Digital Commons Network^™

Assessment Of Sox2 Expression As A Tumor Stem Cell Marker In Ameloblastoma And Dentigerous Cyst, Haneen Mahmoud Zeen El-Abdeen, Noha Ahmed Mansour, Sherif Yousef Elnagdy, Mohamed Abdel-Monem Tawfik

Mansoura Journal of Dentistry

Objective: The pathogenesis of odontogenic lesions remains unclear; however, a probable explanation could mean the presence of tumor stem cells (TSCs). The preservation of stem cells during early dental development is governed by many transcription factors, including sex-determining region Y (SRY)-box 2 (SOX-2). Numerous studies observed the increased expression of SOX2 in various benign and malignant tumors as its impact on tumorigenesis varies according to tumor type. This research aims to determine the predictive importance of the SOX2 stem cell marker by evaluating its immunoexpression in ameloblastoma (Ab) and dentigerous cyst (DC). Materials and Methods: Twenty-Four samples were part of …

Digital Versus Functional Pick-Up Techniques For Two-Implant Retained Mandibular Overdentures: A Crossover Study, Aya E. Elnagar, Khaled M. Zahran, Heba Abo-Elfetouh Elsheikh, Fatma Ahmad El Waseef

Mansoura Journal of Dentistry

Objective: To evaluate two pick-up techniques—digital and functional—for two-implant retained mandibular overdentures with respect to occlusal force distribution using the digital occlusal analysis system (Occlusense®). Patients and Methods: Twenty completely edentulous, healthy patients were selected from the Prosthodontics Department, Faculty of Dentistry, Mansoura University. Conventional complete dentures were first constructed, followed by placement of two implants in the mandibular canine regions using a guided surgical approach and a delayed loading protocol. For each patient, two sets of digitally fabricated mandibular overdentures were constructed. Patients were randomly assigned into two equal groups: Group I received digital complete overdentures with digitally created …

Investigating The Impact Of Phthalate Exposures From Personal Care Products On Uterine Fibroid Incidence And Prevalence In Us-Born Black Women, Ella Brissett

CMC Senior Theses

Uterine fibroids are benign tumors composed of smooth muscle cells and connective tissue that develop within or on the walls of the uterus. Despite being non-cancerous, they can severely affect quality of life by causing heavy bleeding, chronic pain, and reproductive complications. Fibroids are typically found in women of reproductive age, but they disproportionately affect Black women, who experience higher incidence and severity. The underlying causes of this disparity is poorly understood; however, an emerging body of research is highlighting the role of phthalates, endocrine-disrupting chemicals found in many personal care products, in exacerbating fibroid development. Through a critical analysis …

Learning Paradigms For Rhythm Detection And Generation Using Mathematical Models, Biophysical And Artificial Neural Networks, Prianka Bose

Dissertations

Humans possess an inherent ability to recognize evenly-spaced rhythms, known as isochronous rhythms, owing to the brain's predisposition to entrain to external auditory stimuli with regular temporal intervals. The central focus of this research is to understand how the brain learns and retains rhythmic time intervals in the context of music. This dissertation studies rhythm detection and generation through mathematical models, biophysical networks, and artificial neural networks, addressing both isochronous and non-isochronous patterns.

A primary focus of the thesis is on isochronous rhythms. In particular, given a perturbation to an isochronous rhythm such as a tempo change or phase shift …

Histodynamics Of Natural Killer Cells From A Healthy Donor Exposed To Exosomes From The Blood Of Hepatocellular Carcinoma Patients, Indria Asrinda, Radiana Dhewayani Antarianto, Ahmad Aulia Jusuf, Ardhi Rahman Ahani, Chyntia Olivia Maurine Jasirwan, Ni Ken Ritchie, Robby Nur Aditya, Cosphiadi Irawan

Makara Journal of Health Research

Background: Hepatocellular carcinoma (HCC) is the leading form of liver cancer and the second leading cause of cancer-related deaths globally. Exosomes in the HCC microenvironment can induce significant changes in natural killer (NK) cells during endocytosis. The present study aimed to distinguish exosomes in the blood of HCC patients, analyze changes in NK cell phenotype, and evaluate peroxidase and toluidine blue staining as alternative methods for observing the changes.

