Digital Commons Network^™

Laser Interstitial Thermal Therapy And Adjuvant Pembrolizumab In Recurrent High-Grade Astrocytoma: A Phase 1/Randomized Phase 2b Trial, Jian L Campian, Omar H Butt, Yifei Xu, Jingxia Liu, William A Leidig, Tanner Johanns, George Ansstas, Alice Y Zhou, Sangami Pugazenthi, Jiayi Huang, Milan G Chheda, Albert H Kim, Eric C Leuthardt, Et Al.

2020-Current year OA Pubs

Immune checkpoint inhibitors (ICIs) show minimal efficacy in recurrent high-grade astrocytoma (rHGA). Laser interstitial thermal therapy (LITT), a minimally invasive cytoreductive approach, may prime rHGA for ICI response. A phase 1/randomized phase 2b trial (ClinicalTrials.gov: NCT02311582 ) was designed to test pembrolizumab in combination with LITT in patients with rHGA. Nine patients were enrolled in the phase I dose-escalation lead-in study. No dose-limiting toxicities were observed and 200 mg of pembrolizumab every three weeks was determined as the recommended phase 2 dose. The phase 2b study was initially designed to randomize (up to 45) patients 1:1 to either LITT followed …

Supporting Evidence-Based Responses To Emotional Needs In Emphysema (Serene): Protocol For A Randomized, Open-Label Mechanistic Trial Comparing Coping Skills Training And Disease-Specific Education For Depressive Symptoms Conducted In United States Health Systems, Joanna L. Hart, Daniel Carter, Chloe Hinton, James Grilli, Lily A. Brown, Nora Brier, Yingying Lu, Casey Whitman, Michael O. Harhay, Michael Sims, Carmen Alvarez, Lisa R. Miller-Matero, C. Virginia O'Hayer

Department of Psychiatry and Human Behavior Faculty Papers

BACKGROUND: Depressive symptoms and anxiety are highly prevalent among people with chronic obstructive pulmonary disease (COPD), strongly associated with poor outcomes, and rarely recognized or treated. Integrating families into interventions may amplify supportive care treatment effects and overcome common challenges, yet this strategy is understudied. The Supporting Evidence-based Responses to Emotional Needs in Emphysema (SERENE) trial's main objective is to identify the mechanisms through which a family-partnered Coping Skills Training (CST) reduces depressive symptoms among patients with COPD, testing five putative mechanisms: family relationship quality, patient and caregiver self-efficacy, patient loneliness, and caregiver psychological distress.

METHODS: SERENE will enroll 375 …

The Path Forward For T Cell Engagers In Patients With Prostate Cancer, Sumit K. Subudhi, Bilal A. Siddiqui, Kevin K. Zarrabi, William K. Kelly, Charles G. Drake

Department of Medical Oncology Faculty Papers

T cell engagers (TCEs) recruit T cells to the tumor microenvironment (TME) to induce antitumor immune responses. TCEs have demonstrated promising clinical responses in patients with metastatic castration-resistant prostate cancer and have advanced into phase 3 clinical trials. Here we provide an overview of the mechanisms of action of TCEs, including both CD3-targeted and CD28-targeted agents, and review the clinical development of these agents for prostate cancer. We propose a path forward for TCEs in prostate cancer, in which innovative clinical trials will facilitate a biological understanding of mechanisms of efficacy and toxicity to inform: (1) development of predictive biomarkers …

Increasing Ketamine Administration In Children's Hospitals For Youth With Sickle Cell Disease., Ashley M. Jenkins, Erin Hendry, Alexandra Power-Hays, Marin Valentino, Matthew Hall, Kathyrn Kyler, James W. Antoon, Sonya Tang Girdwood, Jennifer Goldman, Armand N. Morel, Timothy J. Savage, Lucas E. Orth, Natasha M. Archer

