Digital Commons Network^™

Short-Term Efficacy And Safety Of Nondamaging Retinal Laser Therapy For Retinitis Pigmentosa-Associated Cystoid Macular Edema, Seda Çevi̇k Kaya, Mehmet Çitirik, Mevlüt Yilmaz, Eyüpcan Şensoy

Turkish Journal of Medical Sciences

Background/aim: To evaluate the short-term efficacy and safety of nondamaging retinal laser therapy (NRT) for retinitis pigmentosa-associated cystoid macular edema (RP-CME) and analyze anatomical and functional outcomes.

Materials and methods: A retrospective case series of 40 eyes from 30 patients with RP-CME was conducted. The patients underwent NRT using a PASCAL laser system with endpoint management (EpM) software. Central macular thickness (CMT) and best-corrected visual acuity (BCVA) were assessed at baseline and 2 months posttreatment. Long-term follow-up data, including recurrence rates were also reviewed.

Results: At the 2-month follow-up, NRT significantly reduced mean CMT by 79.7 μm (p < 0.001) and improved BCVA by 0.10 LogMAR (p < 0.001). Complete resolution of CME was observed in 30% of the eyes, while 52.5% experienced recurrence within 6 months. Unilateral cases exhibited greater CMT reductions than bilateral cases (p < 0.05). No retinal damage from the laser was observed. The long-term sustainability of these effects remains unclear, and repeated treatments have not yet been assessed.

Conclusion: NRT …

Risk Factors For Serious Bacterial Infections Among Young Infants With Hypothermia: Protocol For A Multicenter, Retrospective Case-Control Study, Sriram Ramgopal, Paul Aronson, Douglas Lorenz, Alexander Joseph Rogers, Andrea Tania Cruz

Faculty, Staff and Students Publications

Background: Hypothermia in young infants presenting to the emergency department (ED) may indicate a serious bacterial infection (SBI) such as a urinary tract infection, bacteremia, or bacterial meningitis. Improved understanding of the epidemiology of SBI in infants with hypothermia and the development of prediction models can help avoid unnecessary invasive procedures and antimicrobial exposure.

Objective: The aim of the study is to (1) describe the epidemiology of SBI and herpes simplex virus (HSV) among infants with hypothermia, (2) assess the role of biomarkers in predicting SBI, and (3) derive and internally validate a multivariable predictive model for SBI among infants …

Mucin4 (Muc4) Antibody Labeled With An Nir Dye Brightly Targets Pancreatic Cancer Liver Metastases And Peritoneal Carcinomatosis, Sunidhi Jaiswal, Siamak Amirfakhri, Javier Bravo, Keita Kobayashi, Abhijit Aithal, Sumbal Talib, Kavita Mallya, Maneesh Jain, Aaron M. Mohs, Robert M. Hoffman, Surinder K. Batra, Michael Bouvet

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND/OBJECTIVES: Pancreatic cancer is the fourth leading cause of deaths related to cancer. It is a highly aggressive malignancy and often metastasizes quickly to other parts of the body and organs. The most effective cure is surgical resection, which also is limited by tumor identification and clear tumor margin visualization. Previously, we used MUC4 antibodies labeled with IRDye800CW (anti-MUC4-IR800) to target primary human pancreatic cancer in orthotopic cell line mouse models.

METHODS: In the present study, we established a pancreatic cancer liver metastasis mouse model by implanting a tumor fragment in the liver and a peritoneal carcinomatosis mouse model by …

Btp2 Restricts Tulane Virus And Human Norovirus Replication Independent Of Store-Operated Calcium Entry, Francesca J Scribano, J Thomas Gebert, Kristen A Engevik, Nicole M Hayes, Jorge Villanueva, Son Pham, Soni Kaundal, Janam J Dave, B V Venkataram Prasad, Mary K Estes, Sasirekha Ramani, Joseph M Hyser

Faculty, Staff and Students Publications

Human norovirus is the leading cause of viral gastroenteritis across all age groups. While there is a need for human norovirus antivirals, therapeutic development has been hindered by a lack of cell culture systems and animal models of infection. Surrogate viruses, such as Tulane virus (TV), have provided tractable systems to screen potential antiviral compounds. Our previous work demonstrated that TV encodes a viral ion channel, which dysregulates cytosolic calcium signaling. We set out to investigate whether host pathways triggered by viral ion channel activity, including store-operated calcium entry (SOCE), play a role in virus replication. Using pharmacologic inhibitors and …

