Medical Specialties Commons^™

Aging- And Alcohol-Associated Spatial Transcriptomic Signature In Mouse Acute Pancreatitis Reveals Heterogeneity Of Inflammation And Potential Pathogenic Factors, Rachel R Tindall, Yuntao Yang, Isabella Hernandez, Amy Qin, Jiajing Li, Yinjie Zhang, Thomas H Gomez, Mamoun Younes, Qiang Shen, Jennifer M Bailey-Lundberg, Zhongming Zhao, Daniel Kraushaar, Patricia Castro, Yanna Cao, W Jim Zheng, Tien C Ko

Faculty, Staff and Student Publications

The rapidly aging population is consuming more alcohol, leading to increased alcohol-associated acute pancreatitis (AAP) with high mortality. However, the mechanisms remain undefined, and currently there are no effective therapies available. This study aims to elucidate aging- and alcohol-associated spatial transcriptomic signature by establishing an aging AAP mouse model and applying Visium spatial transcriptomics for understanding of the mechanisms in the context of the pancreatic tissue. Upon alcohol diet feeding and caerulein treatment, aging mice (18 months) developed significantly more severe AAP with 5.0-fold increase of injury score and 2.4-fold increase of amylase compared to young mice (3 months). Via …

Type I Conventional Dendritic Cells Facilitate Immunotherapy In Pancreatic Cancer, Krishnan K Mahadevan, Allison M Dyevoich, Yang Chen, Bingrui Li, Hikaru Sugimoto, Amari M Sockwell, Kathleen M Mcandrews, Lakshmi Kavitha Sthanam, Huamin Wang, Shabnam Shalapour, Stephanie S Watowich, Raghu Kalluri

Faculty, Staff and Student Publications

Inflammation and tissue damage associated with pancreatitis can precede or occur concurrently with pancreatic ductal adenocarcinoma (PDAC). We demonstrate that in PDAC coupled with pancreatitis (ptPDAC), antigen-presenting type I conventional dendritic cells (cDC1s) are specifically activated. Immune checkpoint blockade therapy (iCBT) leads to cytotoxic CD8+ T cell activation and elimination of ptPDAC with restoration of life span even upon PDAC rechallenge. Using PDAC antigen-loaded cDC1s as a vaccine, immunotherapy-resistant PDAC was rendered sensitive to iCBT with elimination of tumors. cDC1 vaccination coupled with iCBT identified specific CDR3 sequences in the tumor-infiltrating CD8+ T cells with potential therapeutic importance. This study …

Randomized Controlled Trial Of Enteral Vitamin D Supplementation (Vides) In Infants <28 Weeks Gestational Age Or <1000 G Birth Weight: Study Protocol, Mar Romero-Lopez, Jon E Tyson, Mamta Naik, Claudia Pedroza, Lindsay F Holzapfel, Elenir Avritscher, Ricardo Mosquera, Amir Khan, Matthew Rysavy

Faculty, Staff and Student Publications

BACKGROUND: Vitamin D is necessary to develop healthy lungs and other organs early in life. Most infants born before 28 weeks' gestation have low vitamin D levels at birth and a limited intake during the first month. Enteral vitamin D supplementation is inexpensive and widely used. The appropriate supplementation regimen for extremely preterm infants is controversial, and the effect of different regimens on their blood levels and outcomes is unclear.

METHODS: Randomized, blinded comparative effectiveness trial to compare two vitamin D supplementation regimens for inborn infants(400 IU/day with established feedings) or increased supplementation (800 IU/day with any feedings) during the …

Neutrophil To Lymphocyte Ratio As A Prognostic Marker For Cardiovascular Outcomes In Patients With St-Segment Elevation Myocardial Infarction After Percutaneous Coronary Intervention: A Systematic Review And Meta-Analysis, Hassan Ul Hussain, Kanwal Ashok Kumar, Marium Zahid, Muhammad Husban Burney, Zayeema Khan, Muqaddus Asif, Syeda Tayyaba Rehan, Huzaifa Ahmad Cheema, Sarya Swed, Farah Yasmin, Waqas Ullah, M. Chadi Alraies

Abington Jefferson Health Papers

BACKGROUND: Neutrophil to lymphocyte ratio (NLR) has been considered a prognostic biomarker of mortality and other major cardiac events. This study investigates NLR's efficacy in predicting in-hospital and long-term outcomes in patients with ST-segment elevated myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI).