Manuscripts, Articles, Book Chapters and Other Papers

Ketamine is recommended as an opioid-sparing adjunct for sickle cell disease (SCD)-related pain management. Little is known regarding its use in hospitalized youth with SCD. We aimed to describe trends in ketamine administration and examine associations between ketamine administration and outcomes in hospitalized youth with SCD. We conducted a cross-sectional, multicenter study examining hospital admissions for youth with SCD from 44 children's hospitals in the United States from 2016 to 2023. Youth aged ≥6 months with SCD were identified using International Classification of Diseases tenth revision codes. Exposures included age, sex, race, payor, childhood opportunity index, hydroxyurea administration, and concomitant …

Regional Brain Age Is Decreased In Children With Sickle Cell Anemia, Amy E Mirro, Landon C Power, Jinli Wang, Paula Germino-Watnick, Heather Roberts, Yonca Cam, Kristin P Guilliams, Slim Fellah, Yasheng Chen, Hongyu An, Jin-Moo Lee, Andria L Ford, Melanie E Fields

2020-Current year OA Pubs

DeepBrainNet, a machine learning tool, uses magnetic resonance imaging (MRI) to predict an individual's brain age, allowing calculation of the brain age gap (predicted chronological age) for use as a biomarker of brain health. We tested the DeepBrainNet tool in sickle cell anemia (SCA) on 210 brain MRIs from 130 children (90 with SCA; 40 healthy controls) to investigate the hypothesis that children with SCA would have a younger predicted brain age than healthy controls as an index of aberrant brain development. DeepBrainNet estimates brain age from 80 axial slices of each brain, with the median used as global brain …

Benefit Of Rituximab Maintenance After First-Line Bendamustine-Rituximab In Patients With Mantle Cell Lymphoma, Yucai Wang, Imran A Nizamuddin, Brad S Kahl, Et Al.

2020-Current year OA Pubs

The benefit of rituximab maintenance after first-line (1L) bendamustine-rituximab (BR) in patients with mantle cell lymphoma (MCL) remains uncertain, with inconsistent results from the phase 2 MAINTAIN trial and several retrospective studies. We conducted a large retrospective study at 27 US and Canadian academic centers to examine the benefit of rituximab maintenance after BR. A total of 911 patients received 1L BR between 2010 and 2020, and 703 had an objective response and no evidence of disease progression at the 3-month post-BR landmark. Among those, 394 (56%) received rituximab maintenance and 309 (44%) did not, with largely similar baseline patient …

Estimating The Baseline Age When Longitudinal Changes In Biomarkers Accelerate: Application To An Imaging Study Of Preclinical Alzheimer Disease, Chengjie Xiong, Folasade Agboola, Jingqin Luo

2020-Current year OA Pubs

BACKGROUND: Biomarkers are routinely measured from human biospecimens and imaging scans in Alzheimer disease (AD) research. Age is a well-known risk factor for AD. Detecting the baseline age at which the longitudinal change in biomarkers starts to accelerate is important to design preventive interventions. METHODS: We analyzed longitudinal biomarker data by a random intercept and random slope model where the slope (longitudinal rate of change) was modeled as a piecewise linear and continuous function of baseline age. We proposed to estimate the baseline age at the intersection of the two linear functions by multiple methods: maximum (profile) likelihood, minimum squared …

Dose-Dependent Ifn Programs In Myeloid Cells After Mrna And Adenovirus Covid-19 Vaccination., Giray N Eryilmaz, Yilmaz Yucehan Yazici, Radu Marches, Eleni P Mimitou, Lisa Kenyon-Pesce, Kim Handrejk, Sonia Jangra, Michael Schotsaert, Adolfo García-Sastre, George A Kuchel, Jacques Banchereau, Duygu Ucar

Faculty Research 2026

BACKGROUND. The SARS-CoV-2 pandemic provided a rare opportunity to study how human immune responses develop to a novel viral antigen delivered through different vaccine platforms. However, to date, no study has directly compared immune responses to all 3 FDA-approved COVID-19 vaccines at single-cell multiomic resolution.

METHODS. We longitudinally profiled SARS-CoV-2–naive adults (n = 31) vaccinated with BNT162b2, mRNA-1273, or Ad26.COV2.S, integrating plasma cytokines, antibody titers, and single-cell multiomic data (DOGMA-Seq).

