Digital Commons Network^™

Development Of 5g-Based Remote Ultrasound Education: Current Status And Future Trends, Jiaojiao Ma, Xinying Jia, Guanghan Li, Dandan Guo, Xuehua Xi, Tongtong Zhou, Ji-Bin Liu, Bo Zhang

Department of Radiology Faculty Papers

The rapid advancement of 5G technology has opened new possibilities for remote ultrasound education, offering the potential to enhance training, real-time consultation, and quality control for primary ultrasound doctors. The 5G remote ultrasound education has the potential to revolutionize the way primary ultrasound doctors are trained and supported, ultimately leading to improved patient care and outcomes. By understanding the current status and development trends of this cutting-edge educational approach, the medical community can better prepare for and contribute to its ongoing evolution. Looking towards the future, the development trends in 5G remote ultrasound education are expected to revolve around continuous …

Considerations In Selecting Venues For The American Thoracic Society International Conference: Balancing Competing Priorities Of The Society's Diverse Membership, Gregory P. Downey, M. Patricia Rivera, Lynn M. Schnapp, Irina Petrache, Jesse Roman, Karen J. Collishaw

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

No abstract provided.

Postoperative Radiotherapy And Facial Nerve Outcomes Following Nerve Repair: A Systematic Review, Hannah L. Kenny, Rachel H. Jonas, Samuel L. Oyer

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVE: To compare outcomes of facial nerve repair or grafting following facial nerve-sacrificing procedures among patients treated with and without postoperative radiotherapy (RT).

DATA SOURCES: PubMed, OVID, Conference Papers Index, Cochrane Library, ClinicalTrials.gov.

REVIEW METHODS: Databases were searched using terms including "facial nerve," "graft," "repair," and "radiotherapy." Abstracts mentioning facial nerve repair and evaluation of facial nerve function were included for full-text review. Studies that utilized the House-Brackmann or similar validated scale for evaluation of postoperative facial nerve function were selected for review. All identified studies were included in a pooled t test analysis.

RESULTS: Twelve studies with 142 patients …

A Word From The Writing Team (June 2023), Pam Walter, Mfa, Liz Declan, Ma, Mfa

A Word From the Writing Team (Newsletter)

This issue includes:

• Happy Pride Month!
• Faculty Days 2023
• Publication Spotlight
• Reminders

Mortality In Asia Impairment Scale Grade A To D Patients With Odontoid Fracture And Magnetic Resonance Imaging Evidence Of Spinal Cord Injury, Bizhan Aarabi, Christopher J Neal, David S. Hersh, James S. Harrop, Michael G. Fehlings, Elizabeth G. Toups, James D. Guest, Beatrice Ugiliweneza, Noori Akhtar-Danesh, Shekar N. Kurpad, Robert G. Grossman

Department of Neurosurgery Faculty Papers

Odontoid fractures are common, often presenting in the elderly after a fall and infrequently associated with traumatic spinal cord injury (tSCI). The goal of this study was to analyze predictors of mortality and neurological outcome when odontoid fractures were associated with signal change on magnetic resonance imaging (MRI) at admission. Over an 18-year period (2001-2019), 33 patients with odontoid fractures and documented tSCI on MRI were identified. Mean age was 65.3 years (standard deviation [SD] = 17.2), and 21 patients were male. The mechanism of injury was falls in 25 patients, motor vehicle accidents in 5, and other causes in …

Therapeutic Strategies Targeting Respiratory Recovery After Spinal Cord Injury: From Preclinical Development To Clinical Translation, Pauline Michel-Flutot, Michael A. Lane, Angelo C. Lepore, Stéphane Vinit

Farber Institute for Neuroscience Faculty Papers

High spinal cord injuries (SCIs) lead to permanent functional deficits, including respiratory dysfunction. Patients living with such conditions often rely on ventilatory assistance to survive, and even those that can be weaned continue to suffer life-threatening impairments. There is currently no treatment for SCI that is capable of providing complete recovery of diaphragm activity and respiratory function. The diaphragm is the main inspiratory muscle, and its activity is controlled by phrenic motoneurons (phMNs) located in the cervical (C3–C5) spinal cord. Preserving and/or restoring phMN activity following a high SCI is essential for achieving voluntary control of breathing. In this review, …

Patient-Provider Communication About Cognition And The Role Of Memory Concerns: A Descriptive Study, Nikki L. Hill, Emily Bratlee-Whitaker, Heejung Jang, Sakshi Bhargava, Andrea Yevchak Sillner, Justin Do, Jacqueline Mogle

Student Papers, Posters & Projects

BACKGROUND: Early identification of cognitive impairment is an important part of health promotion in aging. However, many older adults do not seek help for cognitive problems until their ability to function independently is substantially impacted. The purpose of this descriptive study was to explore older adults' experiences with patient-provider communication specific to cognition as well as compare barriers and facilitators between those with and without memory concerns.

