Medicine and Health Sciences Commons^™

Profiling Tumour-Infiltrating Immune Cells In A Large Paediatric Medulloblastoma Cohort: A Retrospective Analysis, Mingze Chen, Xiangjun Shi, Yi Wang, Jiao Zhang, Jirong Guo, Xiuchen Guan, Yu Sun, Wenhao Wu, Chunde Li, Yongji Tian, Yunwei Ou, Tian Li, Kai Jiang, Michael D Taylor, Xuebin Liao, Liwei Zhang, Tao Sun

Faculty, Staff and Students Publications

Background: Tumour-infiltrating immune cells exert both pro-tumour and anti-tumour effects on intracranial tumours. In this study, we investigated the prognostic value of various infiltrating immune cells in medulloblastoma (MB) within a large cohort.

Methods: We employed multiplex immunofluorescent (mIF) staining of tissue microarrays to assess the densities of T cells, B cells, NK cells, macrophages, and immune checkpoints in tumour samples from 249 primary paediatric patients with primary MB. Overall survival (OS) analysis, progression-free survival (PFS), and Cox regression analyses were utilised to explore potential relationships between immune cell densities and survival outcomes. Subsequently, multivariate Cox regression was validated using …

Factfinders For Patient Safety: Minimizing Complications In Radiofrequency Neurotomy: Part I-Implantable Devices; Part Ii-Preprocedural Bvnrfn Imaging, David Hao, Gerald Yeung, Haewon Lee, Zheyan Chen, Ben Laplante, Paul Kitei, Reza Ehsanian, David Levi

Moss-Magee Rehabilitation Papers

This series of FactFinders presents a brief summary of the evidence and outlines recommendations regarding minimizing risks with radiofrequency neurotomy procedures. The evidence in support of the following facts is presented: (1) While data on the safety of radiofrequency neurotomy in patients with implanted devices are limited, the procedure can likely be performed safely with careful adherence to best practices and manufacturer recommendations. (2) Basivertebral nerve radiofrequency neurotomy can be performed safely and effectively at the L3 through S1 vertebral levels. Scrutiny of preprocedural imaging may minimize risk. Although the transpedicular approach is preferred, patient anatomy may dictate a non-transpedicular …

The Differential Effects Of Camp Mobilizing Agents On Tgf-Β-Induced Extracellular Matrix In Human Lung-Derived Fibroblasts: Insights Into Therapeutic Targets For Lung Fibrosis, Sarah Orfanos, Brian T. Deeney, Gaoyuan Cao, Nikhil Karmacharya, Anjani Ravi, Cynthia J. Koziol-White, Qi Yang, Rennolds S. Ostrom, Reynold A. Panettieri Jr.

Pharmacy Faculty Articles and Research

Background

Injury-repair responses typically induce tissue or organ scarring. Generally, cAMP-mobilizing agents inhibit the activation of fibroblasts and deposition of extracellular matrix. Some but not all cAMP-mobilizing agents inhibit fibrosis. Evidence suggests that inhaled treprostinil, a prostacyclin (IP) analog, increases intracellular cAMP levels [cAMP]I, and slows the decline in pulmonary function in patients with idiopathic pulmonary fibrosis (IPF). However, the molecular mechanisms by which cAMP-mobilizing agents, including treprostinil, alter the expression of matrix proteins in human lung fibroblasts (HLF) remain unclear. Unlike other Gαs -coupled receptors, we posit that the antifibrotic properties of treprostinil are driven by cAMP-mobilizing-dependent and -independent …

Traumatic Fracture Of Kager's Fat Pad: A Case Report., Victoria Di Castro Horn, Margaret Hurley, Emily Andrews, Alberto Giardini

PCOM Scholarly Works

BACKGROUND: Kager's fat pad is a metabolically active adipose structure within Kager's triangle anterior to the Achilles tendon, involved in shock absorption, vascular support, and tendon lubrication. Although most research has focused on its role in Achilles tendinopathy and inflammatory conditions, isolated traumatic disruption without concurrent tendon damage has been rarely documented in the literature, to our knowledge. We report a case of an isolated traumatic fracture of the Kager's fat pad in the absence of concomitant Achilles tendon injury.