Methods: NK cells were collected from healthy donors, and exosomes were extracted from the blood of HCC patients. The exosomes were characterized in accordance with MISEV 2018 guidelines, and …

Supporting Mental Wellness In Transgender Athletes, Abaigeal C. Fields, Zachary K. Winkelmann

Clinical Practice in Athletic Training

N/a

Exploratory Clinical Assessment And Treatment Of Autonomic Nervous System Dysregulation Post Concussion: A Case Study, Megan Coker, James May

Clinical Practice in Athletic Training

The physiological alterations in autonomic nervous system (ANS) function due to concussion are suggested to play a role in persistent post-concussion symptoms (PPCS). Currently, there are few objective and clinically feasible measurements to assess ANS vitality in patients experiencing PPCS. The following case study details an assessment and treatment protocol targeted towards regulating the ANS in an adolescent female suffering from PPCS one month after injury. Pre-intervention, patient-reported outcome measures (PROMs) used to assess perceived pain, anxiety, stress, and breathing function were administered as well as a physical assessment performed for breath function and vagus nerve integrity. The patient was …

Transcriptomic Profile Analysis Of Brain Tissue In The Absence Of Functional Trpm8 Calcium Channel, Erick B Saldes, Alexandra Erdmier, Jai Velpula, Timothy E Koeltzow, Michael X Zhu, Swapna Asuthkar

Faculty, Staff and Student Publications

Background/Objectives: Transient Receptor Potential Melastatin 8 (TRPM8) is a non-selective, Ca2+-permeable cation channel involved in thermoregulation and other physiological processes, such as basal tear secretion, cell differentiation, and insulin homeostasis. The activation and deactivation of TRPM8 occur through genetic modifications, channel interactions, and signaling cascades. Recent evidence suggests a significant role of TRPM8 in the hypothalamus and amygdala related to pain sensation and sexual behavior. Notably, TRPM8 has been implicated in neuropathic pain, migraines, and neurodegenerative diseases such as Parkinson's disease. Our laboratory has identified testosterone as a high-affinity ligand of TRPM8. TRPM8 deficiency appears to influence behavioral traits in …

Disruption Of Distal Appendage Protein Cep164 Causes Skeletal Malformation In Mice, Hiroyuki Yamaguchi, Megumi Kitami, Margaret Li, Sowmya Swaminathan, Radbod Darabi, Ken-Ichi Takemaru, Yoshihiro Komatsu

Faculty, Staff and Student Publications

The primary cilium is a cellular antenna to orchestrate cell growth and differentiation. Deficient or dysfunctional cilia are frequently linked to skeletal abnormalities. Previous research demonstrated that ciliary proteins regulating axoneme elongation are essential for skeletogenesis. However, the role of the ciliary proteins responsible for initiating cilium assembly in skeletal development remains unknown. Here, we investigate the function of centrosomal protein of 164 kDa (CEP164), a key ciliogenesis regulator that localizes at the distal appendages of the mother centriole, during skeletal development in mice. Interestingly, the mesodermal cell-specific Cep164 deletion resulted in severe bone defects and osteoblast-specific deletion of Cep164 …

A Bayesian Pharmacokinetics Integrated Phase I-Ii Design To Optimize Dose-Schedule Regimes, Mengyi Lu, Ying Yuan, Suyu Liu

Faculty, Staff and Student Publications

The schedule of administering a drug has profound impact on the toxicity and efficacy profiles of the drug through changing its pharmacokinetics (PK). PK is an innate and indispensable component of the dose-schedule optimization. Motivated by this, we propose a Bayesian PK integrated dose-schedule finding (PKIDS) design to identify the optimal dose-schedule regime by integrating PK, toxicity, and efficacy data. Based on the causal pathway that dose and schedule affect PK, which in turn affects efficacy and toxicity, we jointly model the three endpoints by first specifying a Bayesian hierarchical model for the marginal distribution of the longitudinal dose-concentration process. …

Addressing Unprofessional Behaviors In The Clinical Learning Environment: Lessons From A Multi-Year Virtual, Intergenerational, Interdisciplinary Workshop, Stacey Rose, Anita Kusnoor, Phuong Huynh, Jocelyn Greely, Yesenia Rojas-Khalil, Doris Kung, Anne Gill, Nadia Ismail, Nital Appelbaum

Faculty, Staff and Students Publications

INTRODUCTION: Optimizing the clinical learning environment (CLE) is a medical education priority nationwide.

