Digital Commons Network^™

Investigative Needle Core Biopsies Support Multimodal Deep-Data Generation In Glioblastoma, Kenny K H Yu, Sreyashi Basu, Gerard Baquer, Ryuhjin Ahn, Jennifer Gantchev, Sonali Jindal, Michael S Regan, Zaki Abou-Mrad, Michael C Prabhu, Marc J Williams, Alicia D D'Souza, Seth W Malinowski, Kelsey Hopland, Yuval Elhanati, Sylwia A Stopka, Alexei Stortchevoi, Charles Couturier, Zhong He, Jingjing Sun, Yulong Chen, Alexsandra B Espejo, Kin Hoe Chow, Smitha Yerrum, Pei-Lun Kao, Brittany Parker Kerrigan, Lisa Norberg, Douglas Nielsen, Vinay K Puduvalli, Jason Huse, Rameen Beroukhim, Betty Y S Kim, Sangeeta Goswami, Adrienne Boire, Sarah Frisken, Michael J Cima, Matthias Holdhoff, Calixto-Hope G Lucas, Chetan Bettegowda, Stuart S Levine, Tejus A Bale, Cameron Brennan, David A Reardon, Frederick F Lang, E Antonio Chiocca, Keith L Ligon, Forest M White, Padmanee Sharma, Viviane Tabar, Nathalie Y R Agar

Faculty, Staff and Student Publications

Glioblastoma (GBM) is an aggressive primary brain cancer with few effective therapies. Stereotactic needle biopsies are routinely used for diagnosis; however, the feasibility and utility of investigative biopsies to monitor treatment response remains ill-defined. Here, we demonstrate the depth of data generation possible from routine stereotactic needle core biopsies and perform highly resolved multi-omics analyses, including single-cell RNA sequencing, spatial transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics on standard biopsy tissue obtained intra-operatively. We also examine biopsies taken from different locations and provide a framework for measuring spatial and genomic heterogeneity. Finally, we investigate the …

Mitochondrial Dysfunction And Parkinson's Disease: A Critical Link, Anika J. Millar

Senior Honors Theses

Parkinson’s disease is a neurodegenerative disorder, caused by the damage to and death of dopamine-releasing neurons in the brain. The substantia nigra is a major region housing dopaminergic neurons and plays a critical role in motor and cognitive function. When these neurons are compromised, dopamine levels decline, leading to the development of motor and cognitive dysfunction. Current treatments include dopamine precursors, which help to replace dopamine and relieve motor symptoms. However, while there is symptomatic treatment for Parkinson’s disease, there are no preventative therapies or cures. A potential link between mitochondrial dysfunction and Parkinson’s disease has prompted further research. Investigating …

An Exploration Of Behavioral Sex Differences Due To A Parkinsonian Gene, Pdr-1, In C. Elegans., Adriana Mulet Miranda, Mary B. Kroetz, Paul J. Kiser

Undergraduate Theses

Parkinson’s disease is a debilitating neurodegenerative disease of the central nervous system classified by the loss of dopaminergic neurons. Males and females exhibit different symptoms however, the cause remains unknown. Through the use of a model organism, C. elegans, we will investigate an ortholog of a Parkinsonian gene, pdr-1, to explore whether or not there are statistical differences between the hermaphrodites and males through known behavioral assays such as Swimming Induced Paralysis and Basal Slowing Rate. In order to compare gender differences, we successfully conducted CRISPR, where we inserted the him-8 mutation, resulting in an increased population …

The Impact Of Epac2-Associated Junction Plakoglobin On Respiratory Syncytial Virus Infection, Chaitra A Takle, Eun-Jin Choi, Eun Seok Choi, Devang Deepak, Kashish Khatkar, Jong Min Choi, Ke Zhang, Sung Yun Jung, Tian Wang, Wenzhe Wu, Xiaoyong Bao

