Medical Genetics Commons^™

Evolving Molecular Subtypes Of Gastric Cancer: From Past Classifications To Present Consensus And Future Directions For Precision Therapy, Ju-Seog Lee

Faculty, Staff and Student Publications

Gastric cancer is a biologically heterogeneous disease. The advent of high-throughput multi-omic technologies has revolutionized our understanding of gastric cancer by deconstructing this heterogeneous entity into distinct and more homogeneous molecular subtypes. Early classifications based on gene expression, methylation, and histology have laid the groundwork for multi-omic frameworks proposed by The Cancer Genome Atlas and Asian Cancer Research Group, which established the foundation of modern molecular taxonomy. Subsequent integrative efforts, particularly the Consensus Genomic Subtypes (Super 6) model, have unified this collected information into clinically relevant subtypes that bridge prognostic stratification with treatment strategies. Established biomarkers such as human epidermal …

A Combinatorial Approach To Synthetic Data Generation For Machine Learning, Krishna Khadka, Jaganmohan Chandrasekaran, Yu Lei, Raghu Kacker, D Richard Kuhn

Faculty, Staff and Student Publications

Datasets used in machine learning often contain sensitive information, including personally identifiable health and financial details. A common challenge faced by organizations and researchers is the risk of privacy breaches when using real-world data. Synthetic data can be used as an alternative to the real-world data. In existing synthetic data generation techniques, an encoder processes the real-world data to map it into a lower-dimensional latent space. Random sampling is then performed in this latent space. Subsequently, a decoder network is utilized to generate synthetic data from these sampled points in the latent space. Such approaches typically require generating a large …

Functional, Pharmacogenomic, And Immune Landscapes Of Long Non-Coding Rnas In Cancer, Runhao Wang, Mei Luo, Yuan Liu, Jingwen Yang, Yamei Chen, Chengxuan Chen, Lifei Ma, Stephanie Ding, James Wengler, Yong Zang, Bora Lim, Wenbo Li, Liuqing Yang, Chunru Lin, Lixia Diao, Leng Han

Faculty, Staff and Student Publications

Long non-coding RNAs (lncRNAs) are emerging as key regulators in cancer, with significant potential as diagnostic, prognostic, and therapeutic targets. Here, this work systematically analyzes lncRNA associations with targeted therapies and immunotherapies across 33 cancer types using The Cancer Genome Atlas (TCGA) and real-world datasets. This work identifies 53,173 lncRNA-pathway associations, millions of lncRNA-drug response associations (via CancerRxTissue and VAEN), and extensive correlations with immune checkpoints and infiltration. This work further identifies 69 lncRNAs associated with immunotherapy response and 2,611 differentially expressed lncRNAs between low and high objective response rate (ORR) groups. Additionally, two lncRNAs are correlated with immune-related adverse …

Knowledge Distillation And Dataset Distillation Of Large Language Models: Emerging Trends, Challenges, And Future Directions, Luyang Fang, Xiaowei Yu, Jiazhang Cai, Yongkai Chen, Shushan Wu, Zhengliang Liu, Zhenyuan Yang, Haoran Lu, Xilin Gong, Yufang Liu, Terry Ma, Wei Ruan, Ali Abbasi, Jing Zhang, Tao Wang, Ehsan Latif, Wei Liu, Wei Zhang, Soheil Kolouri, Xiaoming Zhai, Dajiang Zhu, Wenxuan Zhong, Tianming Liu, Ping Ma

Faculty, Staff and Student Publications

The exponential growth of Large Language Models (LLMs) continues to highlight the need for efficient strategies to meet ever-expanding computational and data demands. This survey provides a comprehensive analysis of two complementary paradigms: Knowledge Distillation (KD) and Dataset Distillation (DD), both aimed at compressing LLMs while preserving their advanced reasoning capabilities and linguistic diversity. We first examine key methodologies in KD, such as task-specific alignment, rationale-based training, and multi-teacher frameworks, alongside DD techniques that synthesize compact, high-impact datasets through optimization-based gradient matching, latent space regularization, and generative synthesis. Building on these foundations, we explore how integrating KD and DD can …

