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Tremor Modulation: A Systematic Review Of Resetting By Single-Pulse Transcranial Magnetic Stimulation ​, Handan Uzunçakmak Uyanik, Çağri Mesut Temuçi̇n

Turkish Journal of Medical Sciences

Background/aim: Tremor arises from mechanical, reflex, or central oscillatory mechanisms. Transcranial magnetic stimulation (TMS) can transiently perturb ongoing tremor and enables the quantitative assessment of phase resetting, offering circuit-level insight into tremor types. Although numerous studies have applied TMS-induced resetting, the findings have not been systematically reviewed. This study systematically reviews human studies evaluating TMS-induced tremor resetting across tremor types.

Materials and methods: A systematic search of PubMed and Google Scholar identified human studies using TMS to perturb tremor or rhythmic movement. Search terms included “tremor resetting,” “resetting of tremor,” “tremor phase shift,” “tremor phase reset,” “transcranial magnetic stimulation,” and …

Comparative Efficacy Of Repetitive Peripheral Magnetic Stimulation And Transcutaneous Electrical Nerve Stimulation In Upper Trapezius Myofascial Pain Syndrome ​, Shahri̇yar Kalbi̇yev, Şehi̇m Kutlay, Ati̇lla Hali̇l Elhan, Yeşi̇m Kurtai̇ş Aytür, Aysun Genç

Turkish Journal of Medical Sciences

Background/aim: In this prospective, randomized, single-blind study, the effects of repetitive peripheral magnetic stimulation (rPMS) and transcutaneous electrical nerve stimulation (TENS) on pain intensity, functional status, and tissue elasticity were evaluated in patients with upper trapezius myofascial pain syndrome (MPS).

Materials and methods: A total of 75 female patients were randomly allocated to three groups: rPMS, TENS, and sham rPMS. All participants were provided with an exercise program consisting of cervical range-of-motion (ROM), stretching, and strengthening exercises. Outcome measures included pain intensity assessed using the visual analog scale, pressure pain threshold (PPT), the Neck Disability Index, cervical ROM, SF-36 subscale …

A Model Based On Dynamic Hematologic Parameters To Predict Short Term Clinical Events In Pediatric Acute Lymphoblastic Leukemia ​, Neryal Tahta, Sali̇h Gözmen, Sultan Okur Acar

Turkish Journal of Medical Sciences

Background/aim: Acute lymphoblastic leukemia (ALL) treatment is frequently complicated by infections, emergency visits, and therapy interruptions, yet early prediction of short-term clinical deterioration remains challenging. Traditional prognostic markers rely on static laboratory values, whereas dynamic hematologic fluctuations may provide earlier warning signals. This study presents and internally validates a clinically applicable prediction model based on dynamic hematologic parameters and clinician-documented symptoms for predicting short-term (7-day) clinical events in children with ALL.

Materials and methods: Included in this retrospective study were 44 pediatric ALL patients treated with Berlin-Frankfurt-Münster-based protocols between January 2023 and June 2025. Weekly observation units were created by …

Biomechanical Analysis Of Skeletal Open Bite Treatment Methods: A Comparative Finite Element Study ​, Ömer Faruk Sari, Muhammed Hi̇lmi̇ Buyukcavus

Turkish Journal of Medical Sciences

Background/aim: The biomechanical effects of zygomatic anchorage plates, vertical chin-caps, and occipital headgear on dentofacial structures in patients with skeletal anterior open bite malocclusion were compared using three-dimensional finite element analysis.

