daniel Roca-Lema, Elia Álvarez-Coiradas, Pablo Garrido, Laureano Simón, Joseph Kim

Markey Cancer Center Faculty Publications

The relative failure of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) despite having a dense, immunosuppressive tumor microenvironment highlights the need to target alternate/escape pathways. We have previously examined C–C chemokine receptor type 9 (CCR9) as a candidate immune checkpoint and developed a targeted, humanized monoclonal antibody (SRB2). Cytotoxicity of SRB2 was evaluated in vitro and in vivo. CCR9 expression on PDAC cells/tissues, immune components of patient-derived organoids (PDOs), and antibody-dependent cell-mediated cytotoxicity were examined. In PANC-1 and MIA PaCa-2 cell lines, we demonstrated highest CCR9 expression; however, no direct cytotoxic effect was observed with SRB2 treatment. In PANC-1 …

An Agrin-Yap/Taz Rigidity Sensing Module Drives Egfr-Addicted Lung Tumorigenesis., Reza Bayat Mokhtari, Divyaleka Sampath, Paige Eversole, Melissa Ong Yu Lin, Dmitriy A. Bosykh, Gandhi T. K. Boopathy, Aravind Sivakumar, Cheng-Chun Wang, Ramesh Kumar, Joe Yeong Poh Sheng, Ellen Karasik, Barbara A. Foster, Han Yu, Xiang Ling, Wenjie Wu, Fengzhi Li, Zoë Weaver Ohler, Christine Fillmore Brainson, David W. Goodrich, Wanjin Hong, Sayan Chakraborty

Markey Cancer Center Faculty Publications

Despite epidermal growth factor receptor (EGFR) is a pivotal oncogene for several cancers, including lung adenocarcinoma (LUAD), how it senses extracellular matrix (ECM) rigidity remain elusive in the context of the increasing role of tissue rigidity on various hallmarks of cancer development. Here it is shown that EGFR dictates tumorigenic agrin expression in lung cancer cell lines, genetically engineered EGFR-driven mouse models, and human specimens. Agrin expression confers substrate stiffness-dependent oncogenic attributes to EGFR-reliant cancer cells. Mechanistically, agrin mechanoactivates EGFR through epidermal growth factor (EGF)-dependent and independent modes, thereby sensitizing its activity toward localized cancer cell-ECM adherence and bulk rigidity …