Digital Commons Network^™

A Class Of Benzofuranoindoline-Bearing Heptacyclic Fungal Ripps With Anticancer Activities, Qiuyue Nie, Fanglong Zhao, Xuerong Yu, Mithun C Madhusudhanan, Caleb Chang, Siting Li, Sandipan Roy Chowdhury, Bryce Kille, Andy Xu, Rory Sharkey, Chunxiao Sun, Hongzhi Zeng, Shuai Liu, Dishu Zhou, Xin Yu, Kevin Yang, Sandra A C Figueiredo, Maria Zotova, Zichen Hu, Alan Y Du, Dongyin Guan, Rui Tang, Todd Treangen, Jin Wang, Pedro N Leão, Yang Gao, Junjie Chen, Peng Liu, Hans Renata, Xue Gao

Children’s Nutrition Research Center Staff Publications

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a promising source of new pharmaceuticals, yet the therapeutic potential of fungal RiPPs remains largely underexplored. Here, we report asperigimycins as a distinct class of fungal RiPPs, featuring a unique heptacyclic scaffold consisting of a benzofuranoindoline core and three additional macrocycles, primarily assembled by six distinct fungi-specific DUF3328 oxidases. Inspired by the enhancement of anticancer activity through the N-terminal pyroglutamate in naturally occurring asperigimycins C and D, we chemically modify the inactive asperigimycin B with a series of lipid substitutions at its N-terminus. A derivative with a C-11 linear fatty …

Bypassing Cisplatin Resistance In Nrf2 Hyperactivated Head And Neck Cancer Through Effective Pi3kinase Targeting, Pedram Yadollahi, Kelli A Mccord, Yang Li, Hussam Dayoub, Kalil Saab, Fonma Essien, Sean Hyslop, Emerald Kan, Kazi M Ahmed, Parker R Kirby, Vasanta Putluri, Chandra Shekar R Ambati, Karthik Reddy Kami Reddy, Patricia Castro, Heath D Skinner, Cristian Coarfa, William K Decker, Abdullah A Osman, Rutulkumar Patel, Jeffrey N Myers, Stephen Y Lai, Nagireddy Putluri, Faye M Johnson, Mitchell J Frederick, William H Hudson, Vlad C Sandulache

Faculty, Staff and Students Publications

Background: For patients with head and neck squamous cell carcinoma (HNSCC), failure of definitive radiation combined with cisplatin nearly universally results in death. Although hyperactivation of the Nrf2 pathway can drive radiation and cisplatin resistance along with suppressed anti-tumor immunity, treatment-refractory HNSCC tumors may retain sensitivity to targeted agents secondary to synergistic lethality with other oncogenic drivers (e.g., NOTCH1 mutations).

Methods: Using state of the science mechanistic, metabolomic and spatial transcriptomic approaches combined with preclinical models of HNSCC, we tested whether a novel PI3K inhibitor, gedatolisib, can bypass hyperactivation of the Nrf2 pathway.

Results: The PI3K pathway is activated in …

Functional Head Tremor: Contrasting Features With Other Tremor Etiologies, José Fidel Baizabal-Carvallo, Joseph Jankovic

Faculty, Staff and Students Publications

Background: Functional tremor (FT) is considered the most common phenomenology among patients with functional movement disorders (FMDs). Most patients have limb tremor, but they can also present with tremor involving the head and trunk.

Objectives and methods: We aimed to assess the clinical phenomenology of functional head tremor (FHT) and contrast it with features of HT observed in 125 patients with other tremor etiologies (OTE), including 71 patients with essential tremor (ET).