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants, young children, and immunocompromised individuals. Currently, FDA-approved monoclonal antibody therapies are limited to infants and young children with severe RSV disease. As a result, there is an urgent need for comprehensive studies of RSV pathogenesis to support the development of new therapeutic strategies. Exchange proteins directly activated by cAMP (EPAC) have recently emerged as key regulators in various viral infections. Our previous work identified EPAC isoform 2 (EPAC2) as a critical factor in RSV replication and host innate immune responses. However, …

Building A Pre-Surgical Multiparametric-Mri-Based Morphologic, Qualitative, Semiquantitative, First And High-Order Radiomic Predictive Treatment Response Model For Undifferentiated Pleomorphic Sarcoma To Replace Recist, Raul F Valenzuela, Elvis Duran-Sierra, Mathew Antony, Behrang Amini, Sam Lo, Keila E Torres, Robert S Benjamin, Jingfei Ma, Ken-Pin Hwang, R Jason Stafford, Dejka Araujo, Andrew J Bishop, Ravin Ratan, Wei-Lien Wang, Jossue Espinoza, Pia V Valenzuela, Chengyue Wu, John E Madewell, William A Murphy, Colleen M Costelloe

Faculty, Staff and Student Publications

Background: Undifferentiated pleomorphic sarcoma (UPS) is the largest subgroup of soft-tissue sarcomas. It demonstrates post-therapeutic hemosiderin deposition, granulation tissue formation, fibrosis, and calcification. Our research aims to establish the multiparametric MRI (mp-MRI) value for predicting UPS treatment response.

Methods: An IRB-approved retrospective study included 33 extremity UPS patients with pre-operative mp-MRI, including diffusion-weighted imaging (DWI), contrast-enhanced susceptibility-weighted imaging (CE-SWI), and perfusion-weighted imaging with dynamic contrast-enhancement (PWI/DCE), and surgical resection between February 2021 and May 2023. Lesions were visually classified on CE-SWI into one of 6 morphology patterns. On PWI/DCE, lesions were classified into one of 6 patterns, and time-intensity curves …

Structural Insights Into The Function, Dysfunction And Modulation Of Kv3 Channels, Manuel Covarrubias, Qiansheng Liang, Linh Nguyen-Phuong, Kyle J. Kennedy, Tyler D. Alexander, Ms, Andrew Sam

Department of Neuroscience Faculty Papers

The third subfamily of voltage-gated K⁺ (Kv) channels includes four members, Kv3.1, Kv3.2, Kv3.3 and Kv3.4. Fast gating and activation at relatively depolarized membrane potentials allows Kv3 channels to be major drivers of fast action potential repolarization in the nervous system. Consequently, they help determine the fast-spiking phenotype of inhibitory interneurons and regulate fast synaptic transmission at glutamatergic synapses and the neuromuscular junction. Recent studies from our group and a team of collaborators have used cryo-EM to demonstrate the surprising gating role of the Kv3.1 cytoplasmic T1 domain, the structural basis of a developmental epileptic encephalopathy caused by the …

Metabolic Theories Of Aging, Chris Burley, Lisa K. Lashley, Charles J. Golden

Essays in Developmental Psychology

Metabolic theories of aging postulate that aging is due to energy expenditure, which ultimately results in the breakdown and eventual death of cells. Historically, within the realm of metabolic theories of aging, there have been three models: The Rate-of-Living theory, The Oxidative Damage/Free Radical theory, and the Metabolic Stability theory. All three theories maintain that aging is directly related to metabolic rate, but the theories differ in how they arrive at that conclusion.