A Preliminary Investigation Of Research Collaboration Through Scientific Paper Co-Authorship In The Gulf Of Mexico, Juliet Vallejo, Evelyn Roozee, Dongkyu Kim, Andrew M Song, Christopher A Gabler, Jasper De Vries, Antonia Sohns, Gordon M Hickey, Owen Temby

Faculty, Staff and Student Publications

It is well known that publications with collaborators from external institutions increase citations. This effect scales with spatial distance. There are also many barriers to long-distance collaborations, including linguistic differences, funding constraints, and the incremental costs of remote collaboration. This paper uses the Gulf of Mexico as a case study to examine long-distance research collaboration because it consists of three countries with diverse development levels and two prominent diplomatic languages, within a singular regional ecosystem of tremendous natural and economic value. This paper uses bibliometric network analysis to examine scientific research article co-authorship in the Gulf of Mexico from 2000 …

Digital Communication Strategies For Culinary Medicine In Cancer Prevention And Survivorship: Information-Seeking Habits And Content Preferences Of Online Cooking Media Among Adults Participating In Four Cancer Prevention And Control Cohort Studies, Margaret Raber, Sara Fares, Maria Vazquez, Larkin Strong, Carrie Daniel-Macdougall, Lorna Mcneill, Karen Basen-Engquist

Faculty, Staff and Student Publications

Introduction

Poor diet and excess weight have been linked to increased risk for at least 13 types of cancer. Culinary medicine utilizes experiential cooking skill development to improve individuals’ capacity for healthy eating. Digital communication strategies offer pathways for scalable culinary medicine interventions, but little research has explored how online cooking tools could be leveraged for cancer prevention messaging. We conducted a cross-sectional survey study exploring online cooking information-seeking habits and content preferences among participants in four cancer prevention and control cohorts to inform future digital culinary medicine interventions.

Methods

A cross-sectional survey study was conducted with a convenience sample …

Prickle4 Drives Microenvironmental Remodeling And Resistance To Parp Inhibition In Idh-Mutant Glioma, Ju Yang, Hua Yang, Yifan Yuan, Chenyang Zhang, Ziwei Fu, Yanyan Chen, Yinghong Xiong, Shuyu Chen, Kexin Ling, Ying Liu, Jason T Huse, Bo Chen, Timothy A Chan, Zengxin Qi, Zhao Zhang, Xiuping Liu, Yuxiang Wang

Faculty, Staff and Student Publications

Mutations in isocitrate dehydrogenase (IDH) genes sensitize gliomas to PARP inhibition (PARPi) by inducing epigenetic reprogramming of DNA damage repair circuits. However, tumors treated with PARPi eventually relapse despite initial responsiveness. In this study, it is demonstrated that the anti-angiogenic agent lenvatinib synergizes effectively with PARPi, resulting in substantial tumor regression and significantly extended survival. Genomic analysis of tumors reveals that PARPi induces widespread transcriptomic changes that are predominantly pro-inflammatory, thereby promoting tumor angiogenesis. Prickle4, a planar cell polarity protein, is identified as a critical mediator of PARPi-induced neovascularization. Targeting Prickle4 effectively overcomes PARPi resistance in these tumors. Collectively, these …

Clinical And Molecular Characteristics Of Patients With Young-Onset And Average-Onset Pancreatic Adenocarcinoma, Adriana C Gamboa, Kever A Lewis, Laura R Prakash, Zhouxuan Li, Wei Qiao, Dan Zhao, Mark W Hurd, Mahmoud Yousef, Naruhiko Ikoma, Michael P Kim, Jeffrey E Lee, Jessica E Maxwell, Ching-Wei D Tzeng, Matthew H G Katz, Rebecca A Snyder

Faculty, Staff and Student Publications

Purpose: The incidence of young-onset pancreatic cancer (YO-PC) has risen over the past two decades, yet its molecular characteristics and long-term outcomes remain poorly defined.

