Digital Commons Network^™

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, …

The Dynamic Immune Behavior Of Primary And Metastatic Ovarian Carcinoma, Elaine Stur, Fuduan Peng, Pang-Ning Teng, Emine Bayraktar, Min Hu, Sara Corvigno, David J Brown, Sanghoon Lee, Kathleen N Moore, Nicholas W Bateman, Kathleen M Darcy, George L Maxwell, Thomas P Conrads, Nidhi Sahni, Ignacio Vázquez-García, Sohrab P Shah, Joseph Celestino, Nicole D Fleming, Nicholas E Navin, Linghua Wang, Anil K Sood

Faculty, Staff and Student Publications

Patients with high-grade serous ovarian carcinoma (HGSC) are usually diagnosed with advanced-stage disease, and the tumors often have immunosuppressive characteristics. Together, these factors are important for disease progression, drug resistance, and mortality. In this study, we used a combination of single-cell sequencing and spatial transcriptomics to identify the molecular mechanisms that lead to immunosuppression in HGSC. Primary tumors consistently showed a more active immune microenvironment than did omental tumors. In addition, we found that untreated primary tumors were mostly populated by dysfunctional CD4 and CD8 T cells in later stages of differentiation; this, in turn, was correlated with expression changes …

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 …

A Pioneering Artificial Intelligence Tool To Predict Treatment Outcomes In Ovarian Cancer Via Diagnostic Laparoscopy, Xiaotian Ma, Yu-Chun Hsu, Amma Asare, Kai Zhang, Deanna Glassman, Katelyn F Handley, Katherine Foster, Khwahish Sharma, Shannon Westin, Amir Jazaeri, Nicole D Fleming, Pratip K Bhattacharya, Xiaoqian Jiang, Anil K Sood, Shayan Shams

Faculty, Staff and Student Publications

Ovarian cancer is associated with high rates of patient mortality and morbidity. Laparoscopic assessment of tumor localization can be used for treatment planning in newly diagnosed high-grade serous ovarian carcinoma (HGSOC). While spread to multiple intra-abdominal areas is correlated with worse outcomes, whether other morphological tumor differences are also associated with patient outcomes is unknown. Given the large volume of visual information in laparoscopic videos, we investigated whether deep-learning models can capture implicit features and predict treatment outcomes. We developed a novel deep-learning framework using pre-treatment laparoscopic images to assess clinical outcomes following upfront standard treatment, defined as short progression-free …

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 …

Primary Central Nervous System Lymphoma: Predictors Of Response To Induction Therapy And Patterns Of Progression, Louis Cappelli, Allison Kayne, Jennifer Newman, Ahmed Elguindy, Narendranath Epperla, Joshua D. Palmer, Ubaldo E. Martinez-Outshoorn, Pierluigi Porcu, Wenyin Shi, Iyad Alnahhas

Department of Radiation Oncology Faculty Papers

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive variant of non-Hodgkin lymphoma. While PCNSL is often sensitive to induction high-dose methotrexate (HDMTX) based chemotherapy, recurrence rates remain high, approaching 50% within 5 years. The most common molecular alterations in PCNSL include mutations in MYD88 and CD79 and CDKN2A homozygous deletion. There are no predictive or prognostic molecular markers in PCNSL.

METHODS: We conducted a retrospective review of 40 patients with PCNSL treated at Thomas Jefferson University and Ohio State University between 2011 and 2023. We created a clinically annotated database of patient characteristics and outcomes. For …

Editorial: Women In Science: Allergy Research, Gemma Carreras-Badosa, Vanesa Esteban, Vivian Hernandez-Trujillo, Elina Toskala, Manali Mukherjee, Saba Al Heialy, Karin Fieten

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

No abstract provided.

High-Grade Astrocytoma With Piloid Features: A Single-Institution Case Series And Literature Review, Eric A Goethe, Subhiksha Srinivasan, Swaminathan Kumar, Sujit S Prabhu, Maria A Gubbiotti, Sherise D Ferguson

Faculty, Staff and Student Publications

High-grade astrocytoma with piloid features (HGAP) is a recently described primary brain tumor and the first requiring a specific methylation pattern for diagnosis, as its histologic features are often compatible with other tumors such as glioblastoma (GBM). Characterized by molecular alterations in CDKN2A/B, NF1, BRAF, FGFR1, and ATRX, they may be located anywhere in the CNS but show a predilection for the posterior fossa. Reports are limited to retrospective case series, and the standard of care is not yet established. We performed a retrospective review of electronic medical records of all patients with HGAP at our institution. Records were queried …

Differences In Hepatocellular Carcinoma Incidence Trends Across Us Census Divisions, 2001 To 2021, Itunu O Sokale, Omar Rosales, Aaron P Thrift, Hashem B El-Serag, Elyse Burgess, Abiodun O Oluyomi

Faculty, Staff and Students Publications

Background/Objectives: Hepatocellular carcinoma (HCC) is a leading cause of cancer diagnoses and deaths in the United States. This study serves as an update on secular trends in national HCC incidence rates while exploring potential geographic and racial/ethnic differences across all nine US census divisions.