RESULTS. We discovered a distinct, transient IFN program termed ISG-dim, which emerged specifically 1–2 days after the first mRNA dose in approximately 10% of myeloid cells. This state was …

Dose-Dependent Ifn Programs In Myeloid Cells After Mrna And Adenovirus Covid-19 Vaccination., Giray N Eryilmaz, Yilmaz Yucehan Yazici, Radu Marches, Eleni P Mimitou, Lisa Kenyon-Pesce, Kim Handrejk, Sonia Jangra, Michael Schotsaert, Adolfo García-Sastre, George A Kuchel, Jacques Banchereau, Duygu Ucar

Faculty Research 2026

BACKGROUNDThe SARS-CoV-2 pandemic provided a rare opportunity to study how human immune responses develop to a novel viral antigen delivered through different vaccine platforms. However, to date, no study has directly compared immune responses to all 3 FDA-approved COVID-19 vaccines at single-cell multiomic resolution.METHODSWe longitudinally profiled SARS-CoV-2-naive adults (n = 31) vaccinated with BNT162b2, mRNA-1273, or Ad26.COV2.S, integrating plasma cytokines, antibody titers, and single-cell multiomic data (DOGMA-Seq).RESULTSWe discovered a distinct, transient IFN program termed ISG-dim, which emerged specifically 1-2 days after the first mRNA dose in approximately 10% of myeloid cells. This state was characterized by ISGF3 complex activation and …

Supt16h-Associated Neurodevelopmental Disorder And Neurocristopathy: Genetic And Phenotypic Spectrum, Eunhye Lee, Seungmin Sim, Hee-Jung Choi, Eugene Y Liang, Carolyn Le, Roya Bina, Ryan Cohen, Elizabeth George, Soo Yeon Kim, Gifty Bhat, Erin Falsey, Richard Sidlow, Kristin Clinard, Shay Ben-Shachar, Eleina England, Beatriz Menendez, Isabella Herman, Shelly Nielsen, Jaya Punetha, Priya Bhola, J Austin Hamm, Megan A Keeney, Nike Sitzman, Sara Berger, Lakshmi Mehta, Alison J Conn, Lilian Downie, Myla Ashfaq, Hope Northrup, Ange-Line Bruel, Sylvie Odent, Justin O Szot, Noelia Nunez Martinez, Sunju Park, Julie Refkin, Jean-Marc Good, Fabienne Maurer, Cédric Le Caignec, David J Coman, Erin Anderson, Linda J Richards, Ryan J Dean, Caleb Yang, Chulwon Choi, Byung Joon Hwang, Jin Sook Lee, William B Dobyns, Murim Choi, Elliott H Sherr, Jong-Hee Chae, Yun Kee, Emanuela Argilli

Faculty, Staff and Student Publications

SUPT16H encodes a subunit of the FACT (FAcilitates Chromatin Transcription) complex, a histone chaperone essential for maintaining chromatin integrity during transcription, replication, and DNA repair. Pathogenic de novo SUPT16H missense variants have previously been linked to neurodevelopmental disorders in eight individuals. Here, we expand the genotypic and phenotypic spectrum by identifying 24 additional individuals harboring ultrarare heterozygous missense or truncating variants, who share overlapping clinical features including intellectual disability, autism spectrum disorder, hypotonia, and characteristic craniofacial dysmorphism. To elucidate the underlying mechanisms, we generated a supt16h knockout zebrafish model using CRISPR/Cas9. The supt16h loss-of-function (LOF) model recapitulated key patient phenotypes …

Stereotactic Adaptive Radiation Therapy For Borderline Resectable Or Locally Advanced Pancreatic Cancer To Minimize Gastrointestinal Toxicity (Artia-Pancreas): Protocol For A Single-Arm Prospective Trial, Lauren E Henke, Hyun Kim, Eric Laugeman, Steven Kohlmyer, Claire Mccann, Kate Pietrovito, Kenneth Russell, Jennifer Woo, Alex T Price

2020-Current year OA Pubs

BACKGROUND: Computed tomography (CT)-guided online stereotactic adaptive radiotherapy (CT-STAR) allows for ablative radiation doses to be delivered to selected patients with borderline resectable (BR) or locally advanced pancreatic cancer (LAPC) or unresectable pancreatic cancer. However, the use of CT-STAR to deliver an ablative dose to the pancreas while minimizing gastrointestinal (GI) side effects to reduce acute and late toxicity rates compared to historic controls has yet to be prospectively evaluated.