Acute Brcaness Induction And Ar Pathway Blockage Through Cdk12/7/9 Degradation Enhances Parp Inhibitor Sensitivity In Prostate Cancer, Fu Gui, Baishan Jiang, Jie Jiang, Zhixiang He, Takuya Tsujino, Tomoaki Takai, Seiji Arai, Celine Pana, Jens Köllermann, Gary Andrew Bradshaw, Robyn Eisert, Marian Kalocsay, Anne Fassl, Steven P Balk, Adam S Kibel, Li Jia

Faculty, Staff and Student Publications

Current treatments for advanced prostate cancer (PCa) primarily target the androgen receptor (AR) pathway. However, the emergence of castration-resistant prostate cancer (CRPC) and resistance to AR pathway inhibitors (APPIs) remains ongoing challenges. Here, we present BSJ-5-63, a proteolysis-targeting chimera (PROTAC) targeting cyclin-dependent kinases (CDKs) CDK12, CDK7, and CDK9, offering a multipronged approach to CRPC therapy. BSJ-5-63 degrades CDK12, diminishing BRCA1 and BRCA2 expression and inducing a sustained "BRCAness" state. This sensitizes cancer cells to PARP inhibitors (PARPis) regardless of their homologous recombination repair (HRR) status. Furthermore, CDK7 and CDK9 degradation attenuates AR signaling, enhancing its therapeutic efficacy. Preclinical studies, including …

Distinct Adipose Progenitor Cells Emerging With Age Drive Active Adipogenesis, Guan Wang, Gaoyan Li, Anying Song, Yutian Zhao, Jiayu Yu, Yifan Wang, Wenting Dai, Martha Salas, Hanjun Qin, Leonard Medrano, Joan Dow, Aimin Li, Brian Armstrong, Patrick T Fueger, Hua Yu, Yi Zhu, Mengle Shao, Xiwei Wu, Lei Jiang, Judith Campisi, Xia Yang, Qiong A Wang

Children’s Nutrition Research Center Staff Publications

Starting at middle age, adults often suffer from visceral adiposity and associated adverse metabolic disorders. Lineage tracing in mice revealed that adipose progenitor cells (APCs) in visceral fat undergo extensive adipogenesis during middle age. Thus, despite the low turnover rate of adipocytes in young adults, adipogenesis is unlocked during middle age. Transplantations quantitatively showed that APCs in middle-aged mice exhibited high adipogenic capacity cell-autonomously. Single-cell RNA sequencing identified a distinct APC population, the committed preadipocyte, age-enriched (CP-A), emerging at this age. CP-As demonstrated elevated proliferation and adipogenesis activity. Pharmacological and genetic manipulations indicated that leukemia inhibitory factor receptor signaling was …

Hepatic Manifestations Following Gene Therapy, Akash Roy, Shalini Bansal, Anand Kulkarni, K. Rajender Reddy

SKMC Student Presentations and Publications

Gene therapy involves the introduction of genetic materials, most commonly using viral vectors, to alter gene expression to ameliorate or cure disease symptoms with minimal adverse events. While interest in gene therapy has been on the increase, concerns have arisen about the potential for hepatotoxicity, which arises from diverse mechanisms. While viral vectors can produce dose-dependent hepatotoxicity secondary to integration, immune responses appear to be the primary driving mechanism. A mild increase in aminotransferases is the most common hepatic manifestation, occurring variably in 20%-80%, while there has been rare progress to acute liver failure. The occurrence of hepatotoxicity is unpredictable …

Idh Status Dictates Ohsv Mediated Metabolic Reprogramming Affecting Anti-Tumor Immunity, Upasana Sahu, Matthew P Mullarkey, Sara A Murphy, Joshua C Anderson, Vasanta Putluri, Abu Hena Mostafa Kamal, Jun Hyoung Park, Tae Jin Lee, Alexander L Ling, Benny A Kaipparettu, Ashok Sharma, Nagireddy Putluri, Pamela L Wenzel, Christopher D Willey, E Antonio Chiocca, James M Markert, Balveen Kaur

Faculty, Staff and Student Publications

Identification of isocitrate dehydrogenase (IDH) mutations has uncovered the crucial role of metabolism in gliomagenesis. Oncolytic herpes virus (oHSV) initiates direct tumor debulking by tumor lysis and activates anti-tumor immunity, however, little is known about the role of glioma metabolism in determining oHSV efficacy. Here we identify that oHSV rewires central carbon metabolism increasing glucose utilization towards oxidative phosphorylation and shuttling glutamine towards reductive carboxylation in IDH wildtype glioma. The switch in metabolism results in increased lipid synthesis and cellular ROS. PKC induces ACSL4 in oHSV treated cells leading to lipid peroxidation and ferroptosis. Ferroptosis is critical to launch an …

