Medical Sciences Commons^™

Primary Tumor Size And Tumor-Vessel Interface Following Capecitabine And Temozolomide For Pancreatic Neuroendocrine Tumor, Jin Guo, Kever A Lewis, Laura Prakash, Priya Bhosale, Ajaykumar Morani, Matthew H G Katz, Ching-Wei D Tzeng, Naruhiko Ikoma, Rebecca Snyder, Michael P Kim, Chandrikha Chandrasekharan, Arvind Dasari, James C Yao, Jeffrey E Lee, Jessica E Maxwell, Daniel M Halperin

Faculty, Staff and Student Publications

Capecitabine/temozolomide (CAPTEM) is an established regimen for patients with metastatic pancreatic neuroendocrine tumors (PanNET) that is being increasingly used for tumor volume reduction in patients with borderline anatomically resectable disease. We sought to understand the response of the primary tumor, defined as changes in the tumor–vascular interface (TVI). This is a retrospective, single-institution study of patients with locally advanced or metastatic PanNET treated with CAPTEM between 2010 and 2020. RECISTv1.1 measurements and TVI assessments of the primary tumor were performed on pre- and post-therapy images. Patients with locally advanced or metastatic PanNET at presentation (n = 47) were included. …

Targeting Oxalate Production By Combining Enzyme Inhibition And Proteolysis Activation: A Novel Therapeutic Approach For Primary Hyperoxaluria Type 1, Fabio Arias, Sumati Rohilla, Yudibeth Sixto-López, Koral S E Richard, Sandeep Das, Sumit K Anand, Pilar Maria Luque-Navarro, Guillermo Bañuelos-Sanchez, Juan Luis Pacheco-García, Reethika Gade, M Peyton Mckinney, Dhananjay Kumar, Jemiah Maxie, W Rylan Corr, Nilesh Pandey, Harpreet Kaur, Jibin Ding, Lin Tan, Elisha Scott, Hyung Nam, Eyal Gottlieb, A Wayne Orr, Nirav Dhanesha, Arif Yurdagul, Angel L Pey, Francisco Franco-Montalbán, José A Gómez Vidal, Oren Rom, Mónica Díaz-Gavilán

Faculty, Staff and Student Publications

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder caused by hepatic oxalate overproduction due to alanine-glyoxylate aminotransferase (AGXT) deficiency. Therapeutic strategies targeting glycolate oxidase (GO) and lactate dehydrogenase A (LDHA), key enzymes in glyoxylate metabolism, have shown promise in reducing oxalate burden. However, recently approved siRNA therapies remain limited by high cost, unfavorable pharmacokinetics, and limited global accessibility. We report the development of compound 2, a dual GO/LDHA inhibitor (K i = 390 and 40 nM, respectively) that also promotes hydrophobic tag-mediated autophagic degradation of LDHA. Its efficacy was evaluated in Agxt –/– mice, both in primary …

Tumor-Immune-Neural Circuit Disrupts Energy Homeostasis In Cancer Cachexia, Xiuhui Shi, Alex X Arreola, Zhijun Zhou, Jingxuan Yang, Mingyang Liu, Yang Cai, Yu Ren, Hao Yuan, Qun Chen, Xinjie Chen, Xinyu Yang, Yimei Meng, Jingyi Wang, Wenyi Luo, Michael C Rudolph, Rohan Varshney, Kar-Ming Fung, Chao Xu, Wei R Chen, Michael S Bronze, Lei Zheng, Yi-Ping Li, Courtney W Houchen, Yuqing Zhang, Min Li

Faculty, Staff and Student Publications

Cancer-induced cachexia and anorexia are debilitating complications across many cancers, yet effective treatments remain limited due to a poor understanding of the underlying mechanisms. Here, we identify an uncharacterized tumor-immune-neural circuit driving these syndromes, centered on growth and differentiation factor 15 (GDF15). Using genetically engineered mouse models, we find that loss of GDF15 protects against appetite loss, muscle wasting, and fat loss in pancreatic, lung, and skin cancers. Single-cell RNA sequencing reveals macrophages as a major source of GDF15, induced by tumor-derived colony-stimulating factor 1 (CSF1). GDF15 acts via the central nervous system to enhance β-adrenergic signaling in the tumor …

Editorial: Unveiling The Next Generation Of Cancer Immunity & Immunotherapy, Mohanraj Sadasivam, Nethaji Muniraj, Chellappagounder Thangavel

Center for Translational Medicine Faculty Papers

[This corrects the article DOI: 10.3389/fimmu.2025.1769324.].