OBJECTIVE: The primary objective of this prospective, single-arm, multicenter phase 2 clinical trial (Adaptive Radiation Therapy Individualized Approach [ARTIA]-Pancreas) is to evaluate the rate of acute grade 3+ GI toxicity …

Economic Evaluation Of Perioperative Pembrolizumab Plus Standard Of Care As Treatment For Resectable Locally Advanced Head And Neck Squamous Cell Carcinoma In The United States, Feng Qian, Arielle G Bensimon, Anjela Tzontcheva, Kimberly Benjamin, Ravindra Uppaluri, Douglas Adkins, Geoffrey Johnson, Catherine Fernan, Dandan Zheng, Yuexin Tang, Biruk Chafamo, Dominic Muston

2020-Current year OA Pubs

AIMS: In the phase 3 KEYNOTE-689 trial (NCT03765918) among patients with resectable locally advanced head and neck squamous cell carcinoma (LA HNSCC), perioperative pembrolizumab (pembrolizumab before surgery, then continued with standard-of-care [SOC] radiotherapy +/- cisplatin after surgery followed by pembrolizumab alone) significantly prolonged event-free survival vs. SOC alone, both in the intention-to-treat population and PD-L1 combined positive score (CPS) ≥1 subgroup. Perioperative pembrolizumab + SOC received Food and Drug Administration approval in June 2025 for resectable LA HNSCC expressing PD-L1 (CPS ≥ 1). The present study evaluated the cost-effectiveness of perioperative pembrolizumab + SOC versus SOC in this indication, from …

Strain-Level Heterogeneity In Gardnerella Urinary Tract Persistence And Pathogenesis In An In Vivo Model Is Consistent With Comparative Phylogenomic Analyses, Lokesh Kumar, Sonia N Whang, Deborah K Verges, Robert F Potter, Nicole M Gilbert

2020-Current year OA Pubs

BACKGROUND: Gardnerella is a bacterial genera commonly present in the female urogenital tract, especially in bacterial vaginosis. Gardnerella are frequently detected in urine collected directly from the bladder and have been implicated in urinary incontinence and recurrent urinary tract infections. Understanding the contribution of Gardnerella to pathogenesis is complicated by its genetic heterogeneity and a shortage of data from in vivo models. One clinical isolate of Gardnerella triggered urothelial exfoliation and promoted urinary tract infection by uropathogenic E. coli in a mouse model. This study was designed to compare diverse Gardnerella strains in vivo to identify genomic variation associated with …

Nci9673 (Part B): Etctn Randomized Phase Ii Study Of Nivolumab With Or Without Ipilimumab In Refractory, Metastatic Squamous Cell Carcinoma Of The Anal Canal, Van K Morris, Kristen K Ciombor, Lianchun Xiao, Joshua K Ochieng, Enrica Marmonti, Blase Polite, Benjamin A Weinberg, John C Krauss, John Hays, Sarbajit Mukherjee, Olivia Aranha, Syma Iqbal, Tony Shields, Al B Benson, Syed Kazmi, Christopher Lieu, Howard Hochster, Jennifer Whisenant, Cara Haymaker, Cathy Eng

Faculty, Staff and Student Publications

Purpose: In the previously completed NCI9673 (part A) single-arm study, the antiprogrammed death (PD)-ligand-1 antibody nivolumab demonstrated efficacy for patients with metastatic anal cancer. In NCI9673 (Part B), we evaluated the anticytotoxic T-cell lymphocyte antigen-4 (CTLA-4) antibody ipilimumab in combination with nivolumab for patients with incurable anal cancer.