Materials and methods: Three-dimensional finite element models were constructed based on computed tomography data obtained from a patient with skeletal anterior open bite. Simulation models representing zygomatic anchorage-supported intrusion, vertical chin-cap, and occipital headgear were generated under fixed orthodontic conditions. In each scenario, a unilateral force of 200 g (1.96 N) was applied along clinically relevant force vectors. Stress distributions in craniofacial bones, sutural structures, teeth, roots, and temporomandibular …

Effects Of Colchicine On Sah-Induced Vascular Damage In An Experimental Subarachnoid Hemorrhage Model ​, Emi̇ne Demi̇r, Cumaali̇ Demi̇rtaş, Cansu Sönmez, Eray Meti̇n Güler, Sarper Kocaoğlu, Hakan Beyaztaş, Eyüp Çeti̇n

Turkish Journal of Medical Sciences

Background/aim: Subarachnoid hemorrhage (SAH) is a severe cerebrovascular condition associated with high morbidity and mortality. Inflammation and oxidative stress play critical roles in its pathophysiology, especially in the development of secondary vascular damage. This study aimed to evaluate the protective effects of colchicine on vascular integrity and biochemical markers following SAH in an experimental rat model.

Materials and methods: Eighteen female Sprague Dawley rats were randomly divided into 3 groups: Control (no SAH), SAH (induced without treatment), and SAH + colchicine (received intraperitoneal colchicine at a dose of 1 mg/kg). SAH was induced by injecting autologous blood into the cisterna …

Retinal Microvascular And Neuroretinal Structural Changes In Pulmonary Arterial Hypertension Assessed By Octa: A Comparative Study ​, Murat Erdağ, Tunahan Çalişkan, Hakan Yildirim, Tarik Kivrak, Mehmet Canleblebi̇ci̇, Ali̇ Dal, Mehmet Balbaba

Turkish Journal of Medical Sciences

Background/aim: Pulmonary arterial hypertension (PAH) is a progressive disorder with systemic vasculopathy, and noninvasive assessment remains challenging. The retina, sharing anatomical similarities with the cerebral microcirculation, is an accessible site for visualizing systemic vascular compromise. This study quantitatively evaluated retinal microvascular and neuroretinal structural changes in PAH patients compared to healthy controls using optical coherence tomography angiography (OCTA).

Materials and methods: In this single-center, cross-sectional case-control study, 40 patients with group 1 PAH and 38 healthy controls were enrolled. For statistical independence, only the right eye of each participant was analyzed (total: 78 eyes). All participants underwent high-resolution OCTA imaging. …

Asthma Data In Türkiye Between 2016 And 2022: A Nationwide Descriptive And Observational Study Covering The Entire Adult Population, Kurtuluş Aksu, Gürgün Tuğçe Vural Solak, Nai̇m Ata, Mustafa Hami̇dullah Türkkani, Mustafa Mahi̇r Ülgü, Şuayi̇p Bi̇ri̇nci̇, Funda Aksu

Turkish Journal of Medical Sciences

Background/aim: Determining the current burden of asthma in countries is important in the diagnosis and follow-up of asthma patients and for the development of national health policies. Our study aimed to clarify the epidemiological and clinical data regarding asthmatic adults in Türkiye.

Materials and methods: The study was designed as a nationwide descriptive, observational cross-sectional study. Data on adult patients who were followed with the diagnosis of asthma in all public, private, and university hospitals in Türkiye between January 2016 and December 2022 were obtained from the e-Nabız database of the Ministry of Health and analyzed.

Results: The number of …

Association Between Superstition Levels On Sports-Specific Success Motivation In Active Athletes: A Study In Ankara Province ​, Canan Sayin Temur

Turkish Journal of Medical Sciences

Background/aim: When athletes perceive themselves as strong, they may seek to maintain their motivation through the control of random external factors. The present study examines the effect of superstitions on sports-specific success motivation among active athletes.

Materials and methods: The research population consisted of licensed athletes in the athletics branch, while the sample comprised licensed and active athletes based in Ankara. A total of 408 athletes participated in the research, including 201 women, and 207 men. The participants completed a three-part questionnaire consisting of a Personal Information Form, the Motivation in Sports Scale, and the Superstitious Beliefs and Behaviors in …

Sun-Macerated Hypericum Perforatum Oleates In Fixed Oils: Analytical Characterization And Comparative Wound-Healing Activity, Ci̇han Çapar, Esra Akkol, Ayli̇n Yaba, Ayhan Parmaksiz, Engi̇n Sümer, Erdem Yeşi̇lada