Methods: We analyzed HCC incidence data reported to the United States Cancer Statistics (USCS) database from 2001 to 2021 (excluding 2020 data, based on the Centers for Disease Control and Prevention's cautionary recommendations for COVID-19 pandemic data usage for trend analysis). We performed trend analyses of age-adjusted incidence rates in the US overall, by census …

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 …

Sleep Deprivation Increases Mortality Risk Among Older Adults With Epilepsy, Srikanta Banerjee, Jagdish Khubchandani, Stanley Nkemjika

Department of Psychiatry and Human Behavior Faculty Papers

Introduction: Among U.S. adults, over 3 million report a history of epilepsy, accounting for nearly 1.2% of the population. Sleep deprivation is a well-known risk factor for increased likelihood, intensity, and length of seizures. However, the long-term impact of sleep deprivation on people with epilepsy is not well explored. The purpose of this study was to assess mortality risk among individuals with epilepsy based on sleep duration.

Methods: Data from the 2008–2018 National Health Interview Survey (NHIS) were linked with mortality data from the National Death Index (NDI) for US adults aged 65 years and older. Survival curves showed the …

Virtual Reality-Enhanced Rehabilitation For Improving Musculoskeletal Function And Recovery After Trauma, Phani Paladugu, Rahul Kumar, Joshua Ong, Ethan Waisberg, Kyle Sporn

SKMC Student Presentations and Publications

Orthopedic trauma remains a critical challenge in modern healthcare, often resulting in severe mobility limitations, acute pain, and delayed recovery. Conventional rehabilitation techniques, though effective, fail to address the individualized, high-precision interventions needed for musculoskeletal injuries like fractures, joint instability, ligament tears, and muscular atrophy. Virtual reality (VR) technologies, such as Apple Vision Pro and HTC Vive Pro, offer a transformative approach by enhancing diagnostic precision, rehabilitation effectiveness, and patient engagement through interactive, immersive environments that improve clinical outcomes. These VR technologies provide real-time biomechanical data, such as joint mechanics, muscle coordination, and movement patterns, allowing clinicians to design personalized …

Is There Evidence For Changes In Antibiotic Resistance Of Microorganisms Causing Postcataract Surgery Endophthalmitis: A Systematic Review, Christina J Flaxel, Justine R Smith, Nieraj Jain, Leo A Kim, Stephen Jae Kim, Maureen G Maguire, Christina Y Weng, Steven Yeh

Faculty, Staff and Students Publications

Background/aims: To review the evidence for changes in antibiotic resistance patterns before and after cataract surgery since the advent of routine use of intracameral (IC) antibiotic prophylaxis and development of newer topical fluoroquinolones pre- and postcataract surgery.

Methods: Literature searches in the National Library of Medicine PubMed database were conducted between 2019 and 2021 and updated in 2024. There were no date restrictions, and the search was limited to high-quality studies published in English. The initial combined searches yielded 583 articles, and the search update in 2024 yielded 9 articles. Of these 592 articles, 26 presented original research that met …

Impact Of Age On Biology, Presentation And Outcomes In Marginal Zone Lymphoma: Results From A Multicenter Cohort Study, Pallawi Torka, Natalie S. Grover, Timothy J. Voorhees, Reem Karmali, Kaitlin Annunzio, Marcus P. Watkins, Andrea Anampa-Guzmán, Heather Reves, Montreh Tavakkoli, Beth Christian, Colin Thomas, Stefan K. Barta, Praveen Ramakrishnan Geethakumari, Nancy L. Bartlett, Geoffrey Shouse, Adam J. Olszewski, Narendranath Epperla

Department of Medicine Faculty Papers

Given the paucity of age-specific data about biology, presentation, and treatment outcomes in adults with MZL, we sought to evaluate differences between younger (≤ 70 years) and older (> 70 years) patients with MZL in a large retrospective cohort treated in the contemporary era (2010 onwards). The primary objective was progression-free survival (PFS), while secondary objectives included the evaluation of overall survival (OS) and the cumulative incidence of transformation between the 2 groups. A total of 598 patients were included in the analysis and among these 32% were > 70 years of age. There were no age-based differences in the prevalence …