Results: There were 101 consecutive patients (68.3% females) with FT from which n = 36 (35.6%) had FHT. Yes-yes tremor was the most common directionality (47.2%). Functional trunk …

A Deep Generative Model For Deciphering Cellular Dynamics And In Silico Drug Discovery In Complex Diseases, Yumin Zheng, Jonas C Schupp, Taylor Adams, Geremy Clair, Aurelien Justet, Farida Ahangari, Xiting Yan, Paul Hansen, Marianne Carlon, Emanuela Cortesi, Marie Vermant, Robin Vos, Laurens J De Sadeleer, Ivan O Rosas, Ricardo Pineda, John Sembrat, Melanie Königshoff, John E Mcdonough, Bart M Vanaudenaerde, Wim A Wuyts, Naftali Kaminski, Jun Ding

Faculty, Staff and Students Publications

Human diseases are characterized by intricate cellular dynamics. Single-cell transcriptomics provides critical insights, yet a persistent gap remains in computational tools for detailed disease progression analysis and targeted in silico drug interventions. Here we introduce UNAGI, a deep generative neural network tailored to analyse time-series single-cell transcriptomic data. This tool captures the complex cellular dynamics underlying disease progression, enhancing drug perturbation modelling and screening. When applied to a dataset from patients with idiopathic pulmonary fibrosis, UNAGI learns disease-informed cell embeddings that sharpen our understanding of disease progression, leading to the identification of potential therapeutic drug candidates. Validation using proteomics reveals …

From Standard To Stratified: Modeling Ntcp And Ear To Personalize Daily Mv-Cbct In Radiotherapy., Duong Thanh Tai, Luong Tien Phat, Tran Trung Kien, Duong Tuan Linh, Nguyen Ngoc Anh, Nguyen Quang Hung, Peter Sandwall, Parham Alaei, David Bradley, James C L Chow

Oncology Articles

PURPOSE: To evaluate the cumulative radiobiological impact of daily megavoltage cone-beam computed tomography (MV-CBCT) imaging dose based on normal tissue complication probability (NTCP) and excess absolute risk (EAR) of secondary malignancies among radiotherapy patients treated for breast, pelvic, and head & neck cancers. This study investigated whether MV-CBCT imaging dose warrants protocol personalization according to patient age, anatomical treatment site, and organ-specific radiosensitivity.

METHODS: This retrospective study included cohorts of breast (n = 30), pelvic (n = 17), and head & neck (n = 20) cancer patients undergoing radiotherapy with daily MV-CBCT. Imaging dose distributions employing two common MV-CBCT protocols …

Extracellular Domain Shedding Of Trop2 Activates Egfr Signaling To Drive Prostate Cancer Metastasis, Shiqin Liu, En-Chi Hsu, Merve Aslan, Fernando Garcia-Marques, Michelle Shen, Alifiani B Hartono, Francisco Solano, Kewei Le, Hyeonji Hwang, Chung S Lee, Abel Bermudez, Rosalie Nolley, Donna M Peehl, James D Brooks, Michael A Liss, Sharon J Pitteri, Tanya Stoyanova

Faculty, Staff and Student Publications

UNLABELLED: Metastasis is the main cause of prostate cancer-associated deaths, highlighting the urgent need to determine the mechanisms underlying prostate cancer progression. TROP2 (also known as tumor-associated calcium signal transducer 2) is an oncogenic transmembrane surface protein that is highly expressed in metastatic prostate cancer. Naturally occurring cleavage of TROP2 leads to a release of the TROP2 extracellular domain (TECD) into the extracellular environment. In this study, we identified an important functional role of TECD in prostate cancer metastasis. TECD was detectable in media from prostate cancer cells and serum from patients with clinically significant prostate cancer. Although shed TECD …

Caspase 3-Specific Cleavage Of Ubiquitin-Specific Peptidase 48 Enhances Drug-Induced Apoptosis In Aml, Zhanglin Zhang, Xiang Lin, Yaling Yang, Xuemei Wang, Yi Wang, Xianbao Huang, Miao Hong, Wei Gao, Hua He, M James You, Yi Yang, Guangyao Kong

Faculty, Staff and Student Publications

Dysfunction or dysregulation of deubiquitination is closely related to the initiation and development of multiple cancers. Targeted regulation of deubiquitination has been recognized as an important strategy in tumor therapy. However, the mechanism by which drugs regulate deubiquitinase is not clear. Here, we identified ubiquitin-specific peptidase 48 (USP48), a member of the ubiquitin-specific protease family highly expressed in various tumors, as a specific substrate for the activated caspase-3. During drug induced apoptosis of AML cells, activated caspase-3 cleaves USP48 through recognizing the conservative motif DEQD located at 611-614 sites of human USP48. Subsequent analysis showed that the cleavage USP48 N-terminal …

Smags-Lasso: A Novel Feature Selection Method For Sensitivity Maximization In Early Cancer Detection, Hamid Khoshfekr Rudsari, Sara Khorami-Sarvestani, Johannes F Fahrmann, James P Long, Samir Hanash, Kim-Anh Do, Ehsan Irajizad

Faculty, Staff and Student Publications

Background: Sensitivity and specificity are foundational metrics for cancer detection tools. However, most machine learning algorithms prioritize overall accuracy during optimization, which fails to align with clinical priorities of early detection. We aim to develop a feature selection machine learning algorithm while maximizing sensitivity at a given specificity.