Turkish Journal of Medical Sciences

Background/aim: Hypericum perforatum L. oleates prepared in fixed oils have long been used for wound management due to their anti-inflammatory, antibacterial, and tissue-regenerative properties. The bioactivity of these oleates is mainly attributed to hypericin, hyperforin, and pseudohypericin. This study aimed to comparatively evaluate the wound-healing potential of H. perforatum oleates prepared in different fixed oils, including Olea europaea L. (olive), Sesamum indicum L. (sesame), Helianthus annuus L. (sunflower), and Nigella sativa L. (black seed).Materials and methodsFixed oils were characterized by GC–MS, while oleuropein in olive oil and thymoquinone in black seed oil were quantified by HPLC, and sesamin and sesamol …

Serum Phosphoproteome Alterations Associated With Cardiac Troponin I Levels In Acute Myocardial Infarction ​, Merve Öztuğ, Meltem Aşicioğlu, Konca Altinkaynak, Evren Kilinç

Turkish Journal of Medical Sciences

Background/aim: Acute myocardial infarction (AMI) triggers systemic biochemical responses, including dynamic changes in the phosphorylation status of circulating proteins. However, the phosphoproteomic profile of serum in the context of AMI remains insufficiently characterized. This study aimed to investigate serum phosphoproteomic alterations associated with AMI and to explore potential correlations with markers of cardiac injury.

Materials and methods: A comparative phosphoproteomic analysis was performed on serum samples obtained from eight patients with AMI and pooled healthy control samples. High-abundance serum proteins were depleted, and phosphopeptides were enriched using TiO2 phosphopeptide enrichment kit. Samples were analyzed by liquid chromatography–tandem mass spectrometry using …

The Importance Of Early Intraoperative Ultrasonography And The Relationship Between Surgical Technique And Allograft Function In Patients With Compartment Syndrome Following Renal Transplantation Surgery ​, Burak Yağdiran, Emre Karakaya, Ravana Ahmadli̇, Adem Şafak, Yağmur Kurtuluş, Nedi̇m Çekmen, Meri̇ç Yavuz Çolak, Mehmet Haberal

Turkish Journal of Medical Sciences

Background/aim: In rare cases, patients undergoing renal transplantation (RT) may develop renal allograft compartment syndrome (RACS) if the renal volume is larger than the retroperitoneal space prepared in the iliac fossa. In such cases, the optimal treatment is early decompression surgery. The primary aim of the present descriptive and comparative study is not to identify the optimal surgical technique, but rather to evaluate the role of early Doppler ultrasonography (DUSG) in the recognition of renal allograft compartment syndrome and to assess outcomes following timely decompressive interventions.

Materials and methods: A total of 275 patients were examined retrospectively for the study, …

Red Cell Cryopreservation For Serologic Testing: Bulk Freezing With Polyvinylpyrrolidone (Pvp) ​, Di̇lek Gürlek Gökçebay, Willy Albert Flegel

Turkish Journal of Medical Sciences

Background/aim: Red cell cryopreservation is essential for immunohematology reference laboratories. Various cryopreservation methods maintain the structural integrity of red cells, such as bulk freezing with glycerol and droplet freezing with polyvinylpyrrolidone (PVP). In this paper, we provide a technical note with real-world data and report our experience with a modified PVP bulk-freezing method in a transfusion medicine setting.Materials and methods. Red cells were separated from whole blood samples and incubated for 1 h at room temperature with PVP with slow agitation or no agitation before freezing. Instead of using the established method of shock freezing droplets in liquid nitrogen, the …

Res-Mnd: Motor Neuron Disease Detection Using Res4net–Convolutional Block Attention Module ​, Shuriya Balusamy, Rakesh Sivalingam, Shobana Rooben, Sony Helen

Turkish Journal of Medical Sciences

Background/aim: Motor neuron diseases (MNDs) are progressive neurological disorders that cause muscle weakness and wasting as a result of ongoing neurodegeneration. MNDs require comprehensive diagnostic approaches that integrate clinical symptoms, laboratory findings, and multimodal imaging data.