MATERIALS AND METHODS: We developed a virtual, one-hour workshop engaging students, housestaff and faculty in small-group discussions of five case scenarios adapted from reported unprofessional behaviors in the CLE, plus didactics regarding mistreatment, microaggressions and bystander interventions.

RESULTS: Over two sessions (2021-2022), we engaged 340 students and 73 faculty/housestaff facilitators. Post-session surveys showed significant improvement in participants' ability to recognize and respond to challenges in the CLE.

DISCUSSION: Our innovative workshop, including scenarios derived from institutional reports of unprofessional behaviors, advanced participants' knowledge and commitment to improve …

The Correlation Of Covid-19 Vaccination With Covid-19 Patient Mortality In Depok City, Indonesia, Dian Nugrahari, Asri Adisasmita Prof, Nurhanifah Hamdah

Jurnal Epidemiologi Kesehatan Indonesia

Vaccination is a disease prevention method recommended by the WHO as it will reduce disease severity, mortality rate and risks. The objective of this study is to discover the impact of COVID-19 vaccination against COVID-19 mortality rate in Indonesia. This was a retrospective cohort research on the data from the NAR COVID-19 database and the KPCPEN COVID-19 Dashboard of the Depok City Health Department from May 2020-February 2023. We performed a Cox proportional hazard analysis to obtain the risk for death. We discovered that COVID-19 vaccination reduced the mortality until it was less than 10% of unvaccinated population (0,24% for …

The Impact Of Smoking Degree On One Year Survival Of Non-Small Cell Lung Cancer (Nsclc) At Persahabatan Hospital, Arief Wicaksono, Asri C. Adisasmita, Andika Chandra Putra

Jurnal Epidemiologi Kesehatan Indonesia

Lung cancer is a major global mortality problem with the worst prognosis compared to other types of cancer. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and smoking is one of the main factors causing lung cancer. This study aims to determine the one-year survival of NSCLC patients with smoking levels and to determine what factors affect survival. This study is an observational study with a retrospective method, looking at medical record data of NSCLC patients both inpatients and outpatients at Persahabatan Hospital between January 2023 and December 2023 and then followed up until September …

Evaluation Of The Effect Of Vitamin D Deficiency On Liver And Kidney Functions Of Iraqi Type Ii Diabetic Patients, Alaa Matar, Sarah Al-Tamimi, Jamilah Borjac

BAU Journal - Science and Technology

Background: Vitamin D deficiency is widespread across different age groups globally, linking to conditions such as cardiovascular diseases, autoimmune disorders, and notably type 2 diabetes mellitus (T2DM). Investigating the impact of vitamin D on T2DM and associated kidney and liver functions has gained recent attention.

Objective: This study aimed to explore the effect of vitamin D deficiency on kidney and liver functions in T2DM Iraqi patients.

Methods: Fifty T2DM patients and 50 controls were enrolled in this study. Blood samples were analyzed for glucose, glycated hemoglobin (HbA1c), vitamin D, urea, creatinine, bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline …

The Complexity And Significance Of Fibroblast Growth Factor (Fgf) Signaling For Fgf-Targeted Cancer Therapies, Anh Nguyen, Caroline Facey, Bruce Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Fibroblast growth factors (FGFs) have diverse functions in the regulation of cell proliferation and differentiation in development, tissue maintenance, wound repair, and angiogenesis. The goal of this review paper is to (i) deliberate on the role of FGFs and FGF receptors (FGFRs) in different cancers, (ii) present advances in FGF-targeted cancer therapies, and (iii) explore cell signaling mechanisms that explain how FGF expression becomes dysregulated during cancer development. FGF is often mutated and overexpressed in cancer and the different FGF and FGFR isoforms have unique expression patterns and distinct roles in different cancers. Among the FGF members, the FGF 15/19 …

Total Polyphenol Content, Antioxidant Potential, Antibacterial And Antifungal Properties Of Ferula L. Species Growing In Tajikistan, Saidbeg Satorov, Sulkhya Mavlonazarova, Salomuddin Yusufi, Vyacheslav Dushenkov

Publications and Research

The plants of the genus Ferula L. have long been recognized for their significant roles in traditional medicine in the Middle East and Asia, a heritage that we deeply respect and appreciate. A diverse array of biologically active compounds, particularly concentrated in the roots of various Ferula species, accounts for their broad range of medicinal properties and applications in folk medicine. Many species within this genus are noted for their high content of phenolic compounds, which exhibit potent antioxidant activity and demonstrate substantial antimicrobial and antifungal properties.