Methods: We developed SMAGS-LASSO, a machine learning algorithm that combines our developed Sensitivity Maximization at a Given Specificity (SMAGS) framework with L1 regularization for feature selection. This approach simultaneously optimizes sensitivity at user-defined specificity thresholds while performing feature selection. SMAGS-LASSO utilizes a custom loss function with L1 regularization and multiple parallel optimization …

Periostin Promotes Sarcoma Growth By Promoting Tumor-Associated Macrophage Migration And Differentiation, Jin-Fen Xiao, Kristin Ishaya, Emily Y Ko, Annaliese Fowler, Marina T Broz, Jlenia Guarnerio

Faculty, Staff and Student Publications

Soft-tissue sarcomas (STS) are characterized by abundant extracellular matrix (ECM) deposition, yet the functional contribution of specific ECM components remains poorly understood. In this study, we identify periostin (POSTN), a matricellular protein, as a regulator of sarcoma progression and the tumor immune microenvironment. Analysis of human sarcoma datasets revealed that high POSTN expression correlates with poor prognosis and elevated expression of ECM-related and myeloid cell–associated genes. In murine genetic models of sarcoma, tumors expressing high levels of Postn displayed enhanced expression of ECM genes and monocyte-recruiting cytokines. Functional silencing of Postnin vivo reduced tumor growth without altering tumor cell …

Tubulin Regulates Stability And Localization Of Stmn2 By Binding Preferentially To Its Soluble Form, Xiang Deng, Gary A Bradshaw, Marian Kalocsay, Timothy Mitchison

Faculty, Staff and Student Publications

The small, tubulin-binding protein STMN2 is highly expressed in neurons and is implicated in amyotrophic lateral sclerosis. STMN2 degrades rapidly and accumulates at axotomy sites, suggesting fast turnover is crucial for its neuroprotective function. We show that STMN2 was primarily degraded by the ubiquitin-proteasome system. Its membrane-targeting N-terminal domain promoted fast turnover, whereas its tubulin-binding domain promoted stabilization. Proximity labeling and imaging showed that tubulin binding reduced STMN2 targeting to trans-Golgi network membranes. Pull-down assays showed that tubulin binds preferentially to soluble over membrane-bound STMN2. Our observations suggest that STMN2 interconverts between a soluble, tubulin-bound form and a membrane-bound, tubulin-free …

Profiling The Preclinical Pharmacokinetics And Biodistribution Of A Platinum(Iv)-Based Oxaliplatin Prodrug Oxalitex And Their Significance To Antitumor Response, Guangan He, Gregory D Thiabaud, Kathryn A Shelton, Luke J Segura, Jonathan F Arambula, Jonathan L Sessler, Rick A Finch, Zahid H Siddik

Faculty, Staff and Student Publications

OxaliTEX (NOVO-111) is a novel gadolinium(III) texaphyrin-platinum(IV) complex that is under development for clinical trials. It was designed as a prodrug of oxaliplatin (1,2-diaminocyclohexane-platinum(II) oxalate) tethered to a tumor-affinic texaphyrin moiety to improve drug delivery to the tumor. However, oxaliTEX was not only more effective as an antitumor agent but also better tolerated in mice. To appreciate this higher therapeutic index and advance its preclinical development, studies were undertaken to profile its plasma pharmacokinetics, distribution to tumor and normal tissues, and pharmacodynamics of the p53/p21 molecular pathway. Nude mice, with or without a subcutaneous colorectal HCT-116 xenograft harboring a phenotypically …