Three-Dimensional Versus Two-Dimensional Echocardiographic Assessment Of Left Atrial Volume And Deformation In Children, Alexander J Kiener, James Croft, Krista N Harris, Ankona Banerjee, Aura A Sanchez, Xander H T Wehrens, Anitha Parthiban, Xiaotian Gao, Tam T Doan, Minh B Nguyen

Faculty, Staff and Students Publications

Background: Left atrial (LA) volume and function are important for assessing pediatric diastolic dysfunction (DD). Three-dimensional echocardiographic (3DE) LA assessment may overcome limitations and assumptions inherent in two-dimensional echocardiographic (2DE).

Methods: We conducted a cross-sectional study of children under 18 years of age with structurally normal hearts, using transthoracic 3DE apical volume datasets. LA volumetric function and phasic deformation analyses were performed using 3DE (GE, EchoPAC 4DLAQ v206, near fully-automated) and 2DE (TomTec, TTA2.51, CPA, manual) was performed by three operators and processing time was collected. Agreement and reproducibility was assessment for each modality.

Results: Fifty patients (median age 12.8 …

Community Participatory Co-Design And Development Of A Digital Diabetes Prevention Education Program For Hispanic Families With Obesity: Mixed Methods Study, Sandra Mihail, Marbelly Partida, Lizette Villanueva, Debbe Thompson, Teresia M O'Connor, Salma M Musaad, Maria J Redondo, Erica G Soltero

Children’s Nutrition Research Center Staff Publications

Background: Digital health interventions (DHIs) can extend the reach of disease prevention interventions; however, few are evidence-based, theoretically grounded, or developed for high-risk youth and families. Co-design approaches engage end users in the design and development of the DHI, which can lead to increased accessibility and engagement.

Objective: This study aimed to describe the adaptation of an evidence-based diabetes prevention program for remote, digital delivery.

Methods: The adaptation of the in-person intervention was guided by a modified Inclusive Digital Health Intervention Design to Promote Health Equity framework and conducted in collaboration with Hispanic adolescents (n=23) with obesity (BMI ≥95th percentile) …

Leveraging Ancestral Recombination Graphs For Scalable Mixed-Model Analysis Of Complex Traits, Jiazheng Zhu, Georgios Kalantzis, Ali Pazokitoroudi, Árni Freyr Gunnarsson, Hrushikesh Loya, Han Chen, Sriram Sankararaman, Pier Francesco Palamara

Faculty, Staff and Student Publications

Recent algorithmic advances have enabled the inference of genome-wide ancestral recombination graphs (ARGs) from large genomic cohorts, providing detailed models of genealogical relatedness along the genome. These inferred ARGs can complement genotype imputation by capturing the effects of unobserved variants, but their use in large-scale linear mixed-model analyses has been computationally prohibitive. Here, we develop methods that leverage the ARG to perform genotype-matrix multiplications in sublinear time and implement scalable randomized algorithms for mixed-model analyses. We introduce ARG-RHE, a randomized Haseman-Elston approach for estimating narrow-sense heritability and performing region-based association testing using ARGs, enabling parallel analysis of multiple quantitative traits. …

Precision Chemotherapy In Biliary Tract Cancer Moving From Empiric Intensification To Biomarker-Guided Treatment: Editorial On "Molecular Determinants Of Outcome To Gemcitabine, Cisplatin, And Nab-Paclitaxel In Patients With Advanced Btc", Sung Hwan Lee, Ahmed O Kaseb, Ju-Seog Lee

Faculty, Staff and Student Publications

No abstract provided.