Diabetic Retinopathy: A Pathophysiological Discussion, Nathanael C. Nicholls

Senior Honors Theses

Diabetic retinopathy is a severe complication of diabetes that is capable of causing vision loss or blindness. As a result of hyperglycemia, the disease increases oxidative stress and activates biochemical processes such as the Hippo pathway and the complement system to cause significant damage to the retina. Overexpression of BTG1 and microRNA-183 enables activation of biochemical pathways that lead to negative effects on the retinal vascular endothelium including angiogenesis and inflammation. Conventional methods of diagnosis for diabetic retinopathy include fundus examination, nucleoside detection, and optical coherence tomography angiography. Photocoagulation and hormonal intravitreal injection are the most popular current treatments, while …

Impact Of Antidiabetic Medication Type On A New Episode Of Depression: A Retrospective Cohort Study In Texas, Usa, Lin-Na Chou, Mukaila A Raji, Holly M Holmes, Yong-Fang Kuo

Faculty, Staff and Student Publications

Objectives: To examine the associations between antidiabetic medication type and a new episode of depression using 100% Texas Medicare database during 2009 and 2018.

Design: A retrospective cohort study.

Setting: A population-based study using the Texas Medicare data.

Interventions: 11 common antihyperglycaemic medication types, alone and in combinations: metformin-only, five non-metformin-containing regimens (dipeptidyl peptidase-4 inhibitor (DPP4i) only, sulfonylureas (SU) only, thiazolidinediones (TZD) only, SU/DPP4i and SU/TZD) and five metformin-containing combination treatments (metformin/DPP4i, metformin/SU, metformin/TZD, metformin/SU/DPP4i and metformin/SU/TZD).

Participants: This study included 59 057 type 2 diabetes (T2D) patients from a cohort of Texas Medicare beneficiaries who were aged ≥66 years, …

Retrospective Analysis Of Cement Extravasation Rates In Vertebroplasty, Kyphoplasty, And Bone Tumor Radiofrequency Ablation, Soun Sheen, Prit Hasan, Xiaowen Sun, Jian Wang, Claudio Tatsui, Kent Nouri, Saba Javed

Faculty, Staff and Student Publications

Background: Percutaneous vertebral augmentation techniques, including vertebroplasty, kyphoplasty, and bone tumor radiofrequency ablation (BT-RFA), are commonly used to treat painful vertebral compression fractures (VCFs). While generally safe and effective, they carry risks, including cement extravasation, which can lead to pulmonary embolism or spinal cord compression. This study aims to compare the rate of cement extravasation across different vertebral augmentation techniques and identify potential risk factors.

Methods: A retrospective cohort study was conducted at a comprehensive cancer center on 1002 procedure encounters in 888 patients who underwent vertebral augmentation for painful VCFs. Data were collected on patient demographics, fracture pathology, procedure …

Environmental Exposures And Familial Background Alter The Induction Of Neuropathology And Inflammation After Sars-Cov-2 Infection, Debotri Chatterjee, Drishya Kurup, Richard Jay Smeyne

Department of Neuroscience Faculty Papers

Post-infection sequela of several viruses have been linked with Parkinson's disease (PD). Here, we investigated whether mice infected with SARS-CoV-2 alone or in combination with two putative Parkinsonian toxins, MPTP and paraquat, increased the susceptibility to develop Parkinsonian pathology. We also examined if G2019S LRRK2 mice had any change in sensitivity to SARS-CoV-2 as well as if vaccination against this virus altered any neuropathology. Infection with WA-1/2020 or Omicron B1.1.529 strains sensitized both WT and G2019S LRRK2 mice to the neuropathological effects of a subtoxic exposure to MPTP, but not paraquat. These neuropathologies were rescued in WT mice vaccinated with …