Forecasting Chemoradiation Response Midtreatment For High-Grade Gliomas Through Patient-Specific Biology-Based Modeling, David A Hormuth, Maguy Farhat, Bikash Panthi, Holly Langshaw, Mihir D Shanker, Wasif Talpur, Sara Thrower, Jodi Goldman, Sophia Ty, Calliope Custer, Jeanne Kowalski, Thomas E Yankeelov, Caroline Chung

Faculty, Staff and Student Publications

Purpose: The entire course of radiation therapy (RT) for high-grade glioma (HGG) is currently derived from pre-RT magnetic resonance imaging (MRI). Although it is possible to adapt RT during the course of treatment, it is often guided only by anatomical changes to the tumor. This study seeks to determine if a biology-based mathematical model, parameterized by patient-specific, multiparametric MRI (mpMRI) data, can accurately forecast HGG response during RT.

Methods and materials: Twenty one patients with HGG planned for 6 weeks of concurrent RT and chemotherapy were imaged weekly with mpMRI during RT and at 1, 2, and 3 months post-RT. …

International Norms For Adult Handgrip Strength: A Systematic Review Of Data On 24 Million Adults Aged 20 To 100+ Years From 69 Countries And Regions, Grant R Tomkinson, Justin J Lang, Lukáš Rubín, Ryan Mcgrath, Bethany Gower, Terry Boyle, Marilyn G Klug, Alexandra J Mayhew, Henry T Blake, Francisco B Ortega, Cristina Cadenas-Sanchez, Costan G Magnussen, Brooklyn J Fraser, Tetsuhiro Kidokoro, Yang Liu, Kaare Christensen, Darryl P Leong

Faculty, Staff and Student Publications

Background: Muscular strength is a powerful marker of current health status and robust predictor of age-related disease and disability. Handgrip strength (HGS) using isometric dynamometry is a convenient, feasible, and widely used method of assessing muscular strength among people of all ages. While adult HGS norms have been published for many countries, no study has yet synthesized available data to produce international norms. The objective of this study was to generate international sex- and age-specific norms for absolute and body size-normalized HGS across the adult lifespan.

Methods: Systematic searches were conducted in 6 databases/web search engines (MEDLINE, SPORTDiscus, Embase, Web …

Research Hotspots And Trends In The Field Of Immune Checkpoint Inhibitors (Icis) For Cervical Cancer: A Bibliometric Study From 2014 To 2024, Chaoyan Shen, Juan Zhang, Guanyu Zhang, Hao Luo, Shuangke Zhang, Quan Yuan, Wei Xu, Wei Wang, Lele Miao

Faculty, Staff and Student Publications

In recent years, immune checkpoint inhibitors (ICIs) have emerged as a novel immunotherapeutic approach, offering renewed hope for enhancing cervical cancer patient prognosis. This study represents the inaugural bibliometric analysis of ICIs in the context of cervical cancer, covering the period from 2014 to 2024. A total of 422 articles were identified through the Web of Science Core Collection database, amassing 10,977 citations, with a consistent annual increase in the number of publications. The leading contributors in terms of countries, institutions, journals, and authors included China, the University of Texas System, Frontiers in Oncology, and Bradley J. Monk, respectively. …

Sars-Cov-2 Rna-Binding Protein Suppresses Extracellular Mirna Release, Hyejin Mun, Chang Hoon Shin, Qingxuan Fei, Andrea Estefania Lopez Giraldo, Kyoung-Min Choi, Ji Won Lee, Kyungmin Kim, Kyung-Won Min, Leilei Shi, Mark T Bedford, Dong-Chan Kim, Yoo Lim Chun, Seonghyun Ryu, Dongin Kim, Jeong Ho Chang, Ryan T Westrope, Michelle Shay, Edward Nguyen, Junho K Hur, Abigail Agyenda, Nam Chul Kim, Sung-Ung Kang, Woonghee Lee, Je-Hyun Yoon