In Silico Screening For Computational Exploration Of Interactions, Synthesis, And Comparative Evaluation Of Novel Furan-2-Quinolone Derivatives As Potent Anticoagulants, Karm A. Khalaf, Noor A. Majeed, Adnan O. Omar

BioMed Visions Journal

There is an urgent need for the design and development of new and safer drugs for the treatment of (Blood coagulation). New derivatives of furan-2-qoinoline as anti-coagulation drug bearing furan, quinolone, were synthesized with the aim of developing new drug inhibitors (Factor Xa enzyme) respectively. In our study, synthesis of the new organic compounds derived from Furo-2-quinolone substituted by treated with ammonia derivatives like hydrazine, give K6, and (1-Amino-4,6-dimethyl furo[3,2-g] quinoline-2-one) K6 then react with Formaldehyde to form K6a. And evaluated their effects on coagulation in the docking (MCULE). then compared this compound, with the Rivaroxaban. compound give the result …

Public Acceptance, Attitude And Perception Toward Covid-19 Vaccination In Mosul City; Iraq, Nadia Hazem Saied

BioMed Visions Journal

Background: No doubt the recent coronavirus disease (COVID-19) pandemic represents the most serious health and life threats globally. Vaccination against the disease is considered the cornerstone for controlling the disease.

Aim of the study is to explore public attitudes, perception toward vaccination against COVID-19 infection.

Material and methods: A cross-sectional study was conducted by using a modified questionnaire form which was translated into Arabic language and transformed into a Google form. The form was disseminated to the population online using different platforms in Mosul City over a period of one month during November 2021 and the participants were volunteered for …

Top Ten Types Of Childhood Cancer In Nineveh Governorate 2018–2022: A Time Series Analysis, Marab Younis Abdullah Al-Fathy, Ahmed Asaad Hussein, Hiba Farooq Mohamed Ameen, Maan Younis Al-Fathi

BioMed Visions Journal

Background: Childhood cancer incidence and deaths reflects the low health status, which can be prevented by setting upstrategies with help of different sectors in community.

Aim: To describe the childhood cancer in Nineveh governorate during 2018–2022.

Methods: A Biometry study used to review 646 a cancer registration form for five years 2018–2022, using Can-Rej 5 inquiryforms adopted by Ministry of Health measuring [sex ratio, sex and cause specific death rate, the incidence rate, the case fatalityrate, the proportion mortality rate and trend of (occurrences and death)].

Results: The total number of participants was 646, the commonest childhood cancer was among …

Intouch Week Of June 16, 2025, New York Medical College

InTouch

• Jonathan Sheindlin, M.D. '93, and John Morningstar to be Honored at NYMC’s Annual Golf Tournament
• 15th Annual Paul K. Woolf, M.D., Pediatric Trainee Research Day Spotlights Outstanding Research
• NYMC Researchers Identify Novel Strain of Syphilis Bacterium
• TCDM Alumni Reunion Celebrates the Class of 2020 and Showcases Innovation in Digital Dentistry
• Alumni Spotlight: 2025 Student Commencement Speakers Reflection on NYMC and What Comes Next
• Alumni Spotlight: The Cooper’s Lifelong Bond with NYMC

The Tumor Suppressor Hnrnpk Induces P53-Dependent Nucleolar Stress To Drive Ribosomopathies, Pedro Aguilar-Garrido, María Velasco-Estévez, Miguel Ángel Navarro-Aguadero, Álvaro Otero-Sobrino, Marta Ibáñez-Navarro, Miguel Ángel Marugal, María Hernández-Sánchez, Prerna Malaney, Ashley Rodriguez, Oscar Benitez, Xiaroui Zhang, Marisa Jl Aitken, Alejandra Ortiz-Ruiz, Diego Megías, Manuel Pérez, Gadea Mata, Jesús Gomez, Miguel Lafarga, Orlando Domínguez, Osvaldo Graña-Castro, Eduardo Caleiras, Pilar Ximénez-Embun, Marta Isasa, Paloma Jimena De Andres, Sandra Rodríguez-Perales, Raúl Torres-Ruiz, Enrique Revilla, Rosa María García-Martín, Daniel Azorín, Josune Zubicaray, Julián Sevilla, Oleksandra Sirozh, Vanesa Lafarga, Joaquín Martínez-López, Sean M Post, Miguel Gallardo

