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Cell-Type-Specific Alternative Polyadenylation Promotes Oncogenic Gene Expression In Non-Small Cell Lung Cancer Progression, Kexin Huang, Yun Zhang, Xiaorui Shi, Zhiqin Yin, Weiling Zhao, Liyu Huang, Fu Wang, Xiaobo Zhou 2023 The Texas Medical Center Library

Cell-Type-Specific Alternative Polyadenylation Promotes Oncogenic Gene Expression In Non-Small Cell Lung Cancer Progression, Kexin Huang, Yun Zhang, Xiaorui Shi, Zhiqin Yin, Weiling Zhao, Liyu Huang, Fu Wang, Xiaobo Zhou

Faculty, Staff and Student Publications

Disrupted alternative polyadenylation (APA) is frequently involved in tumorigenesis and cancer progression by regulating the gene expression of oncogenes and tumor suppressors. However, limited knowledge of tumor-type- and cell-type-specific APA events may lead to novel APA events and their functions being overlooked. Here, we compared APA events across different cell types in non-small cell lung cancer (NSCLC) and normal tissues and identified functionally related APA events in NSCLC. We found several cell-specific 3'-UTR alterations that regulate gene expression changes showed prognostic value in NSCLC. We further investigated the function of APA-mediated 3'-UTR shortening through loss of microRNA (miRNA)-binding sites, and …


Epigenome-Wide Association Study Using Peripheral Blood Leukocytes Identifies Genomic Regions Associated With Periodontal Disease And Edentulism In The Atherosclerosis Risk In Communities Study, Naisi Zhao, Flavia Teles, Jiayun Lu, Devin C Koestler, James Beck, Eric Boerwinkle, Jan Bressler, Karl T Kelsey, Elizabeth A Platz, Dominique S Michaud 2023 The Texas Medical Center Library

Epigenome-Wide Association Study Using Peripheral Blood Leukocytes Identifies Genomic Regions Associated With Periodontal Disease And Edentulism In The Atherosclerosis Risk In Communities Study, Naisi Zhao, Flavia Teles, Jiayun Lu, Devin C Koestler, James Beck, Eric Boerwinkle, Jan Bressler, Karl T Kelsey, Elizabeth A Platz, Dominique S Michaud

Faculty, Staff and Student Publications

AIM: To investigate individual susceptibility to periodontitis by conducting an epigenome-wide association study using peripheral blood.

MATERIALS AND METHODS: We included 1077 African American and 457 European American participants of the Atherosclerosis Risk in Communities (ARIC) study who had completed a dental examination or reported being edentulous at Visit 4 and had available data on DNA methylation from Visit 2 or 3. DNA methylation levels were compared by periodontal disease severity and edentulism through discovery analyses and subsequent testing of individual CpGs.

RESULTS: Our discovery analysis replicated findings from a previous study reporting a region in gene ZFP57 (6p22.1) that …


A Single Dominant Locus Restricts Retrovirus Replication In Ybr/Ei Mice, Helen A Beilinson, Amanda Sevilleja, Jessica Spring, Fernando Benavides, Vera Beilinson, Nickolas Neokosmidis, Tatyana Golovkina 2023 The Texas Medical Center Library

A Single Dominant Locus Restricts Retrovirus Replication In Ybr/Ei Mice, Helen A Beilinson, Amanda Sevilleja, Jessica Spring, Fernando Benavides, Vera Beilinson, Nickolas Neokosmidis, Tatyana Golovkina

Faculty, Staff and Student Publications

Differential responses to viral infections are influenced by the genetic makeup of the host. Studies of resistance to retroviruses in human populations are complicated due to the inability to conduct proof-of-principle studies. Inbred mouse lines, which have a range of susceptible phenotypes to retroviruses, are an ideal tool to identify and characterize mechanisms of resistance and define their genetic underpinnings. YBR/Ei mice become infected with Mouse Mammary Tumor Virus, a mucosally transmitted murine retrovirus, but eliminate the virus from their pedigrees. Virus elimination correlates with a lack of virus-specific neonatal oral tolerance, which is a major mechanism for blocking the …