Materials and methods: In this study, a novel residual network for motor neuron disease detection (RES-MND) framework is proposed for detecting MNDs using multimodal imaging data. Initially, the input multimodal images, including MRI, CT, PET, and DTI, are preprocessed using adaptive dynamic histogram equalization and the total variation bilateral filter. The preprocessed multimodal images are processed through Res4Net-CBAM for feature extraction to enhance image …

Role Of Novel Renal Biomarkers In Prognosticating Patients With Chronic Kidney Disease: A Prospective Cohort Study, Raghavan Padmanabhan, Kaviya Manoharan, Melina Sahay, Pooja Bhujangarao, Luxitaa Goenka, Solai Priya, Kumaraswamy Subramaniyan, Damal Kandadai Sriram, Melvin George

Turkish Journal of Medical Sciences

Background/aim: Several biomarkers have been assessed for the diagnosis of chronic kidney disease (CKD). However, limited data are available regarding their ability to predict mortality in CKD. The aim of this study was to assess the ability of lipocalin-2, receptor for advanced glycation end products (RAGE), tissue inhibitor of metalloproteinase 1 (TIMP-1), osteopontin, and trefoil factor 3 (TFF-3) in predicting the prognosis of patients with CKD.

Materials and methods: We included patients with CKD as defined by an estimated glomerular filtration rate of <60 mL/min/1.73 m2 of either sex who were above the age of 18 years. Patients with a history of acute-on-chronic kidney disease were excluded. The novel markers of interest were estimated from patients’ plasma samples using the multiplex enzyme-linked immunosorbent assay. These patients were followed for 1 year to assess mortality.

Results: The median (with interquartile range) plasma concentrations of lipocalin-2, RAGE, TIMP-1, osteopontin, and TFF-3 were 56.9 …

Post-Exposure Prophylaxis For Hiv Among Healthcare Workers In Türkiye: A Descriptive, Multicenter Retrospective Study, Veysel Akca, İlkay Akbulut, Gül Ruhsar Yilmaz, Alper Tahmaz, Nefi̇se Öztoprak Çuvalci, İlknur Esen Yildiz, Mehmet Çabalak, Şeyma Topal, Özgür Günal, Bi̇rcan Kayaaslan, Fatma Eser, Tuba Damar Çakirca, Deni̇z Ölmez, Ali̇ye Baştuğ, Fi̇rdevs Aksoy, Hani̇fe Nur Karakoç Parlayan, Beyza Süllü, Damla Verendağ, Hatun Öztürk Çeri̇k, Mehmet Ali̇ Aşan, Ayhan Akbulut, Gülden Eser Karlidağ, Behi̇ce Kurtaran, Hüsnü Pullukçu, Turhan Togan

Turkish Journal of Medical Sciences

Background/aim: Post-exposure prophylaxis (PEP) for human immunodeficiency virus (HIV) plays a vital role in preventing transmission among healthcare workers following occupational exposure. Despite its clinical importance, epidemiological data regarding PEP implementation in Türkiye remain scarce. This study aimed to assess PEP practices, prophylactic treatment regimens, and follow-up outcomes among healthcare workers at risk of occupational HIV exposure.

Materials and methods: This retrospective, multicenter study was conducted between January 2020 and December 2024 across 16 healthcare facilities participating in the National HIV/AIDS Working Group. Healthcare workers aged 18 years and older who presented for evaluation following occupational exposure to HIV were …

Artificial Intelligence-Assisted Neuropharmacology: Reshaping Drug Discovery And Translational Strategies For Neurological Diseases ​, Pri̇yanka Rathee, Suni̇thi̇ Lohan, Sari̇ta Khatkar, Neelam Mali̇k, Esra Akkol, Renu Sehrawat, Pooja Rathee, Anurag Khatkar