Cultivating Compassion: A Cross-Sectional Evaluation Of Empathy Among Medical Undergraduate Students, Anchu R Nath, Ishika Jindal, Nayanabai Shabadi, Sunil Kumar D

Digital Journal of Clinical Medicine

ABSTRACT:

BACKGROUND: Empathy plays a crucial role in medical practice, profoundly affecting patient outcomes and treatment. Understanding the factors that influence empathy among medical students can help in developing strategies to enhance empathetic skills during medical training. This study aims to evaluate the correlates of empathy among medical undergraduate students using an epidemiological cross-sectional design.

MATERIALS AND METHODS:

A cross-sectional study was conducted among 270 medical undergraduate students from various academic years at JSS Medical College for four months (September 2023-December 2023). Convenient sampling was used to select study participants. Participants completed a standardized empathy questionnaire, the Jefferson Scale …

Nos Inhibition Sensitizes Metaplastic Breast Cancer To Pi3k Inhibition And Taxane Therapy Via C-Jun Repression, Tejaswini Reddy, Akshjot Puri, Liliana Guzman-Rojas, Christoforos Thomas, Wei Qian, Jianying Zhou, Hong Zhao, Bijan Mahboubi, Adrian Oo, Young-Jae Cho, Baek Kim, Jose Thaiparambil, Roberto Rosato, Karina Ortega Martinez, Maria Florencia Chervo, Camila Ayerbe, Noah Giese, David Wink, Stephen Lockett, Stephen Wong, Jeffrey Chang, Savitri Krishnamurthy, Clinton Yam, Stacy Moulder, Helen Piwnica-Worms, Funda Meric-Bernstam, Jenny Chang

Faculty, Staff and Student Publications

Metaplastic breast cancer (MpBC) is a highly chemoresistant subtype of breast cancer with no standardized therapy options. A clinical study in anthracycline-refractory MpBC patients suggested that nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (L-NMMA) may augment anti-tumor efficacy of taxane. We report that NOS blockade potentiated response of human MpBC cell lines and tumors to phosphoinositide 3-kinase (PI3K) inhibitor alpelisib and taxane. Mechanistically, NOS blockade leads to a decrease in the S-nitrosylation of c-Jun NH

Orthogonal And Multiplexable Genetic Perturbations With An Engineered Prime Editor And A Diverse Rna Array, Qichen Yuan, Hongzhi Zeng, Tyler C Daniel, Qingzhuo Liu, Yongjie Yang, Emmanuel C Osikpa, Qiaochu Yang, Advaith Peddi, Liliana M Abramson, Boyang Zhang, Yong Xu, Xue Gao

Faculty, Staff and Students Publications

Programmable and modular systems capable of orthogonal genomic and transcriptomic perturbations are crucial for biological research and treating human genetic diseases. Here, we present the minimal versatile genetic perturbation technology (mvGPT), a flexible toolkit designed for simultaneous and orthogonal gene editing, activation, and repression in human cells. The mvGPT combines an engineered compact prime editor (PE), a fusion activator MS2-p65-HSF1 (MPH), and a drive-and-process multiplex array that produces RNAs tailored to different types of genetic perturbation. mvGPT can precisely edit human genome via PE coupled with a prime editing guide RNA and a nicking guide RNA, activate endogenous gene expression …

Age-Dependent Regulation Of Axoglial Interactions And Behavior By Oligodendrocyte Ankyring, Xiaoyun Ding, Yu Wu, Anna Vainshtein, Victoria Rodriguez, Emily Ricco, James T Okoh, Yanhong Liu, Daniel C Kraushaar, Elior Peles, Matthew N Rasband