METHODS: We conducted an online survey with individuals aged 65 + years (n = 409; mean age = 71.4(4.73); 54% female; 79% non-Hispanic White), purposively sampled to include those with and without memory …

Analysis Of Trustworthiness And Readability Of English And Spanish Hypo- And Hyperthyroid-Related Online Patient Education Information, Chitra Parikh, Adam M. Ostrovsky

Student Papers, Posters & Projects

This study aims to determine the readability and trustworthiness of English and Spanish hypo- and hyperthyroid-related online information. Google searches were conducted for four search terms: hypothyroidism, Hashimoto's Disease, hyperthyroidism, and Graves’ Disease. For each search term, the first 10 websites were analyzed with a total of 40 websites analyzed. Readability formulas were used to determine English and Spanish readability. Trustworthiness was determined using HONcode status, JAMA Benchmark Criteria, and NLM Trustworthy Score. Overall readability largely exceeded recommended grade levels. Only 1 website (2.5%) presented information below the eighth-grade reading level based on overall Readability Consensus score, while 31 websites …

The Effects Of Dual Iqos And Cigarette Smoke Exposure On Airway Epithelial Cells: Implications For Lung Health And Respiratory Disease Pathogenesis, Pritam Saha, Siddhi Jain, Ipsita Mukherjee, Samir R. Panda, Amir A. Zeki, V.G.M. Naidu, Pawan Sharma

Center for Translational Medicine Faculty Papers

Background Cigarette smoking remains a primary cause of chronic lung diseases. After a steady decline, smoking rates have recently increased especially with the introduction of newer electronic nicotine delivery devices, and it is also emerging that dual- or poly-product usage is on the rise. Additionally, with the introduction of IQOS (a heated tobacco product) globally, its impact on human health needs to be investigated. In this study we tested if dual exposure (cigarette smoke (CS)+IQOS) is detrimental to lung epithelial cells when compared with CS or IQOS exposure alone.

Methods Human airway epithelial cells (BEAS-2B) were exposed to either CS, …

What Regenerative Agriculture Can Teach Medical Students About Human Health, David Ebbott, Dimitrios Papanagnou

Department of Emergency Medicine Faculty Papers

No abstract provided.

Improving Surgeon-Patient Communication In Thyroid Cancer Diagnosis And Treatment Discussions: A Narrative Review, Lauren Schlegel, Roberta S. Perry, Elizabeth Cottrill

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Background and Objective: Patient experience is greatly influenced by physician-patient communication. Yet, unmet communication needs continue to be well documented in patients with thyroid cancer. This review discusses factors that may impact this communication and presents communication interventions that are currently being used with thyroid cancer patients.

Methods: A narrative review of articles on the physician-patient relationship and communication in thyroid cancer published between 1985 and 2022 was conducted through PubMed and Google. An additional review of the articles referenced in the bibliography of the included articles was performed.

Key Content and Findings: This review discusses communication components impacting the …

Artificial Intelligence And Machine Learning In The Diagnosis And Management Of Stroke: A Narrative Review Of United States Food And Drug Administration-Approved Technologies, Anirudha S. Chandrabhatla, Elyse A. Kuo, Jennifer D. Sokolowski, Ryan T. Kellogg, Min Park, Panagiotis Mastorakos

Department of Neurosurgery Faculty Papers

Stroke is an emergency in which delays in treatment can lead to significant loss of neurological function and be fatal. Technologies that increase the speed and accuracy of stroke diagnosis or assist in post-stroke rehabilitation can improve patient outcomes. No resource exists that comprehensively assesses artificial intelligence/machine learning (AI/ML)-enabled technologies indicated for the management of ischemic and hemorrhagic stroke. We queried a United States Food and Drug Administration (FDA) database, along with PubMed and private company websites, to identify the recent literature assessing the clinical performance of FDA-approved AI/ML-enabled technologies. The FDA has approved 22 AI/ML-enabled technologies that triage brain …