Turkish Journal of Medical Sciences

The rapid expansion of data-driven technologies, particularly machine learning (ML) and artificial intelligence (AI), has substantially influenced biomedical research and drug discovery. In neuropharmacology, the availability of large-scale genomic, proteomic, chemical, and clinical datasets has stimulated the adoption of AI-based approaches to address persistent challenges in neurological drug development, including high attrition rates and the scarcity of disease-modifying therapies. Unlike prior reviews that broadly discuss AI applications in drug discovery or neurology, this narrative review focuses specifically on neuropharmacology, with an emphasis on translational relevance, disease-oriented examples, and real-world constraints. We critically examine the application of AI and ML across …

Impact Of Two Sedation Protocols On Cardiac Electrophysiology During Spinal Anesthesia ​, Selvi̇naz Durantaş, Burak Nalbant, Fatma Kavak Akelma, Gökhan Erdem, Abdulkadi̇r But

Turkish Journal of Medical Sciences

Background/aim: Perioperative factors such as anesthetic drugs, central blocks, surgical stress, pain, and anxiety can affect cardiac electrophysiology and increase the risk of arrhythmias. Arrhythmia susceptibility can be assessed using ventricular markers such as the QT interval (QT), heart rate-corrected QT interval (QTc), QT dispersion (QTd), time between peak and end of T wave (Tp–e), cardiac electrophysiologic balance index (iCEB), and heart rate-corrected index of cardiac electrophysiologic balance (iCEBc), obtained from noninvasive electrocardiography (ECG) data. This study compared the effects of propofol and dexmedetomidine sedation on these parameters in patients undergoing total knee arthroplasty performed under spinal anesthesia.

Materials and …

Analysis Of Calr-Mutated Essential Thrombocythemia As A Distinct Disease Entity Compared With Jak2 V617f-Mutated And Triple-Negative Patients ​, Gökhan Sami̇ Aydin, Eli̇f Aksoy, İpek Yönal Hi̇ndi̇lerden, Aynur Dağlar Aday, Emi̇ne Gültürk, Meli̇ha Nalçaci, Fehmi̇ Hi̇ndi̇lerden

Turkish Journal of Medical Sciences

Background/aim: Calreticulin (CALR) mutations in essential thrombocythemia (ET) are associated with younger age, higher platelet counts, and lower thrombosis rates. The present study analyzes the demographic, laboratory, and clinical features of the CALR mutation and its prognostic impact.

Materials and methods: The clinical impact of CALR mutations was assessed in 391 ET patients.

Results: CALR-mutation patients were more commonly male than JAK2 V617F-positive and triple-negative patients. Age at diagnosis was similar across all groups, although patients with type 2 CALR mutations were younger than those with nontype 1/nontype 2 mutations. Compared with JAK2 V617F-positive patients, CALR-mutation patients had lower leukocyte …

Comprehensive Profiling Of Gut Microbiota In Postmenopausal Osteoporosis ​, Gülsemi̇n Ertürk Çeli̇k, Sedat Yildiz, Münevver Aksoy Bektaş, Yaprak Engi̇n-Üstün

Turkish Journal of Medical Sciences

Background/aim: Osteoporosis is a multifactorial skeletal disease that predominantly affects postmenopausal women and is characterized by reduced bone mass and an increased risk of fractures. Growing evidence suggests that the gut microbiota plays a pivotal role in bone metabolism through immunological, endocrine, and metabolic pathways, forming the basis of the so-called gut– bone axis. This study aimed to characterize gut microbiota composition in postmenopausal women with osteoporosis compared with healthy controls.

Materials and methods: Forty postmenopausal women aged 55–65 years were classified into osteoporosis (n = 20) and healthy control (n = 20) groups based on dual-energy X-ray absorptiometry T-scores. …

Prognostic Significance And Clinicopathological Associations Of Tumor Budding And Poorly Differentiated Clusters In Endometrioid Endometrial Carcinoma ​, Hani̇fe Seda Mavi̇li̇, Ömer Atmiş, Fatma Seher Pehli̇van, Fatma Sezen Çavdaroğlu Deveci̇, Ali̇ Riza Kandi̇loğlu

Turkish Journal of Medical Sciences

Background/aim: Tumor budding (TB) and poorly differentiated clusters (PDCs) are histopathological parameters that have been associated with poor prognosis in various malignancies, particularly colorectal carcinoma. Although numerous studies have demonstrated an association between the microcystic, elongated, and fragmented (MELF) pattern in endometrial carcinomas and lymphovascular invasion as well as lymph node metastasis, the literature regarding TB and PDCs in this context remains limited. This study aimed to investigate the potential associations of the MELF pattern, TB, and PDCs with overall survival, progression-free survival, and clinicopathological parameters in cases of endometrioid endometrial carcinoma (EEC).