Methods: In this phase II NCI ETCTN trial, 100 patients with refractory, incurable anal cancer were randomly assigned to receive nivolumab (480 mg IV once every 4 weeks) alone or with ipilimumab (1 mg/kg IV once every 8 weeks). The primary end point was progression-free survival (PFS). Secondary endpoints included radiographic response, …

Genetic Modifiers Of Apoe-Ε4-Associated Cognitive Decline, Alex G Contreras, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease. However, APOE-ε4 is not deterministic, highlighting the need to identify additional genetic and environmental factors. APOE-ε4 has been linked to accelerated cognitive decline, so we sought to investigate genetic factors that modify APOE-ε4-associated cognitive decline. We conduct cross-ancestry APOE-ε4-stratified and interaction GWAS using harmonized cognitive data from 32,778 participants, including 29,354 non-Hispanic White and 3,424 non-Hispanic Black individuals. Our primary outcome is late-life cognition, measured using harmonized composite scores for memory, executive function, and language, modeled as continuous traits reflecting both normative cognitive aging and disease-related decline. …

The Neuroprotective Effects Of Alpha-Tocopherol As An Anti-Inflammatory Agent: Mechanistic Insights And Therapeutic Challenges, Megumi H Seese, Yuanzhong Xu

The Brown Foundation: Institute of Molecular Medicine

Vitamin E (alpha-tocopherol, αToc), an antioxidant fat-soluble vitamin that prevents lipid peroxidation and modulates pro-inflammatory cytokine production, is well-known to be critical for neuroprotection. However, the underlying mechanism remains poorly understood. Accumulating evidence demonstrates that αToc influences neuroinflammatory processes. Here, we review recent research progress on the effects of αToc on neuroinflammation. Preclinical studies included in this narrative review were identified through PubMed searches using the keywords "alpha-tocopherol AND neuroinflammation or alpha-tocopherol AND brain AND inflammation". While many studies support a neuroprotective role of αToc, the magnitude and direction of its effects vary substantially depending on dosage, route of administration, …

Cardiac Output-Guided Vs. Mean Arterial Pressure-Guided Hemodynamic Management In Craniotomy Patients With Cardiovascular Disease: A Randomized Trial, Na Chen, Minjing Yang, Renhua Li, Chunyan Ye, Lu Wang, Xingyang Liu, Jinghan Wu, Daniel I Sessler, E Wang

Faculty, Staff and Student Publications

We tested the primary hypothesis that cardiac output (CO)-guided versus mean arterial pressure (MAP)-guided hemodynamic management reduces the fraction of patients with 90-day Glasgow Outcome scores ≤ 4 (on a 1–5 scale, 5 better) after supratentorial brain tumor resections in adults with cardiovascular disease. 202 adults were randomized to intraoperative hemodynamic management guided by either CO or MAP. In patients assigned to CO guidance, clinicians targeted CO > 4 L/min and > 90% of baseline values using a combination of fluids and vasoactive agents. In patients assigned to MAP guidance, clinicians targeted MAP within ± 20% of baseline and ≥ 65 mmHg. …

Unbalanced Chromatin Binding Of Polycomb Complexes Drives Neurodevelopmental Disorders, Rodrigo L Borges, Gretter González-Blanco, Harikumar Arigela, Yingyu Huang, Lucas D Caeiro, Nikolai Fattakhov, Stefano Lepore, Liliana Garcia-Martinez, Matea Maurice, Pushti D Mehta, Emily J Park, Kailynn Macgillivray, Jevithen Nehru, Matthew Chau, Maria C Robayo, Clemer Abad, Alicia Bilbao-Martinez, Fabiola Monteiro, Xi Luo, Song Tan, Daniel Bilbao, Simone Sidoli, Bruno Di Stefano, Katherina Walz, Arneet L Saltzman, Ramiro E Verdun, Ramin Shiekhattar, Lluis Morey

Faculty, Staff and Students Publications

The prevalence of neurodevelopmental disorders (NDDs) in children is increasing, yet their underlying causes remain largely unknown. We identified heterozygous mutations in the Polycomb repressive complex 1 (PRC1) E3 ligases RING1 and RNF2 in individuals with NDDs and revealed distinct mechanisms by which they compromise PRC1 activity. We developed cellular and mouse models carrying the Ring1b

Neurophysiological Connectomic Signatures Of Consciousness During Propofol-Induced General Anesthesia, Yuqin Li, Xiaoxiao Chen, Hui Zheng, Senqi Li, Qingyu Teng, Chengyu Wang, Fali Li, Zhongcong Xie, Daniel Sessler, Zhe Zhang, Peng Xu, Ti-Fei Yuan, Tao Xu