CASE PRESENTATION: An otherwise healthy 31 year-old female presented to the outpatient musculoskeletal office with reported pain at the distal …

At1-Aa Induced Hypertension During Pregnancy Contributes To Developmental Programming Of Hypertension In Female Offspring, Nathan Campbell, James P. Lemon, Melissa Helmich, Dylan Solise, Alexandra Demesa, Ella Goolsby, Evan Lamarca, Evangeline Deer, Denise C. Cornelius, Ty Turner, Lorena M. Amaral, Baoying Zheng, Babbette Lamarca

Pharmacology and Toxicology

Preeclampsia (PE), new-onset hypertension during pregnancy, is accompanied by organ dysfunction, in addition to placental dysfunction, and is associated with chronic inflammation and fetal growth restriction. Agonistic autoantibodies against the angiotensin II type 1 receptor (AT1-AA) are produced in PE women and induce a PE-like phenotype when infused into pregnant rats. PE offspring are at higher risk for cardiovascular disease and hypertension; however, AT1-AA’s role in these risks is unknown. Therefore, we hypothesized that AT1-AA exposure during pregnancy contributes to hypertension in adult offspring. We infused AT1-AA (1:40) starting on gestational day (GD) 14, allowed the dams to give birth, …

Evaluating The Effectiveness Of Clinical Practice Guideline Adherence For Patellofemoral Pain (Knee-Capp): Protocol For A Multisite, Parallel-Arm Randomized Clinical Trial In The Military Health System, Emma H. Beisheim-Ryan, Timothy C. Mauntel, Daniel I. Rhon, Charity G. Patterson, Nathan Parsons, Scott Paradise, Megan H. Roach, Marisa Pontillo, Sara R. Gorczynski, Ariana Emory, Shawn Farrokhi

Physical Therapy Faculty Articles and Research

Importance

Patellofemoral pain (PFP) frequently affects military personnel, caused by the physical demands of duty-related training. Clinical practice guidelines (CPG) can guide PFP management, yet physical therapist practice patterns vary and often exclude CPG-recommended, evidence-based interventions. Objective

The Evaluating the Effectiveness of Clinical practice guideline Adherence for Patellofemoral Pain (knEE-CAPP) trial assesses whether a CPG-adherent physical therapy approach more significantly reduces pain, disability, health care utilization, and analgesic medication prescription in Service members with PFP as compared to usual physical therapist care. Design

This is a multisite, parallel arm randomized controlled trial. Setting

The study will be conducted at 4 …

An Experiential Learning Lab Activity On Skeletal Muscle Physiology In Undergraduate Md Pre-Clerkship Curriculum, Angela Martinez, Daniel Salinas, Meyer Maddox, Kelsey A. Potter-Baker, Amin Shah

School of Medicine Publications

Experiential learning is an important part of the medical education curriculum. Due to clinical relevance of skeletal muscle strength in evaluating patients’ complaints of muscle weakness or imbalance, skeletal muscle physiology is an important concept with extensive potential for experiential learning opportunities. Our goal was to establish an experiential learning skeletal muscle physiology lab activity that would improve undergraduate MD pre-clerkship students’ skill to collect muscle force measurements using a hand-held dynamometer (HHD) and expand knowledge of core physiological concepts. We developed a muscle lab activity where students performed two experiments using an HHD: (1) The Elbow Flexion Experiment and …

Divergent Prefrontal Cortex Circuits Regulate Cued Food Seeking Under Distinct Metabolic Or Emotional States, Xu O Zhang, Guillermo Aquino-Miranda, Claire E Cho, Yongzhe Wang, Duy Hoang Ha, Nikita Elinson-Watson, Allen Dong, Caleb Kemere, Fabricio H Do-Monte

Faculty, Staff and Student Publications

Flexibly adjusting food-seeking behaviour in response to food-associated cues and internal states is crucial for animals' survival. However, the neural mechanisms that modulate cued food-seeking behaviour during varying metabolic (i.e., hungry vs. satiated) and emotional (i.e., safe vs. threatened) states remain elusive. Here, we show that the encoding of metabolic or threat states in projection-defined neurons in the prelimbic cortex (PL) mediates cued food-seeking responses in rats. Using microendoscopic imaging, we demonstrate that neural population dynamics in PL consistently represent food cues, task-relevant behaviours, and internal state changes by recruiting distinct subsets of cue-responsive neurons at each state. Single-unit recording …

Multidomain Therapy For Alzheimer's Disease: A Scoping Review Of Cognitive Decline Trials, Jared C Roach, Cyrus A Raji, Et Al.