Inhibition Of Soluble Epoxide Hydrolase Confers Neuroprotection And Restores Microglial Homeostasis In A Tauopathy Mouse Model, Shuo Wang, Chuangye Qi, Chetan Rajpurohit, Baijayanti Ghosh, Wen Xiong, Baiping Wang, Yanyan Qi, Sung Hee Hwang, Bruce D Hammock, Hongjie Li, Li Gan, Hui Zheng

Center on Aging Staff Publications

Background: The epoxyeicosatrienoic acids (EETs) are derivatives of the arachidonic acid metabolism with anti-inflammatory activities. However, their efficacy is limited due to the rapid hydrolysis by soluble epoxide hydrolase (sEH). Inhibition of sEH has been shown to stabilize the EETs and reduce neuroinflammation in Aβ mouse models of Alzheimer's disease (AD). However, the role of the sEH-EET signaling pathway in other CNS cell types and neurodegenerative conditions are less understood.

Methods: Here we investigated the mechanisms and functional role of the sEH-EET axis in tauopathy by treating PS19 mice with a small molecule sEH inhibitor TPPU and by crossing the …

The Combined Effect Of High-Intensity Interval Training And Time-Restricted Feeding On The Akt-Igf-1-Mtor Signaling Pathway In The Muscle Tissue Of Type 2 Diabetic Rats, Motahareh Mohebinejad, Fatemeh Kazeminasab, Mahtab Ghanbari Rad, Reza Bagheri, Mazdak Razi, Darryn Willoughby, Fred Dutheil

Faculty, Staff and Students Publications

Background/Objectives: High-intensity interval training (HIIT) and time-restricted feeding (TRF) have shown potential in enhancing glucose metabolism, increasing insulin sensitivity, and promoting muscle health. This study investigates the combined effects of HIIT and TRF on the AKT-IGF-1-mTOR signaling pathway in the muscle tissue of type 2 diabetic (T2D) rats.

Methods: 42 male Wistar rats (4-5 weeks of age) were included in the study. The animals were randomly divided into two groups: 1. Standard diet (SD) non-diabetic (n = 7) and 2. High-fat diet (HFD n = 35) for 4 weeks. T2D was induced by intraperitoneal injection (IP) of streptozotocin (STZ) …

Tobacco Smoking Functional Networks: A Whole-Brain Connectome Analysis In 24 539 Individuals, Yezhi Pan, Chuan Bi, Zhenyao Ye, Hwiyoung Lee, Jiaao Yu, Luba Yammine, Tianzhou Ma, Peter Kochunov, L Elliot Hong, Shuo Chen

Faculty, Staff and Student Publications

Introduction: Nicotine addiction, a multifaceted neuropsychiatric disorder, profoundly impacts brain functions through interactions with neural pathways. Despite its significance, the impact of tobacco smoking on the whole-brain functional connectome remains largely unexplored.

Aims and methods: We conducted a whole-brain analysis on 24 539 adults aged 40 and above from the United Kingdom Biobank cohort. Subjects were categorized into individuals who use nicotine and those who do not use nicotine based on current and chronic tobacco smoking information. Functional connectivity was assessed using resting-state functional magnetic resonance imaging. We employed a network analysis method to assess the systematic effects of tobacco …

Can The Discovery Of High-Impact Diagnostics Be Improved By Matching The Sampling Rate Of Clinical Diagnostics To The Frequency Domain Of Diagnostic Information?, Steven W Millward, Peng Wei, David Piwnica-Worms, Seth T Gammon