Faculty, Staff and Students Publications

The bipolar disorder (BD) risk gene ANK3 encodes the scaffolding protein AnkyrinG (AnkG). In neurons, AnkG regulates polarity and ion channel clustering at axon initial segments and nodes of Ranvier. Disruption of neuronal AnkG causes BD-like phenotypes in mice. During development, AnkG is also expressed at comparable levels in oligodendrocytes and facilitates the efficient assembly of paranodal junctions. However, the physiological roles of glial AnkG in the mature nervous system, and its contributions to BD-like phenotypes, remain unexplored. Here, we show that oligodendroglia-specific AnkG conditional knockout results in destabilization of axoglial interactions in aged but not young adult mice. In …

Vaccines Targeting P53 Mutants Elicit Anti-Tumor Immunity, Dafei Chai, Xu Wang, Chunmei Fan, Junhao Wang, Jing Ming Lim, Xinfang Yu, Ken H Young, Yong Li

Faculty, Staff and Students Publications

The p53 tumor suppressor is commonly mutated in cancer; however, there are no effective treatments targeting p53 mutants. A DNA vaccine gWIZ-S237G targeting the p53 S237G mutant, which is highly expressed in A20 murine tumor cells, was developed and administered intramuscularly via electroporation, either alone or in combination with PD1 blockade. The anti-p53-S237G immunization elicited a robust protective response against subcutaneous A20 tumors and facilitated the infiltration of immune cells including CD8+ T cells, NK cells, and DCs. The vaccine enhanced the induction and maturation of CD11c+, CD103+CD11c+, and CD8+CD11c+ cells, which in turn promoted tumor-specific antibody production, as well …

Role Of Nf2 Mutation In The Development Of Eleven Different Cancers, Shervin Hosseingholi Nouri, Vijay Nitturi, Elizabeth Ledbetter, Collin W English, Sean Lau, Tiemo J Klisch, Akash J Patel

Faculty, Staff and Students Publications

Background/Objectives: With the rise in prevalence of diagnostic genetic techniques like RNA sequencing and whole exome sequencing (WES), as well as biological treatment regiments for cancer therapy, several genes have been implicated in carcinogenesis. This review aims to update our understanding of the Neurofibromatosis 2 (NF2) gene and its role in the pathogenesis of various cancers. Methods: A comprehensive search of five online databases yielded 43 studies that highlighted the effect of sporadic NF2 mutations on several cancers, including sporadic meningioma, ependymoma, schwannoma, mesothelioma, breast cancer, hepatocellular carcinoma, prostate cancer, glioblastoma, thyroid cancer, and melanoma. Of note were key biological …

Parp Inhibition Radiosensitizes Brca1 Wildtype And Mutated Breast Cancer To Proton Therapy, Mariam Ben Kacem, Scott J Bright, Emma Moran, David B Flint, David K J Martinus, Broderick X Turner, Ilsa Qureshi, Rishab Kolachina, Mandira Manandhar, Poliana C Marinello, Simona F Shaitelman, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Aggressive breast cancers often fail or acquire resistance to radiotherapy. To develop new strategies to improve the outcome of aggressive breast cancer patients, we studied how PARP inhibition radiosensitizes breast cancer models to proton therapy, which is a radiotherapy modality that generates more DNA damage in the tumor than standard radiotherapy using photons. Two human BRCA1-mutated breast cancer cell lines and their isogenic BRCA1-recovered pairs were treated with a PARP inhibitor and irradiated with photons or protons. Protons (9.9 and 3.85 keV/µm) induced higher cell kill independent of BRCA1 status. PARP inhibition amplified the cell kill effect to both photons …

Cancer Organoids As Reliable Disease Models To Drive Clinical Development Of Novel Therapies, Giovanni Blandino, Ronit Satchi-Fainaro, Ingeborg Tinhofer, Giovanni Tonon, Sarah C Heilshorn, Yong-Jun Kwon, Ana Pestana, Carlotta Frascolla, Luca Pompili, Aurora Puce, Sara Iachettini, Annalisa Tocci, Sofia Karkampouna, Marianna Kruithof-De Julio, Piera Tocci, Nicla Porciello, Klizia Maccaroni, Daniela Rutigliano, Xiling Shen, Gennaro Ciliberto

Faculty, Staff and Student Publications

On September 23-24 (2024) the 6th Workshop IRE on Translational Oncology, titled "Cancer Organoids as Reliable Disease Models to Drive Clinical Development of Novel Therapies," took place at the IRCCS Regina Elena Cancer Institute in Rome. This prominent international conference focused on tumor organoids, bringing together leading experts from around the world.A central challenge in precision oncology is modeling the dynamic tumor ecosystem, which encompasses numerous elements that evolve spatially and temporally. Patient-derived 3D culture models, including organoids, explants, and engineered or bioprinted systems, have recently emerged as sophisticated tools capable of capturing the complexity and diversity of cancer cells …