2020-Current year OA Pubs

BACKGROUND: Alzheimer’s disease (AD) leading to cognitive decline and dementia results from the interplay of multiple interacting dysfunctional biological systems. These systems can be categorized by domain, such as inflammation, cardiovascular health, proteostasis, or metabolism. Specific causes of AD differ between individuals, but each individual is likely to have causes stemming from multiple domains. Personalized multidomain therapy has been proposed as a standard of care for AD. OBJECTIVES: We sought to enumerate and describe prospective randomized controlled trials (RCTs) for multidomain interventions for AD, and to extract their inclusion criteria, trial design parameters (length, number of participants), and outcome measures. …

Bilateral Concomitant Infection Of Cytomegalovirus And Varicella-Zoster Virus Retinitis In An Immunocompromised Adult, Henry C Skrehot, Amer Alsoudi, Daniel Olson, Nhon Le, Asad Loya, Tahira Scholle

Faculty, Staff and Students Publications

Purpose: To report a novel case of bilateral concomitant cytomegalovirus (CMV) retinitis and acute retinal necrosis (ARN) due to varicella-zoster virus (VZV) in an immunocompromised adult.

Methods: A case report was evaluated.

Results: A 36-year-old immunocompromised man presented with acute painful vision loss in the left eye. On initial presentation, uncorrected distance visual acuity was 20/20 in the right eye and counting fingers at 3 feet (≈1 m), which deteriorated to no light perception (NLP) in the left eye. Fundus examination showed necrotizing retinitis in both eyes, with features of both CMV retinitis and ARN. One week after initiation of …

Guide For Selecting Experimental Models To Study Dietary Fat Absorption, Andromeda M. Nauli, Ann Phan, Karen Mai, Kathleen Tran, Surya M. Nauli

Pharmacy Faculty Articles and Research

Dietary fat absorption is a complex, multi-step process involving digestion, enterocyte uptake, intracellular trafficking, re-esterification, and transport via lipoproteins into circulation. Because dietary fat absorption plays a central role in lipid homeostasis, metabolic syndrome, and fat malabsorption disorders, its study has a broad biomedical significance. However, experimental investigation of this process is technically challenging due to the short lifespan of enterocytes, the dual lymphatic and portal transport routes, and the need to trace the metabolic fate of absorbed lipids. This review summarizes and critically evaluates the major experimental systems used to study dietary fat absorption, highlighting their respective strengths, limitations, …

Tinkering In Clinical Practice: Exemplars From Slps Working With Persons In Disordered States Of Consciousness, Ann Guernon, Christina Papadimitriou, Jennifer A. Weaver, Trudy Mallinson, Marla Clayman, Jay Meehan, Keith Cox, Luke Lindemann, Patricia Grady

Rehabilitation and Health Sciences Department Faculty Conferences

Speech-language pathologists (SLPs) providing care for people living with disordered states of consciousness frequently navigate ambiguity and uncertainty. Using interview and video data we will show how SLPs clinically reason via tinkering or “thinking in action”. This undervalued and understudied clinical reasoning skill is a caring practice comprised of curiosity, experimentation, flexibility and adaptation to attend to a person’s needs. SLPs will have the opportunity to reflect and discuss their experiences with tinkering in a wide range of patient populations.

Epidemiology Of Metabolic Syndrome In Patients With Inflammatory Bowel Disease: A Population-Level Cohort Study From The United States, Aakash Desai, Himsikhar Khataniar, Jana G. Hashash, Priya Sehgal, Francis A. Farraye, Gursimran S. Kochhar

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Epidemiological data on metabolic syndrome (MetS) in patients with inflammatory bowel disease (IBD) are limited.

METHODS: A retrospective cohort study was conducted using the United States (US) Collaborative Network (TriNetX) to obtain data for patients with IBD between 2010 and 2023. The primary aim of the study was to estimate the prevalence of MetS in ulcerative colitis (UC) and Crohn's disease (CD). Prevalence was further characterized by age, sex, race, disease location, IBD medications, history of surgery, and IBD phenotype.

RESULTS: Among 100,890 patients with IBD, metabolic syndrome (MetS) affected 34.4% overall (UC 32.4%, CD 34.3%). Prevalence rose sharply …

High Phosphorus Intake: The Role Of Phosphorus And Health Outcomes Through The Lens Of High Phosphorus Additive Intake, Taigen M. Mayes

Senior Honors Theses

Phosphorus is a commonly consumed mineral in the traditional human diet and plays an essential role in human physiological functions. With the use of phosphate additives, high phosphate intake has become increasingly prevalent in recent years. Phosphate is regulated in the body by a homeostasis mechanism. A disruption to the homeostasis has a link to various pathologies such as bone health, cardiovascular disease, cancers, and kidney issues. Various studies have investigated the role of phosphate and its effects on human function. Bone health, cardiovascular disease, cancer, premature aging, dementia, and kidney disease are linked with high phosphorus intake.