METHODS: Electronic databases (PUBMED, Cochrane CENTRAL, ERIC, Embase, Ovid, and Google Scholar) were searched till June 2022 to identify studies having STEMI patients who underwent PCI. Risk ratios and mean differences (MDs), along with their corresponding 95% confidence intervals (Cis) and standard deviations (SDs), were pooled using a random-effect model. This meta-analysis has been registered on Prospero …

Interval Training Using A Slide Board Is Superior To Cycloergometer Regarding Aerobic Capacity And Specific Fitness In Elite Ice Hockey Players, Robert Roczniok, Artur Terbalyan, Daria Manilewska, Grzegorz Mikrut, Tomas Mika, Petr Stastny

Baltic Journal of Health and Physical Activity

Introduction: Ice hockey is a physically demanding sport that requires a combination of aerobic and anaerobic capacities, as well as specific on-ice skills. This study aimed to compare the effectiveness of individualized interval training on a slide board with training on a cyclo-ergometer, focusing on aerobic capacity and specific fitness in elite ice hockey players. Materials and Methods: Thirty players were randomly divided into an experimental (slide board) and a control (cyclo-ergometer) group. Both groups underwent a 6-week training program with the same intensity and volume. Results: The results showed that both forms of training led to significant improvements in …

Cerebellopontine Angle Meningioma Mimicking Acute Stroke, Milan Terzic, Yash B. Patel

Graduate Medical Education Research Journal

Cerebellopontine angle meningiomas are slow-growing benign tumors of the brain with a largely indolent course until compressive and mass effects occur with adjacent neural structures. Clinical presentations are variable and dependent on the rate of growth and location and tend to progress over a longer period. Acute presentations are less common and require consideration of ubiquitous etiologies. A 62-year-old male with a history of hypertension, benign prostatic hyperplasia, dyslipidemia, and gout presented to the emergency department with a sudden onset of dizziness, loss of balance, and persistently elevated blood pressure. The examination was positive for left dysmetria, dysdiadochokinesia, and tandem …

Breathless Laughter: Tackling Tussive Syncope In The Shadows Of Obstructive Sleep Apnea, Milan Terzic, Yash B. Patel

Graduate Medical Education Research Journal

Cough is a common complaint in the inpatient and outpatient setting. Most cases are caused by upper airway syndrome, gastroesophageal reflux disease, asthma, bronchitis, or infections. Complications that can be life-threatening include syncope and arrhythmias. Our case is of a 67-year-old obese male who had a chronic cough that led to syncope. The chronic cough was present for months, non-responsive to symptomatic treatment, and negative on outpatient work up with no clear common causes leading to hospitalization. After extensive imaging and cardiopulmonary work up yielding normal results, his underlying obstructive sleep apnea and therapy noncompliance was a likely cause. After …

Impact Of Frailty On Patient Morbidity And Outcomes Following Surgery For Urolithiasis: A Nsqip Analysis, David Fu, Kaeli Samson, Bryant Van Leeuwen, Andrew J. Blazek, Andrew Christiansen

Graduate Medical Education Research Journal

Background: Kidney stones are prevalent, and surgical treatment is based on multiple factors. Frailty is the collective decline of organ systems that can lead to adverse events and is considered prior to surgery for risk-benefit analysis. The National Surgical Quality Improvement Program (NSQIP) utilizes risk-adjusted data to monitor outcomes, provide quality benchmarks, and decrease complications. The impact of frailty with the modified 5-item frailty index has not previously been evaluated for patients undergoing urolithiasis procedures.

Methods: Data was collected from 1329 patients who underwent surgery for urolithiasis. The primary outcome was 30-day all-cause morbidity. Associations between variables, including those …

Trends, Predictors, And Outcomes Of Hepatic Encephalopathy Treatment At A Quaternary Transplant Center From 2012-2022, Patrick Twohig, Thoetchai Peeraphatdit, Kaeli Samson, Makayla Schissel, Lynette M. Smith, Kyaw Min Tun, Ellen Tan, Kyle Scholten, Jason Barbaretta, Kevin Brittan, Timothy Mccashland

Graduate Medical Education Research Journal

Background: Hepatic encephalopathy (HE) is a devastating complication of cirrhosis that increases mortality. Many patients do not receive guideline recommended HE treatment.

Our aim is to evaluate trends in HE treatment over time, variables associated with receiving treatment, and outcomes based on the type of treatment received.