Genetic Control Of Mrna Splicing As A Potential Mechanism For Incomplete Penetrance Of Rare Coding Variants, Jonah Einson, Dafni Glinos, Eric Boerwinkle, Peter Castaldi, Dawood Darbar, Mariza de Andrade, Patrick Ellinor, Myriam Fornage, Stacey Gabriel, Soren Germer, Richard Gibbs, Craig P Hersh, Jill Johnsen, Robert Kaplan, Barbara A Konkle, Charles Kooperberg, Rami Nassir, Ruth J F Loos, Deborah A Meyers, Braxton D Mitchell, Bruce Psaty, Ramachandran S Vasan, Stephen S Rich, Michael Rienstra, Jerome I Rotter, Aabida Saferali, Moore Benjamin Shoemaker, Edwin Silverman, Albert Vernon Smith, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium; Pejman Mohammadi, Pejman Mohammadi, Stephane E Castel, Ivan Iossifov, Tuuli Lappalainen 2023 The Texas Medical Center Library

Genetic Control Of Mrna Splicing As A Potential Mechanism For Incomplete Penetrance Of Rare Coding Variants, Jonah Einson, Dafni Glinos, Eric Boerwinkle, Peter Castaldi, Dawood Darbar, Mariza De Andrade, Patrick Ellinor, Myriam Fornage, Stacey Gabriel, Soren Germer, Richard Gibbs, Craig P Hersh, Jill Johnsen, Robert Kaplan, Barbara A Konkle, Charles Kooperberg, Rami Nassir, Ruth J F Loos, Deborah A Meyers, Braxton D Mitchell, Bruce Psaty, Ramachandran S Vasan, Stephen S Rich, Michael Rienstra, Jerome I Rotter, Aabida Saferali, Moore Benjamin Shoemaker, Edwin Silverman, Albert Vernon Smith, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium; Pejman Mohammadi, Pejman Mohammadi, Stephane E Castel, Ivan Iossifov, Tuuli Lappalainen

Faculty, Staff and Student Publications

Exonic variants present some of the strongest links between genotype and phenotype. However, these variants can have significant inter-individual pathogenicity differences, known as variable penetrance. In this study, we propose a model where genetically controlled mRNA splicing modulates the pathogenicity of exonic variants. By first cataloging exonic inclusion from RNA-sequencing data in GTEx V8, we find that pathogenic alleles are depleted on highly included exons. Using a large-scale phased whole genome sequencing data from the TOPMed consortium, we observe that this effect may be driven by common splice-regulatory genetic variants, and that natural selection acts on haplotype configurations that reduce …


Role Of Phosphorylated Dicer1 In Tumor Progression, Raisa Reyes-Castro 2023 University of Texas MD Anderson Cancer Center

Role Of Phosphorylated Dicer1 In Tumor Progression, Raisa Reyes-Castro

Dissertations and Theses (Open Access)

DICER1 is a multidomain enzyme discovered and widely recognized for its function in small non-coding microRNA (miRNA) synthesis. In cancer development, DICER1 functions as a haploinsufficient tumor suppressor which regulates miRNAs and Epithelial-to-Mesenchymal Transition (EMT). The Arur laboratory discovered that DICER1 is phosphorylated by active ERK and that ERK-mediated phosphorylation triggers DICER1 to translocate from the cytoplasm to the nucleus of cells in worms, mice and humans. Further, a heterozygous allele of a genetically engineered mouse model of phosphomimetic Dicer1 when combined with heterozygous Kras oncogenic background contributes to lung tumor progression in vivo. Mechanisms through which phosphomimetic Dicer1 …