Faculty, Staff and Student Publications

General anesthesia induces reversible changes in consciousness through cortical activity and connectivity alterations, yet the functional connectome dynamics underlying propofol-induced unconsciousness remains unclear. We analyze high-density 128-channel electroencephalogram (EEG) from 31 surgical patients using source localization to identify neurobiological connectome signatures of propofol anesthesia. Propofol anesthesia increases delta and theta functional connectivity and decreases alpha, beta, and gamma connectivity. A classification model and dynamic analysis of consciousness loss reveals that alpha-band connectivity between parietal, occipital, and subcortical regions is critical for sustaining consciousness, with its disruption marking a key transition to unconsciousness. EEG from 46 additional patients under mild sedation …

S6k1 Modulates Stat3 Activation To Promote Resistance To Radiotherapy In Lung Cancer, Ali Calderon-Aparicio, Noelle Francois, Tyler Grenda, Shan Xu, Olugbenga Okusanya, Jun He, Nicole L Simone

Department of Radiation Oncology Faculty Papers

Radiotherapy is a mainstay in the management of locally advanced lung cancer; however, intrinsic and acquired radioresistance contribute to poor prognosis. S6K1, a serine/threonine kinase, regulates cell growth, protein synthesis, and survival, and is increased in tumors, which is linked to enhanced survival under therapeutic stress, including radiation. The mechanisms, however, are not fully understood. This study investigates the role of S6K1 in lung cancer radioresistance and the mechanisms involved. Intrinsic radioresistance in lung cancer cells was associated with increased S6K1 activation. Pharmacologic inhibition or genetic deletion of S6K1 enhanced radiosensitivity both in vitro and in vivo, highlighting the therapeutic …

Expectant Management Vs Medication For Patent Ductus Arteriosus In Preterm Infants: The Pda Randomized Clinical Trial, Matthew M Laughon, Sonia M Thomas, Kristi L Watterberg, Kathleen A Kennedy, Martin Keszler, Namisavayam Ambalavanan, Alexis S Davis, Jonathan L Slaughter, Ronnie Guillet, Tarah T Colaizy, C Michael Cotten, Megan A Dhawan, Carl L Bose, Jennifer Talbert, Sarah Smucny, William E Benitz, Matthew A Rysavy, Robin K Ohls, Mariana C Baserga, Sara B Demauro, Mambarambath Jaleel, Wesley M Jackson, Waldemar A Carlo, Karen M Puopolo, Anna Maria Hibbs, Anup Katheria, Pablo J Sánchez, Carl T D'Angio, Ravi M Patel, Beth Ann Johnson, Valerie Y Chock, Abhay J Bhatt, Stephanie L Merhar, Ryan Moore, Abbot R Laptook, Sarvin Ghavam, Janell Fuller, Shilpa Vyas-Read, Stephen D Kicklighter, Baiba Steinbrekera, Kathryn Anderson, Praveen K Chandrasekharan, Myra H Wyckoff, Cassandra Montoya, Abhik Das, Barbara Do, Samantha Chang, Rosemary D Higgins, Michele C Walsh

Faculty, Staff and Student Publications

Importance: The management of patent ductus arteriosus (PDA) in preterm infants is controversial.

Objective: To determine whether expectant management compared with active treatment of a protocol-defined PDA in preterm infants decreases the incidence of death or bronchopulmonary dysplasia (BPD).

Design, setting, and participants: A randomized clinical trial including infants born at 22 to 28 weeks' gestation and diagnosed with a protocol-defined PDA between the age of 48 hours and 21 days at screening. The trial was conducted from December 2018 to December 2024 at 33 hospitals within the National Institute of Child Health and Human Development Neonatal Research Network. The …

