Digital Commons Network^™

Fronto-Cerebellar Features Associate With Cognitive Dysfunction In Childhood-Onset Systemic Lupus Erythematosus, Hanne Van Der Heijden, Gabrielle Alonzi, Amanda Cao, Raquel Van Gool, Merve Koç Yekedüz, Lise Vrolix, Itamar Ronen, Vanessa Rameh, Kyle Mcbrearty, Aditi Deokar, Robert P Sundel, Eyal Muscal, Joseph Gonzalez-Heydrich, Andrea Knight, Joyce C Chang, Jaymin Upadhyay

Faculty, Staff and Students Publications

Objective: Cognitive dysfunction (CD) is a prevalent symptom in childhood-onset systemic lupus erythematosus (cSLE). This study aimed to investigate the neurobehavioral basis of CD in cSLE.

Methods: Patients with cSLE (N=20) and age- and sex-matched healthy controls (HCs, N=20) completed questionnaires and multiple neurocognitive tests. The Systemic Lupus Erythematosus Disease Activity Index 2000 and laboratory markers were used to monitor patients' clinical status. Neuroimaging assessments included functional near-infrared spectroscopy (fNIRS), functional magnetic resonance imaging (fMRI), and structural MRI.

Results: cSLE patients demonstrated moderate disease activity with high inflammation and immune dysregulation, alongside low medication adherence. Relative to HCs, cSLE patients …

The Impact Of Estrogen Replacement During Perimenopause On Lung Function And Airway Inflammation In The Vcd Mouse Model, William P Pederson, Laurie Michelle Ellerman, Riley D Hellinger, Joselyn Joanna Rojas Quintero, Francesca Polverino, John P Konhilas, Julie G Ledford

Faculty, Staff and Students Publications

Background:

Menopause associated asthma impacts a subset of women and is less responsive to current treatments. Mechanisms driving this late onset asthma are unknown. We recently developed a mouse model of menopause associated asthma using a combination of 4-Vinylcyclohexene Diepoxide (VCD) and House Dust Mite (HDM) exposures. The goal of this study was to determine how hormone replacement therapy during perimenopause impacts lung function and inflammation.

Methods:

The experimental groups included menopausal mice (VCD) with and without exposure to HDM (to model allergic airways disease) and menopausal mice with and without hormone replacement therapy (HRT; via estrogen pellet implantation). Lung …

Black Equality In Ocd Neurogenomics (Belong): Study Protocol, Iasha J Williams, Dalia Y Marquez, Kara E Lopez-Lengowski, Malini Bommiasamy, Ogechi Cynthia Onyeka, Slayton J Underwood, Juliana E Avery, Jacob Gluckman, Thariana Pichardo, Rhea Chandler, Yulu Brown, Katie Mangen, Emma Grace Choplin, Black Equality In Ocd Neurogenomics (Belong) Study Team, Sonyia C Richardson, Joseph D Buxbaum, Eric A Storch, James J Crowley, Sidney H Hankerson, Dorothy E Grice

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) is a chronic, serious psychiatric disorder that affects 2%-3% of the population and is associated with high personal and societal costs. Genetic factors are estimated to explain roughly half the risk of developing OCD, and genomic studies are just beginning to identify common and rare genetic variants mediating this risk. A major goal of genomic studies is to yield insights into the etiology of OCD and identify molecular targets for the development of novel therapeutics. However, the overwhelming majority of subjects in existing genetic studies are of European ancestry, limiting the generalizability of these findings. To address …

The International Pediatric Headache Didactic Series: A Novel Curriculum Innovation, Sara Pavitt, Sruthi Ilangovan, Zoë Allen, Samantha L Irwin, Irene Patniyot

Faculty, Staff and Students Publications

Objectives: The International Pediatric Headache Didactic Series (IPHDS) was developed to provide free, comprehensive pediatric headache education to healthcare professionals worldwide. The objective of this study was to describe the design, implementation, and impact of this prospective educational intervention.