Risk Factors For Unexpected Death In Patients Identified By A Communication And Resolution Program, Peter Lodato, Neal D. Goldstein, Alexandra M, Mapp, Adebayo Gbadebo, David A. Paul

Department of Pediatrics Faculty Papers

Many patients experience unexpected harm while receiving healthcare, with a lasting impact on patients, families, and caregivers. Communication and Resolution Programs are being adopted with increased frequency, as a more systematic, transparent, and equitable approach to these unexpected outcomes. The aim of this study was to identify whether demographic factors played a role in identifying patients with unexpected death, as managed in our CRP. This nested case-controlled compared 236 patients who experienced an unanticipated death with 2,360 controls who died expectedly over a 10-year period. Patients with unexpected death were more likely to be Black (AOR 2.18 95% CI 1.01-4.68), …

Characterizing Global Dermatologic Engagement And Needs: A Cross-Sectional Study From 83 Countries, Alexis G. Strahan, Christine Li, Maud Guérin, Tom Allison, Gene Colón, Jehireh Peraza-Williams, Olyvia Zarchin, Morvarid Zehtab, Ann M. Pacheco, Jadesola Akinwuntan, Shivani Jain, Marlous L. Grijsen, Wendemagegn Enbiale, Wingfield Rehmus, L. Claire Fuller, Karolyn Wanat, Esther E. Freeman

School of Medicine Faculty Publications

No abstract provided.

The Associations Between Meniscus Tear Location And The Prevalence And Severity Of Cartilage Wear In Different Knee Compartments Using An Arthroscopic Grading System, Tara Korbal, Claudia Leonardi, Amy Bronstone, Vinod Dasa

School of Medicine Faculty Publications

Introduction: Meniscus tears are associated with progressive cartilage degeneration and worsening osteoarthritis. Although several previous studies have explored the relationship between meniscus tears and cartilage damage, few have examined the relationship between tear location and cartilage wear in all knee compartments using an arthroscopic grading system. Objectives: Evaluate the association between meniscus tear location and the prevalence and severity of high-grade cartilage wear in knee compartments. Methods: A total of 210 patients were categorized into groups based on meniscus tear location: medial meniscus tear (MMT, n = 106), lateral meniscus tear (LMT, n = 41), and medial-lateral meniscus tear (MLMT, …

The Time-Dependent Association Between Irritable Bowel Syndrome And All-Cause And Cause-Specific Mortality In The Nih-Aarp Cohort Study, Daniela S Gutiérrez-Torres, Fangyu Li, Linda M Liao, Carrie R Daniel, Shreela V Sharma, Ruosha Li, Eric L Brown, Qing Lan, Maki Inoue-Choi, Baharak Moshiree, Paul Albert, Rashmi Sinha, Emily Vogtmann

Faculty, Staff and Student Publications

Introduction: Evidence on the association between irritable bowel syndrome (IBS) and mortality is conflicting. In this study, we estimated the association between IBS and all-cause and cause-specific mortality in the NIH-AARP Diet and Health Study.

Methods: IBS diagnoses between 1994 and 2008 were identified from Medicare claims data, and mortality outcomes through 2019 were obtained through linkage to the National Death Index. Using multivariable Cox proportional hazards regression models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality within partitioned follow-up time categories (>2-5, >5-8, >8-11, >11-14, >14-17, and >17 years) with adjustment …

Mpox Insights: From Structure To Human Cell Interaction, Md. S. Zaman, Robert C. Sizemore, Draven Rodriguez, Emilio Lopez, S. M. Golam Alam, Suleyman Tufa, Juan C Lopez Alvarenga, Nuraly S. Akimbekov, Mohammed S. Razzaque

School of Medicine Publications

Mpox, a zoonotic viral disease, has emerged as a global concern due to outbreaks in both endemic and non-endemic regions in 2022. Rodents, including African squirrels and Gambian pouched rats, are suspected key reservoirs, with human infections occurring through direct contact with infected animals or bushmeat consumption. Previously confined to rural Africa, mpox has spread via international travel and the exotic pet trade. Human-to-human transmission occurs mainly via respiratory droplets and direct contact with bodily fluids or lesions. The virus has a double-stranded DNA genome within a lipid envelope. Despite lower mutation rates in DNA viruses, mpox has developed mutations, …

