Medicine and Health 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. …

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 …

Weight Loss Patterns And Clinical Outcomes Of Glp1 Receptor Agonists In Breast Cancer Survivors, Jasmine S Sukumar, Akshara Singareeka Raghavendra, Sarah Pasyar, Roland L Bassett, Debu Tripathy, Carlos H Barcenas, Karen M Basen-Engquist, Banu K Arun

Faculty, Staff and Student Publications

Use of glucagon-like peptide-1 receptor agonists (GLP1-RA) for weight loss is increasing; implications in breast cancer (BC) survivors remain unclear.This retrospective cohort study evaluated treatment patterns, weight loss, and outcomes in BC survivors at an academic institution receiving GLP1-RA. We evaluated patients with non-metastatic (ductal carcinoma in situ (DCIS), stage 1-3) BC who received GLP1-RA (2005 - 2024). Linear regression models estimated associations between weight change and clinical factors. After excluding DCIS, propensity score matching (1:2) was used to match patients who received GLP1-RA with patients who did not, based on confounding covariates. Kaplan-Meier estimates and log-rank tests compared disease-free …

Heavy Metals As Endocrine Disruptors, Arzu Or Koca

Turkish Journal of Medical Sciences

Heavy metals are widely recognized as endocrine-disrupting agents primarily originating from anthropogenic sources and persisting in soil, air, and water. This review aims to present an updated and comprehensive synthesis of current evidence regarding the endocrine-disrupting effects of heavy metals, with particular emphasis on their roles in the pathogenesis of common endocrine and metabolic disorders. The toxicological impact of these elements depends on the level and duration of exposure, their chemical form, and the biological susceptibility of target tissues. Chronic exposure, even at low doses, has been implicated in the development of diabetes mellitus, obesity, autoimmune thyroiditis, thyroid cancer, pubertal …

Prevalence Of Gout In The Sincan District Of Ankara, Türkiye: A Primary Care-Based Cross-Sectional Study, Riza Can Kardaş, Yasemi̇n Ünsal, Derya Yildirim, Hakan Tüzün, Mustafa Necmi̇ İlhan, Hami̇t Küçük, Abdurrahman Tufan, M. Aki̇f Öztürk

Turkish Journal of Medical Sciences

Background/aim: Gout, the most prevalent form of inflammatory arthritis, has shown a global increase in prevalence; however, data from Türkiye remain scarce, inconsistent, and largely confined to western regions. This study aimed to estimate the prevalence of gout among adults in the Sincan district of Ankara, Türkiye, and to provide updated data from a previously understudied region.

Materials and methods: This cross-sectional, community-based study employed a multistage design. Adults aged ≥18 years who presented to selected family health centers in Sincan between February and June 2023 were screened using a structured questionnaire. Individuals with suspected gout underwent comprehensive clinical evaluation, …

Assessing The Influence Of Third Molar Classification On The Risk Of Caries In Adjacent Teeth, Si̇nan Yasi̇n Ertem, Fati̇h Doğanoğlu, Fehi̇me Alkan Aygör

Turkish Journal of Medical Sciences

Background/aim: This study aimed to evaluate the relationship between the impaction level and angulation of third molars and the incidence of caries in the adjacent second molars.

Materials and methods: A total of 690 panoramic radiographs obtained from patients at Ankara Yıldırım Beyazıt University between May 2022 and January 2024 were retrospectively analyzed. Third molars were classified based on their eruption status using the Pell and Gregory classification (levels A, B, and C), and angulation (mesioangular, distoangular, vertical, horizontal, and inverted). The presence of caries in adjacent second molars was assessed using the international caries detection and assessment system/international caries …

Developing Liposomal And Ethosomal Formulations With Potent Antioxidant And Cytotoxic Effects: Unleashing The Power Of Achillea Millefolium L., Esra Akkol, Sena Akçakaya Mutlu, Gökçe Şeker Karatoprak, Çi̇ğdem Yücel, Selen İlgün, Esra Köngül Şafak, Murat Koç

Turkish Journal of Medical Sciences

Background/aim: Achillea millefolium L., a plant rich in phenolics and flavonoids, has been shown to possess strong antioxidant and cytotoxic properties. However, no pharmaceutical formulations have yet been developed for this plant. This study aimed to create and characterize an A. millefolium extract with high antioxidant and cytotoxic activities.

Materials and methods: A total of 10 extracts were prepared from the plant’s aerial parts using ethanol concentrations ranging from 10% to 99.9%. The DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) radical scavenging tests were used to assess the antioxidant properties of the extracts. Cytotoxic effects were assessed using the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium …

Nonclassical Philadelphia-Positive Fish Signal Patterns In Cml And Seven Cases With Variant Philadelphia, Sevgi̇ Işik, Oğuz Çi̇li̇ngi̇r, Gülçi̇n Günden, Fi̇li̇z Yavaşoğlu, Hülya Özen, Mert Burak Raşan, Beyhan Durak Aras

Turkish Journal of Medical Sciences

Background/aim: Chronic myeloid leukemia (CML) is characterized by the Philadelphia chromosome (Ph), which occurs as a result of t(9;22). In 5%–10% of CML cases, variant t(9;22)s are observed. Additionally, while t(9;22) is formed, deletions can be observed in chromosomes 9 and 22. These deletions are observed more frequently in variant t(9;22). There is conflicting information in the literature about the prognostic effects of variant t(9;22) and deletions of 9q and 22q. There is also limited information about the frequency and breakpoints of other chromosomes involved in the variant t(9;22). Signal patterns other than the classical signal pattern of FISH analysis …

Small Patients, Big Gaps: Why Adult Crrt Timing Evidence Does Not Translate To Children, Katja M Gist, Dana Y Fuhrman, Ayse Akcan-Arikan

Faculty, Staff and Students Publications

No abstract provided.

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.].

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. …

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 …

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 …

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.

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 …

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, …

Performance Of An Automated Sleep Scoring Approach For Actigraphy Data In Children And Adolescents, Pin-Wei Chen, Erica C Jansen, Christopher M Cielo, Ariel A Williamson, Margaret Banker, Michael Kaye, Peter X K Song, Karen E Peterson, Alejandra Cantoral, Martha María Téllez-Rojo, Cathy Goldstein, Khadija Zanna, Akane Sano, Jennette P Moreno, Heidi Kalkwarf, Babette S Zemel, Jonathan A Mitchell

Children’s Nutrition Research Center Staff Publications

Study objectives: GGIR is an R package for processing raw acceleration data to estimate sleep health parameters. We aimed to (1) assess the performance of three sleep algorithms within GGIR against PSG for detecting sleep/wake in clinically referred, typically-developing children (criterion validity); and (2) describe GGIR-derived sleep estimates from typically developing children enrolled in multiple cohort studies (face validity).

Methods: For criterion evaluation, children (8-16 years, N = 30) wore an actigraphy device for one night during in-lab polysomnography with performance assessed using epoch-by-epoch analyses. For face validity evaluation, four community/free living datasets were used: (1) Bone Mineral Accretion in …

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, …

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 …

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 …

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.

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, …