Materials and methods: A total of 190 …

Acute Traumatic Aortic Injury: What The Radiologist Needs To Know, Kristina Ramirez-Garcia, Catalina Jaramillo, Emma Ferguson, Jason Au, Erika Odisio, Gustavo S Oderich, Daniel Ocazionez, Cihan Duran, Thanila Macedo

Faculty, Staff and Students Publications

Acute traumatic aortic injury (ATAI) is a rare but life-threatening consequence of blunt trauma that requires prompt diagnosis and accurate imaging assessment. This review presents an imaging-based approach to ATAI, with emphasis on computed tomography angiography (CTA) as the first-line modality for diagnosis, grading, treatment planning, and follow-up. CTA enables the detection of both direct and indirect signs while also allowing for the assessment of lesion severity, extent, and associated findings that may influence management. Familiarity with common mimics and anatomic variants improves diagnostic confidence and helps avoid false positive interpretations. Careful protocol optimization, including multiphasic acquisition, bolus timing, and …

A Multidomain Peptide Hydrogel-Liposome Composite For Controlled Release Of A Cyclic Dinucleotide In Oral Cancer, Joseph W R Swain, Andrea H Molina, Gemalene M Sunga, Danielle Chew-Martinez, Neeraja Dharmaraj, Alejandra Cobos Perez, Arghadip Dey, Ephraim J Vázquez-Rosado, Simon Young, Jeffrey D Hartgerink

Faculty, Staff and Student Publications

While immunotherapy is a promising treatment strategy for cancer, the majority of head and neck squamous cell carcinoma (HNSCC) patients treated with single-agent immunotherapy do not respond. Therefore, researchers are investigating combination treatments with immunostimulatory molecules that can maximize anti-tumor responses. Cyclic dinucleotides (CDNs) are STING agonists that hold promise in combination approaches, but they require frequent intratumoral administration when used in both preclinical models of HNSCC and clinical trials. To reduce administration frequency, we have created a peptide hydrogel–liposome composite system, K2-Lip(CDN), for local and prolonged availability of CDN. We investigated the loading limits of cationic liposomes in both …

H3 Dopaminylation And Camkii Modulate Diffuse Midline Glioma Response To Cdk9 Inhibition, Rebecca L Murdaugh, Brittany R Eberl, Rosemary U Richard, Ena I Campos-Hensley, Adanze N Nnyagu, W Austin Elam, Ai-Ni Tsao, Jack R Tremblay, Ruiying Ma, Alfred K Dei-Ampeh, Kieu Pham, Daniel C Kraushaar, Kwanha Yu, Calla M Olson, Akdes Serin-Harmanci, Benjamin Deneen, Jamie N Anastas

Faculty, Staff and Students Publications

Aberrant neurotransmitter signaling and transcriptional dysregulation are hallmarks of gliomagenesis and represent potential therapeutic targets. Monoamine neurotransmitters such as dopamine and serotonin primarily activate GPCRs but can also function epigenetically as histone H3 modifications. Here, we uncover mechanisms of crosstalk between monoamine neurotransmitter signaling, H3 dopaminylation, and RNA polymerase II (Pol2) transcription in diffuse midline glioma (DMG). We find that co-treatment with Pol2-targeting CDK9 inhibitors (CDK9i) and FDA-approved neuropsychiatric drugs, including selective serotonin reuptake inhibitors (SSRIs), synergistically reduces DMG growth. Mechanistically, CDK9i+SSRI treatment alters H3 dopaminylation patterns and represses synaptic and neurodevelopmental gene transcription associated with CDK9i resistance. Further phospho-proteomic …