Methods: Retrospective single-center cohort study of hospitalized patients with HE from July 2012 – June 2022. HE treatment was defined as receiving lactulose, rifaximin, or combination therapy.

Results: A total of 1,683 unique patients were included, 72% of patients received HE treatment. Fewer HE patients received any treatment in 2022 (65.9%) compared to …

Assessment Of Postural Stability Of 14-Year-Old Girls Training Volleyball, Robert Walaszek, Wiesław Chwała, Katarzyna Burdacka, Marcin Burdacki, Paweł Kurowski

Baltic Journal of Health and Physical Activity

Introduction: Measurements of postural stability are carried out for the prevention of injuries and for rehabilitation of athletes who have sustained traumatic injuries. The aim of the study was to assess postural stability measured in static and dynamic conditions in 14-year-old girls, of whom some were training volleyball, and some were not. Materials and Methods: The study involved a group of 30 girls aged 14, attending volleyball classes. This group was compared with the control group (n = 30) of girls of the same age who regularly participated only in regular physical education (PE) classes. The tests were conducted twice. …

Understanding And Managing Right Bundle Branch Block, Muhammad Mohsin Zafar, Muhammad Asad Hanif, Tayyab Ali Waheed, Aniruddha Singh

Transformative Medicine

No abstract provided.

Small Intestinal Bacterial Overgrowth, Sandesh R. Parajuli, Anish C. Paudel, Anthony Donato

Transformative Medicine

No abstract provided.

The Transgenerational Transmission Of Physical Attractiveness Perceptions: Role Of Parents' Physical Activity And Nutrition Habits In Modelling Body-Focused Health Attitudes And Body Shape Perception In Five-Year-Old Offspring, Agata Kamionka, Mariusz Lipowski, Sebastian Lizińczyk, Urszula Sajewicz-Radtke, Bartosz Radtke, Ariadna Łada-Maśko, Dariusz Olszewski-Strzyżowski, Małgorzata Lipowska

Baltic Journal of Health and Physical Activity

Introduction: Observing parents’ body-focused behaviours during middle childhood is one of the initial ways in which children model their perceptions of pro-health attitudes and their connection to physical attractiveness. This study aimed to investigate the relationship between parents' health behaviours, their appearance, and the perceptions of adult body types (skinny, medium, obese) by their five-year-old children. Moreover, the role of gender in the above relationship for both children and parents was also examined. Materials and methods: This study participants were 680 families with five-year-old children (330 girls). Participation was limited to the moth-er-father-child triad. The Beauty and Health Scale, Healthy …

عدوى المستشفيات, Afaf Taha

Al Jinan الجنان

Despite the progress in the medical fields and technologies used, and the use of a number of antibiotics to eliminate microorganisms that attack the human body, bacterial infections still a major cause of patient deaths. The irony is that hospitals patients turn to for hospitalization are the source of infection caused by microorganisms resistant to a number of antibiotics. The researcher discusses this problem and tells us that the hospital is an ideal place for transmitting pathogens because patients with similar diseases placed in closed groups and are in contact with health workers so that both become a hotbed for …

Antimicrobial Peptide Screening For Designing Custom Bactericidal Hydrogels, Matthias Recktenwald, Muskanjot Kaur, Mohammed M. Benmassaoud, Aryanna Copling, Tulika Khanna, Michael Curry, Dennise Cortes, Gilbert Fleischer, Valerie J. Carabetta, Sebastian Vega

Rowan-Virtua School of Translational Biomedical Engineering & Sciences Departmental Research

Staphylococcus aureus (S. aureus) is an opportunistic pathogen that lives on surfaces and skin and can cause serious infections inside the body. Antimicrobial peptides (AMPs) are part of the innate immune system and can eliminate pathogens, including bacteria and viruses, and are a promising alternative to antibiotics. Although studies have reported that AMP-functionalized hydrogels can prevent bacterial adhesion and biofilm formation, AMP dosing and the combined effects of multiple AMPs are not well understood. Here, three AMPs with different antibacterial properties were synthesized and the soluble minimum inhibitory concentrations (MICs) of each AMP against methicillin-susceptible S. aureus (MSSA) and methicillin-resistant …

Inter-Institutional Analysis Of Skin Of Color Representation In Dermatological Lecture Content At Md And Do Medical Schools, Oluwafunke Ogunremi