Faculty, Staff and Student Publications

The nucleolus is a membraneless organelle and an excellent stress sensor. Any changes in its architecture or composition lead to nucleolar stress, resulting in cell cycle arrest and interruption of ribosomal activity, critical factors in aging and cancer. In this study, we identified and described the pivotal role of the RNA-binding protein HNRNPK in ribosome and nucleolar dynamics. We developed an in vitro model of endogenous HNRNPK overexpression and an in vivo mouse model of ubiquitous HNRNPK overexpression. These models showed disruptions in translation as the HNRNPK overexpression caused alterations in the nucleolar structure, resulting in p53-dependent nucleolar stress, cell …

Enhancing Neuronal Viability: The Protective Role Of 10% Human Cerebrospinal Fluid In Primary Neuronal Cultures, Vineet Arora, Alicia Bernhardt, Alessandro Naopli, Mijail Serruya

Farber Institute for Neuroscience Faculty Papers

Human cerebrospinal fluid (hCSF) is a physiologically rich medium containing neurotrophic factors, signaling molecules, and essential metabolites that support neuronal development, survival, and function. While its neuroprotective properties have been demonstrated in organotypic brain slices and human iPSC-derived models, its application in primary rodent cortical neuron cultures-a foundational system for studying synaptic development and neurodegeneration-remains underexplored. In this study, we systematically evaluated the effects of hCSF supplementation on neuronal viability in primary cortical cultures derived from embryonic day 18 (E18) rat embryos. To determine the optimal concentration, we tested a range of media:hCSF ratios and identified 90:10 (i.e., 10% hCSF) …

Carbon Monoxide Releasing Polymeric Micelles, Riya Joshi

Electronic Theses and Dissertations

Carbon monoxide (CO), traditionally known as a toxic gas, has emerged as a potential therapeutic agent due to its cytoprotective, anti-inflammatory, and vasodilatory properties. This study explores the development of CO-releasing polymeric micelles as a controlled delivery system for biomedical applications. Using ring-opening metathesis polymerization (ROMP), we synthesized diblock copolymers incorporating CO-releasing moiety diphenylcyclopropenone (DPCP) with hydrophilic polyethylene glycol (PEG) to enhance solubility and stability of the overall CO releasing system. Dynamic light scattering (DLS) and electron microscopy (EM) confirmed the formation of well-defined micelles, while fluorescence assays demonstrated efficient CO release with the use of Iridium photocatalyst under 470 …

Common Aav Gene Therapy Vectors Show Nonselective Transduction Of Ex Vivo Human Brain Tissue, J P Mcginnis, Joshua Ortiz-Guzman, Maria Camila Guevara, Sai Mallannagari, Benjamin D W Belfort, Suyang Bao, Snigdha Srivastava, Maria Morkas, Emily Ji, Angela Addison, Evelyne K Tantry, Sarah Chen, Ying Wang, Zihong Chen, Kalman A Katlowitz, Jeffrey J Lange, Melissa M Blessing, Carrie A Mohila, M Cecilia Ljungberg, Guillermo Aldave, Ali Jalali, Akash Patel, Sameer A Sheth, Howard L Weiner, Shankar Gopinath, Ganesh Rao, Akdes Serin Harmanci, Daniel J Curry, Benjamin R Arenkiel

Children’s Nutrition Research Center Staff Publications

The ability to deliver a therapeutic sequence to a specific cell type in the human brain would make possible innumerable therapeutic options for some of our most challenging diseases; however, studies on adeno-associated virus (AAV) vector tropism have generally relied on animal models with limited translational utility. For this reason, establishing the tropism of common adeno-associated virus (AAV) vectors in living human brain tissue serves as an important baseline for further optimization, as well as a determination of human brain cell types transduced by clinically approved gene therapy vectors AAV2 and AAV9. We have adapted an

Who Seeks Help? A Sociodemographic Analysis Of Cannabis Use Disorder Treatment In New York, Ayodele Atolagbe, Ekenedilichukwu Theresa Emembolu, Stanley Nkemjika

Department of Psychiatry and Human Behavior Faculty Papers

Introduction: Cannabis use disorder (CUD) is being increasingly diagnosed in the United States, but access to treatment remains unequal, particularly in New York. Identifying the factors that contribute to disparities in receiving treatment for CUD among different population groups is essential for ensuring effective and targeted interventions. This study explores the sociodemographic factors influencing treatment utilization for CUD in New York.