The Role Of Bispecific Antibodies In Relapsed Refractory Multiple Myeloma: A Systematic Review, Razwana Khanam, Omer S. Ashruf, Syed Hamza Bin Waqar, Zunairah Shah, Saba Batool, Rameesha Mehreen, Pranali Pachika, Zinath Roksana, Mohammad Ebad Ur Rehman, Faiz Anwer

Abington Jefferson Health Papers

Multiple myeloma is a heterogeneous clonal malignant plasma cell disorder, which remains incurable despite the therapeutic armamentarium's evolution. Bispecific antibodies (BsAbs) can bind simultaneously to the CD3 T-cell receptor and tumor antigen of myeloma cells, causing cell lysis. This systematic review of phase I/II/III clinical trials aimed to analyze the efficacy and safety of BsAbs in relapsed refractory multiple myeloma (RRMM). A thorough literature search was performed using PubMed, Cochrane Library, EMBASE, and major conference abstracts. A total of 18 phase I/II/III studies, including 1283 patients, met the inclusion criteria. Among the B-cell maturation antigen (BCMA)-targeting agents across 13 studies, …

Association Of Smoking And Respiratory Disease History With Pancreatic Pathologies Requiring Surgical Resection, Carolyn Ream, Matthew Sabitsky, Rachel Huang, Emma Hammelef, Theresa P. Yeo, Harish Lavu, Charles J. Yeo, Wilbur Bowne, Avinoam Nevler

Student Papers, Posters & Projects

Background: The purpose of this study was to examine the relationship between various respiratory conditions, including hypercapnic respiratory disease, and a multitude of resected pancreatic lesions. Methods: This retrospective case-control study queried a prospectively maintained database of patients who underwent pancreaticoduodenectomy between January 2015 and October 2021. Patient data, including smoking history, medical history, and pathology reports, were recorded. Patients with no smoking history and no concomitant respiratory conditions were designated as the control group. Results: A total of 723 patients with complete clinical and pathological data were identified. Male current smokers showed increased rates of PDAC (OR 2.33, 95% …

A Comparison Of Radiographic Alignment Between Bilateral And Unilateral Interbody Cages In Patients Undergoing Transforaminal Lumbar Interbody Fusion, Mark J. Lambrechts, Jeremy Heard, Nicholas D. D'Antonio, John Bodnar, Gregory Schroeder, Evan Bloom, Jose Canseco, Barrett Woods, Ian David Kaye, Mark Kurd, Jeffrey Rihn, Alan Hilibrand, Gregory D. Schroeder, Alex R. Vaccaro, Christopher Kepler

Rothman Institute Papers

Study Design

Purpose:

Overview of Literature

Methods:

Safety And Indications For Endoscopic Retrograde Cholangiopancreatography In Liver Transplant Patients: An Analysis Of The United States’ National Inpatient Sample Database, Zahid Ijaz Tarar, Umer Farooq, Mustafa Gandhi, Muhammad Usman Zafar, Saad Saleem, Faisal Kamal

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is performed to treat biliary complications after a liver transplantation; however, the previously available literature on the safety of ERCP in liver transplant patients is limited. We aimed to study the safety of ERCP in liver transplant patients.

METHODS: We used a National Inpatient Sample database from 2016-2019 to identify patients who underwent ERCP and had a history of a liver transplantation, using the international classification of diseases, 10

RESULTS: Liver transplant patients who underwent ERCP had a higher rate of post-ERCP pancreatitis and bleeding compared to the general adult population (11.39% vs. 9.19%, 0.83% …

Comparing Performance Of Spectral Image Analysis Approaches For Detection Of Cellular Signals In Time-Lapse Hyperspectral Imaging Fluorescence Excitation-Scanning Microscopy, Marina Parker, Naga S. Annamdevula, Donald Pleshinger, Zara Ijaz, Josephine Jalkh, Raymond Penn, Deepak Deshpande, Thomas C. Rich, Silas J. Leavesley