Agent-Based Modeling Of Cellular Dynamics In Adoptive Cell Therapy, Yujia Wang, Stefano Casarin, May Daher, Vakul Mohanty, Merve Dede, Mayra Shanley, Eleonora Dondossola, Ludovica La Posta, Rafet Başar, Katayoun Rezvani, Ken Chen

Faculty, Staff and Student Publications

Adoptive cell therapies (ACT) leverage tumor-immune interactions to cure cancer. Despite promising phase I/II clinical trials of chimeric-antigen-receptor natural killer (CAR-NK) cell therapies, molecular mechanisms and cellular properties required to achieve clinical benefits in broad cancer spectra remain underexplored. While in vitro and in vivo experiments are essential, they are expensive, laborious, and limited to targeted investigations. Here, we present ABMACT (Agent-Based Model for Adoptive Cell Therapy), an in silico approach employing agent-based models (ABM) to simulate the continuous course and dynamics of an evolving tumor-immune ecosystem, consisting of heterogeneous "virtual cells" created based on knowledge and omics data observed …

Third-Party Effects On Intergroup Trust: The Role Of Punishment/Compensation And Group Regulatory Focus, Xiaowei Geng, Jie Cui, Jie Wang, Feng Zhang, Wei Wang

Faculty, Staff and Student Publications

Intergroup trust refers to a collective prediction and belief among members of one group regarding those of another in intergroup interactions. It plays an important role in avoiding intergroup conflicts, and thereby sustaining social development. This study was designed to investigate the effects of third-party punishment and compensation, as well as group regulatory focus, on intergroup trust. The findings revealed that, at both individual and group levels, prevention-focused groups exhibited higher levels of intergroup trust than promotion-focused groups under third-party compensation conditions. In contrast, under the third-party punishment conditions, promotion-focused groups displayed greater trust than prevention-focused groups, although this difference …

Bioprinting: Revolutionizing Biology With 3d Innovation, Gopalarethinam Janani Ms, Naven Kumar Rk, Agnishwar Girigoswami Prof, Koyeli Girigoswami Prof

Chulalongkorn Medical Journal

3D bioprinting is an innovative technology that enables the creation of bioengineered structures through computer-guided processes. This technique has been in use for more than 35 years and has made a huge contribution in the biomedical field. Utilizing biomaterials with regenerative properties has significantly impacted tissue engineering, regenerative medicine, and pharmaceutical research. Various bioprinting techniques, including inkjet, extrusion, laser-assisted, and stereolithography, offer unique advantages for precise tissue construction. Bioinks used for printing, can be derived from natural and synthetic sources. It ensures biocompatibility, mechanical integrity, and controlled degradation. Advanced bioinks—such as nanoengineered, biomolecular, multimaterial, self-assembling, and stimuli-responsive variants—enhance applications in …

Diagnostic Accuracy Of Cerebral Amyloid Angiopathy Criteria In The First Pathologically Confirmed Thai Cohort: A Pilot Study, Thanapoom Taweephol, Thachamai Smitasiri, Thanakit Pongpitakmetha, Sekh Thanprasertsuk, Anand Viswanathan

Chulalongkorn Medical Journal

Background: The gold standard for diagnosing cerebral amyloid angiopathy (CAA), full brain post-mortem examination, is rarely performed. Current diagnostic criteria, primarily based on clinico-radiological features, were developed from Western populations and may have limited applicability to Asian populations.

Objective: We aimed to evaluate the accuracy of current diagnostic criteria and examine the clinico-radiological characteristics of Thai CAA patients.

Methods: Brain histopathological specimens from patients with clinical symptoms of CAA who underwent neurosurgical procedures, including intracerebral hemorrhage (ICH) evacuation, between 2011 and 2021 at King Chulalongkorn Memorial Hospital, Thailand, were reviewed. Patient characteristics and clinical events for each individual were retrospectively …

Elucidation Of Hub Genes And Pathway Associated With Gut Microbiome Dysbiosis And Alzheimer’S Disease Via Data Analytic Approaches, Premaanand Rawi, Ying Pei Wong, Ee Xion Tan, Anna Pick Kiong Ling

Chulalongkorn Medical Journal

Background: Recent studies have highlighted the relationship between gut microbiome and Alzheimer’s disease (AD), revealing the ways of how gut microbial balance impacts conditions ranging from inflammatory bowel diseases to neurological disorders. The emerging field of the gut-brain-axis suggests production of microbial metabolites influences AD progression. However, there is limited understanding of molecular mechanisms involved in neurological disease when gut microbiome dysbiosis occurs. This study aimed to identify hub genes and pathways associated with gut microbiome dysbiosis and AD through data analytics approaches.