Integrative Profiling Strategies To Guide Personalized Therapy In Mantle Cell Lymphoma: A Pilot Study, Yang Liu, Holly A Hill, Yijing Li, Joseph Mcintosh, Vivian Jiang, Fangfang Yan, Yixin Yao, Yue Fei, Jared Zhang, Lawrence Qu, Jun Yao, Preetesh Jain, Ken Chen, Michael Wang

Faculty, Staff and Student Publications

Mantle cell lymphoma (MCL) responds to frontline therapy but is susceptible to relapse. While Bruton's tyrosine kinase inhibitors (BTKi) achieve high response rates, most patients eventually experience disease progression. Predicting responses to subsequent treatments remains challenging due to the lack of an established platform. Heterogeneity in gene alterations and cellular pathways contribute to resistance, complicating treatment approaches. Here, we present a multi-modal profiling platform, targeting key pathways rather than focusing on singular DNA-associated lesions. We identified dysregulated signaling pathways by performing gene expression profiling on 20 MCL samples using a custom MCL MATCH gene set and analyzed the data with …

Shp2: A Redox-Sensitive Regulator Linking Immune Checkpoint Inhibitor Therapy To Cancer Treatment And Vascular Risk, Silvia Fernanda López Moreno, Stefania Assunto Lenz, Bernardo Casso-Chapa, Angelica Paniagua-Bojorges, Jung Hyun Kim, Nicolas L Palaskas, Kevin T Nead, Venkata S K Samanthapudi, Gilbert Mejia, Oanh Hoang, Jonghae Lee, Steven H Lin, Joerg Herrmann, Guangyu Wang, Syed Wamique Yusuf, Cezar A Iliescu, Noah I Beinart, Charlotte Manisty, Masuko Ushio-Fukai, Tohru Fukai, Pietro Ameri, Roza I Nurieva, Michelle A T Hildebrandt, Keri Schadler, Efstratios Koutroumpakis, Sivareddy Kotla, Nhat-Tu Le, Jun-Ichi Abe

Faculty, Staff and Student Publications

Src homology 2-domain containing protein tyrosine phosphatase 2 (SHP2), encoded by the Ptpn11 gene (Tyrosine-protein phosphatase non-receptor type 11), is a key downstream effector of PD-1/PD-L1 signaling and is likely important, in addition to immune modulation, in tumor development and vascular homeostasis. SHP2 conveys PD-1 mediated inhibitory signaling in T cells, and is emerging as a therapeutic target. Importantly, there is an association between immune checkpoint inhibitors (ICIs), immune-related adverse events (irAEs), and cardiovascular complications, underscoring the need to understand SHP2’s role in these processes. This review aims to summarize current knowledge on SHP2/PTPN11 biology, its role in immune …

Exploring The Interplay Between Hypertension And Osteoporosis: A Narrative Review, Yolanda V. Gutierrez, Ronald Shaju, Alyssa A. Sepulveda, Seval Coban

School of Medicine Publications

Hypertension and osteoporosis are highly prevalent chronic conditions that have significant implications for global health, especially in aging populations. While these conditions have traditionally been viewed as separate, emerging research suggests a strong pathophysiological link between the two. Understanding these shared mechanisms may help improve screening and guide integrated management strategies. This narrative review was conducted between January 2024 and July 2025 using PubMed, ScienceDirect, and Google Scholar. The search strategy used the Boolean string: (“hypertension” OR “high blood pressure”) AND (“osteoporosis” OR “bone loss”), supplemented with pharmacologic terms (“ACE inhibitors,” “angiotensin receptor blockers,” “thiazide diuretics,” “beta-blockers”, “SERMS”, “Bisphosphonates”, “Denosumab”, …

Impact Of Peek Implant Surface Design On Postoperative Complications In Cranioplasty: A Retrospective Review, Carmen A Zavala, Laura Zima, Subhiksha Srinivasan, Sanjay V Neerukonda, Mark J Dannenbaum

Faculty, Staff and Student Publications

Background: The aim of this study was to evaluate and compare complication rates and clinical outcomes associated with smooth and perforated polyetheretherketone (PEEK) implants used in cranioplasty.