Background: Headache is the most common neurological symptom within the pediatric population. Yet, only nine fellowships are offered in pediatric headache medicine. Limitations in access to education and training are often cited as reasons for diagnostic and management barriers. To address this gap, the IPHDS was established in July 2022.

Methods: IPHDS is a recurring series consisting of 23 biweekly lectures. …

Results Of A Randomized, Double-Masked, Placebo-Controlled Phase 1/2 Study Of A Trpv1 Antagonist Sjp-0132 In Participants With Dry Eye Disease, Tomoyuki Wada, Kazunori Omatsu, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Purpose: To investigate the safety, tolerability, pharmacokinetic profile, and efficacy of SJP-0132 in participants with dry eye disease (DED).

Design: Phase 1/2, randomized, double-masked, single-center, placebo-controlled single and multiple ascending dose study.

Participants: Generally healthy adults aged ≥18 years with a patient-reported history of DED for ≥6 months, eye dryness visual analog scale (VAS: 0-100) ≥40 mm, 5-item dry eye questionnaire (DEQ-5) ≥6, and central corneal fluorescein staining (CFS) of 2 to 4 (Baylor scale: 0-5 for each of five zones).

Methods: This study consisted of Part A and Part B, containing four single- and two multiple-ascending dose cohorts, respectively. …

Utility Of Diagnostic Arthroscopy Before Medial Patellofemoral Ligament Reconstruction In Pediatric And Adolescent Patients Without Articular Findings On Magnetic Resonance Imaging, Holden Archer, Kaleb Patterson, Jonathan D Schwartzman, Scott D Mckay, Indranil Kushare

Faculty, Staff and Students Publications

BACKGROUND: Medial patellofemoral ligament (MPFL) reconstruction is frequently used to manage recurrent patellar instability. Diagnostic arthroscopy is commonly performed before MPFL reconstruction to identify, confirm, and address intra-articular pathology. However, when preoperative magnetic resonance imaging (MRI) does not demonstrate intra-articular lesions, it is unclear how often diagnostic arthroscopy in pediatric patients alters surgical management.

PURPOSE: To determine the utility of diagnostic arthroscopy in young patients undergoing MPFL reconstruction who had no intra-articular chondral or osteochondral pathology, meniscal tears, or loose bodies identified on preoperative MRI, and to characterize intra-articular pathology detected on arthroscopy but not identified on MRI.

STUDY DESIGN: …

Variability In The Orthopaedic Residency Trainee Trauma Surgical Experience, Todd Phillips, Benjamin Fiedler, Joshua T Morrow, Zbigniew Gugala, Melvyn Harrington, Douglas R Dirschl

Faculty, Staff and Students Publications

Background: The aim of this study was to analyze fracture fixation case logs from residents training at a level 1 trauma center to assess variability across residents' surgical experiences within a single residency program. The authors hypothesize that notable variability exists between residents' surgical experiences in fracture care.

Methods: A retrospective case series was conducted at a single, urban residency program with a level 1 trauma center. Completed case logs were collected from program graduates from 2022 to 2024. All surgical cases involving fracture fixation at the level 1 trauma center were included for analysis. The anatomic region of the …

Feasibility Of A Large Language Model Chatbot To Support Parental Understanding In The Picu, R Brandon Hunter, Satid Thammasitboon, Sreya Rahman, Sriya Kakarla, Pamela Petersen, Shelley Kumar, Thomas Rappold, Sanjiv Mehta

Faculty, Staff and Students Publications

Objectives: To evaluate the feasibility of a large language model (LLM)-based chatbot for answering parental questions in the PICU and inform design of a randomized controlled trial (RCT).

Design: Prospective single-arm feasibility study conducted from August 2024 to December 2024.

Setting: Quaternary PICU.

Subjects: Fourteen parents of children admitted to the PICU.

Interventions: Parents engaged in 10-minute sessions with a HIPAA-compliant GPT-4o- (Generative Pretrained Transformer 4o, OpenAI, San Francisco, CA) based chatbot prompted with patient-specific electronic health record (EHR) data.