Methods: We retrospectively evaluated patients with PC treated at a tertiary referral center from 2016 to 2022 who had available molecular data. Patients were classified as YO-PC (≤50 years) or average-onset PC (AO-PC, >50 years). A subset analysis examined outcomes in those who underwent curative-intent pancreatectomy. Primary end points included overall survival (OS) and recurrence-free survival (RFS).

Results: Among 511 patients, 10.9% had YO-PC (n = 56; median age 44 years). Patients with YO-PC more …

Case Report: Management Of A Challenging Case Presenting With Dysphagia After Thyroidectomy Requiring Administration Of Liquid 131i Via Mic-Key Low-Profile Tube—A Multidisciplinary Approach, Ahmed Ebada Salem, Sandra Ramirez, Brian R Weston, Akram Hussein, Simone Krebs

Faculty, Staff and Student Publications

Radioactive iodine (RAI) therapy with 131-iodine (131I) remains a cornerstone in the postoperative management of differentiated thyroid carcinoma (DTC). The standard route of administration is oral, typically in capsule form and less commonly as a liquid. However, in patients with severe dysphagia and compromised airway, traditional oral 131I delivery may be contraindicated due to the risk of aspiration and radioactivity contamination. These scenarios present unique clinical challenges that necessitate deviation from conventional protocols. While liquid 131I may be administered through the mouth or via nasogastric or percutaneous gastrostomy tubes, there is currently no standardized approach, and potential risks, such as …

A Gut-Activated Nhr-86-Cyp Pathway Mediates The Neuroprotective Effects Of Enterococcus Faecium Probiotics In A Nematode Model Of Amyotrophic Lateral Sclerosis, Yu Sang, Jie Ren, Alejandro Aballay

Faculty, Staff and Student Publications

Neurodegenerative diseases are often associated with oxidative stress, and while probiotics may influence neuronal health, the underlying mechanisms remain poorly understood. Using the sod-1 A4VM amyotrophic lateral sclerosis (ALS) model in Caenorhabditis elegans, we investigated the protective effects of the probiotic Enterococcus faecium against oxidative stress-induced neurodegeneration. Animals fed E. faecium showed reduced motor neuron degeneration under oxidative stress compared to those maintained on a standard Escherichia coli diet. Transcriptome analysis revealed a significant enrichment of oxidoreductase genes, including cytochrome P450 (cyp) genes. RNAi-mediated knockdown of cyp genes impaired E. faecium-mediated neuroprotection, and this loss correlated with increased reactive oxygen …

Guadecitabine Improved Relapse-Free Survival In High-Risk Acute Myeloid Leukemia And Myelodysplastic Syndrome Patients After Transplant: Phase Ii Results From A Single Center, Betül Oran, Peter Thall, Amin Alousi, Gheath Al-Atrash, Rohtesh Mehta, David Marin, Partow Kebriaei, Uday Popat, Roland Bassett, Qaiser Bashir, Jin Im, Amanda Olson, Jessica Jewell, Portia Smallbone, Elizabeth Shpall, Richard Champlin

Faculty, Staff and Student Publications

This phase II, single-center clinical trial evaluated the efficacy and safety of guadecitabine, with or without donor lymphocyte infusion, following allogeneic stem cell transplantation in adult patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The study had three treatment cohorts based on post-transplant disease status. Cohort 1 included patients with hematologic relapse after transplant (N=13). Cohort 2 consisted of patients with minimal residual disease (MRD) detected after transplant (N=18). Cohort 3 compromised patients in remission without MRD within 100 days after transplant (N=24). The primary objectives were achievement of morphological complete remission in cohort 1 and MRD eradication …