Methods: Data for this study were retrieved from the 2018 Treatment Episode Data Set—Discharges (TEDS-D) of the U.S. Substance Abuse and Mental Health Services Administration (SAMHSA). Sample size for the study is 422,319 people with CUD. Logistic regression analysis …

The Multifunctional Ascorbate Peroxidase Moapx1 Secreted By Magnaporthe Oryzae Mediates The Suppression Of Rice Immunity, Muxing Liu, Ziqian Guo, Jiexiong Hu, Yuke Chen, Fang Chen, Weizhong Chen, Wenya Wang, Boyang Ye, Zhixiang Yang, Gang Li, Xinyu Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Graduate Studies Faculty Publications

Fungi secrete effector proteins, including extracellular redox enzymes, to inhibit host immunity. Redox enzymes have been hypothesized to inhibit host reactive oxygen species (ROS); however, how they suppress host immunity remains unknown. We characterized an extracellular ascorbate peroxidase (MoApx1) that is secreted into rice chloroplasts by the rice blast fungus Magnaporthe oryzae. MoApx1 displays multifunctional capabilities that significantly contribute to fungal virulence. Firstly, MoApx1 neutralizes host-derived H2O2 within the chloroplast through its peroxidase activity, thereby inhibiting chloroplast ROS (cROS)-mediated defense responses. Secondly, MoApx1 targets the photosystem I subunit OsPsaD, disrupting photosynthetic electron transport to further suppress cROS production. Most importantly, …

Citrullinated Eno1 Vaccine Enhances Pd-1 Blockade In Mice Implanted With Murine Triple-Negative Breast Cancer Cells, Ricardo A León-Letelier, Alejandro M Sevillano-Mantas, Yihui Chen, Soyoung Park, Jody Vykoukal, Johannes F Fahrmann, Edwin J Ostrin, Candace Garrett, Rongzhang Dou, Yining Cai, Fu-Chung Hsiao, Jennifer B Dennison, Eduardo Vilar, Banu K Arun, Samir Hanash, Hiroyuki Katayama

Faculty, Staff and Student Publications

Background/Objectives:Cancer vaccine targets mostly include mutations and overexpressed proteins. However, cancer-associated post-translational modifications (PTMs) may also induce immune responses. Previously, our group established the enzyme protein arginine deiminase type-2 (PADI2), which catalyzes citrullination modification, is highly expressed in triple-negative breast cancer (TNBC), promoting antigenicity.

Methods: Here, we show the workflow of designing citrullinated enolase 1 (citENO1) vaccine peptides identified from breast cancer cells by mass spectrometry and demonstrate TNBC vaccine efficacy in the mouse model. Immunized mice with citENO1 peptides or the corresponding unmodified peptides, plus Poly I:C as an adjuvant, were orthotopically implanted with a TNBC murine …

Inactivation Of The Fusobacterium Nucleatum Rnf Complex Reduces Fada-Mediated Amyloid Formation And Tumor Development, Timmie A Britton, Ju Huck Lee, Chungyu Chang, Aadil H Bhat, Yi-Wei Chen, Rusul Mohammed Ali, Chenggang Wu, Asis Das, Hung Ton-That

Faculty, Staff and Student Publications

The Gram-negative anaerobe Fusobacterium nucleatum is an oral oncobacterium that promotes colorectal cancer (CRC) development with the amyloid-forming cell surface adhesin FadA integral to CRC tumorigenesis. We describe here molecular genetic studies uncovering a novel mode of metabolic regulation of FadA-mediated tumor formation by a highly conserved respiratory enzyme known as the Rnf complex. First, we show that genetic disruption of Rnf, via rnfC deletion, significantly reduces the level of fadA transcript, accompanied by a near-complete abolishment of the precursor form of FadA (pFadA), reduced assembly of FadA at the mature cell pole, and severe defects in the osmotic stress-induced …