Syndecan-1-Targeted Therapeutic Antibody Impairs Macropinocytosis And Elicits Antitumor Immunity In Pancreatic Cancer, Zecheng Yang, Madelaine S Theardy, Shuaitong Chen, Yongkun Wei, Mitsunobu Takeda, Yue Zeng, Xiaofei Wang, Jun Yao, Jennifer Li, Prapassorn Thirasastr, Jangho Park, Yangxi Zheng, Long T Vien, Khalida M Wani, Huamin Wang, Sisi Gao, Tim Heffernan, Lawrence Kwong, Ignacio I Wistuba, Laura Bover, Giulio F Draetta, Haoqiang Ying, Wantong Yao

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with a 5-year survival rate of just 13%. While the development and early clinical use of small molecules targeting oncogenic KRAS mutations, key drivers of PDAC, have shown promise, resistance to these targeted therapies remains a significant challenge. We recently identified Syndecan-1 (SDC1), a highly expressed heparan sulfate proteoglycan, as a critical KRAS effector protein that promotes nutrient salvage and tumor growth. Here, we report the development of a human-specific monoclonal antibody (anti-SDC1 mAb) that inhibits PDAC cell proliferation in vitro and suppresses PDAC tumor growth in vivo. Mechanistically, …

Evaluating The American Society Of Hematology Quality Measure On Timeliness Of Analgesics For Sickle Cell Disease Pain Crisis, Ibrahim Gwarzo, Harish Chandra Dega, Paula Tanabe, Robin Miller, David C. Brousseau

Department of Medicine Faculty Papers

The American Society of Hematology (ASH) proposed the median time to first emergency department (ED) administration of pain medication for patients with sickle cell disease (SCD) vaso-occlusive pain episodes (VOE) as a site-level quality measure. Generalizable studies assessing current guideline adherence recommending pain medications within 60 minutes are lacking. We leveraged multisite electronic health record data from Epic's Cosmos research platform to analyze ED encounters for SCD VOE from 1 January 2019 to 31 December 2024, with administration of at least 1 pain medication. We calculated the quality measure (median time to first pain medication) and ranked sites based on …

Spatiotemporal Histogenesis Of The Developing Human Cerebellum Reveals Dynamic Layering Of Bergmann Glia, Guanyi He, Simon Du, Henry Tan, Sri Yellampally, Anders W Erickson, Virginia Fernandez, Ferechte Encha-Razavi, Kimberley A Phillips, Christine Haberler, Nicole Amberg, Victor Borrell, Paul A Northcott, Michael D Taylor, Kathleen J Millen, Parthiv Haldipur

Faculty, Staff and Students Publications

Bergmann glia (BG) are a specialized glial population essential for cerebellar development, yet their developmental timeline and molecular identity in the human cerebellum remain poorly understood. Here, we combined detailed histopathological analysis with spatial transcriptomics and single-nucleus RNA sequencing to generate a developmental atlas of human cerebellar BG. Histology revealed that BG emerge around 11 post-conception weeks (PCW), initially serving as a scaffold for Purkinje cells (PCs) migrating into the PC layer of the cerebellar cortex. Following the establishment of a multilayered PC arrangement, BG form a distinct parallel layer separated from the PCs by the lamina dissecans (LD), with …

Associations Between The Microbiome And Immune Responses To An Adenovirus-Based Hiv-1 Candidate Vaccine Are Distinct Between African And Us Cohorts, Yuhao Li, Daniel J Stieh, Lindsay Droit, Andrew Hyoungjin Kim, Rachel Rodgers, Kathie A Mihindukulasuriya, Leran Wang, Maria G Pau, Olive Yuan, Herbert W Virgin, Dan H Barouch, Megan T Baldridge, Scott A Handley

2020-Current year OA Pubs

Optimization of prophylactic vaccine regimens to elicit strong, long-lasting immunity is an urgent need highlighted by the COVID-19 pandemic. Stronger vaccine immunogenicity is frequently reported in individuals living in high-income countries compared to individuals living in low- and middle-income countries. While numerous host genetic and immune factors may influence vaccine responses, geographic restrictions to vaccine effectiveness may also be influenced by the intestinal microbiota, which modulates host immune systems. However, the potential role of the gut microbiota on responses to HIV-1 vaccines has not yet been explored. We analyzed the bacteriome by targeted 16S sequencing and the virome by virus-like …

Community-Associated Quinolone-Resistant And Extended-Spectrum Beta-Lactamase-Producing Escherichia Coli Isolates Are Similar To Clinical Infection Isolates By Sequence Type And Resistome, Emily E Benedict, Wesley Agee, Tiffany Hink, Katelyn L Parrish, Kimberly A Reske, Kate Peacock, Rachel E Bosserman, Alyssa Valencia, Akshay Saluja, Elianora Ovchiyan, Olivia Arter, Kevin Jolani, Erik R Dubberke, Gautam Dantas, Jennie H Kwon

2020-Current year OA Pubs

No abstract provided.