Measurements and main results: Feasibility was assessed through four criteria: parental engagement and satisfaction, provider perceptions, accuracy and safety, and …

Identifying The Strongest Novel Gene-Respiratory Disease Interactions For Rheumatoid Arthritis Risk, Vanessa L Kronzer, Rebecca T Brooks, Anne K Shurtz, Xiaosong Wang, Elizabeth J Atkinson, John M Davis, Jeffrey A Sparks, James R Cerhan, Elena K Joerns, Robert Vassallo, Cynthia S Crowson

Faculty, Staff and Students Publications

Objective: We aimed to identify the strongest individual gene-respiratory interactions for rheumatoid arthritis (RA) risk.

Methods: This case-control study used the Mayo Clinic (MC) and Mass General Brigham (MGB) biobanks for discovery and validation, respectively. We matched criteria-confirmed incident RA cases to four non-RA controls on age, sex, and duration electronic health record (EHR) history. Genetic exposures included known RA risk alleles. We identified respiratory diseases by codes and defined "respiratory burden" as the total number of respiratory codes divided by EHR duration before index date of RA. Using logistic regression models adjusting for potential confounders, we estimated odds ratios …

Methodological Progress Note: Logic Models, Molly J Horstman, Kyler M Godwin

Faculty and Staff Publications

Logic models are an accessible tool to organize the planning, management, and evaluation of programs across healthcare disciplines. This methodological progress note describes the five standard components of a logic model (Inputs, Activities, Outputs, Outcomes, and Impact) and provides guidance for developing a logic model. Logic models offer a visual representation of the work and theory of a program and should be created with input from all interested parties. Logic models are living tools that need to be revised as programs evolve and new information becomes available.

Breast Cancer-Derived Extracellular Vesicle Mir-425-5p (Mir-425) Promotes Brain Metastasis Via Activating Astrocytes Through The Novel Mir-425-Znf24-Ccl8 Signaling Axis, Grace L Wong, Munazza S Khan, Sara Manore, Shivani Bindal, Ravi Singh, Hui-Wen Lo

Faculty, Staff and Student Publications

Mechanisms underlying breast cancer brain metastasis (BCBM) are still not well understood. Here, we identified that BCBM patient serum contained extracellular vesicles (EVs) with high levels of microRNAs (miRNAs)-107 and -425. Levels of miR-107 and miR-425 were elevated in brain metastases, and the elevation was associated with poor patient prognoses. Ectopic expression of miR-107 and miR-425 promoted mammospheres; however, the inhibition of miR-425, but not miR-107, suppressed breast cancer mammosphere formation. We further observed that EVs from miR-425-overexpressing breast cancer cells strongly activated astrocytes whereas their inhibitors abrogated the effect. Conditioned media from miR-425-activated astrocytes promoted mammospheres. To elucidate how …

High-Power Dual-Channel Chamber For High-Frequency Magnetic Neuromodulation, Xiaoyang Tian, Hui Wang, Boshuo Wang, Jinshui Zhang, Dong Yan, Jeannette Ingabire, Samantha Coffler, Guillaume Duret, Quoc-Khanh Pham, Gang Bao, Junzhe Wang, Ashok Veeraraghavan, Jacob T Robinson, Stefan M Goetz, Angel V Peterchev

Faculty, Staff and Students Publications

Objective. Several novel methods, including magnetogenetics and magnetoelectric stimulation, use high frequency alternating magnetic fields to precisely manipulate neural activity. To quantify the behavioral effects of such interventions in a freely moving mouse, we developed a dual-channel magnetic chamber, specifically designed for rate-sensitive magnetothermal-genetic stimulation, and adaptable for other uses of alternating magnetic fields.