Endogenous Processes Underlying Clock-Like Mutational Signatures, Teresa Druck, Rami I Aqeilan, C Marcelo Aldaz, Nicola Zanesi, Kay Huebner

Faculty, Staff and Student Publications

Wellcome Trust scientists have shown that “mutational signatures” in specific nucleotide contexts accumulate in genomes of mammalian tissues, providing clues to underlying causes of specific signatures. Analysis of cancer genomes has identified more than 50 single‐base substitution (SBS) signatures, with SBS1, SBS5, and SBS40 linked to aging and present in normal tissues. SBS1 results from cytosine demethylation, whereas SBS5 and SBS40 arise from unknown endogenous mechanisms. We hypothesized that loss of fragile‐site genes drives these two signatures. FHIT, located at FRA3B, is frequently deleted in cancers, and Fhit‐deficient mouse tissues exhibit a mutation profile resembling human SBS5. Data mining of …

Preclinical Ischemic Stroke Multicenter Trials (Prism) Collective Statement: Opportunities, Challenges, And Recommendations For A New Era, Cenk Ayata, Philip M Bath, Anna M Planas, Stuart M Allan, Johannes Boltze, Ryan P Cabeen, Claire L Gibson, Marilyn J Cipolla, Marcio A Diniz, Stefano Fumagalli, Fahmeed Hyder, Raymond C Koehler, Arthur Liesz, Sarah K Mccann, Tim Magnus, Louise D Mccullough, Emily S Sena, Simone Beretta, Jaroslaw Aronowski, Francesca Bosetti, Clinton B Wright, Patrick D Lyden, Lauren H Sansing

Faculty, Staff and Student Publications

Preclinical stroke research faces a critical translational gap, with animal studies failing to reliably predict clinical efficacy. To address this, the field is moving toward rigorous, multicenter preclinical randomized controlled trials (mpRCTs) that mimic phase 3 clinical trials in several key components. This collective statement, derived from experts involved in mpRCTs, outlines considerations for designing and executing such trials. mpRCTs offer advantages such as increased sample sizes, robust statistical design, incorporation of heterogeneity, and standardized protocols, but they face challenges in finding the right balance between standardization and heterogeneity, appropriate stroke model selection, and outcome measures, as well as the …

Management Of Retropharyngeal Lymph Node Metastases In Thyroid Cancer, Isabelle Fournier, Ashwini Venkata Bandi, Sarah Hamidi, Priyanka Iyer, Naifa L Busaidy, Maria E Cabanillas, Ramona Dadu, Mimi I Hu, Steven G Waguespack, Ugur Nur Basmaci, Michelle D Williams, Mena Mansour, Maria Gule Monroe, Neil D Gross, Ryan P Goepfert, Nancy D Perrier, Victoria Banuchi, Jennifer R Wang, Anastasios Maniakas, Mark E Zafereo

Faculty, Staff and Student Publications

Background: Retropharyngeal lymph node (RPLN) metastases in thyroid cancer are rare, with optimal management underreported.

Methods: Retrospective study of consecutive thyroid cancer patients with RPLN metastases treated at MD Anderson Cancer Center between 2000 and 2024.

Results: One hundred and sixty-seven patients (75% differentiated, 21% medullary, 4% poorly differentiated thyroid cancer) were divided into three groups: active surveillance (AS) (13%), surgery (56%), and nonsurgical treatment (31%). In the AS group (median follow-up 2.3 years), RPLN metastases grew a median 3% (range: 0-56) or 0.02 cm (range: 0-0.7) per year. Surgical therapy included transcervical (73%), transoral robotic (14%), transoral (12%), and …

Nampt Inhibition Uncovers Therapeutic Vulnerabilities To Venetoclax And Chemotherapy In Acute Myelogenous Leukemia, John R Sanchez, Chaomei Liu, Vishakha Pawar, Yanqing Huang, Daisy Diaz-Rohena, Jyotsana Singh, Priya Koppikar, Tzung-Huei Lai, Lisa St John, Vinay Puduvalli, Jeffrey Molldrem, Palaniraja Thandapani, Nitin Jain, Rosa Lapalombella, Deepa Sampath