Parallel Use Of Low-Complexity Automated Nucleic Acid Amplification Tests On Respiratory And Stool Samples With Or Without Lateral Flow Lipoarabinomannan Assays To Detect Pulmonary Tuberculosis Disease In Children, Laura Olbrich, Bada Yang, Hayley Poore, Alia Razid, Brittney Sweetser, Mathias Weis Damkjær, Alexander W Kay, Johanna Åhsberg, Ruvandhi R Nathavitharana, Ian Schiller, Nandini Dendukuri, Andreas Lundh, Maunank Shah, Stephanie Bjerrum, Devan Jaganath

Faculty, Staff and Students Publications

Background: Low-complexity automated nucleic acid amplification tests (LC-aNAATs) are molecular assays widely used to diagnose tuberculosis disease in children. The lateral flow urine lipoarabinomannan assay (LF-LAM) is recommended for use amongst children with HIV. Previous systematic reviews have assessed the diagnostic accuracy of LC-aNAATs and LF-LAM separately in children, but in clinical practice the tests may be used concurrently, i.e. in 'parallel'.

Objectives: To compare the diagnostic accuracy of the parallel use of LC-aNAAT on respiratory and stool specimens in children, and with LF-LAM on urine amongst children with HIV, versus each assay alone for detecting pulmonary tuberculosis disease.

Search …

Sickle Cell Disease Induces Chromatin Introversion And Ferroptosis In Cd8+ T Cells To Suppress Anti-Tumor Immunity, Zilong Zhao, Benxia Hu, Yalan Deng, Melinda Soeung, Jun Yao, Lanxin Bei, Yaohua Zhang, Pengju Gong, Lisa A Huang, Zhou Jiang, Jian Gao, Shuang Peng, Tina K Nguyen, Menuka Karki, Bora Lim, Cassian Yee, Jared K Burks, Qing Zhang, Li Ma, Jianjun Gao, Nizar M Tannir, Leng Han, Dihua Yu, Linghua Wang, Michael A Curran, Maria A Gubbiotti, Giannicola Genovese, Boyi Gan, Wenbo Li, Pavlos Msaouel, Liuqing Yang, Chunru Lin

Faculty, Staff and Student Publications

Understanding how genetic disorders affect CD8+ T cells in the tumor microenvironment is key to improving cancer immunotherapy. Individuals with sickle cell disease (SCD), the most prevalent inherited blood disorder, have a higher risk of developing certain cancers than the general population, but the mechanisms driving this increased risk remain unclear. Our study revealed that SCD altered CD8+ T cell 3D genome architecture, triggering ferroptosis and weakening anti-tumor immunity, thereby promoting tumor growth. Using murine and humanized SCD models, we found that disrupted chromosomal interactions in CD8+ T cells reduced the expression of anti-ferroptotic genes, including SLC7A11 and hydrogen sulfide …

Arid4b: An Orchestrator From Stem Cell Fate To Carcinogenesis, Rakhee Rathnam Kalari Kandy, Madan Kumar Arumugam, Mukesh Pratap Yadav, Bibhuti Bhusan Mishra, Jyotika Sharma

Faculty, Staff and Student Publications

All biological processes, from embryonic development to cancer, are tightly controlled by the interactions between genetics and epigenetics. An array of epigenetic modifications, such as DNA methylation, histone/chromatin modifications, and noncoding RNA-mediated targeting, are essential to regulate the heritable changes that occur during multiple cellular processes. A failure in proper regulation results in inappropriate gene expression that ultimately leads to pathological states. Groundbreaking advances in genomics and transcriptomics have revealed the potential involvement of epigenetics in various physiological and pathological states. The promising clinical and preclinical results shown by epigenetics drugs further underscore the central role of epigenetics in multiple …

Structural Basis For The Substrate Specificity Of Helix Pomatia Amp Deaminase And A Chimeric Adgf Adenosine Deaminase, Gundeep Kaur, John R Horton, George Tzertzinis, Jujun Zhou, Ira Schildkraut, Xiaodong Cheng

Faculty, Staff and Student Publications

Helix pomatia AMP deaminase (HPAMPD), an enzyme enriched in the foot muscle of the mollusk H. pomatia, exhibits deaminase activity on adenosine-5'-monophosphate (AMP). HPAMPD is the first member of the adenosine deaminase-related growth factor (ADGF) family to prefer the nucleotide AMP over the nucleoside adenosine. To investigate the substrate selectivity of HPAMPD, we determined its structure in both the apo form and in complex with the adenosine analogs pentostatin and pentostatin-5'-monophosphate. Structurally, HPAMPD adopts a fold similar to human ADA2, an ADGF family member. HPAMPD has acquired the ability to interact with the 5'-monophosphate group of AMP through polar and …