Methods: A retrospective analysis of 94 patients who underwent cranioplasty with either smooth (n = 45) or perforated (n = 49) PEEK implants over a five-year period was conducted. Patient demographics, comorbidities, reasons for initial craniectomy, time interval between craniectomy and cranioplasty, postoperative complications, hospital stays, and rates of revision surgeries were analyzed. Multivariate logistic regression was used to control for confounding factors.

Results: No statistically significant differences were observed in demographic characteristics, …

Norms For Scaling Up Small And Sick Newborn Care: An Overview Of Reviews, Natalie A. Strobel, Georgia Whisson, Derek Swe, Amy Budrikis, Karen M. Edmond

Research outputs 2022 to 2026

Background: The World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) currently have no benchmarks or 'norms' for scaling up small and sick newborn (SSN) service delivery in health facilities in low- and middle-income countries (LMICs). Our objective was to understand which systematic reviews had addressed the following norms in the last five years: number of SSN beds per live births in a district or similar administrative unit (admission beds); space requirements for SSN units, including mother-infant dyads (space); health workforce ratios in SSN units (workforce); and travel time to health facilities with SSN units (travel time). Methods: …

Liver-Directed Base Editing Of Abcc6 Prevents Ectopic Calcification In A Variant-Humanized Mouse Model Of Pseudoxanthoma Elasticum, Lauren C. Testa, Dora Obiri-Yeboah, Hooda Said, Ping Qu, Michael A. Levine, Mohamad-Gabriel Alameh, Kiran Musunuru, Qiaoli Li, Xiao Wang

Department of Biochemistry and Molecular Biology Faculty Papers

Pseudoxanthoma elasticum (PXE) is an autosomal recessive connective tissue disorder characterized by ectopic calcification of elastic fibers throughout the skin, retina, and arteries. It is caused by pathogenic variants in ABCC6 , which encodes a transmembrane transporter that primarily localizes to hepatocytes. Loss of ABCC6 function in hepatocytes leads to systemic deficiency of inorganic pyrophosphate (PPi), a potent inhibitor of calcification; such depletion of PPi from the circulation is responsible for multisystemic ectopic calcification seen in PXE. Therefore, liver-targeted variant correction by genome editing and subsequent restoration of systemic PPi may offer a one-and-done therapeutic approach for PXE. The ABCC6 …

A Cluster-Randomized Controlled Trial Assessing The Effectiveness Of A Multifaceted Versus A Discrete Implementation Strategy On Fidelity To An Occupational Guideline For The Prevention Of Mental Health Problems At The Workplace: A Dual Perspective From Swedish Schools, Andreas Rödlund, Anna Toropova, Rebecca Lengnick-Hall, Byron J Powell, Liselotte Schäfer Elinder, Christina Björklund, Lydia Kwak

2020-Current year OA Pubs

BACKGROUND: Although the management of psychosocial risks in the work environment represents an evidence-based approach to the prevention of mental health problems, its implementation is limited, including in schools, and knowledge on how to support better implementation is scarce. This study compares the effectiveness of a multifaceted vs. a discrete implementation strategy on fidelity to an occupational guideline for the prevention of mental health problems. Dual perspectives were used to assess fidelity, an important aspect of the measurement agenda.

METHODS:  A cluster-randomized controlled trial was conducted among 55 schools in Sweden. A multifaceted strategy (educational meeting, implementation teams, ongoing training, …

Diras3-Derived Cyclic Peptides Disrupt Kras-Raf Interaction And Kras Nanoclustering, Suppressing Kras-Driven Pancreatic And Ovarian Tumors, Joshua P Gray, Gamze Bildik, Ha-Neul Kim, Margie N Sutton, Jing Wang, Amarachi O Osuji, Nefeli Batistatou, Hailing Yang, Weiqun Mao, Zhi Tan, Geneviève M C Gasmi-Seabrook, Junchen Liu, John F Hancock, Christopher B Marshall, Joshua A Kritzer, Mitsuhiko Ikura, Robert C Bast, Steven W Millward, Zhen Lu