Faculty, Staff and Student Publications

SARS-CoV-2 is the betacoronavirus causing the COVID-19 pandemic. Although the SARS-CoV-2 genome and transcriptome were reported previously, the function of individual viral proteins is largely unknown. Utilizing biochemical and molecular biology methods, we identified that four SARS-CoV-2 RNA-binding proteins (RBPs) regulate the host RNA metabolism by direct interaction with mature miRNA let-7b revealed by Nuclear Magnetic Resonance spectroscopy (NMR). SARS-CoV-2 RBP Nsp9 primarily binds mature miRNA let-7b, a direct ligand of the Toll-like Receptor 7 (TLR7), one of the potential SARS-CoV-2 therapeutics. Nsp9 suppresses host gene expression possibly by promoting let-7b-mediated silencing of a cellular RNA polymerase, POLR2D. In addition, …

A Review Of Engraftment Assessments Following Fecal Microbiota Transplant, Chloe Herman, Bridget M Barker, Thais F Bartelli, Vidhi Chandra, Rosa Krajmalnik-Brown, Mary Jewell, Le Li, Chen Liao, Florencia Mcallister, Khemlal Nirmalkar, Joao B Xavier, J Gregory Caporaso

Faculty, Staff and Student Publications

Fecal Microbiota Transplant (FMT) is a treatment for recurrent Clostridium difficile infections and is being explored for other clinical applications, from alleviating digestive and neurological disorders, to restoring microbiomes impacted by cancer treatment. Quantifying the extent of engraftment following an FMT is important in understanding a recipient's response to treatment. Engraftment and clinical response need to be investigated independently to evaluate an FMT's role (or lack thereof) in achieving a clinical response. Standardized bioinformatics methodologies for quantifying engraftment extent would not only improve assessment and understanding of FMT outcomes, but also facilitate comparison of FMT results and protocols across studies. …

Tumor Intrinsic Mettl5 Modulates Atf4 Translation To Prevent T Cell-Induced Ferroptosis In Ovarian Cancer, Jiakai Hou, Cheng-Wei Ju, Nicholas A Egan, Yanjun Wei, Yunfei Wang, Minghao Dang, Tianyi Zhou, Leilei Shi, Ningbo Zheng, Si Chen, Ashley M Guerrero, Xiaofang Liang, Wanfu Wu, Areej Akhtar, Chitra Dhiman, Debanwita Roy Burman, Andro E Gerges, Mason D Flores, Han Li, Li-Sheng Zhang, Marleen Kok, Xiaobo Mao, Linghua Wang, Qin Feng, Yiwen Chen, Sanghoon Lee, Daniel J Mcgrail, Nidhi Sahni, Chuan He, Amir A Jazaeri, Weiyi Peng

Faculty, Staff and Student Publications

Poor clinical responses to immune checkpoint blockade (ICB) observed in ovarian cancer (OC) highlight an unmet need to understand the mechanisms driving immune evasion in this disease. To address this, an integrative analysis is conducted by combining in vitro genome‐wide immune screens, in vivo ICB screens, and clinical data mining, and METTL5 is identified as a crucial OC‐intrinsic factor that promotes immune resistance. Immunologically “cold” OC tumors and poor responders to ICB exhibit elevated METTL5 expression. Mechanistically, knocking out (KO) METTL5 in OC disrupts ATF4 translation by altering 18S rRNA m6A levels, leading to the downregulation of SLC7A11 and SLC3A2 …

Kras Inhibition Activates An Actionable Cd24 "Do Not Eat Me" Signal In Pancreatic Cancer, Yongkun Wei, Minghui Liu, Er-Yen Yen, Jun Yao, Zhenzhen Xun, Phuoc T Nguyen, Xiaofei Wang, Zecheng Yang, Abdelrahman Yousef, Dean Pan, Yanqing Jin, Ching-Fei Li, Madelaine S Theardy, Jangho Park, Yiming Cai, Mitsunobu Takeda, Matthew Vasquez, Elizabeth M Park, David H Peng, Yong Zhou, Hong Zhao, Timothy P Heffernan, Andrea Viale, Huamin Wang, Stephanie S Watowich, Han Liang, Dan Zhao, Ronald A Depinho, Wantong Yao, Haoqiang Ying