Parallel Use Of Low-Complexity Automated Nucleic Acid Amplification Tests And Lateral Flow Urine Lipoarabinomannan Assays To Detect Tuberculosis Disease In Adults And Adolescents Living With Hiv, Stephanie Bjerrum, Bada Yang, Johanna Åhsberg, Laura Olbrich, Mathias Weis Damkjær, Ruvandhi R Nathavitharana, Tobias Broger, Ioana Diana Olaru, Brittney Sweetser, Hayley Poore, Alia Razid, Alexander W Kay, Claudia M Denkinger, Ian Schiller, Nandini Dendukuri, Devan Jaganath, Andreas Lundh, Maunank Shah

Faculty, Staff and Students Publications

Background: Low-complexity automated nucleic acid amplification tests (LC-aNAATs) are molecular World Health Organization (WHO)-recommended rapid diagnostic tests (also known as mWRDs) widely used to diagnose tuberculosis disease. The lateral flow urine lipoarabinomannan assay (LF-LAM) is recommended by the WHO to assist in diagnosing tuberculosis disease amongst people with HIV. Previous systematic reviews have assessed the diagnostic accuracy of LC-aNAATs and LF-LAM used in isolation for the detection of tuberculosis, but in clinical practice the tests may be used in parallel (i.e. LC-aNAAT in combination with LF-LAM).

Objectives: To compare the diagnostic accuracy of the parallel use of LC-aNAAT on respiratory …

Determining Accurate Pore Structures Of Polypropylene Membrane For Ecmo Using Fe-Sem Under Optimized Conditions, Makoto Fukuda, Yoshiaki Nishite, Eri Murata, Koki Namekawa, Tomohiro Mori, Tsutomu Tanaka, Kiyotaka Sakai

Children’s Nutrition Research Center Staff Publications

Long-term ECMOs are expected to be put into practical use in order to prepare for the next emerging severe infectious diseases after the novel coronavirus pandemic in 2019-2023. While polypropylene (PP) and polymethylpentene (PMP) are currently the mainstream materials for the hollow fiber membranes of ECMO, the PP membrane coated with a silicone layer on the outer surface has also been commercialized. In this study, we sought a method to accurately observe the detailed pore morphologies of the PP membrane by suppressing irreversible changes in the morphology in SEM observation, which is a general-purpose observation with higher resolution. As a …

Radiotherapy Promotes Cuproptosis And Synergizes With Cuproptosis Inducers To Overcome Tumor Radioresistance, Guang Lei, Mingchuang Sun, Jun Cheng, Rui Ye, Zhengze Lu, Amber Horbath, David Huo, Shengrong Wu, Anagha Alapati, Sadhna Aggarwal, Zhihao Xu, Chao Mao, Yuelong Yan, Jun Yao, Qidong Li, Xiong Chen, Hyemin Lee, Li Zhuang, Dadi Jiang, Apar Pataer, Jack A Roth, Nicholas Navin, Albert C Koong, Mingjian James You, Steven H Lin, Boyi Gan

Faculty, Staff and Student Publications

Cuproptosis is a recently identified form of copper-dependent cell death. Here, we reveal that radiotherapy (RT) induces cuproptosis in cancer cells, independent of apoptosis and ferroptosis, and depletes lipoylated proteins and iron-sulfur (Fe-S) cluster proteins-both hallmarks of cuproptosis-in patient tumors. Mechanistically, RT elevates mitochondrial copper levels by upregulating copper transporter 1 (CTR1) and depleting mitochondrial glutathione, a copper chelator, thereby triggering cuproptosis. Integrated analyses of RNA sequencing (RNA-seq) from radioresistant esophageal cancer cells and single-cell RNA-seq from esophageal tumors of patients unresponsive to RT link radioresistance to the downregulation of BTB and CNC homology 1 (BACH1). This downregulation de-represses the …