Optimizing Ewing Sarcoma And Osteosarcoma Biopsy Acquisition: A Children's Oncology Group Bone Tumor Committee Consensus Statement, Matthew S Dietz, Alyaa Al-Ibraheemi, Jessica L Davis, C Matthew Hawkins, Brian T Craig, Roshni Dasgupta, David S Geller, David S Shulman, Sarah Cohen-Gogo, Ajay Gupta, Susan L Whiteway, Emily K Slotkin, Christine M Heske, Safia K Ahmed, Daniel J Indelicato, Catherine M Albert, Nicole Montgomery, Jesse K Sandberg, Holcombe E Grier, Mark Krailo, Michael S Isakoff, Elyssa Rubin, Elizabeth R Lawlor, Steven G Dubois, Leo Mascarenhas, Patrick J Grohar, Odion Binitie, Damon Reed, Katherine Janeway, Ryan D Roberts, Kelly M Bailey

Faculty, Staff and Students Publications

Trends in diagnostic biopsy sample collection approaches for primary bone sarcomas have shifted in the past 2 decades. Although open/incisional biopsies used to be the predominant approach to obtain diagnostic material for Ewing sarcoma and osteosarcoma, image-guided core needle biopsies have increased in frequency and are safe for patients. These procedures are less invasive and reduce recovery times but have potential limitations. The quantity and quality of tissue obtained through these procedures vary between institutions. Acquired viable tissue volumes can be low, limiting the conduct of downstream expanded clinical workup, molecular analyses, and research. Patients with advanced Ewing sarcoma and …

Immune Checkpoint Inhibitor-Associated Cutaneous Adverse Events: Mechanisms Of Occurrence, Abdulaziz M. Eshaq, Thomas W. Flanagan, Abdulqader A. Ba Abbad, Zain Alabden A. Makarem, Mohammed S. Bokir, Ahmed K. Alasheq, Sara A. Al Asheikh, Abdullah M. Almashhor, Faroq Binyamani, Waleed A. Al-Amoudi, Abdulaziz S. Bawzir, Youssef Haikel, Mossad Megahed, Mohamed Hassan

School of Medicine Faculty Publications

Immunotherapy, particularly that based on blocking checkpoint proteins in many tumors, including melanoma, Merkel cell carcinoma, non-small cell lung cancer (NSCLC), triple-negative breast (TNB cancer), renal cancer, and gastrointestinal and endometrial neoplasms, is a therapeutic alternative to chemotherapy. Immune checkpoint inhibitor (ICI)-based therapies have the potential to target different pathways leading to the destruction of cancer cells. Although ICIs are an effective treatment strategy for patients with highly immune-infiltrated cancers, the development of different adverse effects including cutaneous adverse effects during and after the treatment with ICIs is common. ICI-associated cutaneous adverse effects include mostly inflammatory and bullous dermatoses, as …

Update On Strategies To Reduce Early Brain Injury After Subarachnoid Hemorrhage, Bosco Seong Kyu Yang, Aaron M Gusdon, Xuefang Sophie Ren, Han-Gil Jeong, Chang-Hun Lee, Spiros Blackburn, Huimahn Alex Choi

Faculty, Staff and Student Publications

Purpose of review: Early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (SAH) is the most influential clinical determinant of outcomes. Despite significant advances in understanding of the pathophysiology of EBI, currently no treatments to target EBI have been developed. This review summarizes recent advances in EBI research over the past five years with a focus on potential therapeutic targets.