Faculty, Staff and Student Publications

KRASG12C inhibitors (G12Ci) have produced encouraging, albeit modest and transient, clinical benefit in pancreatic ductal adenocarcinoma (PDAC). Identifying and targeting resistance mechanisms to G12Ci treatment is therefore crucial. To better understand the function of KRASG12C and possible G12Ci bypass mechanisms, we developed an autochthonous KRASG12C-driven PDAC model. Compared to the classical KRASG12D PDAC model, the G12C model exhibits slower tumor growth, yet similar histopathological and molecular features. Aligned with clinical experience, G12Ci treatment of KRASG12C tumors produced modest impact despite stimulating a ‘hot’ tumor immune microenvironment. Immunoprofiling revealed that CD24, a ‘don’t eat me’ signal, is significantly upregulated on cancer …

Knowledge Mapping And Visualized Analysis Of Research Progress In Onconephrology: A Bibliometric Analysis, Yiwei Wang, Shuling Fan, Wei Wang

Faculty, Staff and Student Publications

Objectives: Onconephrology is an expanding subspecialty focused on the management of cancer patients with renal injury. This study used a comprehensive bibliometric analysis to emphasize the need for cooperation between oncologists and nephrologists, exploring current trends and future research areas in onconephrology.

Methods: Relevant literature on onconephrology published between 1 January 2000 and 27 April 2024 was retrieved from the Science Citation Index Expanded of the Web of Science Core Collection, followed by manual screening. Bibliometric analyses were performed using CiteSpace, VOSviewer, and Bibliometrix software.

Results: A total of 1,853 publications, including 1,647 articles and 206 reviews, by 11,606 authors …

Lymphodepletion, Tumor-Infiltrating Lymphocytes, And High Versus Low Dose Il-2 Followed By Pembrolizumab In Patients With Metastatic Melanoma, Merve Hasanov, Simin Kiany, Marie-Andrée Forget, Roland Bassett, Michael A Davies, Adi Diab, Jeffrey E Gershenwald, Isabella C Glitza, Jeffrey E Lee, Anthony Lucci, Jennifer L Mcquade, Sapna P Patel, Merrick I Ross, Hussein A Tawbi, Jennifer A Wargo, Michael K Wong, Chantale Bernatchez, Patrick Hwu, Cara Haymaker, Rodabe N Amaria

Faculty, Staff and Student Publications

This study evaluated the efficacy and safety of unengineered tumor-infiltrating lymphocytes (TILs) combined with pembrolizumab and either high (HD, Arm-1) or low (LD, Arm-2) doses of IL-2 in patients with metastatic melanoma (MM). Patients were lymphodepleted with cyclophosphamide and fludarabine, followed by TIL infusion and IL-2 (Arm-1: 720,000 IU/kg IV q 8 hrs up to 15 doses; Arm-2: 2 million IU SC for 14 days). Patients received pembrolizumab 200 mg IV starting 21 days post-TIL infusion, and every 3 weeks for up to 2 years. The primary endpoint was overall response rate (ORR) per RECIST 1.1. Blood samples were collected …

Monte Carlo Simulations Of Geometric Deformation Of Harrison-Anderson-Mick Applicators Used In Intraoperative Radiation Therapy, Benjamin Insley, Brett Bocian, Sam Beddar, Reza Reiazi, Patrick James Jensen, Rachael M Martin-Paulpeter, Joshua Scott Niedzielski, David Flint, Gabriel Oliveira Sawakuchi, Luis Augusto Perles

Faculty, Staff and Student Publications

Background: The Harrison-Anderson-Mick (HAM) applicator is a high-dose-rate intraoperative radiotherapy (HDR-IORT) applicator used to position Ir-192 brachytherapy sources over surgically-accessed tumor volumes or post-resection tumor beds. Because of the lack of a 3D imaging system, dwell times are optimized pre-surgery by a TG-43-based treatment planning system (TPS) that assumes a perfectly flat applicator surface surrounded by an infinite water phantom. These assumed conditions are disparate from typical treatment conditions, especially in the pelvic regions, which often involve uneven patient surfaces and superficial irradiations with little to no backscatter material.