Approach. Through an optimized coil design, the system allows independent control of two spatially orthogonal uniform magnetic fields delivered at different frequencies within a 10 × 10 × 6 cm3 chamber suitable for mouse studies. The two channels have nominal frequencies of 50 and 550 kHz …

Oral Pcsk9 Inhibitor Enlicitide Versus Oral Nonstatin Therapies: A Phase 3 Randomized Clinical Trial, Alberico L Catapano, Elina Mikhailova, Ann Marie Navar, Puja Banka, Pablo Corral, Manish Saxena, P Gabriel Steg, Subodh Verma, Andrew Yacoub Kordahi, Geraldine Mendizabal, Pengfei Zhu, Christie M Ballantyne, Coralreef Addon Investigators

Faculty, Staff and Students Publications

Background: Many adults fail to achieve guideline-directed low-density lipoprotein cholesterol (LDL-C) goals on statin monotherapy, requiring additional nonstatin lipid-lowering medication. Enlicitide, an oral proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor, lowered LDL-C by 60% compared with placebo; its efficacy compared with other oral nonstatin therapies has yet to be examined.

Objectives: This study assessed the efficacy of enlicitide, a novel oral PCSK9 inhibitor, vs other oral nonstatin therapies.

Methods: In this phase 3, randomized, double-blind, active-comparator trial, statin-treated adults aged ≥18 years with LDL-C ≥55 mg/dL and a previous major atherosclerotic cardiovascular disease (ASCVD) event, or LDL-C ≥70 mg/dL if at …

Response To Letter: Assessment Of Postoperative Range Of Motion In Pediatric Patients Undergoing Surgical Reduction And Fixation Of Lateral Condyle Fractures, Gabrielle Rogie, Timothy Borden, Lindsay Crawford, Surya Mundluru, Brennan Roper, Rohini Mahajan Vanodia, Shiraz Younas

Faculty, Staff and Student Publications

No abstract provided.

Letter To The Editor: Evidence For A Two-Step Species-Level Pulmonary Nocardiosis Diagnostic Approach, John Halphen, Mohadese Ahmadzade, Babith Mankidy, Ashkan Berenji, Mohammad Ghasemi-Rad

Faculty, Staff and Students Publications

Pulmonary nocardiosis, a rare and diagnostically challenging infection, usually presents with heterogeneous radiographic findings, compounded by the low sensitivity of traditional confirmatory cultures. In their most recent work, Wang et al analyzed 102 patients with pulmonary nocardiosis to address these concerns, investigating species-characteristic imaging patterns, pathological associations, and the role of metagenomic next-generation sequencing (mNGS) in the diagnostic approach. High-resolution computed tomography (CT) in adult patients with pulmonary infections caused by Nocardia wallacei was demonstrated to have a sensitive (85.71%) and specific (83.34%) presentation of bronchopneumonia in relation to the five Nocardia species in the sample with CT data. The …

Influenza Infection Has Higher Risk Of Postoperative Complications Than Covid-19 In Shoulder Arthroplasty Patients, Jad J Lawand, Umar Ghilzai, Caleb Witsken, Dion Birhiray, Abdullah Ghali, Youssef M Khalafallah, Rohan G Reddy, Sameer R Khawaja, Adil Shahzad Ahmed

Faculty, Staff and Students Publications

INTRODUCTION: The COVID-19 pandemic has captured the attention of healthcare systems worldwide, and testing remains a mainstay of preoperative testing before all surgical procedures, including shoulder arthroplasty. Other viral illnesses, specifically influenza, while still having severe complications, are either overshadowed by testing for COVID-19 or not tested at all.

METHODS: A multi-institutional cohort study using the TriNetX network examined patients undergoing total or hemi shoulder arthroplasty from January 2020 to March 2024. Matched cohorts were created: one with influenza and one with COVID-19 infection, 14 days before surgery.

RESULTS: A total of 3233 and 18,209 patients were included in the …

Mendeley: Cite Smarter Not Harder, Jennifer Stockton

Library Class: Lunch & Learn

Tired of manually formatting bibliographies and struggling to keep your research organized? This class introduces you to Mendeley, the free, powerful reference manager that will revolutionize how you handle citations. Learn how to quickly capture and organize references, generate bibliographies in various citation styles (e.g., APA, MLA, Chicago), and deduplicate your results. Join us to save time, reduce errors, and focus on your research, not your formatting!