Sanford School of Medicine Posters and Presentations

The purpose of this study was to analyze the lecture materials provided in medical schools through a diversity lens. Skin pathologies manifest distinctively on various shades of skin and physicians must be equipped with the proper knowledge to identify and diagnose these conditions accurately and promptly. For most medical students, images in prominent textbooks and lecture slides are their first encounter with disease presentations. Therefore, it is important to analyze the diversity of skin tones in the content that is being delivered. Specifically, the use of images featuring darker skin tones compared to those depicting lighter skin tones. This study …

Remote Monitoring App For Endocrine Therapy Adherence Among Patients With Early-Stage Breast Cancer: A Randomized Clinical Trial, Ilana Graetz, Xin Hu, Mehmet Kocak, Rebecca A. Krukowski, Janeane N. Anderson, Teresa M. Waters, Andrea N. Curry, Andrew Robles, Andrew Paladino, Edward Stepanski, Gregory A. Vidal, Lee S. Schwartzberg

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

IMPORTANCE: Adjuvant endocrine therapy (AET) use among women with early-stage, hormone receptor-positive breast cancer reduces the risk of cancer recurrence, but its adverse symptoms contribute to lower adherence.

OBJECTIVE: To test whether remote monitoring of symptoms and treatment adherence with or without tailored text messages improves outcomes among women with breast cancer who are prescribed AET.

DESIGN, SETTING, AND PARTICIPANTS: This nonblinded, randomized clinical trial (RCT) following intention-to-treat principles included English-speaking women with early-stage breast cancer prescribed AET at a large cancer center with 14 clinics across 3 states from November 15, 2018, to June 11, 2021. All participants had …

Changes In Lean Body Mass With Glucagon-Like Peptide-1-Based Therapies And Mitigation Strategies, Ian J. Neeland

Faculty Scholarship

Weight loss induced by glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucagon-like peptide-1 receptor (GLP-1R)/glucose-dependent insulinotropic polypeptide receptor agonists is coming closer to the magnitudes achieved with surgery. However, with greater weight loss there is concern about potential side effects on muscle quantity (mass), health and function. There is heterogeneity in the reported effects of GLP-1-based therapies on lean mass changes in clinical trials: in some studies, reductions in lean mass range between 40% and 60% as a proportion of total weight lost, while other studies show lean mass reductions of approximately 15% or less of total weight lost. There …

The Frailty Trajectory's Additional Edge Over The Frailty Index: Retrospective Cohort Study Of Veterans With Heart Failure, Javad Razjouyan, Ariela R Orkaby, Molly J Horstman, Parag Goyal, Orna Intrator, Aanand D Naik

Faculty, Staff and Students Publications

No abstract provided.

A Systematic Review Of Telehealth Utilization For Bowel Management Programs In Pediatric Colorectal Surgery., Elizaveta Bokova, Ismael Elhalaby, Seth Saylors, Irene Isabel P. Lim, Rebecca M. Rentea

Manuscripts, Articles, Book Chapters and Other Papers

Recent advancements in pediatric surgery have embraced telehealth (TH) modalities, transitioning from traditional in-person consultations to virtual care. This shift has broadened access to healthcare, potentially enhancing affordability, patient and caregiver satisfaction, and clinical outcomes. In pediatric colorectal surgery, telehealth has been effectively utilized to support Bowel Management Programs (BMPs) for children suffering from constipation and fecal incontinence. A systematic review was conducted to assess the effectiveness of virtual BMPs, analyzing studies from January 2010 to December 2023, sourced from MEDLINE (via PubMed), Embase, and the Cochrane Library, with five studies included. Remote BMPs, implemented through video or telephone consultations, …

Cgmp Compliant One-Step, One-Pot Automated [18f]Fbntp Production For Clinical Imaging Of Mitochondrial Activity, Mai Lin, Cong-Dat Pham, Robert T Ta, H Charles Manning

Faculty, Staff and Student Publications

Background

4-[18F]fluorobenzyl-triphenylphosphonium ([18F]FBnTP) is a lipophilic cation PET tracer. The cellular uptake of [18F]FBnTP is correlated with oxidative phosphorylation by mitochondria, which has been associated with multiple critical diseases. To date, [18F]FBnTP has been successfully applied for imaging myocardial perfusion, assessment of severity of coronary artery stenosis, delineation of the ischemic area after transient coronary occlusion, and detection/quantification of apoptosis in various animal models. Recent preclinical and clinical studies have also expanded the possibilities of using [18F]FBnTP in oncological diagnosis and therapeutic monitoring. However, [18F]FBnTP is typically prepared through a tediously lengthy four-step, three-pot reaction and required multiple synthesizer modules; …