Center for Translational Medicine Faculty Papers

Hyperspectral imaging (HSI) technology has been applied in a range of fields for target detection and mixture analysis. While HSI was originally developed for remote sensing applications, modern uses include agriculture, historical document authentication, and medicine. HSI has also shown great utility in fluorescence microscopy. However, traditional fluorescence microscopy HSI systems have suffered from limited signal strength due to the need to filter or disperse the emitted light across many spectral bands. We have previously demonstrated that sampling the fluorescence excitation spectrum may provide an alternative approach with improved signal strength. Here, we report on the use of excitation-scanning HSI …

Incidence, Risk Factors, And Outcomes Of Incidental Durotomy During Lumbar Spine Decompression With Or Without Fusion, Gregory Toci, Mark James Lambrechts, Tariq Issa, Brian A. Karamian, Nicholas Siegel, Nicholas D'Antonio, Jose Canseco, Mark Kurd, Barrett Woods, Ian D. Kaye, Alan Hilibrand, Christopher K. Kepler, Alexander Vaccaro, Gregory Schroeder

Rothman Institute Papers

STUDY DESIGN: Retrospective cohort study.

PURPOSE: The primary objective of this study was to determine the incidence and risk factors for incidental durotomies during lumbar decompression surgeries. In addition, we aimed to determine the changes in patient-reported outcome measures (PROMs) based on incidental durotomy status.

OVERVIEW OF LITERATURE: There is limited literature investigating the affect of incidental durotomy on patient reported outcome measures. While the majority of research does not suggest differences in complications, readmission, or revision rates, many studies rely on public databases, and their sensitivity and specificity for identifying incidental durotomies is unknown.

METHODS: Patients undergoing lumbar decompression …

Usability And Acceptability Testing Of A Plan Of Safe Care In A Mobile Health Platform, Krystyna R. Isaacs, Elina Bajracharya, Shantae Taylor, Katie Chung, Yukiko Washio, Trenee Parker, David A. Paul, Tony X. Ma

Department of Pediatrics Faculty Papers

Purpose: Women who are pregnant or parenting while recovering from substance use disorder (SUD) are at risk for insufficient recovery support. With the federal mandate, implementation has been left to each state for the Plan of Safe Care (POSC), leading to challenges in providing comprehensive care coordination and meeting federal reporting requirements.

Methods: This research tests the usability and acceptability of a POSC platform, called SAFE4BOTH, which combines a mobile health (mHealth) app for use by mothers with substance use disorder (MSUD) with a web-based case management system for use by stakeholders to reduce the issue of fragmented postnatal maternal …

Driving Under The Influence Of Cannabis: Impact Of Combining Toxicology Testing With Field Sobriety Tests, Robert L. Fitzgerald, Anya Umlauf, Jacqueline A. Hubbard, Melissa A. Hoffman, Philip M. Sobolesky, Shannon E. Ellis, David J. Grelotti, Raymond T. Suhandynata, Marilyn A. Huestis, Igor Grant, Thomas D. Marcotte

Institute of Emerging Health Professions Faculty Papers

BACKGROUND: Cannabis is increasingly used both medically and recreationally. With widespread use, there is growing concern about how to identify cannabis-impaired drivers.

METHODS: A placebo-controlled randomized double-blinded protocol was conducted to study the effects of cannabis on driving performance. One hundred ninety-one participants were randomized to smoke ad libitum a cannabis cigarette containing placebo or delta-9-tetrahydrocannabinol (THC) (5.9% or 13.4%). Blood, oral fluid (OF), and breath samples were collected along with longitudinal driving performance on a simulator (standard deviation of lateral position [SDLP] and car following [coherence]) over a 5-hour period. Law enforcement officers performed field sobriety tests (FSTs) to …

Study Protocol: Type Iii Hybrid Effectiveness-Implementation Study Implementing Age-Friendly Evidence-Based Practices In The Va To Improve Outcomes In Older Adults, Kirstin Manges Piazza, Laura Ellen Ashcraft, Liam Rose, Daniel E. Hall, Rebecca T. Brown, Mary Elizabeth (Libby) Bowen, Shahrzad Mavandadi, Alison C. Brecher, Shimrit Keddem, Bruce Kiosian, Judith A. Long, Rachel M. Werner, Robert E. Burke