Associations Between Caregiver-Provider Communication Quality And Unmet Care Needs Among Older Adults, Jiaming Liang, Rafael Samper-Ternent, Brian Downer, Zhigang Xie

Faculty, Staff and Student Publications

BACKGROUND: Unmet care needs (lack of assistance with daily activities) among older adults are common and linked to adverse health outcomes, greater healthcare utilization, and caregiver burden. While effective patient-provider communication is known to improve care quality, less is understood about the role of caregiver-provider communication, particularly across sociodemographic, health, and caregiving contexts. METHODS: We conducted a cross-sectional secondary analysis of pooled 2021–2023 National Health and Aging Trends Study (NHATS) and National Study of Caregiving (NSOC) data, restricted to community-dwelling older adults (65 + years) who received assistance from caregivers due to difficulty with daily activities, and had at least …

Functional And Structural Basis Of A Hypermorphic Trpc3 Variant, Briar Bell, Angela M Jaramillo-Granada, Luis O Romero, Irene A Gutierrez, Venkata K P S Mallampalli, Guizhen Fan, Sameer Varma, Matthew L Baker, Irina I Serysheva, Valeria Vásquez, Julio F Cordero-Morales

Faculty, Staff and Student Publications

Cerebellar ataxias are characterized by impaired motor coordination resulting from neuronal dysfunction within the cerebellum. The mechanisms underlying this pathology and its cerebellar-specific neurodegeneration remain unknown. We uncover how a gain-of-function canonical transient receptor potential member 3 (TRPC3) mutation, coupled with a cerebellum-specific isoform, stabilizes the channel’s open state, resists the leading inhibitor Pyr3, and drives calcium-dependent cell death. Restoring calcium homeostasis by expressing a Purkinje cell calcium pump improves cell viability. Transgenic expression of the TRPC3 hypermorphic variant in Caenorhabditis elegans induces neurodegeneration, confirming its pathogenicity across species. Cryo–electron microscopy and molecular simulations reveal the structural basis for the …

Deprescribing Following Access To Lifestyle Treatment: A Retrospective Chart Review Of Primary Care Outcomes In Patients With Type 2 Diabetes, Yoav Jacob, Kara L Staffier, Samveda Menon, Puja B Gandhi, Joeita F Macfield, Gia Merlo, Stefanie M Meyer, Shivani S Patel, Caroline Rhéaume, Madeline Watson, David Donohue, Wayne S Dysinger, Micaela C Karlsen

Faculty, Staff and Student Publications

Background: Among individuals with type 2 diabetes (T2D), lifestyle improvements can restore glycemic control, yet few studies have examined deprescribing in settings where it was necessitated by improvements in health. This study aimed to (1) identify instances of medication deprescribing among adults with T2D in a primary care setting where patients had access to lifestyle medicine (LM), (2) document lifestyle changes among deprescribed patients, (3) assess changes in body mass index (BMI), glucose, and hemoglobin A1c (HbA1c) following deprescribing, and (4) assess the safety of deprescribing in the context of LM-informed care by identifying adverse events.

Methods: A …

3'Utr Mapping Reveals Alternative Polyadenylation In Right Ventricular Failure, Rahul Neupane, Kartiga Natarajan, Erik E Suarez, Henry J Pownall, Kai-Lieh Huang, Eric J Wagner, Ajay Kumar Verma, Rambabu Majji, Hari Krishna Yalamanchili, Ashrith Guha, Rajarajan A Thandavarayan

Children’s Nutrition Research Center Staff Publications

No abstract provided.