Recent findings: Mechanism-specific translational studies are converging on several pathophysiologic pathways: improved antioxidant delivery and the Sirt1/Nrf2 pathway for reactive oxygen species; NLRP3 inflammasome and microglial polarization for inflammation; and the PI3K/Akt pathway for apoptosis. Recently identified mechanistic components, such as …

Stem Cell Activity-Coupled Suppression Of Endogenous Retrovirus Governs Adult Tissue Regeneration, Ying Lyu, Soo Jin Kim, Ericka S Humphrey, Richa Nayak, Yinglu Guan, Qingnan Liang, Kun Hee Kim, Yukun Tan, Jinzhuang Dou, Huandong Sun, Xingzhi Song, Priyadharsini Nagarajan, Kamryn N Gerner-Mauro, Kevin Jin, Virginia Liu, Rehman H Hassan, Miranda L Johnson, Lisa P Deliu, Yun You, Anurag Sharma, H Amalia Pasolli, Yue Lu, Jianhua Zhang, Vakul Mohanty, Ken Chen, Youn Joo Yang, Taiping Chen, Yejing Ge

Faculty, Staff and Student Publications

Mammalian retrotransposons constitute 40% of the genome. During tissue regeneration, adult stem cells coordinately repress retrotransposons and activate lineage genes, but how this coordination is controlled is poorly understood. Here, we observed that dynamic expression of histone methyltransferase SETDB1 (a retrotransposon repressor) closely mirrors stem cell activities in murine skin. SETDB1 ablation leads to the reactivation of endogenous retroviruses (ERVs, a type of retrotransposon) and the assembly of viral-like particles, resulting in hair loss and stem cell exhaustion that is reversible by antiviral drugs. Mechanistically, at least two molecularly and spatially distinct pathways are responsible: antiviral defense mediated by hair …

High Peripheral T Cell Diversity Is Associated With Lower Risk Of Toxicity And Superior Response To Dual Immune Checkpoint Inhibitor Therapy In Patients With Metastatic Nsclc, Mehmet Altan, Ruoxing Li, Ziyi Li, Runzhe Chen, Ajay Sheshadri, Hai T Tran, Latasha Little, Joshua Baguley, Jefferson Sinson, Natalie Vokes, Saumil Gandhi, Mara B Antonoff, Stephen G Swisher, Greg Lizee, Alexandre Reuben, John V Heymach, Jianjun Zhang

Faculty, Staff and Student Publications

INTRODUCTION: Despite significant successes, immune checkpoint blockade fails to achieve clinical responses in a significant proportion of patients, predictive markers for responses are imperfect and immune-related adverse events (irAEs) are unpredictable. We used T-cell receptor (TCR) sequencing to systematically analyze prospectively collected patient blood samples from a randomized clinical trial of dual immune checkpoint inhibitor therapy to evaluate changes in the T-cell repertoire and their association with response and irAEs.

METHODS: Patients with immunotherapy-naïve metastatic non-small cell lung cancer (NSCLC) were treated with ipilimumab and nivolumab according to trial protocol (LONESTAR, NCT03391869). Blood samples were systematically obtained at baseline (n=107), …

Targeted Degradation Of Oncogenic Krasg12v Triggers Antitumor Immunity In Lung Cancer Models, Dezhi Li, Ke Geng, Yuan Hao, Jiajia Gu, Saurav Kumar, Annabel T Olson, Christina C Kuismi, Hye Mi Kim, Yuanwang Pan, Fiona Sherman, Asia M Williams, Yiting Li, Fei Li, Ting Chen, Cassandra Thakurdin, Michela Ranieri, Mary Meynardie, Daniel S Levin, Janaye Stephens, Alison Chafitz, Joy Chen, Mia S Donald-Paladino, Jaylen M Powell, Ze-Yan Zhang, Wei Chen, Magdalena Ploszaj, Han Han, Shengqing Stan Gu, Tinghu Zhang, Baoli Hu, Benjamin A Nacev, Medard Ernest Kaiza, Alice H Berger, Xuerui Wang, Jing Li, Xuejiao Sun, Yang Liu, Xiaoyang Zhang, Tullia C Bruno, Nathanael S Gray, Behnam Nabet, Kwok-Kin Wong, Hua Zhang

Faculty, Staff and Student Publications

Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most frequently mutated oncogene in lung adenocarcinoma, with G12C and G12V being the most predominant forms. Recent breakthroughs in KRASG12C inhibitors have transformed the clinical management of patients with the G12C mutation and advanced our understanding of the function of this mutation. However, little is known about the targeted disruption of KRASG12V, partly due to a lack of specific inhibitors. Here, we leverage the degradation tag (dTAG) system to develop a KRASG12V-transgenic mouse model. We explored the therapeutic potential of KRASG12V degradation and characterized its effect on the tumor microenvironment (TME). …