Extracellular Trna-Derived Rnas As Emerging Activators Of Endosomal Toll-Like Receptors: A Narrative Review, Justin Gumas, Yohei Kirino 2023 Thomas Jefferson University

Extracellular Trna-Derived Rnas As Emerging Activators Of Endosomal Toll-Like Receptors: A Narrative Review, Justin Gumas, Yohei Kirino

Computational Medicine Center Faculty Papers

Background and Objective: The innate immune system deploys various pattern-recognition receptors (PRRs), including Toll-like receptors (TLRs), to detect the invasion of pathogens and initiate protective responses. TLR7 and TLR8 are located within the endosome of immune cells and are activated by single-stranded RNAs (ssRNAs). In addition to foreign ssRNAs from bacteria and viruses, endogenous self-ssRNAs, such as microRNAs (miRNAs), have been shown to activate TLR7 and TLR8, but such endogenous ssRNA ligands have not yet been fully elucidated. This scientific knowledge gap is partly derived from the technical limitations of standard RNA-seq, particularly its inability to capture non-miRNA-short non-coding RNAs …


Federated Generalized Linear Mixed Models For Collaborative Genome-Wide Association Studies, Wentao Li, Han Chen, Xiaoqian Jiang, Arif Harmanci 2023 The Texas Medical Center Library

Federated Generalized Linear Mixed Models For Collaborative Genome-Wide Association Studies, Wentao Li, Han Chen, Xiaoqian Jiang, Arif Harmanci

Faculty, Staff and Student Publications

Federated association testing is a powerful approach to conduct large-scale association studies where sites share intermediate statistics through a central server. There are, however, several standing challenges. Confounding factors like population stratification should be carefully modeled across sites. In addition, it is crucial to consider disease etiology using flexible models to prevent biases. Privacy protections for participants pose another significant challenge. Here, we propose distributed Mixed Effects Genome-wide Association study (dMEGA), a method that enables federated generalized linear mixed model-based association testing across multiple sites without explicitly sharing genotype and phenotype data. dMEGA employs a reference projection to …


Fast Inference Of Genetic Recombination Rates In Biobank Scale Data, Ardalan Naseri, William Yue, Shaojie Zhang, Degui Zhi 2023 The Texas Medical Center Library

Fast Inference Of Genetic Recombination Rates In Biobank Scale Data, Ardalan Naseri, William Yue, Shaojie Zhang, Degui Zhi

Faculty, Staff and Student Publications

Although rates of recombination events across the genome (genetic maps) are fundamental to genetic research, the majority of current studies only use one standard map. There is evidence suggesting population differences in genetic maps, and thus estimating population-specific maps, are of interest. Although the recent availability of biobank-scale data offers such opportunities, current methods are not efficient at leveraging very large sample sizes. The most accurate methods are still linkage disequilibrium (LD)-based methods that are only tractable for a few hundred samples. In this work, we propose a fast and memory-efficient method for estimating genetic maps from population genotyping data. …


Incubation With Porcine Urinary Bladder Matrix Yields A Late-Stage Wound Transcriptome In Endothelial Cells And Keratinocytes Isolated From Both Diabetic And Non-Diabetic Subjects, John T. Paige, Daniel J. Lightell, Hunter F. Douglas, Natasha C. Klingenberg, Thaidan Pham, T. Cooper Woods 2023 LSU Health Sciences Center - New Orleans

Incubation With Porcine Urinary Bladder Matrix Yields A Late-Stage Wound Transcriptome In Endothelial Cells And Keratinocytes Isolated From Both Diabetic And Non-Diabetic Subjects, John T. Paige, Daniel J. Lightell, Hunter F. Douglas, Natasha C. Klingenberg, Thaidan Pham, T. Cooper Woods