Faculty, Staff and Student Publications

Over the past 30 years, academic and industrial research investigators have developed molecular reporters to visualize cell death in complex biological systems. In parallel, clinical researchers, chemists, biochemists, and molecular biologists have endeavored to translate these molecular tools into clinical imaging agents. Despite these efforts, there are no clinically approved imaging methodologies with which to image cell death consistently and quantitatively. One reason may reside in the intrinsic mismatch between the sampling frequency of translational molecular imaging and the biochemical kinetics that define cell death. Beyond cell death imaging, many active research programs are now attempting to create translational diagnostic …

New Insights Into Epileptic Spasm Generation And Treatment From The Ttx Animal Model, John W Swann, Carlos J Ballester-Rosado, Chih-Hong Lee

Duncan NRI Faculty and Staff Publications

Currently, we have an incomplete understanding of the mechanisms underlying infantile epileptic spasms syndrome (IESS). However, over the past decade, significant efforts have been made to develop IESS animal models to provide much-needed mechanistic information for therapy development. Our laboratory has focused on the TTX model and in this paper, we review some of our findings. To induce spasms, tetrodotoxin (TTX) is infused into the neocortex of infant rats. TTX produces a lesion at its infusion site and thus mimics IESS resulting from acquired structural brain abnormalities. Subsequent electrophysiological studies showed that the epileptic spasms originate from neocortical layer V …

The Havcr1-Centric Host Factor Network Drives Zika Virus Vertical Transmission, Wenzhe Yu, Jun Tao, Hongmin Cao, Wanshan Zheng, Beiang Zhang, Yue Zhang, Peiqun Xu, Yiwei Zhang, Xuan Liu, Yinan Wang, Han Cai, Gang Liu, Fan Liu, Haibin Wang, Haiyan Zhao, Indira U Mysorekar, Xiaoqian Hu, Bin Cao

Center on Aging Staff Publications

Zika virus (ZIKV) vertical transmission results in devastating congenital malformations and pregnancy complications; however, the specific receptor and host factors facilitating ZIKV maternal-fetal transmission remain elusive. Here, we employ a genome-wide CRISPR screening and identify multiple placenta-intrinsic factors modulating ZIKV infection. Our study unveils that hepatitis A virus cellular receptor 1 (HAVCR1) serves as a primary receptor governing ZIKV entry in placental trophoblasts. The GATA3-HAVCR1 axis regulates heterogeneous cell tropism in the placenta. Notably, placenta-specific Havcr1 deletion in mice significantly impairs ZIKV transplacental transmission and associated adverse pregnancy outcomes. Mechanistically, the immunoglobulin variable-like domain of HAVCR1 binds to ZIKV via …

Liposomes As Imaging Agents Of Inflammation And Oxidative Stress In Bone Implants, Delia Danila, Patricia S Pardo, R Devesh Kumar Misra, Aladin M Boriek

Faculty, Staff and Students Publications

Liposomes are tiny, spherical vesicles made from cholesterol and natural phospholipids that are promising imaging agents for detecting medical complications. They can carry fluorescent markers or other imaging agents, making them effective for medical imaging. Furthermore, liposomes can target specific cells involved in inflammation, such as macrophages, and accumulate at inflammation sites when injected. Additionally, liposomes can be designed to respond to oxidative stress, which is often associated with bone implant complications. By detecting areas of stress, liposomes provide valuable information about implant health. However, challenges such as rapid clearance from the body, precise targeting, immune reactions, and high production …

Tips For Quality Publishing; Lessons From The Neuroscience Editorial Team, Francesca Cirulli, Rachael Dangarembezi, Victor De Lafuente, Anthony J Hannan, Amanda C Kentner, Tatsuya Mima, Laurel Morris, Sarah J Spencer, Long-Jun Wu, Chen Zhang

The Brown Foundation: Institute of Molecular Medicine

In pursuit of excellence in scholarly publishing, the Neuroscience editorial team shares valuable insights that are essential for authors, reviewers, and the broader scientific community. Firstly, we emphasize that impactful research is built on rigorous study design and execution. Beyond fundamental methodological safeguards such as randomization and blinded analysis, we highlight the importance of thoughtfully selecting study models, with deliberate attention to biological variables like sex and gender, as well as appropriate nomenclature. Secondly, as technological innovations reshape research landscapes, we advocate for combining methodological rigor with suitable analytical tools to ensure robust data collection and transparent reporting. Thirdly, for …