The Development Of A Framework To Classify Medication Deprescribing Among Patients With Type 2 Diabetes In Primary Care Practices, Puja B Gandhi, Yoav Jacob, Joeita F Macfield, Gia Merlo, Stefanie M Meyer, Shivani S Patel, Caroline Rhéaume, Kara L Staffier, Madeline Watson, Micaela C Karlsen

Faculty, Staff and Student Publications

No abstract provided.

Nerandomilast In Progressive Pulmonary Fibrosis: Data From The Whole Follow-Up Period Of The Fibroneer-Ild Trial, Marlies S Wijsenbeek, Shervin Assassi, Arata Azuma, Vincent Cottin, Anna-Maria Hoffmann-Vold, Toby M Maher, Fernando J Martinez, Justin M Oldham, Luca Richeldi, Claudia Valenzuela, Hui Gu, Ivana Ritter, Susanne Stowasser, Michael Kreuter

Faculty, Staff and Student Publications

Background: In the FIBRONEER-ILD trial in patients with progressive pulmonary fibrosis (PPF), nerandomilast 9 mg bid and 18 mg bid reduced the decline in forced vital capacity at week 52 compared with placebo (the primary endpoint). We assessed the effects of nerandomilast up to the final database lock.

Methods: Time to first acute exacerbation of ILD, hospitalisation for respiratory cause, or death (key secondary endpoint) and other time-to-event endpoints were assessed.

Results: 1176 patients, of whom 512 were taking background nintedanib, received nerandomilast or placebo. At final database lock, mean (sd) exposure to trial medication was 15.1 (5.7) months and …

Monitoring Relapse In Post-Transplant Acute Myeloid Leukemia Requires Integrated Assessment, With Flow Cytometry Showing The Highest Efficacy, Wei J Wang, Sa A Wang, Hong Fang, Qing Wei, Shimin Hu, Sanam Loghavi, Gheath Al-Atrash, Chenxuan Zang, Peng Wei, Jeffrey L Medeiros, Wei Wang

Faculty, Staff and Student Publications

No abstract provided.

Patiromer For Patients With Heart Failure At Risk Of Hyperkalemia: Care-Hk In Hf Registry, Omar Cantu-Martinez, Stephen J Greene, Khaja M Chinnakondepalli, Stefan D Anker, Biykem Bozkurt, Javed Butler, John G Cleland, Nihar Desai, Diederick E Grobbee, Ellie Kelepouris, Giuseppe Rosano, Tibor Kempf, Martin Schulz, Carla-Maria Brandes, Victoria Donachie, Andrew J Sauer

Faculty, Staff and Students Publications

Background: For patients with heart failure (HF), hyperkalemia (HK) may prevent optimal renin-angiotensin system inhibitor (RASi) use. Randomized trials show that patiromer, a contemporary potassium binder, reduces serum potassium (sK+) concentrations and HK, potentially enabling RASi optimization. We sought to assess the real-world effectiveness of patiromer in facilitating RASi optimization in HF patients at increased risk of HK.

Methods and results: The CARE-HK in HF (Cardiovascular and Renal Treatment in HF Patients with HK or at High Risk of HK) (NCT04864795) was a prospective registry of patients with chronic HF at increased risk of HK (prior or current …

Residual Risk Of Hyperkalemia Among Patients With Heart Failure Treated With Both Sglt2i And Arni, Stephen J Greene, Shachi Patel, Khaja Chinnakondepalli, Stefan D Anker, Michael Böhm, Biykem Bozkurt, Javed Butler, John Gf Cleland, Andrew J Coats, Nihar Desai, Victoria Donachie, Ellie Kelepouris, Giuseppe Rosano, Carla-Maria Brandes, Andrew J Sauer

Faculty, Staff and Students Publications

No abstract provided.