College of Population Health Faculty Papers

Background

Unmet care needs among older adults accelerate cognitive and functional decline and increase medical harms, leading to poorer quality of life, more frequent hospitalizations, and premature nursing home admission. The Department of Veterans Affairs (VA) is invested in becoming an “Age-Friendly Health System” to better address four tenets associated with reduced harm and improved outcomes among the 4 million Veterans aged 65 and over receiving VA care. These four tenets focus on “4Ms” that are fundamental to the care of older adults, including (1) what Matters (ensuring that care is consistent with each person’s goals and preferences); (2) …

Differential Response Of C9orf72 Transcripts Following Neuronal Depolarization, Layla T. Ghaffari, Davide Trotti, Aaron R. Haeusler

Farber Institute for Neuroscience Faculty Papers

The (G4C2)n nucleotide repeat expansion (NRE) mutation in C9orf72 is the most common genetic cause of ALS and FTD. The biological functions of C9orf72 are becoming understood, but it is unclear if this gene is regulated in a neural-specific manner. Neuronal activity is a crucial modifier of biological processes in health and neurodegenerative disease contexts. Here, we show that prolonged membrane depolarization in healthy human iPSC-cortical neurons leads to a significant downregulation of a transcript variant 3 (V3) of C9orf72, with a concomitant increase in variant 2 (V2), which leads to total C9orf72 RNA transcript levels remaining unchanged. However, the …

Gm1 Ganglioside As A Disease-Modifying Therapeutic For Parkinson’S Disease: A Multi-Functional Glycosphingolipid That Targets Multiple Parkinson’S Disease-Relevant Pathogenic Mechanisms, Jay S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting millions of patients worldwide. Many therapeutics are available for treating PD symptoms but there is no disease-modifying therapeutic that has been unequivocally shown to slow or stop the progression of the disease. There are several factors contributing to the failure of many putative disease-modifying agents in clinical trials and these include the choice of patients and clinical trial designs for disease modification trials. Perhaps more important, however, is the choice of therapeutic, which for the most part, has not taken into account the multiple and complex pathogenic mechanisms and processes involved …

Species Delineation And Comparative Genomics Within The Campylobacter Ureolyticus Complex, Joel J Maki, Mondraya Howard, Sara Connelly, Matthew Pettengill, Dwight J Hardy, Andrew Cameron

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Campylobacter ureolyticus is an emerging pathogen increasingly appreciated as a common cause of gastroenteritis and extra-intestinal infections in humans. Outside the setting of gastroenteritis, little work has been done to describe the genomic content and relatedness of the species, especially regarding clinical isolates. We reviewed the epidemiology of clinical C. ureolyticus cultured by our institution over the past 10 years. Fifty-one unique C. ureolyticus isolates were identified between January 2010 and August 2022, mostly originating from abscesses and blood cultures. To clarify the taxonomic relationships between isolates and to attribute specific genes with different clinical manifestations, we sequenced 19 available …

Starvation Sensing By Mycobacterial Rela/Spot Homologue Through Constitutive Surveillance Of Translation, Yunlong Li, Soneya Majumdar, Ryan Treen, Manjuli R. Sharma, Jamie Corro, Howard B. Gamper, Swati R. Manjari, Jerome Prusa, Nilesh K. Banavali, Christina L. Stallings, Ya-Ming Hou, Rajendra K. Agrawal, Anil K. Ojha

Department of Biochemistry and Molecular Biology Faculty Papers

The stringent response, which leads to persistence of nutrient-starved mycobacteria, is induced by activation of the RelA/SpoT homolog (Rsh) upon entry of a deacylated-tRNA in a translating ribosome. However, the mechanism by which Rsh identifies such ribosomes in vivo remains unclear. Here, we show that conditions inducing ribosome hibernation result in loss of intracellular Rsh in a Clp protease-dependent manner. This loss is also observed in nonstarved cells using mutations in Rsh that block its interaction with the ribosome, indicating that Rsh association with the ribosome is important for Rsh stability. The cryo-EM structure of the Rsh-bound 70S ribosome in …

Membrane Compression By Synaptic Vesicle Exocytosis Triggers Ultrafast Endocytosis, Tyler H Ogunmowo, Haoyuan Jing, Sumana Raychaudhuri, Grant F Kusick, Yuuta Imoto, Shuo Li, Kie Itoh, Ye Ma, Haani Jafri, Matthew B. Dalva, Edwin R Chapman, Taekjip Ha, Shigeki Watanabe, Jian Liu