School of Medicine Faculty Publications

Proper wound closure requires the functional coordination of endothelial cells (ECs) and keratinocytes. In the late stages of wound healing, keratinocytes become activated and ECs promote the maturation of nascent blood vessels. In diabetes mellitus, decreased keratinocyte activation and impaired angiogenic action of ECs delay wound healing. Porcine urinary bladder matrix (UBM) improves the rate of wound healing, but the effect of exposure to UBM under diabetic conditions remains unclear. We hypothesized that keratinocytes and ECs isolated from both diabetic and non-diabetic donors would exhibit a similar transcriptome representative of the later stages of wound healing following incubation with UBM. …


Sars-Cov-2 Next Generation Sequencing (Ngs) Data From Clinical Isolates From The East Texas Region Of The United States, Rob E. Carpenter, Vaibhav K. Tamrakar, Advanta Genetics 2023 University of Texas at Tyler

Sars-Cov-2 Next Generation Sequencing (Ngs) Data From Clinical Isolates From The East Texas Region Of The United States, Rob E. Carpenter, Vaibhav K. Tamrakar, Advanta Genetics

Human Resource Development Faculty Publications and Presentations

The SARS-CoV-2 virus has evolved throughout the pandemic and is likely to continue evolving into new variants. Some of these variants may affect functional properties, including infectivity, interactions with host immunity, and disease severity. And compromised vaccine efficacy is an emerging concern with every new viral variant. Next-generation sequencing (NGS) has emerged as the tool of choice for discovering new variants and understanding the transmission dynamics of SARS-CoV-2. Deciphering the SARS-CoV-2 genome has enabled epidemiological survivance and forecast of altered etiologically. Clinical presentations of the infection are influenced by comorbidities such as age, immune status, diabetes, and the infecting variant. …


Deep Single-Cell Rna-Seq Data Clustering With Graph Prototypical Contrastive Learning, Junseok Lee, Sungwon Kim, Dongmin Hyun, Namkyeong Lee, Yejin Kim, Chanyoung Park 2023 The Texas Medical Center Library

Deep Single-Cell Rna-Seq Data Clustering With Graph Prototypical Contrastive Learning, Junseok Lee, Sungwon Kim, Dongmin Hyun, Namkyeong Lee, Yejin Kim, Chanyoung Park

Faculty, Staff and Student Publications

MOTIVATION: Single-cell RNA sequencing enables researchers to study cellular heterogeneity at single-cell level. To this end, identifying cell types of cells with clustering techniques becomes an important task for downstream analysis. However, challenges of scRNA-seq data such as pervasive dropout phenomena hinder obtaining robust clustering outputs. Although existing studies try to alleviate these problems, they fall short of fully leveraging the relationship information and mainly rely on reconstruction-based losses that highly depend on the data quality, which is sometimes noisy.

RESULTS: This work proposes a graph-based prototypical contrastive learning method, named scGPCL. Specifically, scGPCL encodes the cell representations using Graph …