Incidence Of Autoimmune Diseases In Children With Atopy Treated With Dupilumab, Stanislaw J Gabryszewski, Kathryn Hirabayashi, Morgan Botdorf, Mitchell Maltenfort, Christopher B Forrest, Theresa W Guilbert, Madeline Schutt, Hiroki Morizono, Gerardo Vazquez Garcia, Anna Cristina Garza-Mayers, Joseph Demetrius Hernandez, Sara Anvari, Suchitra Rao, Jonathan M Spergel

Faculty, Staff and Students Publications

Background: The type 2 inflammation-blocking agent dupilumab has gained traction as an effective treatment of multiple atopic diseases. New-onset autoimmune manifestations have been infrequently reported in dupilumab-treated atopic patients, primarily among adults. Autoimmune outcomes in atopic children on dupilumab are less clear.

Objective: We aimed to determine if dupilumab treatment of atopic children is associated with increased autoimmune or autoinflammatory disease diagnosis risk.

Methods: Using a multi-institutional electronic health record database composed of 10 PEDSnet academic health systems, we performed a retrospective cohort study of children aged 6-17 with atopy (ie, moderate-to-severe atopic dermatitis and/or persistent asthma, as defined by …

Genome-Wide Crispr Screen Identifies A Cytokine-Enhancer Circuit Driving Hif-2Α Activation In Renal Cancer, Jun Fang, Jeremy M Simon, Tao Wang, Yunpeng Gao, Xianju Bi, Lianxin Hu, Chengheng Liao, Cheng Zhang, Yayoi Adachi, Jin Zhou, Hongyi Liu, Qian Liang, James A Nathan, Ram Mani, James Brugarolas, Qing Zhang

Faculty, Staff and Student Publications

Resistance to HIF-2α inhibitors such as Belzutifan underscores the need to better understand how HIF-2α is transcriptionally regulated in clear cell renal cell carcinoma (ccRCC). Here, we uncover a cytokine-driven enhancer mechanism that sustains HIF-2α expression through the JAK1-STAT3 signaling pathway. Using a genome-wide CRISPR screen in VHL-deficient ccRCC cells, we identified SOCS3 as a key negative regulator of HIF-2α. Mechanistically, loss of SOCS3 activates JAK1-STAT3 signaling, leading to the recruitment of STAT3 to distal enhancers upstream of EPAS1 that physically loop to its promoter to drive HIF-2α transcription. This cytokine-enhancer circuit was recapitulated in ccRCC patient samples and functionally …

Tulane Virus Protease As A Structural Surrogate For Inhibitor Screening Of Human Norovirus Proteases, Son Pham, Nikhil Sharma, Banumathi Sankaran, Jalen Nguyen, Mary K Estes, Joseph M Hyser, B V Venkataram Prasad

Faculty, Staff and Students Publications

Human norovirus (HuNoV) is a significant cause of gastroenteritis worldwide, affecting people of all age groups. There are currently no vaccines or drugs available, leaving susceptible populations vulnerable to severe or protracted illness. A HuNoV cultivation system is pivotal for screening norovirus antivirals. While the human intestinal enteroid cultivation system allows robust replication of multiple HuNoV strains, it presents technical and cost barriers. Tulane virus (TV), a surrogate for HuNoV, replicates well in monkey kidney cell lines and is closely related to norovirus in cellular biology. Here, we determined the structures of TV protease (TV-Pro) alone and in complex with …

Γδ T Cells At The Interface Of Innate And Adaptive Immunity In Cancer, Arnau Solé Casaramona, Martin F Bachmann, Eva Sevick-Muraca, Mona O Mohsen

The Brown Foundation: Institute of Molecular Medicine

γδ T cells are unconventional lymphocytes that bridge innate and adaptive immunity by combining recognition of stress-induced ligands independently of classical major histocompatibility complex molecules with the capacity to undergo clonal expansion and long-term adaptation. Their unusual ability to detect malignant transformation using semi-invariant T-cell receptors, butyrophilin recognition and natural killer-like receptors positions them as powerful effector cells in tumors that evade classical immune escape mechanisms. Furthermore, distinct γδ subsets have distinct phenotyping and specific tissue-residencies, which could be leveraged to modulate immunological responses. We evaluate engineered therapies and different experimental platforms for studying γδ T cell biology. We conclude …