Ensemble Learning With Explainable Ai For Improved Heart Disease Prediction Based On Multiple Datasets, Shahid Mohammad Ganie, Pijush Kanti Dutta Pramanik, Zhongming Zhao

Faculty, Staff and Student Publications

Heart disease is one of the leading causes of death worldwide. Predicting and detecting heart disease early is crucial, as it allows medical professionals to take appropriate and necessary actions at earlier stages. Healthcare professionals can diagnose cardiac conditions more accurately by applying machine learning technology. This study aimed to enhance heart disease prediction using stacking and voting ensemble methods. Fifteen base models were trained on two different heart disease datasets. After evaluating various combinations, six base models were pipelined to develop ensemble models employing a meta-model (stacking) and a majority vote (voting). The performance of the stacking and voting …

High-Pressure Excursion In Oxygenators During Adult Cardiopulmonary Bypass: A Scoping Review, Anne Nguyen

Student Works

Background: High-pressure excursions (HPE) in oxygenators during cardiopulmonary bypass (CPB) are rare but clinically significant events that can lead to compromised perfusion and adverse patient outcomes. HPE occurs due to fibrin and platelet deposition within the oxygenator, leading to increased transmembrane pressure and potential obstruction of blood flow. Despite its clinical importance, HPE remains an underrecognized issue with limited standardized guidelines for detection, prevention, and management.

Methods: A comprehensive literature search was conducted across multiple databases and grey literature sources to identify studies reporting on HPE in CPB oxygenators. The selection process followed the PRISMA-ScR framework, with articles screened based …

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 …

Swi/Snf Complex-Mediated Znf410 Cooperative Binding Maintains Chromatin Accessibility And Enhancer Activity, Siyuan Xu, Chuxuan Peng, Ren Ren, Haowen Lu, Han Zhao, Sijian Xia, Yijie Shen, Bin Xu, Haoyue Zhang, Xiaodong Cheng, Gerd A Blobel, Xianjiang Lan

Faculty, Staff and Student Publications

The clustering of multiple transcription factor binding sites (TFBSs) for the same TF has proved to be a pervasive feature of cis-regulatory elements in the eukaryotic genome. However, the contribution of binding sites within the homotypic clusters of TFBSs (HCTs) to TF binding and target gene expression remains to be understood. Here, we characterize the CHD4 enhancers that harbor unique functional ZNF410 HCTs genome wide. We uncover that ZNF410 controls chromatin accessibility and activity of the CHD4 enhancer regions. We demonstrate that ZNF410 binds to the HCTs in a collaborative fashion, further conferring transcriptional activation. In particular, three ZNF410 motifs …

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) …

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 …

Epidemiology Of Tourette Syndrome, Abdullah Yasir Yilmaz, Joseph Jankovic

Faculty, Staff and Students Publications

Background/Objectives: Tourette syndrome (TS) is a neurodevelopmental disorder, manifested by tics and a variety of behavioral comorbidities that cluster strongly within families, suggesting a combination of genetic and environmental risk factors. The underlying pathophysiology of TS remains to be elucidated. Understanding the incidence and prevalence across different populations provides valuable insights into the etiology and pathogenesis of the condition and aids in the development of effective treatment strategies.

Methods: A comprehensive literature search was conducted on PubMed covering the period from 1 January 2000 to 1 January 2025. The search used the terms "Tourette syndrome", "tics", "tic disorders", "epidemiology", "prevalence", …

Unveiling The Potential Of Urolithin A In Cancer Therapy: Mechanistic Insights To Future Perspectives Of Nanomedicine, Vinita Karumuru, Anupam Dhasmana, Narsimha Mamidi, Subhash Chauhan, Murali Yallapu

School of Medicine Publications

Cancer remains a leading global health challenge, with high mortality rates persisting despite significant advancements in therapeutic interventions. Major obstacles, including systemic toxicity, therapy resistance, metastasis, and relapses, emphasize the urgent need for safer, more effective, and readily accessible treatment strategies. Among emerging alternatives, natural bioactive compounds have gained considerable attention because of their diverse therapeutic potential and lower toxicity profiles. Urolithin A (UA), a metabolite derived from ellagic acid through gut microbiota metabolism, has emerged as a compelling anticancer agent. UA has multiple mechanisms of action, including the regulation of autophagy, enhancement of mitochondrial function, and inhibition of tumor …