Engineering Chimeric Antigen Receptor Cd4 T Cells For Alzheimer's Disease, Pavle Boskovic, Rotem Shalita, Wenqing Gao, Hailey Vernon, Yu Lin Deng, Marco Colonna, Robbie G Majzner, Ido Amit, Jonathan Kipnis

2020-Current year OA Pubs

Alzheimer's disease (AD) is the prevailing cause of age-associated dementia worldwide. Current standard of care relies on antibody-based immunotherapy. However, antibody-based approaches carry risks for patients, and their effects on cognition are marginal. Increasing evidence suggests that T cells contribute to AD onset and progression. Unlike the cytotoxic effects of CD8

Accurate Interpretation Of Within-Host Dissemination Using Barcoded Bacteria, Rachel T Giorgio, My T Le, Ting Zhang, Caitlyn L Holmes, Karthik Hullahalli

2020-Current year OA Pubs

Bacterial dissemination across tissues is a critically important process influencing infection outcomes. Monitoring within-host dissemination is challenging because conventional measures of bulk bacterial burden cannot distinguish between lineages that are shared between tissues and those that replicate locally. This limitation can be overcome using barcoded bacteria, where deep sequencing of the barcode locus and comparisons of barcodes between tissues define which lineages spread within the host. Numerous studies have used barcoded bacteria to generate high-resolution maps of dissemination. However, since multiple cells in the infectious inoculum can contain identical barcodes, inferences about dissemination can be confounded when distinct lineages from …

General Anesthesia Versus Conscious Sedation For Mechanical Thrombectomy In Patients With Acute Ischemic Stroke In The Most Trial, Umeshkumar Athiraman, Akash Roy, Andrew Barreto, Joseph Broderick, Colin Derdeyn, Jordan Elm, James C Grotta, James Ingles, Achala Vagal, Max Wintermark, Opeolu Adeoye

2020-Current year OA Pubs

BACKGROUND: Several observational studies have supported the use of conscious sedation (CS) for endovascular thrombectomy in patients with acute ischemic stroke and associated general anesthesia (GA) with poor functional outcomes. Recently, few randomized controlled trials have shown no difference in the functional outcomes between GA and CS. The aim of this paper is to compare the outcomes of GA versus CS in patients with acute ischemic stroke undergoing mechanical thrombectomy in the MOST (Multi-arm Optimization of Stroke Thrombolysis) trial.

METHODS: Patients who underwent mechanical thrombectomy for acute ischemic stroke under GA or CS in the MOST trial were included. The …

Long-Acting Interleukin-7 Improves The Efficacy Of Oncolytic Viral Therapy In Glioblastoma, Yuping Derek Li, David A Giles, Yi Huang, Ashwani Kesarwani, Tong Hu, Logan Page, Amanda De Andrade Costa, Jingqin Luo, Mai T Dang, Albert H Kim, John F Dipersio, David T Curiel, Michael S Diamond, Milan G Chheda, Et Al.

2020-Current year OA Pubs

Despite advances in immunotherapy, the prognosis for patients with glioblastoma (GBM) remains poor. The efficacy of GBM-targeted immunotherapies is limited by the paucity of functional T cells in the tumor microenvironment, a consequence of the local and systemic immunosuppression prevalent in patients with GBM. To overcome these challenges, here we develop a treatment strategy we term "expand and pull," which uses systemic administration of rhIL-7-hyFc, a long-acting recombinant human interleukin-7, to increase peripheral T cell abundance ("expand"), followed by intratumoral oncolytic virus treatment to recruit these cells to the tumor microenvironment ("pull"). We show that rhIL-7-hyFc improves the efficacy of …