Methods: Public gene expression datasets on gut microbiome dysbiosis, and AD were obtained from the GEO and …

A Framework For Assessing The Trustworthiness Of Scientific Research Findings, Brian A Nosek, David B Allison, Kathleen Hall Jamieson, Marcia Mcnutt, A Beau Nielsen, Susan M Wolf

Children’s Nutrition Research Center Staff Publications

Vigorous debate has erupted over the trustworthiness of scientific research findings in a number of domains. The question "what makes research findings trustworthy?" elicits different answers depending on whether the emphasis is on research integrity and ethics, research methods, transparency, inclusion, assessment and peer review, or scholarly communication. Each provides partial insight. We offer a systems approach that focuses on whether the research is accountable, evaluable, well-formulated, has been evaluated, controls for bias, reduces error, and whether the claims are warranted by the evidence. We tie each of these components to measurable indicators of trustworthiness for evaluating the research itself, …

Molecular Determinant Of Low-Voltage Dependence Of Human Nav1.7 Inactivation Revealed By Efficacy-Based Nav1.7 Selective Inhibitor, Fang Zhao, Chuchu Xi, Jie Li, Kerui Ren, Qinglian Tang, Huaduan Liang, Shilong Yang, Michael X Zhu, Zhengyu Cao

Faculty, Staff and Student Publications

Nav1.7 is a voltage-gated sodium channel (VGSC) subtype predominantly expressed in sensory neurons, amplifying threshold currents. Here, we identify that Uvarigranol D (UGD) suppresses human (h) Nav1.7 with a much greater maximal inhibition than other VGSC subtypes, despite having similar apparent affinities. We demonstrate that Thr1398 determines the greater inhibitory efficacy of UGD, the leftward shift in voltage-dependence and faster inactivation kinetics of hNav1.7. UGD binds to the inactivated state, with Gln360, Ile394, Lys1395, Phe1737, and Tyr1744 being critically involved. Moreover, while UGD suppresses action potentials in both rat dorsal root ganglion neurons and human induced pluripotent stem cell-derived cardiomyocytes, …

Leveraging Clinical Sleep Data Across Multiple Pediatric Cohorts For Insights Into Neurodevelopment: The Retrospective Analysis Of Sleep In Pediatric (Rasp) Cohorts Study, Naihua N Gong, Aditya Mahat, Samya Ahmad, Daniel Glaze, Mirjana Maletic-Savatic, Matthew Mcginley, Anne Marie Morse, Alcibiades J Rodriguez, Audrey Thurm, Susan Redline, Kiran Maski, Peter Davis, Shaun Purcell, Ashura Buckley

Faculty, Staff and Students Publications

Sleep disturbances are prominent across neurodevelopmental disorders (NDDs) and may reflect specific abnormalities in brain development and function. Overnight polysomnography (PSG) allows for detailed investigation of sleep architecture, offering a unique window into neurocircuit function. Analysis of existing pediatric PSGs from clinical studies could enhance the availability of sleep studies in pediatric patients with NDDs towards a better understanding of mechanisms underlying abnormal development in NDDs. Here, we introduce and characterize a retrospective collection of 1527 clinical pediatric overnight PSGs across five different sites. We first developed an automated stager trained on independent pediatric sleep data, which yielded better performance …

Decitabine-Cedazuridine In Patients With Mds And Tp53 Mutations, Samuel Urrutia, Koji Sasaki, Alex Bataller, Hagop Kantarjian, Guillermo Montalban-Bravo, James Mccloskey, Elizabeth A Griffiths, Karen Yee, Amer Zeidan, Michael Savona, Aram Oganesian, Yuri Sano, Harold N Keer, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

No abstract provided.