Purpose: Develop and validate a Monte Carlo (MC) model of HDR-IORT …

Plasma Metabolomic And Proteomic Signatures Of Blood Pressure Management After Bariatric Surgery Among Adolescents, Shudi Pan, Zhenjiang Li, Juan Pablo Lewinger, Jesse A Goodrich, Hongxu Wang, Sarah Rock, Carmen Chen, Todd M Jenkins, Stephanie Sisley, Stephen R Daniels, Douglas I Walker, Max T Aung, Erika Garcia, Rob Mcconnell, Sandrah P Eckel, Michele A La Merrill, Tanya L Alderete, Zhuanghua Chen, Frank D Gilliland, Thomas H Inge, David V Conti, Justin R Ryder, Lida Chatzi

Faculty, Staff and Students Publications

Background: Emerging omics approaches, including metabolomics and proteomics, can be integrated into obesity treatment for better blood pressure management. We tested whether preoperative metabolomic and proteomic profiles predict long-term elevated blood pressure (EBP) changes better than known risk factors in adolescents undergoing bariatric surgery.

Methods: We included 108 participants from the Teen-LABS (Teen-Longitudinal Assessment of Bariatric Surgery). Plasma untargeted metabolomics (via liquid chromatography with high-resolution mass spectrometry) and Olink proteomics were assessed pre surgery. An elastic net model with stability selection was used to identify features predictive of EBP reductions 5 years post surgery. Models including identified metabolites, proteins, and …

Adrenomedullin Overexpression Protects Mice From Experimental Bronchopulmonary Dysplasia And Associated Pulmonary Hypertension, Shyam Thapa, Poonam Sarkar, M Waleed Gaber, Roberto Barrios, Madhulata Chauhan, Chandrasekhar Yallampalli, Binoy Shivanna

Faculty, Staff and Students Publications

Bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) or BPD-PH is a lung disease of infants with significant morbidity. Adrenomedullin (Adm) is an angiogenic peptide that signals through calcitonin receptor-like receptor (Calcrl) and receptor activity modifying protein 2 (RAMP2). Adm deficiency potentiates hyperoxia-induced experimental BPD-PH in mice; however, whether Adm overexpression can mitigate this lung disease is unclear. Thus, we tested the hypothesis that Adm overexpression attenuates hyperoxia (HO)-induced murine experimental BPD-PH by using a novel transgenic mouse that overexpresses Adm globally (Admhi/hi mice). One-day-old Admhi/hi mice or their wild-type littermates (Adm+/+ mice) were exposed to …

Left And Right Ventricular Strain Mechanics In Fetal Tachyarrhythmia., Rukmini Komarlu, Janelle R. Noel-Macdonnell Phd, Neha Chellu, Geetha Haligheri

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: Assessment of myocardial function in fetuses with supraventricular tachyarrhythmia is challenging. Speckle-tracking echocardiography (STE) is a newer sensitive method to assess ventricular systolic function. We sought to assess left (LV) and right (RV) ventricular myocardial strain mechanics in fetuses with tachyarrhythmia and hypothesized that strain mechanics are impaired in this patient population even after conversion to sinus rhythm.

METHODS: This was a single-center retrospective review. LV and RV strain parameters were assessed using STE in tachyarrhythmia and after conversion to sinus rhythm and, compared to gestational age (GA), matched control fetuses in sinus rhythm.

RESULTS: Eighteen fetuses with tachyarrhythmia …

Cross-Species Standardised Cortico-Subcortical Tractography, Stephania Assimopoulos, Shaun Warrington, Davide Folloni, Katherine Bryant, Ali-Reza Mohammadi-Nejad, Wei Tang, Saad Jbabdi, Sarah R Heilbronner, Rogier B Mars, Stamatios N Sotiropoulos

Faculty, Staff and Students Publications

Despite their importance for brain function, cortico-subcortical white matter tracts are under-represented in diffusion magnetic resonance imaging tractography studies. Their non-invasive mapping is more challenging and less explored compared to other major cortico-cortical bundles. We introduce a set of standardised tractography protocols for delineating tracts between the cortex and various deep subcortical structures, including the caudate, putamen, amygdala, thalamus, and hippocampus. To enable comparative studies, our protocols are designed for both human and macaque brains. We demonstrate how tractography reconstructions follow topographical principles obtained from tracers in the macaque and how these translate to humans. We show that the proposed …

Muc15 Ectodomain Architecture Regulates Integrin Clustering To Control Cancer Metastasis, Simei Zhang, Guy M Genin, Et Al.