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) cells depend on nicotinamide adenine dinucleotide (NAD

Respiratory Motion Effects And Plan Robustness For Lattice Radiation Therapy, Rachael M Martin-Paulpeter, Peter A Balter, Luis A Perles, Ethan B Ludmir, Joshua S Niedzielski

Faculty, Staff and Student Publications

Introduction: Lattice radiation therapy (LRT), a form of spatially fractionated radiation therapy (SFRT), has shown promise in treating bulky tumors. It consists of hot and cold spots within the tumor, and the ratio between these doses is thought to be important in clinical outcomes. Respiratory motion is expected to degrade these peak-to-valley dose ratios (PVDRs) but has largely been ignored in LRT literature and clinical practice. This work aims to quantify the response of LRT dose distributions to motion to better inform motion management decisions and improve clinical outcomes.

Methods: Respiratory motion of peak-to-peak amplitudes from 0.3 to 2 cm …

Poly(A) Probe Hcr Rna-Fish Specifically Marks Pyriform Nurse Cells In The Brown Anole Lizard Ovary, Zoe B Griffin, Bonnie K Kircher, Richard R Behringer

Faculty, Staff and Student Publications

Hybridization chain reaction RNA-fluorescent in situ hybridization (HCR RNA-FISH) is a powerful and increasingly used method for visualizing gene expression in cells and tissues. A probe set against polyadenylated RNA (poly(A)) is often used as a positive control for RNA integrity and staining quality. While optimizing this technique in the ovary of the brown anole lizard (Anolis sagrei), we found that the poly(A) probe produced a strikingly specific and intense signal in pyriform cells, a specialized lizard-specific nurse cell type. This staining pattern was found in both whole-mount samples and paraffin sections, suggesting that poly(A) signal intensity can serve as …

Uncertainty-Guided Test-Time Optimization For Personalizing Segmentation Models In Longitudinal Medical Imaging, Jaehee Chun, Austin Castelo, Mckell Woodland, Caleb O'Connor, Mais Al Taie, Mohamed Eltaher, Aashish Gupta, Bilel Daoud, Shanli Ding, Jeddy Bennett, Anirban Maitra, Matthew A Firpo, Kimberly Kirkwood, Eugene J Koay, Kristy K Brock

Faculty, Staff and Student Publications

Background: Accurate and consistent image segmentation across longitudinal scans is essential in many clinical applications, including surveillance, treatment monitoring, and adaptive interventions. While personalized model adaptation using patient-specific prior scans has shown promise, current approaches typically rely on fixed training durations and lack mechanisms to determine optimal stopping points on a per-patient basis, particularly in the absence of validation labels.

Purpose: We propose an uncertainty-guided test-time optimization (TTO) framework that dynamically adjusts the personalization duration for each patient using a validation-free stopping criterion based on predictive uncertainty.

Methods: Our framework personalizes a generalized segmentation model using patient-specific prior imaging and …

Bop2-Comb: Bayesian Optimal Phase Ii Design For Optimizing Doses And Assessing Contribution Of Components In Drug Combinations, Xiaohan Chi, Ying Yuan, Ruitao Lin

Faculty, Staff and Student Publications

Background: Personalized cancer treatment using combination therapies offers substantial therapeutic benefits over single-agent treatments in most cancers. However, unmet clinical needs and increasing market competition pressure drug developers to quickly optimize combination doses and clearly demonstrate the contribution of each component when developing and evaluating new combination treatments.