Progesterone Signaling In Oviductal Epithelial Cells Modulates The Immune Response To Support Preimplantation Embryonic Development, Emily A Mcglade, Jiude Mao, Kalli K Stephens, Ryan M Marquardt, Feyza Nur Arguc, Peter F Lais, San-Pin Wu, Sarayut Winuthayanon, Haval Shirwan, Esma S Yolcu, Mark I Hunter, James K Pru, John P Lydon, Francesco J Demayo, Wipawee Winuthayanon

Faculty, Staff and Students Publications

More than 60% of pregnancy losses occur during the first trimester, highlighting the need to understand the role of the oviduct in early pregnancy. In this study, we conditionally ablated the classical progesterone receptor (Pgr) in oviductal epithelial cells, called the Pgrd/d mouse model. We found that 40% of embryos collected from Pgrd/d females were nonviable or developmentally delayed, indicating that epithelial PGR expression is crucial for embryonic development. Single-cell RNA sequencing revealed up-regulation of proinflammatory genes, including interleukin-22 (IL-22), in the epithelial cells of Pgrd/d females. Pharmacological inhibition of inflammation using nonsteroidal anti-inflammatory drugs …

Rnase1-Driven Alk-Activation Is An Oncogenic Driver And Therapeutic Target In Non-Small Cell Lung Cancer, Zhengyu Zha, Chunxiao Liu, Meisi Yan, Cong Chen, Cheng Yu, Yaohui Chen, Chenhao Zhou, Lu Li, Yi-Chuan Li, Hiro Yamaguchi, Leiguang Ye, Tong Liu, Ying-Nai Wang, Heng-Huan Lee, Wen-Hao Yang, Li-Chuan Chan, Baozhen Ke, Jennifer L Hsu, Lieming Ding, Dong Ji, Peng Pan, Yiran Meng, Yue Pu, Lunxu Liu, Mien-Chie Hung

Faculty, Staff and Student Publications

Targeted therapy has achieved significant success in the treatment of non-small cell lung cancer (NSCLC), particularly in patients harboring common oncogenic driver mutations such as EGFR, KRAS, and ALK rearrangement. However, ~35-50% of NSCLC patients without tyrosine kinase mutation or rearrangement (non-mutated) cannot benefit from these targeted treatments, highlighting the urgent need for novel therapeutic strategies for this patient population. In this study, we report a non-canonical role of human secretory ribonuclease 1 (RNase1), which binds to and activates wild-type ALK in lung cancer cells, thereby triggering its downstream signaling pathway. RNase1-driven ALK-activation (RDAA) cells exhibit enhanced cell proliferation, migration, …

Enriched Pathways In Gut Microbiome Predict Response To Immune Checkpoint Inhibitor Treatment Across Demographic Regions And Various Cancer Types, Xunhui Cai, Jennifer Y Cho, Lijun Chen, Yufeng Liu, Fenghu Ji, Katia Salgado, Siyi Ge, Dehua Yang, Hui Yu, Jianbo Shao, P Andrew Futreal, Boris Sepesi, Don Gibbons, Yaobing Chen, Guoping Wang, Chao Cheng, Meng Wu, Jianjun Zhang, Ansel Hsiao, Tian Xia

Faculty, Staff and Student Publications

Understanding the effect of gut microbiota function on immune checkpoint inhibitor (ICI) responses is urgently needed. Here, we integrated 821 fecal metagenomes from 12 datasets to identify differentially abundant genes and construct random forest models to predict ICI response. Gene markers demonstrated excellent predictive performance, with an average area under the curve (AUC) of 0.810. Pathway analyses revealed that quorum sensing (QS), ABC transporters, flagellar assembly, and amino acid biosynthesis pathways were enriched between responders (R) and non-responders (NRs) across 12 datasets. Furthermore,