Single-Cell Tcr Mapping Reveals Spatially Coordinated T Cell States In Head And Neck Cancer, Kelli A Mccord, Emerald Kan, Sean Hyslop, Amanda Y Xia, Colby J Hofferek, James S Lewis, Andreas Wieland, David J Hernandez, Vlad C Sandulache, William H Hudson

Faculty, Staff and Students Publications

Current spatial T cell receptor (TCR) profiling approaches lack the resolution needed to link clonal identity, transcriptional state, and spatial positioning of individual T cells in the tumor microenvironment. Here, we introduce a spatial TCR profiling strategy that resolves individual T cell clones together with their transcriptional states at single-cell resolution and applied the method to human head and neck squamous cell carcinoma. Presumed tumor-specific T cells were broadly dispersed throughout the tumor microenvironment, and cells of the same clone occupied distinct transcriptional states in different locations: Immune-rich regions contained more plastic or progenitor cells, whereas tumor-dense regions were enriched …

Loss Of Znrf3/Rnf43 Unleashes Egrfr In Cancer, Fei Yue, Amy T Ku, Payton D Stevens, Megan N Michalski, Weiyu Jiang, Jianghua Tu, Zhongcheng Shi, Yongchao Dou, Yi Wang, Xin-Hua Feng, Galen Hostetter, Xiangwei Wu, Shixia Huang, Noah F Shroyer, Bing Zhang, Bart O Williams, Qingyun Liu, Xia Lin, Yi Li

Faculty, Staff and Students Publications

ZNRF3 and RNF43 are closely related transmembrane E3 ubiquitin ligases with significant roles in development and cancer. Conventionally, their biological functions have been associated with regulating WNT signaling receptor ubiquitination and degradation. However, our proteogenomic studies have revealed EGFR as the protein most negatively correlated with ZNRF3/RNF43 mRNA levels in multiple human cancers. Through biochemical investigations, we demonstrate that ZNRF3/RNF43 interact with EGFR via their extracellular domains, leading to EGFR ubiquitination and subsequent degradation facilitated by the E3 ligase RING domain. Overexpression of ZNRF3 reduces EGFR levels and suppresses cancer cell growth in vitro and in vivo, whereas knockout of …

Tracking Hiv Through Wastewater: Ethical Considerations In Public Health Surveillance, Faith E Fletcher, Olive R Pertuit, Catherine Troisi, Jelani Kerr, Dakotah Kinsella, Grace Elizabeth White, Steven Vargas, Anthony Maresso, Thomas P Giordano

Faculty, Staff and Students Publications

Ending the HIV epidemic requires timely identification of new HIV infections and promptly linking patients to high-quality care. Innovative methods are needed to capture real-time HIV incidence data to more effectively identify persons in need of HIV care access. Emerging advancements in wastewater surveillance (WWS) offer the potential to identify geographic areas with elevated prevalence of detectable viral loads among people who are undiagnosed or no longer receiving care, enabling more targeted interventions to reduce HIV transmission. The introduction of new public health technologies requires balancing potential risks with the significant clinical and population-level benefits of decreasing the number of …

Versatile Smad2 And Smad3 Epitope-Tagged Mouse Models For Genomic Profiling Of Tgfβ Signaling: Uncovering Gdf9-Smad2/3 Targets, Zian Liao, Qian Zhang, Keisuke Shimada, Kaori Nozawa, Suni Tang, Masahito Ikawa, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Transforming growth factor β (TGFβ) signaling pathways are integral for a plethora of biological processes. SMAD2 and SMAD3 are the principal transcriptional effectors of TGFβ superfamily ligands, yet quantitative, genome-wide mapping of their DNA-associated complexes under physiological contexts has remained limited due to the lack of specific, robust models. Here, we generated two versatile epitope-tagged mouse models in which endogenous SMAD2 and SMAD3 proteins are globally tagged with hemagglutinin (HA) and podoplanin (PA) sequences, respectively, enabling high-fidelity profiling of SMAD2 and SMAD3 binding across tissues. To demonstrate the broad application of our models, we exemplified the usage of our lines …