The Significant Associations Between Epigenetic Clocks And Bladder Cancer Risks, Yang Deng, Chia-Wen Tsai, Wen-Shin Chang, Yifan Xu, Maosheng Huang, Da-Tian Bau, Jian Gu

Faculty, Staff and Student Publications

Bladder cancer is an age-related disease, with over three-quarters of cases occurring in individuals aged 65 years and older. Accelerated biological aging has been linked to elevated cancer risks. Epigenetic clocks serve as excellent predictors of biological age, yet it remains unclear whether they are associated with bladder cancer risk. In this large case-control study, we assessed the associations between four well-established epigenetic clocks-HannumAge, HorvathAge, GrimAge, and PhenoAge-and bladder cancer risk. Utilizing single nucleotide polymorphisms (SNPs), which were identified in a genome-wide association study (GWAS), linked to these clocks as instruments, we constructed a weighted genetic risk score (GRS) for …

Developing A Fit-For-Purpose Composite Symptom Score As A Symptom Burden Endpoint For Clinical Trials In Patients With Malignant Pleural Mesothelioma, Charles S Cleeland, Karen N Keating, Brian Cuffel, Cem Elbi, Jonathan M Siegel, Christoph Gerlinger, Tara Symonds, Jeff A Sloan, Amylou C Dueck, Andrew Bottomley, Xin Shelley Wang, Loretta A Williams, Tito R Mendoza

Faculty, Staff and Student Publications

We developed a composite symptom score (CSS) representing disease-related symptom burden over time in patients with malignant pleural mesothelioma (MPM). Longitudinal data were collected from an open-label Phase IIB study in which 239 patients completed the validated MD Anderson Symptom Inventory for MPM (MDASI-MPM). A blinded, independent review committee of external patient-reported outcomes experts advised on MDASI-MPM symptoms to include in the CSS. Through iterative analyses of potential symptom-item combinations, 5 MPM symptoms (pain, fatigue, shortness of breath, muscle weakness, coughing) were selected. The CSS correlated strongly with the full MDASI-MPM symptom set (0.92-0.94) and the Lung Cancer Symptom Scale-Mesothelioma …

Beyond The Airway, Volume 1, Issue 1, May 2024

Beyond the Airway

Table of Contents

3 - Foreword from the Editors-In-Chief

4 - A message from Dr. Eric S. Schwenk

5 - An Interview with Dr. Rishi Kothari

7 - Anesthesia Considerations for Patients on Semaglutide

9 - An Interview with Dr. Jeffrey Mojica

11 - The National Resident Matching Program (NRMP) Match: Is Anesthesiology Becoming More Competitive?

13 - An Interview with Dr. Katherine Dillon and Dr. Matteo Petrera

15 - History of Ketamine in Anesthesia

17 - Editorial Staff

Deciphering Dyspnea: Exercise-Related Flail Mitral Valve Masquerading As Pneumonia, Mehtab Galeh, Amjad Nader, Rania Esteitie

Journal of Shock and Hemodynamics

A 62-year-old male presented with a sudden onset of dyspnea following a racquetball session. Vital signs revealed a blood pressure of 136/63 mm Hg, heart rate of 116 beats/min, respiratory rate of 26 breaths/min, temperature of 98.7º F, and oxygen saturation of 85% on room air. The physical examination was notable for tachycardia, no audible murmur, and bilateral coarse breath sounds on lung auscultation. Pertinent laboratory data showed leukocytosis, elevated lactic acidosis, and elevated brain natriuretic peptide. Arterial blood gas analysis on room air revealed a pH of 7.39, partial pressure of carbon dioxide of 32 mm Hg, and arterial …

The Effects Of Transcutaneous Electrical Nerve Stimulation On Pain And Function In Patients With Knee Osteoarthritis: A Critically Appraised Topic, P. Drake Short, Rileigh T. Ricken, Jennifer L. Volberding

Internet Journal of Allied Health Sciences and Practice

Purpose: Knee osteoarthritis (OA) is a common condition that impacts upwards of 40% of patients over the age of 70, and transcutaneous electrical stimulation (TENS) is a common treatment protocol. To date, there is no consensus on the effectiveness of TENS as a modality for knee OA. Thus, this critically appraised topic (CAT) aims to determine the impact of TENS on the pain and functional outcome of patients with knee OA. Methods: To assess the therapeutic efficacy of TENS, a systematic search of the available literature was conducted, focusing on pain and function in knee osteoarthritis. Online databases were searched …