Channel Gating In Bacteriorhodopsin-Like Channelrhodopsins With Contrasting K+ And Na+ Selectivity, Oleg A Sineshchekov, Elena G Govorunova, Hai Li, Yumei Wang, John L Spudich

Faculty, Staff and Student Publications

Two closely homologous channelrhodopsins from Hyphochytrium catenoides, known as HcKCR1 (kalium channelrhodopsin 1) and HcCCR (cation channelrhodopsin), exhibit >100 times different K+/Na+ relative permeabilities and are emerging optogenetic tools for controlling neurons and cardiomyocytes. Key residue motifs and trimeric organization relate them structurally to bacteriorhodopsin-like cation channelrhodopsins (BCCRs). Here, we demonstrate that they utilize a specific gating mechanism previously suggested for the earlier-discovered BCCR from cryptophytes. Using a comparative analysis of transient absorption changes and photocurrents under single-turnover conditions, we identified an early, far-UV-absorbing photocycle intermediate that precedes channel opening in wild-type HcKCR1 and HcCCR. The UV-absorbing product is a …

Immune-Mediated Necrotizing Myopathy In Association With Statin Exposure, Charlie E. Babcock, Phebie Rossi, Jennifer Hasvold

Aesculapius Journal (Health Sciences & Medicine)

Statins are first-line therapy for hyperlipidemia and are widely prescribed in primary care. Although generally safe, they carry rare but serious risks that must be considered on an individual basis. One such complication is immune-mediated necrotizing myopathy (IMNM), an autoimmune condition characterized by persistent muscle weakness and elevated creatine kinase (CK) despite discontinuation of the statin. We describe an 87-year-old man with a history of atorvastatin intolerance who was reinitiated on the medication five years later. Shortly thereafter, he developed progressive weakness, recurrent hospitalizations, and ultimately was diagnosed with IMNM confirmed by biopsy and HMG-CoA reductase antibodies. Despite treatment with …

Intouch Week Of February 9, 2026, New York Medical College

InTouch

• Shaun Desai, M.D., to Lead Department of Otolaryngology
• NYMC Supports National Heart Month
• NYMC Alums Share Marriage, Memories, and a Lifetime Together
• CDM Strengthens Emergency Response Skills Through TECC and RTF Courses
• TCDM Celebrates Match Day Success
• Student Spotlight: SOM Student Juliet Manu Named SEQUINS Scholar

Tumor Necrosis Factor Alpha Inhibition Improves Fetal Growth In A Rat Model Of Preeclampsia, Laura E. Coats, Nathan Campbell, Dylan Solise, Gabrielle M. Chamoun, Adam Z. Rawls, Alexandra Demesa, Ty Turner, Baoying Zheng, Barbara T. Alexander, Babbette Lamarca

Physiology & Biophysics

Introduction

Integrating Zotero With Your Writing: From Research To Publication – Hslic Workshop Feb 2026, Evelyn Wang

HSLIC Faculty and Staff Instructional Resources

This HSLIC workshop presentation provides a practical, step‑by‑step guide to integrating Zotero into the research and writing workflow. Topics include installing and configuring Zotero and the Zotero Connector, collecting references from databases and web pages, organizing items with collections, subcollections, tags, and PDF attachments, inserting citations and generating bibliographies in Microsoft Word and Google Docs, managing and annotating PDFs, handling title case versus sentence case, detecting and merging duplicate records, and using advanced features such as Zotero sync, group libraries, collaboration tools, custom citation styles, and ZoteroBib.

Familial History Of Aortic Disease Does Not Affect Outcomes Of Fenestrated-Branched Endovascular Aortic Repair In Patients With Complex Aortic Aneurysms, Aidin Baghbani, Safa Savadi, Titia A L Sulzer, Emanuel R Tenorio, Thomas Mesnard, Andrea Vacirca, Bernardo C Mendes, Naveed U Saqib, Steven Maximus, Ying Huang, Gustavo S Oderich

Faculty, Staff and Student Publications

Purpose: Familial history of aortic disease has been associated with increased risk of aneurysm-related complications after standard endovascular aortic repair. The aim of this study was to evaluate outcomes of fenestrated-branched endovascular aortic repair (FB-EVAR) for complex aortic aneurysms in patients with or without familial aortic aneurysms (FAAs).