Methods: We propose a Bayesian optimal phase II drug-combination (BOP2-Comb) design that optimizes the combination dose and evaluates the proof-of-concept as well as the contribution of each component in two seamless stages. Our optimal calibration scheme minimizes the total trial sample size while controlling incorrect decision rates at nominal levels. This calibration …

Peripheral Cd200r Signaling: A Critical Regulator Of Post-Stroke Inflammation In Aged Mice, Conelius Ngwa, Afzal Misrani, Yan Xu, Jingjing Wang, Rodney Ritzel, Fudong Liu

Faculty, Staff and Student Publications

The immune responses to ischemic stroke are subjected to endogenous inhibitory pathways that delimitate the post-stroke inflammation. Among them, the interaction between CD200 and its receptor (CD200R) is increasingly recognized for its role in regulating neuroinflammation across various central nervous system (CNS) disorders. In the present study, we have examined the role of central (brain) vs. peripheral CD200R signaling in acute ischemic stroke using aged bone marrow chimeric (BMC) mice (16-19 months old). These chimeras were generated by transplanting bone marrow from CD200R knockout (KO), green fluorescent protein (GFP), or wild-type (WT) donor mice into irradiated recipient mice, and then …

Ai-Powered Immune Cell Knowledge Graph (Ickg) With Granular Immune Contexts Enables Immune Program Interpretation, Shan He, Yukun Tan, Qing Ye, Matthew M Gubin, Merve Dede, Hind Rafei, Weiyi Peng, Katayoun Rezvani, Vakul Mohanty, Ken Chen

Faculty, Staff and Student Publications

The widespread application of single-cell and spatial omics to models and patient samples has transformed immune cell profiling across physiological conditions. However, knowledge of immune cell states, functions, and gene regulation remains fragmented across publications, limiting our ability to synthesize insights and derive mechanistic understanding from the literature. To address this gap and facilitate literature integration, we constructed Immune Cell Knowledge Graphs (ICKGs)-four cell type-specific graphs derived from over 24,000 cancer immunotherapy-focused PubMed abstracts using large language models (LLMs) with "human verifiable" validation. Unlike conventional databases, which provide context-agnostic pathways, ICKGs capture directed, literature-supported relationships among genes, pathways and immune …

Dosimetric Effect Of Abdominal Compression In Online Adaptive Planning For Abdominal Cancers Treated With A 15 Tesla Magnetic Resonance-Guided Linear Accelerator, Moghadaseh Khaleghibizaki, Angela Sobremonte, Luis Perles, Surendra Prajapati, Ergys Subashi, Yao Ding, Kristy Brock, Roya Barati, Eugene Koay, Chad Tang, Jinzhong Yang

Faculty, Staff and Student Publications

Compression belts (CBs) are sometimes used to reduce respiratory motion during stereotactic body radiotherapy of abdominal cancers with magnetic resonance (MR)-guided online adaptive planning. This study evaluated the dosimetric effects of overriding the relative electron density (ED) value of CBs in creating synthetic computed tomography (CT) scans for MR-guided adaptive planning. We evaluated plans for 12 patients with abdominal cancer and identified that ED values between 0.2 and 0.3 achieved the best approximation of CB ED in dose calculation. Our study presented an approach to estimate appropriate ED overrides for CBs in MR-guided online adaptive planning.

Perspective: Radiotherapy And Body Composition: Unmet Needs In Low- And Middle-Income Countries, Alexia J Murphy-Alford, Aaron J Grossberg, Vickie E Baracos, Maha Barbar, Judy Bauer, Jonathan P Bennett, Elena Fidarova, Clifton D Fuller, Anastassia Löser, Amy C Moreno, Anurima Patra, Deepa Puttaswamy, David I Rosenthal, Judy Schoeman, Yavuz Anacak

Faculty, Staff and Student Publications

Radiotherapy plays a vital role in cancer treatment, yet its effects on patients' nutritional status can precipitate muscle loss, with significant implications for treatment tolerance and outcomes. Evidence from high-income countries increasingly links radiation-induced muscle loss to adverse clinical outcomes. In contrast, low- and middle-income countries face a stark evidence gap, despite the heightened vulnerability of cancer patients in these settings due to delayed diagnosis, limited access to care, and high rates of co-morbidities. This paper highlights the critical gaps in nutritional care for radiotherapy patients in low- and middle-income countries.