A Forward Genetic Screen Identifies Potassium Channel Essentiality In Shh Medulloblastoma Maintenance, Jerry J Fan, Anders W Erickson, Julia Carrillo-Garcia, Xin Wang, Patryk Skowron, Xian Wang, Xin Chen, Guanqiao Shan, Wenkun Dou, Shahrzad Bahrampour, Yi Xiong, Weifan Dong, Namal Abeysundara, Michelle A Francisco, Ronwell J Pusong, Wei Wang, Miranda Li, Elliot Ying, Raúl A Suárez, Hamza Farooq, Borja L Holgado, Xiaochong Wu, Craig Daniels, Adam J Dupuy, Juan Cadiñanos, Allan Bradley, Anindya Bagchi, Branden S Moriarity, David A Largaespada, A Sorana Morrissy, Vijay Ramaswamy, Stephen C Mack, Livia Garzia, Peter B Dirks, Xuejun Li, Siyi Wanggou, Sean Egan, Yu Sun, Michael D Taylor, Xi Huang

Faculty, Staff and Students Publications

Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo, and applied this to SHH medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver. KCNB2 governs cell volume of MB-propagating cells, with KCNB2 depletion causing osmotic swelling, decreased plasma membrane tension, and elevated endocytic internalization of EGFR, thereby mitigating proliferation of MB-propagating cells to ultimately impair MB growth. …

Regulation Of Myogenesis By Mechanomir-200c/Foxo3 Axis, Junaith S Mohamed, Aladin M Boriek

Faculty, Staff and Students Publications

Cyclic mechanical stretch has been shown to inhibit myoblast differentiation while promoting proliferation. However, the underlying molecular mechanisms are not well understood. Here, we report that mechanical stretch inhibits the differentiation of mouse primary myoblasts by promoting the cell cycle program and by inhibiting the expression of the myogenic regulator MyoD. Stretch alters the miRNA expression profile as evidenced by miRNA microarray analysis. We identified miR-200c as one of the highly downregulated mechanosensitive miRNAs (mechanomiRs) whose expression level was increased during differentiation. This suggests that mechanomiRs-200c is a myogenic miRNA. Overexpression of mechanomiR-200c revoked the effect of stretch on myoblast …

Rewired M6a Of Promoter Antisense Rnas In Alzheimer’S Disease Regulates Neuronal Genes In 3d Nucleome, Benxia Hu, Yuqiang Shi, Feng Xiong, Yi-Ting Chen, Xiaoyu Zhu, Elisa Carrillo, Xingzhao Wen, Nathan Drolet, Chetan Singh Rajpurohit, Xiangmin Xu, Dung-Fang Lee, Claudio Soto, Sheng Zhong, Vasanthi Jayaraman, Hui Zheng, Wenbo Li

Faculty, Staff and Student Publications

N6-methyladenosine (m6A) is an abundant internal RNA modification that can impact gene expression at both post-transcriptional and transcriptional levels. However, the landscapes and functions of m6A in human brains and neurodegenerative diseases, including Alzheimer's disease (AD), are under-explored. Here, we examined RNA m6A methylome using total RNA-seq and meRIP-seq in middle frontal cortex of post-mortem brains from individuals with or without AD, which revealed m6A alteration on both mRNAs and various noncoding RNAs. Notably, many promoter-antisense RNAs (paRNAs) displayed cell-type-specific expression and changes in AD, including one produced adjacent to MAPT that encodes the Tau protein. MAPT-paRNA is highly expressed …

Olaparib And Radiotherapy Induce Type I Interferon- And Cd8+ T Cell-Dependent Sensitization To Immunotherapy In Pancreatic Cancer, Victoria M Valvo, Qiang Zhang, Long Jiang, Erin A Holcomb, Ashley N Pearson, Anna G Edmunds, Hailey G Faulkner, Jadyn G James, Akshay Tate, Amanda K Huber, Zhuwen Wang, Yupei Guo, David Karnak, Leslie A Parsels, Joshua D Parsels, Yu L Lei, Alnawaz Rehemtulla, Heng Lin, Eileen S Carpenter, Daniel R Wahl, Vaibhav Sahai, Theodore S Lawrence, Michael D Green, Meredith A Morgan