Faculty, Staff and Students Publications

Mutations in KRAS drive 88% of pancreatic ductal adenocarcinomas (PDAC) and up to 40% of low-grade serous ovarian cancers (LGSOC), making KRAS a long-standing therapeutic target. We previously showed that DIRAS3 binds RAS, forming heterodimers that disrupt RAS clustering and downstream MAPK signaling. Building on this, we developed conformationally constrained DIRAS3-derived peptides using two cyclization strategies and characterized them by NMR and biolayer interferometry. These cyclic peptides attenuate the interaction between KRAS and the BRAF RAS-binding domain, penetrate cells efficiently, and inhibit KRAS nanoclustering on the inner leaflet of the plasma membrane. Functionally, they reduce cell viability and suppress PDAC …

Deletion Of Fibro-Adipogenic Progenitors-Specific Follistatin Impairs Muscle Function And Accelerates Skeletal Muscle Atrophy In Obese Mice, Muhammad Rahil Aslam, Muhammad Bilal, Allah Nawaz, Tomonobu Kado, Shinya Abe, Nguyen Quynh Phuong, Memoona, Sana Khalid, Le Duc Anh, Ayumi Nishimura, Yoshiyuki Watanabe, Yoshiko Igarashi, Naeem Iqbal, Maki Yokoyama, Yasuhiro Onogi, Kennichi Hirabayashi, Hiroyuki Miwa, Takumi Era, Martin M Matzuk, Seiji Yamamoto, Koichi Ikuta, Isao Usui, Kohta Kobayashi, Toshihiko Satake, Masaru Kato, Shiho Fujisaka, Kazuyuki Tobe

Faculty, Staff and Students Publications

Background: Follistatin is a potent regulator of various TGF-β superfamily members, including myostatin (MSTN) and activin A. Previous studies have shown that follistatin is crucial in enhancing myogenesis during acute muscle injury. The mechanism by which fibro-adipogenic progenitors (FAPs)-specific follistatin influences muscle homeostasis in obese mice remains unknown. Therefore, we investigated the physiological role of follistatin in PDGFRα-positive FAPs in the regulation of muscle homeostasis and exercise in obese mice.

Methods: A PDGFRα-specific follistatin knockout (follistatin KO) mouse model was generated using PDGFRα-GFP-CreERT2 (PDGFRα-GCE) and follistatinflox/flox mice. These mice were fed a 60% high-fat diet (HFD) for 20 weeks, followed …

The Effect Of Uterine Entry Technique On Chorioamniotic Membrane Separation In Fetoscopic Laser Photocoagulation For Twin-To-Twin Transfusion Syndrome: Protocol For A Randomized Controlled Trial, Brian A Burnett, Jessian L Munoz, Rebecca M Johnson, Christian M Parobek, Luis E Delgadillo Chabolla, Cara Buskmiller, Roopali V Donepudi, Magdalena Sanz Cortes, Michael A Belfort, Ahmed A Nassr

Faculty, Staff and Students Publications

Background: Chorioamniotic membrane separation (CAS) is a recognized complication of fetoscopic laser photocoagulation (FLP) for twin-to-twin transfusion syndrome (TTTS), associated with increased risks of preterm prelabor rupture of membranes (PPROM) and preterm birth (PTB). Although CAS is well described, its incidence and relationship to specific surgical techniques, particularly the method of uterine entry, are not well defined in the published literature. No randomized trials have evaluated whether entry technique influences the risk of CAS.

Methods: We present the protocol for a randomized controlled trial comparing sharp-trocar and Seldinger uterine entry techniques for FLP in TTTS diagnosed between 16 + 0 …

Identifying Compounds To Treat Opiate Use Disorder By Leveraging Multi-Omic Data Integration And Multiple Drug Repurposing Databases, Jeran K Stratford, Megan Ulmer Carnes, Caryn Willis, Melyssa S Minto, Logain Elnimeiry, Ravi Mathur, Matthew Schu, Bryan C Quach, Javan Carter, Tracy Nolen, Nathan Vandergrift, Thomas R Kosten, Eric Otto Johnson, Bradley T Webb

Faculty, Staff and Students Publications

Genes influencing opioid use disorder (OUD) biology have been identified via genome-wide association studies (GWAS), gene expression, and network analyses. These discoveries provide opportunities to identifying existing compounds targeting these genes for drug repurposing studies. However, systematically integrating discovery results and identifying relevant available pharmacotherapies for OUD repurposing studies is challenging. To address this, we've constructed a framework that uses existing results and drug databases to identify candidate pharmacotherapies. For this study, two independent OUD related meta-analyses were used including a GWAS and a differential gene expression (DGE) study of post-mortem human brain. Protein-Protein Interaction (PPI) sub-networks enriched for GWAS …