Genomic Determinants Of Response And Resistance To Pirtobrutinib In Relapsed/Refractory Chronic Lymphocytic Leukemia, Jennifer R Brown, Bastien Nguyen, Sai Prasad Desikan, Helen Won, Shady I Tantawy, Samuel C Mcneely, Narasimha Marella, Hetal S Randeria, Lauren M Hanson, Andrew Parker, Salomé Calado Botelho, Jennifer A Woyach, Krish Patel, Constantine S Tam, Toby A Eyre, Chan Y Cheah, Nirav N Shah, Paolo Ghia, Wojciech Jurczak, Minna Balbas, Binoj Nair, Paolo Abada, Chunxiao Wang, Denise Wang, Lindsey E Roeker, Varsha Gandhi, William G Wierda

Faculty, Staff and Student Publications

Pirtobrutinib, a noncovalent, reversible Bruton tyrosine kinase inhibitor (BTKi), demonstrated efficacy in patients with chronic lymphocytic leukemia (CLL), resistant to covalent BTKi (cBTKi). We analyzed genomic correlations with response and resistance to pirtobrutinib in relapsed/refractory (R/R) patients with CLL pretreated with cBTKi enrolled in the phase 1/2 BRUIN trial. DNA sequencing was performed on peripheral blood mononuclear cells at baseline, on treatment, and at progressive disease (PD). Common alterations at baseline included mutations in BTK (43%), TP53 (38%), SF3B1 (25%), NOTCH1 (23%), ATM (19%), XPO1 (11%), PLCG2 (9%), BCL2 (8%), and 17p deletion (28%). Common baseline BTK mutations included C481S …

Preliminary Examination Of Orexin Receptor Antagonism With Suvorexant In Individuals With Methamphetamine Use Disorder: A Case Series Study, Heather Webber, Jessica Badawi, Douglas Calvillo, Jin Yoon, Michael Weaver, Scott Lane, Joy Schmitz

Faculty, Staff and Student Publications

No abstract provided.

Intratumoral Bacteria Are Immunosuppressive And Promote Immunotherapy Resistance In Head And Neck Squamous Cell Carcinoma, Natalie L Silver, Jin Dai, Travis D Kerr, Jessica Altemus, Rekha Garg, Hannah Simmons, Tyler Alban, Laura Noel-Romas, Vladimir Makarov, David J H Shih, Shwetha V Kumar, Akeem Santos, Rehan Akbani, Adam Burgener, Mohammed Dwidar, Neil Gross, Andrew G Sikora, Elias J Sayour, Apollo Stacy, Christian Jobin, Timothy A Chan, Renata Ferrarotto, Daniel J Mcgrail

Faculty, Staff and Student Publications

Despite the promise of immune checkpoint blockade (ICB) in head and neck squamous cell carcinoma (HNSCC), mediators of response are poorly understood. To address this, here we analyzed oropharyngeal HNSCCs treated with neoadjuvant durvalumab (anti-PDL1) alone or in combination with tremelimumab (anti-CTLA4) from the CIAO clinical trial ( NCT03144778 ). We found that only the total abundance of intratumoral bacteria predicted ICB response, which was validated in multiple independent cohorts. High intratumoral bacteria abundance was associated with an immunosuppressive tumor microenvironment, characterized by an accumulation of neutrophils coupled with depletion of T cells and other adaptive immune cells. Experimental elevation …