Robust Sex Determination In The Caenorhabditis Nigoni Germ Line, Jonathan P Harbin, Yongquan Shen, Shin-Yi Lin, Kevin Kemper, Eric S Haag, Erich M Schwarz, Ronald E Ellis

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Sexual characteristics and reproductive systems are dynamic traits in many taxa, but the developmental modifications that allow change and innovation are largely unknown. A leading model for this process is the evolution of self-fertile hermaphrodites from male/female ancestors. However, these studies require direct analysis of sex-determination in male/female species, as well as in the hermaphroditic species that are related to them. In Caenorhabditis nematodes this has only become possible recently, with the discovery of new species. Here, we use gene editing to characterize major sex-determination genes in C. nigoni, a sister to the widely studied hermaphroditic species C. briggsae. These …

Evaluation Of Clinical Features And Treatment Modality Of Pediatric Patients With Steven Johnson Syndrome/Toxic Epidermal Necrolysis: A Single-Center Experience, Funda Ayteki̇n Güveni̇r, Vi̇ldan Seli̇n Çayhan, Selman Kürşat Balci, Ragip Dere, Hati̇ce Irmak Çeli̇k, Serhat Emeksi̇z, Ahmet Selmanoğlu, Zeynep Şengül Emeksi̇z, Emrah Şenel, Emi̇ne Di̇bek Misirlioğlu

Turkish Journal of Medical Sciences

Background/aim: Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rare but life-threatening severe cutaneous drug hypersensitivity reactions. The aim of our study was to evaluate the clinical features of pediatric patients diagnosed with SJS, TEN or SJS/TEN overlap and to examine treatment modalities.

Materials and methods: Patients aged 0–18 years who were followed up with SJS, TEN or SJS/TEN overlap at Ankara Bilkent City Hospital between August 2019 and January 2024 were retrospectively analyzed.

Results: Twelve patients who met the inclusion criteria were included in the study. Five of the patients had SJS, four had SJS/TEN overlap, and …

Comparative Vasorelaxant Effects Of Atorvastatin And Rosuvastatin In Rat Aorta:Investigating The Role Of Perivascular Adipose Tissue, Deni̇z Kaleli̇ Durman, Meryem Aras, Gülsüm Ruveyda Aktaş, Bi̇rsel Sönmez Uydeş Doğan

Turkish Journal of Medical Sciences

Background/aim: Statins are known to display pleiotropic effects on the vascular system, beyond their lipid-lowering properties. Studieson isolated vascular preparations have demonstrated their acute relaxant effects on vascular tone. Considering the increased evidence inregard to the contribution of perivascular adipose tissue (PVAT) in the regulation of vascular homeostasis, we aimed to investigate thepossible modulatory role of PVAT in the vascular effects of atorvastatin and rosuvastatin in isolated rat aorta.

Materials and methods: Thoracic aortas isolated from young male Wistar rats were divided into two groups: rings with intact PVAT(+) and rings without PVAT (-), and then mounted in an isolated …

The Effects Of Liraglutide On Expressions Of Insulin Secretion And Beta Cell Survive Associated Gpcr Genes In Pancreatic Beta Cells, Meli̇kenur Türkol, Türker Bi̇lgen

Turkish Journal of Medical Sciences

Background/aim: Liraglutide as a long-acting glucagon-like peptide drug has anti-hyperglycemic and antiobesity effects. G protein-coupled receptors (GPCRs) are well- known drug target molecules that conduct critical signaling pathways related with diseases. Research has confirmed the role of many GPCRs genes in the regulation of pancreatic beta cell functions and insulin secretion. Liraglutide dependent expressional changes in GPCR genes may let us determine new drug targets.

Materials and methods: Therefore, we investigated the changes in expression of GPR75, GPR56, GLP1R, M3R, and CB1R genes, which are the GPCR family members, in response to liraglutide treatment in the NIT-1 mouse pancreatic beta …