Randomized Controlled Trial Of Enhanced Recovery After Surgery Protocols In Live Kidney Donors: Eraskt Study, Jacob Saks, Uzung Yoon, Natalie Neiswinter, Eric Schwenk, Stephen Goldberg, Linh Nguyen, Marc Torjman, Elia Elia, Ashesh Shah

Department of Anesthesiology Faculty Papers

BACKGROUND: Enhanced recovery after surgery (ERAS) pathways represent a comprehensive approach to optimizing perioperative management and reducing hospital stay and cost. In living donor kidney transplantation, key impediments to postoperative discharge include pain, and opioid associated complications such as nausea, vomiting, and the return of gastrointestinal function.

METHODS: In this randomized controlled trial, living kidney transplantation donors were assigned to either the ERAS or control group. The ERAS group patients received 15 preoperative, 17 intraoperative, 19 postoperative element intervention. The control group received standard care. The ERAS group received a multimodal opioid sparing pain management including an intraoperative transverse abdominis …

Real-Life Experience On The Effect Of Sglt2 Inhibitors Vs. Finerenone Vs. Combination On Albuminuria In Chronic Kidney Disease, Mohamad Hanouneh, Dustin Le, Bernard G. Jaar, Christina Tamargo, C. Elena Cervantes

Division of Nephrology Faculty Papers

BACKGROUND: There have been several recent advances in the care of patients with chronic kidney disease (CKD), including the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and selective mineralocorticoid receptor antagonists (MRAs). There are very few data reporting the outcomes of these treatments in real-world experience. The aim of this retrospective study is to report the effects of SGLT2 inhibitors, finerenone, and their combination in CKD patients in our community-based setting.

METHODS: Ninety-eight patients with CKD with an estimated glomerular filtration rate (eGFR) between 25 and 90 mL/min per 1.73 m² and a urine albumin-to-creatinine ratio (UACR) ≥ …

Neuroendocrine Gene Subsets Are Uniquely Dysregulated In Prostate Adenocarcinoma, Nicole M. Naranjo, Anne Kennedy, Anna Testa, Cecilia E. Verrillo, Adrian D. Altieri, Rhonda Kean, D. Craig Hooper, Jindan Yu, Jonathan Zhao, Oliver Abinader, Maxwell W. Pickles, Adam Hawkins, William Kevin Kelly, Ramkrishna Mitra, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Prostate cancer has heterogeneous growth patterns, and its prognosis is the poorest when it progresses to a neuroendocrine phenotype. Using bioinformatic analysis, we evaluated RNA expression of neuroendocrine genes in a panel of five different cancer types: prostate adenocarcinoma, breast cancer, kidney chromophobe, kidney renal clear cell carcinoma and kidney renal papillary cell carcinoma. Our results show that specific neuroendocrine genes are significantly dysregulated in these tumors, suggesting that they play an active role in cancer progression. Among others, synaptophysin (SYP), a conventional neuroendocrine marker, is upregulated in prostate adenocarcinoma (PRAD) and breast cancer (BRCA). Our analysis shows that SYP …

Mettl3-Mediated Chromatin Contacts Promote Stress Granule Phase Separation Through Metabolic Reprogramming During Senescence, Chen Wang, Hideki Tanizawa, Connor Hill, Aaron Havas, Qiang Zhang, Liping Liao, Xue Hao, Xue Lei, Lu Wang, Hao Nie, Yuan Qi, Bin Tian, Alessandro Gardini, Andrew V Kossenkov, Aaron Goldman, Shelley L Berger, Ken-Ichi Noma, Peter D Adams, Rugang Zhang

Faculty, Staff and Student Publications

METTL3 is the catalytic subunit of the methyltransferase complex, which mediates m6A modification to regulate gene expression. In addition, METTL3 regulates transcription in an enzymatic activity-independent manner by driving changes in high-order chromatin structure. However, how these functions of the methyltransferase complex are coordinated remains unknown. Here we show that the methyltransferase complex coordinates its enzymatic activity-dependent and independent functions to regulate cellular senescence, a state of stable cell growth arrest. Specifically, METTL3-mediated chromatin loops induce Hexokinase 2 expression through the three-dimensional chromatin organization during senescence. Elevated Hexokinase 2 expression subsequently promotes liquid-liquid phase separation, manifesting as stress granule phase …