Faculty, Staff and Student Publications

PARP inhibitors sensitize pancreatic ductal adenocarcinoma (PDAC) to radiation by inducing DNA damage and replication stress. These mechanisms also have the potential to enhance radiation-induced type I interferon (T1IFN) mediated anti-tumoral immune responses. We hypothesized that the PARP inhibitor olaparib would also potentiate radiation-induced T1IFN to promote anti-tumor immune responses and sensitization of otherwise resistant PDAC to immunotherapy. To test this hypothesis, we assessed the effects of olaparib and radiation on T1IFN production and sensitivity to αPD-L1 immunotherapy, as well as on the tumor microenvironment by single-cell RNA sequencing (scRNA-seq). We found that olaparib enhanced T1IFN production following radiation and …

Lmp7-Specific Inhibitor M3258 Modulates The Tumor Microenvironment Of Triple-Negative Breast Cancer And Inflammatory Breast Cancer, Xuemei Xie, Jangsoon Lee, Ganiraju C Manyam, Troy Pearson, Gina Walter-Bausch, Manja Friese-Hamim, Sheng Zhao, Julia Jabs, Angela A Manginelli, Nadine Piske, Thomas Mrowiec, Corinna M Wolf, Bharat S Kuntal, Debu Tripathy, Jing Wang, Michael P Sanderson, Naoto T Ueno

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) and inflammatory breast cancer (IBC) are the most aggressive molecular subtypes of breast cancer. Poor clinical outcomes highlight the pressing need to discover novel targets for the effective treatment of these diseases. LMP7 (β5i/PSMB8), a proteolytic subunit of the immunoproteasome, is implicated in the pathogenesis of multiple myeloma, autoimmune and inflammatory diseases, and inflammation-related cancers. However, the role of LMP7 in TNBC and IBC remains poorly characterized. Here, we evaluated the function of LMP7 in TNBC and IBC using the selective LMP7 inhibitor M3258. In human TNBC patient samples, LMP7 expression correlated strongly with CD8+ T …

Eph Receptors Activate Myeloid Checkpoint Receptor Lilrb5 To Support Tumor Development, Yubo He, Chengcheng Zhang, Lingxiao Tan, Mi Deng, Xiaoye Liu, Ryan Huang, Xing Yang, Jingjing Xie, Qi Lou, Meng Fang, Caroline Smith, Samuel John, Wei Xiong, Xin Li, Cheryl Lewis, Jade Homsi, Ankit Gupta, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang

Faculty, Staff and Student Publications

Immunosuppressive myeloid cells are critical obstacles to T cell-centered immune checkpoint blockade therapies, which have been successful in treating a fraction of patients with cancer. How tumor cells interact with myeloid cells to regulate immune responses and tumor development is unclear. In this study, we report that certain membrane tyrosine kinase Eph receptors, including EphA7 and EphB1, specifically bind the immune inhibitory receptors leukocyte Ig-like receptor family B 5 (LILRB5) and LILRB2. These Eph receptors induce LILRB5-mediated signaling activation, and LILRB5 also activates Eph receptor signaling. Activation of LILRB5 promoted immunosuppressive marker expression and inhibited activating marker expression on myeloid …

Mesenchymal Stem Cells And Fibroblasts Contribute To Microvascular Proliferation In Glioblastoma And Are Correlated With Immunosuppression And Poor Outcome, Candice C Poon, Shelley M Herbrich, Yulong Chen, Anwar Hossain, Gregory N Fuller, Sonali Jindal, Sreyashi Basu, Daniel Ledbetter, Marc Macaluso, Lynnette M Phillips, Joy Gumin, Zhong He, Brittany C Parker Kerrigan, Sanjay K Singh, Pratishtha Singh, Mohammed Fayyad Zaman, Derek Ng Tang, Sangeeta Goswami, Frederick F Lang, Padmanee Sharma

Faculty, Staff and Student Publications

Microvascular proliferation (MVP) is a disease-defining hallmark of glioblastoma and other World Health Organization grade 4 gliomas. MVP also serves as a poor prognostic marker in various solid tumors. Despite its clinical significance, the mechanisms and biological consequences of MVP are controversial and remain unclear. In this study, we performed single-cell RNA sequencing on paired CD45-CD105+ vascular/perivascular stromal cells (PVSC) and CD45+CD105± immune cells from 16 primary glioma patient samples, both with and without MVP. This analysis revealed the presence of developmentally related mesenchymal stem cells alongside cancer-associated fibroblasts, pericytes, fibromyocytes, and smooth muscle cells within the CD45-CD105+ compartment. RNA …