Biallelic Fgf4 Variants Linked To Thoracic Dystrophy And Respiratory Insufficiency, Laura M. Watts, Esther Kinning, Donald R. Latner, Marla Johnston, Jessica Patrick-Esteve, Gregory M. Cooper, Stephen R.F. Twigg, Alistair T. Pagnamenta, Jenny C. Taylor

School of Medicine Faculty Publications

The thoracic dystrophies are inherited skeletal conditions where abnormal embryonic development of the thoracic skeleton results in a narrow chest, pulmonary hypoplasia, and respiratory insufficiency, which can be severe or lethal. The majority of thoracic dystrophies are due to biallelic alterations in genes needed for normal ciliary function. However, despite the identification of over 20 genes as causal for the thoracic dystrophy phenotype, around 20% of patients remain without a molecular diagnosis. We present two unrelated families with a clinical diagnosis of thoracic dystrophy with associated respiratory insufficiency without a molecular diagnosis on previous genetic testing. Both harbor rare biallelic …

Partnering With Social Media Influencers To Promote Hpv Vaccination In Diverse Communities, Amy Leader, Amelia Burke-Garcia, Dasha Afanaseva, Erin Cutroneo, Preethi Selvan, Kayla Madden, Joshua Banks, Angela Sustaita-Ruiz

Department of Medical Oncology Faculty Papers

BACKGROUND: While human papillomavirus (HPV) vaccination is one of the most effective ways to prevent HPV-related cancers, many children and adolescents remain unvaccinated. Resistance often stems from parental vaccine hesitancy and mistrust of the health care system, both of which may be higher in communities of color. Partnering with social media influencers may be an effective method for disseminating health messages. We tested the impact of HPV social media posts developed by influencers on outcomes of knowledge, attitudes, and intentions to vaccinate.

METHODS: Ten social media influencers who identified as African American or Hispanic created posts about the HPV vaccine. …

Trends In Celecoxib Prescribing: A Single Institution 16-Month Review, Ivo H Cerda, Helen Jung, Maria C Guerrero, Rodrigo Diez Tafur, Robert Jason Yong, Christopher L Robinson, Jamal J Hasoon

Faculty, Staff and Student Publications

Background/Objectives: Celecoxib, a COX-2 selective nonsteroidal anti-inflammatory drug (NSAID), is widely prescribed for pain management due to its efficacy and improved gastrointestinal safety profile compared to traditional NSAIDs. Understanding prescription trends and their comparison to other NSAIDs provides valuable insight into prescribing behaviors in clinical settings.

Methods: This retrospective study analyzed celecoxib prescriptions written by three pain management physicians in a single institution over a 16-month period from 1 January 2023 to 30 April 2024. Prescription data were collected and grouped into four 4-month intervals to assess temporal trends. Additionally, we compared celecoxib prescriptions to other commonly prescribed NSAIDs, including …

Short Report: The Variants In Chek2 In Metastatic Uveal Melanoma, Mizue Terai, Rino S. Seedor, Usman Ashraf, Gretchen Hubbard, Sergei A. Koshkin, Marlana Orloff, Takami Sato

Department of Medical Oncology Faculty Papers

No abstract provided.

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, …

Association Between B-Cell Marker Expression And Runx1 Lesions In Acute Myeloid Leukemia, Beyond Runx1::Runx1t1 Fusion: Diagnostic Pitfalls With Mixed-Phenotype Acute Leukemia—B/Myeloid, Giby V George, Malgorzata Kajstura, Audrey N Jajosky, Hong Fang, Fatima Zahra Jelloul, Andrew G Evans, W Richard Burack, John M Bennett, L Jeffrey Medeiros, Wei Wang, Siba El Hussein

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) with RUNX1::RUNX1T1 fusion is well known to often demonstrate aberrant upregulation of CD19 expression. We studied the clinicopathologic and genetic features of 16 cases of AML with various RUNX1 lesions, including mutations, copy number gains, and translocations other than fusions with RUNX1T1. Most of these cases were classified as AML-myelodysplasia-related or AML-post-cytotoxic therapy based on the cytogenetic and molecular work-up. These neoplasms showed partial expression of one or more B-cell antigens by flow cytometry and/or immunohistochemistry, fulfilling the criteria for mixed-phenotype acute leukemia (MPAL)-B/myeloid (i.e., ≥20% blasts expressing B and myeloid lineage antigens) …

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 …