Department of Neuroscience Faculty Papers

Compensatory endocytosis keeps the membrane surface area of secretory cells constant following exocytosis. At chemical synapses, clathrin-independent ultrafast endocytosis maintains such homeostasis. This endocytic pathway is temporally and spatially coupled to exocytosis; it initiates within 50 ms at the region immediately next to the active zone where vesicles fuse. However, the coupling mechanism is unknown. Here, we demonstrate that filamentous actin is organized as a ring, surrounding the active zone at mouse hippocampal synapses. Assuming the membrane area conservation is due to this actin ring, our theoretical model suggests that flattening of fused vesicles exerts lateral compression in the plasma …

Acute Diplopia After Glabellar Hyaluronic Acid Filler Injection, Caroline W. Chung, Eric J. Shiuey, César A. Briceño, Vivian Lee

SKMC Student Presentations and Publications

Purpose: Blindness is a well-known complication of filler injection in the glabellar region. Acute diplopia from filler injection without vision loss is a rare complication that typically results in clinical ophthalmoplegia which can have permanent sequelae. Here, we describe a patient who presented with acute diplopia with grossly intact full extraocular motility after glabella hyaluronic acid filler injection that resolved after 1 month.

Observations: A previously healthy 43-year-old woman underwent her first hyaluronic acid injection in the glabella and developed immediate binocular double vision with severe pain and skin mottling above her right eyebrow and central forehead. Hyaluronidase injections, nitroglycerin …

Gp38 As A Vaccine Target For Crimean-Congo Hemorrhagic Fever Virus, Gabrielle Scher, Dennis A. Bente, Megan C. Mears, Maria N.B. Cajimat, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is a tick-borne virus that causes severe hemorrhagic disease in humans. There is a great need for effective vaccines and therapeutics against CCHFV for humans, as none are currently internationally approved. Recently, a monoclonal antibody against the GP38 glycoprotein protected mice against lethal CCHFV challenge. To show that GP38 is required and sufficient for protection against CCHFV, we used three inactivated rhabdoviral-based CCHFV-M vaccines, with or without GP38 in the presence or absence of the other CCHFV glycoproteins. All three vaccines elicited strong antibody responses against the respective CCHFV glycoproteins. However, only vaccines containing GP38 …

Extracellular-Vesicle-Based Therapeutics In Neuro-Ophthalmic Disorders, Hamed Massoumi, Sohil Amin, Mohammad Soleimani, Bita Momenaei, Mohammad Javad Ashraf, Victor H Guaiquil, Peiman Hematti, Mark I Rosenblatt, Ali R Djalilian, Elmira Jalilian

Wills Eye Hospital Papers

Extracellular vesicles (EVs) have been recognized as promising candidates for developing novel therapeutics for a wide range of pathologies, including ocular disorders, due to their ability to deliver a diverse array of bioactive molecules, including proteins, lipids, and nucleic acids, to recipient cells. Recent studies have shown that EVs derived from various cell types, including mesenchymal stromal cells (MSCs), retinal pigment epithelium cells, and endothelial cells, have therapeutic potential in ocular disorders, such as corneal injury and diabetic retinopathy. EVs exert their effects through various mechanisms, including promoting cell survival, reducing inflammation, and inducing tissue regeneration. Furthermore, EVs have shown …

Changes In Nascent Chromatin Structure Regulate Activation Of The Pro-Fibrotic Transcriptome And Myofibroblast Emergence In Organ Fibrosis, Morgan D. Basta, Svetlana Petruk, Ross Summer, Joel Rosenbloom, Peter J. Wermuth, Edward J. Macarak, Alex V. Levin, Alexander Mazo, Janice L. Walker

Department of Biochemistry and Molecular Biology Faculty Papers

Cell reprogramming to a myofibroblast responsible for the pathological accumulation of extracellular matrix is fundamental to the onset of fibrosis. Here, we explored how condensed chromatin structure marked by H3K72me3 becomes modified to allow for activation of repressed genes to drive emergence of myofibroblasts. In the early stages of myofibroblast precursor cell differentiation, we discovered that H3K27me3 demethylase enzymes UTX/KDM6B creates a delay in the accumulation of H3K27me3 on nascent DNA revealing a period of decondensed chromatin structure. This period of decondensed nascent chromatin structure allows for binding of pro-fibrotic transcription factor, Myocardin-related transcription factor A (MRTF-A) to nascent DNA. …