2020-Current year OA Pubs

Cancer metastasis is governed by physical cues at the cell-matrix interface, with matrix stiffness, ligand density, and topography established as key determinants. Here, a fourth critical factor in cancer metastasis, the architecture of the cell-surface glycocalyx is identified. Using MUC15 as a representative small glycoprotein, mathematical modeling and domain truncation experiments are combined to show that glycoprotein size distribution governs integrin adhesion states and metastatic outcomes. MUC15 localizes to focal adhesions and interact with integrins, while larger glycoproteins such as MUC1 are sterically excluded. These physical effects, rather than intracellular signaling, dictate adhesion state transitions: removing MUC15's ectodomain eliminated its …

Lilrb4 Regulates Circadian Disruption-Induced Mammary Tumorigenesis Via Non-Canonical Wnt Signaling Pathway, Olajumoke Ogunlusi, Mrinmoy Sarkar, Kayla Carter, Arhit Chakrabarti, Devon J Boland, Tristan Nguyen, James Sampson, Christian Nguyen, Danielle Fails, Yava Jones-Hall, Loning Fu, Gus Wright, Da Mi Kim, James J Cai, Bani Mallick, Alex C Keene, Jeff R Jones, Tapasree Roy Sarkar

Faculty, Staff and Students Publications

Epidemiological studies have shown that circadian rhythm disruption (CRD) is associated with the risk of breast cancer. However, the role of CRD in mammary gland morphology and aggressive basal mammary tumorigenesis and the molecular mechanism underlying CRD-induced carcinogenesis remain unknown. To investigate the effect of CRD on aggressive tumorigenesis, a genetically engineered mouse model of aggressive breast cancer was used. The impact of CRD on the tumor microenvironment was investigated using the tumors from LD12:12 and CRD mice via scRNA-seq, flow cytometry, multiplexing immunostaining, and realtime PCR. The effect of LILRB4-immunotherapy on CRD-induced tumorigenesis was also investigated. Here we investigated …

Buprenorphine Treatment During The Extended Postpartum Period: A Survey Of Patient Experiences, Bridget Galati, Heather Jacobsen, Melissa Krauss, Melissa Mills, Brittaney Vaughn, Sam Williams, Michael Wenzinger, Cynthia Rogers, Nandini Raghuraman, Jeannie Kelly

2020-Current year OA Pubs

OBJECTIVE: The late postpartum period, defined as greater than 6 weeks to 12 months, is a high-risk time for individuals with opioid use disorder (OUD). Discontinuation rates of buprenorphine treatment for OUD during this period are high. Little is known about patients' subjective experience with buprenorphine treatment during this time. We sought to assess patient treatment experience, goals, facilitators and barriers to continued buprenorphine treatment throughout the extended postpartum period.

METHODS: We performed a cross-sectional survey of postpartum patients who received buprenorphine treatment, including sublingual and long-acting injectable formulations, in an interdisciplinary, wrap-around clinic for maternal OUD between February 2022 …

State Of Omics-Based Microbial Diagnostics Of Crc, Jerome Prusa, Mark G Gorelik, Kevin S Blake, Gautam Dantas

2020-Current year OA Pubs

Colorectal cancer (CRC) remains a major burden of cancer-related morbidity and mortality globally, especially when detected at later stages. Early detection through improved and more accessible diagnostics is critical for reducing the severity of CRC. As our understanding of CRC and the microbial inhabitants of the gastrointestinal tract continues to improve, it has become increasingly recognized that the bacterial component of the gut microbiome may provide diagnostic utility for detecting CRC. This is because CRC is often accompanied by shifts in bacterial taxa, and the metabolites produced or utilized by the CRC-associated gut bacterial community. Advances in sequencing and metabolite …

Pan-Cancer Single Cell Transcriptomic Clustering Reveals Heterogeneous Cd8+ Exhausted T Cell Populations With Different Immune Checkpoint Inhibitor Responses, Rui Mu, Rasha Barakat, David H Gutmann

2020-Current year OA Pubs

In most cancers, T lymphocytes comprise an essential cellular component of the non-neoplastic microenvironment, where they have the capacity to both suppress and support tumor growth. One specialized T lymphocyte population is the CD8