Alternative Polyadenylation Signatures Distinguish Maladaptive Right Ventricular Remodeling In Pulmonary Hypertension: Implications For Rna-Based Diagnostics And Therapeutics, Janani Subramaniam, Venkata Jonnakuti, Scott D Collum, Sandra Martineau, Kai-Lieh Huang, Sandra Breuils-Bonnet, Andrea L Frump, Bindu H Akkanti, Jayeshkumar A Patel, Manish K Patel, Ismael Salas De Armas, Isabella N Lefebvre, Rajko Radovancevic, Elvin Blanco, Eric J Wagner, Igor Gregoric, Sriram Nathan, Biswajit Kar, Steeve Provencher, Sebastien Bonnet, François Potus, Hari Krishna Yalamanchili, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Increased pulmonary vascular pressures due to vascular remodeling, elevated vascular resistance, and vasoconstriction characterize Pulmonary Arterial Hypertension (PAH). The narrowing of the pulmonary arteries and obstruction of blood flow increase the Right Ventricular (RV) afterload, forcing the RV to undergo structural and functional changes. While adaptive remodeling leads to RV compensation by maintaining function, maladaptive remodeling leads to RV decompensation, characterized by worsening function and eventual failure. At present, there is no effective treatment for these patients as therapies for left ventricular failure are ineffectual, and there are no therapies specifically targeting the RV. Therefore, there is a clear need …

T Cells Modulate The Development And Maintenance Of Painful Paclitaxel-Induced Peripheral Neuropathy In Rnu Rats, Ahmed Olalekan Bakare, Gerard Limerick, Vasudha Goel, Ratan K Banik, Lei Zheng, Andrew J Shepherd, Kristine Glunde, Qin Zheng, Eellan Sivanesan

Faculty, Staff and Student Publications

The role of T cells in chemotherapy-induced peripheral neuropathy (CIPN) is complex and shaped by biological and experimental factors, including sex, hormonal status, genetic background, and cancer model. This complexity has contributed to inconsistent findings among studies, limiting therapeutic progress. In this study, we investigate how T cells contribute to painful paclitaxel (PTX)-induced peripheral neuropathy (PIPN). Adult male T cell-competent (RNU+/−) and T cell-deficient (RNU−/−) rats were subcutaneously inoculated with tumor cells and subsequently treated with intraperitoneal PTX (8 mg/kg total dose). Reflexive (mechanical, heat, cold) and non-reflexive (burrowing, gait) pain behaviors were assessed from baseline through week 6. Immunohistochemistry …

Interventional Oncology: A Primer For Clinicians On The Role Of Ablation And Embolization For Solid Tumors, Mohamed E Abdelsalam, Kamran Ahrar, Rahul A Sheth, Ketan Y Shah, Steven Yevich, Varshana Gurusamy, Bruno C Odisio, Alda L Tam, Armeen Mahvash, Peiman Habibollahi

Faculty, Staff and Student Publications

Interventional radiology (IR) is a rapidly evolving medical field that combines advanced imaging with minimally invasive techniques for both diagnosis and treatment. Interventional oncology (IO), a subspecialty of IR, focuses on the minimally invasive, image-guided intervention for cancer and cancer-related conditions. IR plays an important and increasingly recognized role within the multidisciplinary care of patients with cancer, contributing meaningfully to diagnosis, therapy, and palliation. IO therapies, particularly tumor ablation and transarterial embolization, aim to target tumors directly while preserving surrounding healthy tissue. These therapies are increasingly supported by clinical guidelines and have shown favorable outcomes in cancers such as hepatocellular …

The Myopia Epidemic: Integrating Genetic, Environmental, And Epigenetic Pathways To Define A Critical Window For Intervention, Pranavika Balaji

Undergraduate Research Posters

Myopia, or nearsightedness, has increased rapidly worldwide and is now a major public health concern caused by both genetic and environmental factors. Current understanding shows that too much near work, limited time spent outdoors, and prolonged screen use contribute to abnormal eye growth in individuals who may already have a genetic predisposition. At the molecular level, epigenetic changes and shifts in DNA activity, often influenced by environmental conditions, affect the signaling pathways that regulate eye development and may help explain why myopia is increasingly common among children. This paper synthesizes recent environmental, genetic, and epigenetic research to explain how these …