Materials and methods: We reviewed the clinical data of consecutive patients enrolled in a prospective non-randomized study to investigate outcomes after FB-EVAR for treatment of complex aortic aneurysms between 2013 and 2022. Familial aortic aneurysm was defined as occurrence of an aortic aneurysm or dissections in a first- or second-degree relative and …

Myokine Sirpα Exacerbates Kidney Disease In Diabetes, Jiao Wu, Elisa Russo, Daniela Verzola, Qingtian Li, Helena Zhang, Bhuvaneswari Krishnan, David Sheikh-Hamad, Zhaoyong Hu, William E Mitch, Sandhya S Thomas

Faculty, Staff and Students Publications

Mechanisms responsible for skeletal muscle kidney crosstalk have not been defined. We have determined that a circulating mediator, signal regulatory protein α (SIRPα), impairs intracellular insulin-mediated functions. To elucidate the effect of myokine SIRPα on diabetic kidney disease (DKD), flox mice and muscle-specific (m-specific) SIRPα-KO mice were subjected to an obesity-induced model of diabetes, high-fat diet (HFD; 60%) or insulin-deficient hyperglycemia model, streptozotocin (STZ), and were subsequently exposed to anti-SIRPα monoclonal antibodies. In the obesity-induced diabetic mice, serum SIRPα increased. Genetic deletion of muscle SIRPα protected against obesity and improved intracellular insulin signaling in muscle and adipose tissue, with reduced …

Consensus Paper: Models Of Cerebellar Functions, Shinji Kakei, Andreea C Bostan, Timothy J Ebner, Mohammad Amin Fakharian, Hiroaki Gomi, Xavier Guell, Marie Hemelt, Huu Hoang, Court Hull, Masato Inoue, Takahiro Ishikawa, Masashi Kameda, Mitsuo Kawato, Shigeru Kitazawa, Mario Manto, Javier F Medina, Hiroshi Mitoma, Keiko Ohmae, Shogo Ohmae, Ken-Ichi Okada, Laurentiu S Popa, Jeremy D Schmahmann, Reza Shadmehr, Peter L Strick, Hirokazu Tanaka, Masaki Tanaka, Tadashi Yamazaki

Faculty, Staff and Students Publications

For a long time, from the nineteenth century to most of the twentieth century, the cerebellum was thought to be an organ that regulates movement. Towards the end of the twentieth century, the brain functions associated with the cerebellum began to extend beyond motor control. Now, there is a consensus that the cerebellum is involved not only in motor functions but also in the most basic autonomic functions and the most complex cognitive and emotional functions, with a focus on predictions and internal models. A new functional model of the cerebellum is needed to explain all layers of brain functions …

Fractionated Radiotherapy Adjuvant To Surgery Of Who-2 Meningioma With And Without Gross Total Resection: A Multicenter, Retrospective Cohort Study Of 1,452 Patients, Christian Mirian, Lasse Rehné Jensen, Adam Gorm Hoffmann, Tareq A Juratli, Andrea Daniela Maier, Pernilla Lindner, Anders Broechner, Sverre H Torp, Helen A Shih, Ramin A Morshed, Jacob S Young, Stephen T Magill, Walter Stummer, Dorothee Cäcilia Spille, Benjamin Brokinkel, Martin Proescholdt, Yasuhiro Kuroi, Konstantinos Gousias, Matthias Simon, Ricardo Prat-Acin, Stéphane Goutagny, Johannes Wach, Erdem Güresir, Junkoh Yamamoto, Young Zoon Kim, Joo Ho Lee, Daniel W Kim, Matthew Koshy, Donald M Cannon, Dennis C Shrieve, Chang-Ok Suh, Jong Hee Chang, Maria Kamenova, Sven Straumann, Jehuda Soleman, Ilker Y Eyüpoglu, Tony Catalan, Austin Lui, Philip V Theodosopoulos, Michael W Mcdermott, Pedro Góes, Fang Wang, Luis Souhami, Marie-Christine Guiot, Tamás Csonka, Toshiki Endo, Tejpal Gupta, Akash J Patel, Tiemo J Klisch, Jun Won Kim, Francesco Maiuri, Valeria Barresi, María Dolores Tabernero, Simon Skyrman, Mechthild Krause, Ian Law, Bjarne Winther Kristensen, Tina Nørgaard Munch, Torstein Meling, Kåre Fugleholm, Paul Blanche, Tiit Mathiesen

Faculty, Staff and Students Publications

Purpose

The role of adjuvant fractionated radiotherapy (aFRT) after gross total resection (GTR) of WHO-2 meningiomas remains unclear. We aimed to estimate the effect of aFRT on recurrence risk and survival following GTR and subtotal resection (STR).