Claudins Interact With Lilrb Immune Inhibitory Receptors To Promote Myeloid Immunosuppression In Cancer, Xiaoye Liu, Ryan Huang, Zhiqiang Ku, Jingjing Xie, Heyu Chen, Yubo He, Qi Lou, Chengcheng Zhang, Xing Yang, Cheryl Lewis, Jade Homsi, Ankit Gupta, Lei Dong, Kenian Chen, Annabel Tu, Liming Du, Hailong Yu, Qing Hu, Meng Fang, Bufan Li, A E M Adan Khan, Caroline Simith, Samuel John, Lin Xu, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang

The Brown Foundation: Institute of Molecular Medicine

The mechanisms underlying tumor cell-myeloid cell interactions in the tumor microenvironment (TME) remain unclear, and predictive biomarkers for patient response to myeloid checkpoint blockade are lacking. This study identified specific binding between tight junction claudins (CLDNs) and leukocyte immunoglobulin-like receptor subfamily B2 (LILRB2) and LILRB5. In multiple human cancer cohorts, the spatial proximity of LILRB2-positive macrophages to CLDN-expressing cancer cells correlated with clinical outcomes, highlighting this spatial relationship as a potential biomarker. In syngeneic LILRB2-transgenic and humanized mouse models, CLDN18.2-LILRB2 interactions triggered bidirectional signaling, enhanced the immunosuppressive activity of myeloid cells, and accelerated tumor progression. These effects were reversed by …

Nanog Proximity Proteomics Maps Neighborhood Hubs Linked To Mesenchymal Stem Cell Stemness And Chromatin Control, Kyoung-Jae Choi, Michail Tyryshkin, Harathi Jonnagaddala, Allan Chris M Ferreon, Marian Kalocsay, Josephine C Ferreon

Faculty, Staff and Students Publications

NANOG overexpression has been reported to reverse aging-associated decline in mesenchymal stem/stromal cell (MSC) function, but the molecular machinery engaged by NANOG in MSCs remains incompletely defined. Here, we applied APEX proximity labeling coupled with quantitative mass spectrometry to define the NANOG proximity interactome (proxeome) in human MSCs. Of 1040 quantified proteins, 828 were significantly enriched in the APEX-NANOG (H2O2 labeling) samples, consistent with a broad NANOG-centered neighborhood rather than a single stoichiometric complex. Enriched proteins encompass RNA-processing pathways (including splicing/RNP factors and selected m6A-related proteins), transcriptional coactivation and elongation control (Mediator and 7SK/P-TEFb regulators), chromatin repression/poising modules (Polycomb and …

Effects Of Tubulin-Binding Medications On Microplastic Uptake And Cyotoskeletal Functionality Across Diverse Cell Types, Alejandra D. Favela Santos

Posters - 2026

• Microtubules are composed of of a- and b- tubulin heterodimers, vital for cell structure, shape, and intracellular transport • Microtubules are also useful as they separate chromosomes during cell division • Microplastics (< 5 mm) are considered a health threat and have been found throughout the whole body (1) o In several studies, microplastics have been correlated to higher rates cardiorespiratory issues, endocrine disruption, and cancer (1) • Tubulin-binding medications are widely used as chemotherapeutic agents as they are known for disrupting cell division and targeting tubulin (2,3) o In this study, these medications were used to determine whether microtubules play a role in microplastic uptake § Colchicine typically binds to tubulins and arrests polymerization and growth § Nocodazole disrupts polymerization and prevents spindle formation § Vinblastine inhibits microtubule assembly and disruptions miotic spindle formation.

• The purpose of this study was to determine if different concentrations of tubulin-binding medications affect microplastic uptake o C2C12, RAW 264.7, and MOVAS cell lines were used to evaluate whether these changes are cell type specific 

If microtubule dynamics are disrupted, microplastic uptake can be affect in a concentration-dependent and cell type- specific manner.