Methods

We analyzed 1452 patients with WHO-2 from our international, multicenter database (followed between 1989 and 2019). Outcomes were recurrence (10-year follow-up) and death (5-year follow-up). Risk estimates were obtained using competing risks and survival analysis. Average treatment effects were estimated by G-computation, adjusted for potential confounding by age, sex, Simpson grade, Ki-67 proliferation index, location, country group (universal healthcare or not), …

“U’R-In(E)!- Urine-Albumin-Creatinine Ratio–The Old Kid On A New Block!, Yakubu Bene-Alhasan, Vijay Nambi, Christie Ballantyne

Faculty, Staff and Students Publications

No abstract provided.

High-Throughput Multi-Organ Proteomics Workflow For Drug Efficacy And Toxicity Analysis, Yun Xiong, Lin Tan, Wai-Kin Chan, Dandan Zhu, Huimin Zhang, Eric S Yin, Sri Ramya Donepudi, Jibin Ding, Bo Wei, Bao Tran, Sara Martinez, Iqbal Mahmud, Faiza Hanif Waghu, Hamish I Stewart, Daniel J Hermanson, Rehan Akbani, John N Weinstein, Junjie Chen, Philip L Lorenzi

Faculty, Staff and Student Publications

Rapid and comprehensive analysis of complex proteomes across large sample sets is vital for unlocking the potential of systems biology. We present a high-throughput mass spectrometry (MS) proteomics method that integrates narrow-window data-independent acquisition (nDIA) with short-gradient micro-flow chromatography, enabling profiling of >240 samples per day. This optimized MS approach identifies 6,201 and 7,466 human proteins with 1- and 2-min gradients, respectively. As a practical application, we analyzed 507 samples composed of 13 different tissues from mice treated with the enzyme-drug L-asparaginase (ASNase) or its glutaminase-free Q59L mutant, generating a quantitative profile of 11,472 proteins following drug treatment. The MS …

Ubiquitination-Directed Cytosolic Dna Degradation Governs Cgas-Sting-Mediated Immune Response To Dna Damage, Lei Li, Qi Ye, Jinlu Ma, Zixi Wang, Tianjie Liu, Yuzeshi Lei, Mingming Lu, Jialu Kang, Haohan Xiang, Buyun Li, Shan Xu, Ke Wang, Yule Chen, Jiaqi Chen, Bohan Ma, Wenyue Huang, Mengjiao Cai, Nan Wu, Yanqiang Li, Jiale An, Chongming Jiang, Rui Ye, Jing Liu, Steven H Lin, Yang Gao, Jian Ma, Lei Li

Faculty, Staff and Student Publications

Activation of cGAS-STING signaling in cancer cells requires cytosolic DNA produced by intrinsic or treatment-induced DNA damage. However, clinical efforts to exploit this pathway to improve immunotherapy have yielded limited success, highlighting gaps in understanding the link between DNA damage and immunotherapy. Here, we identify ubiquitination-directed cytosolic DNA degradation as a critical determinant for cGAS-STING activation following DNA damage. Mechanistically, the cytosolic DNA exonuclease TREX1 is degraded by the E3 ubiquitin ligase SPOP but is reversely stabilized by the deubiquitinase USP7. Cancer-associated SPOP mutations or USP7 overexpression elevate TREX1 levels, promoting cytosolic DNA degradation and impairing cGAS-STING-mediated immune activation. Notably, …

Prevalence Of Her2-Low Status And Outcomes In Early-Stage Her2-Negative Breast Cancer, Akshara Singareeka Raghavendra, Diane D Liu, Sarah Pasyar, Senthil Damodaran, Yu Shen, Jason A Mouabbi, Carlos H Barcenas, Debu Tripathy

Faculty, Staff and Student Publications

HER2-low breast cancer (IHC 1+ or 2+ without HER2 gene amplification) is a distinct and understudied subtype. In a cohort of 14,593 early-stage breast cancer patients treated at MD Anderson from 2006 to 2019, 60.4% were HER2-low. Multivariable analysis showed HER2-low status was independently associated with race, histologic subtype, higher nuclear grade and stage, and estrogen receptor (ER) positivity. Among 2464 patients receiving neoadjuvant chemotherapy, HER2-low status was not linked to pathologic complete response (pCR), overall survival (OS), or disease-free survival (DFS) compared to HER2-0 tumors. Factors predicting pCR included nuclear grade III, stage I, invasive ductal carcinoma, lower ER/PR …