Genome-Wide Association Study Of Lung Adenocarcinoma In East Asia And Comparison With A European Population, Jianxin Shi, Kouya Shiraishi, Jiyeon Choi, Keitaro Matsuo, Tzu-Yu Chen, Juncheng Dai, Rayjean J Hung, Kexin Chen, Xiao-Ou Shu, Young Tae Kim, Maria Teresa Landi, Dongxin Lin, Wei Zheng, Zhihua Yin, Baosen Zhou, Bao Song, Jiucun Wang, Wei Jie Seow, Lei Song, I-Shou Chang, Wei Hu, Li-Hsin Chien, Qiuyin Cai, Yun-Chul Hong, Hee Nam Kim, Yi-Long Wu, Maria Pik Wong, Brian Douglas Richardson, Karen M Funderburk, Shilan Li, Tongwu Zhang, Charles Breeze, Zhaoming Wang, Batel Blechter, Bryan A Bassig, Jin Hee Kim, Demetrius Albanes, Jason Y Y Wong, Min-Ho Shin, Lap Ping Chung, Yang Yang, She-Juan An, Hong Zheng, Yasushi Yatabe, Xu-Chao Zhang, Young-Chul Kim, Neil E Caporaso, Jiang Chang, James Chung Man Ho, Michiaki Kubo, Yataro Daigo, Minsun Song, Yukihide Momozawa, Yoichiro Kamatani, Masashi Kobayashi, Kenichi Okubo, Takayuki Honda, Dean H Hosgood, Hideo Kunitoh, Harsh Patel, Shun-Ichi Watanabe, Yohei Miyagi, Haruhiko Nakayama, Shingo Matsumoto, Hidehito Horinouchi, Masahiro Tsuboi, Ryuji Hamamoto, Koichi Goto, Yuichiro Ohe, Atsushi Takahashi, Akiteru Goto, Yoshihiro Minamiya, Megumi Hara, Yuichiro Nishida, Kenji Takeuchi, Kenji Wakai, Koichi Matsuda, Yoshinori Murakami, Kimihiro Shimizu, Hiroyuki Suzuki, Motonobu Saito, Yoichi Ohtaki, Kazumi Tanaka, Tangchun Wu, Fusheng Wei, Hongji Dai, Mitchell J Machiela, Jian Su, Yeul Hong Kim, In-Jae Oh, Victor Ho Fun Lee, Gee-Chen Chang, Ying-Huang Tsai, Kuan-Yu Chen, Ming-Shyan Huang, Wu-Chou Su, Yuh-Min Chen, Adeline Seow, Jae Yong Park, Sun-Seog Kweon, Kun-Chieh Chen, Yu-Tang Gao, Biyun Qian, Chen Wu, Daru Lu, Jianjun Liu, Ann G Schwartz, Richard Houlston, Margaret R Spitz, Ivan P Gorlov, Xifeng Wu, Ping Yang, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, Bu-Tian Ji, H-Erich Wichmann, David C Christiani, Gadi Rennert, Susanne Arnold, Paul Brennan, James McKay, John K Field, Sanjay S Shete, Loic Le Marchand, Geoffrey Liu, Angeline Andrew, Lambertus A Kiemeney, Shan Zienolddiny-Narui, Kjell Grankvist, Mikael Johansson, Angela Cox, Fiona Taylor, Jian-Min Yuan, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Hyo-Sung Jeon, Shih Sheng Jiang, Jae Sook Sung, Chung-Hsing Chen, Chin-Fu Hsiao, Yoo Jin Jung, Huan Guo, Zhibin Hu, Laurie Burdett, Meredith Yeager, Amy Hutchinson, Belynda Hicks, Jia Liu, Bin Zhu, Sonja I Berndt, Wei Wu, Junwen Wang, Yuqing Li, Jin Eun Choi, Kyong Hwa Park, Sook Whan Sung, Li Liu, Chang Hyun Kang, Wen-Chang Wang, Jun Xu, Peng Guan, Wen Tan, Chong-Jen Yu, Gong Yang, Alan Dart Loon Sihoe, Ying Chen, Yi Young Choi, Jun Suk Kim, Ho-Il Yoon, In Kyu Park, Ping Xu, Qincheng He, Chih-Liang Wang, Hsiao-Han Hung, Roel C H Vermeulen, Iona Cheng, Junjie Wu, Wei-Yen Lim, Fang-Yu Tsai, John K C Chan, Jihua Li, Hongyan Chen, Hsien-Chih Lin, Li Jin, Jie Liu, Norie Sawada, Taiki Yamaji, Kathleen Wyatt, Shengchao A Li, Hongxia Ma, Meng Zhu, Zhehai Wang, Sensen Cheng, Xuelian Li, Yangwu Ren, Ann Chao, Motoki Iwasaki, Junjie Zhu, Gening Jiang, Ke Fei, Guoping Wu, Chih-Yi Chen, Chien-Jen Chen, Pan-Chyr Yang, Jinming Yu, Victoria L Stevens, Joseph F Fraumeni, Nilanjan Chatterjee, Olga Y Gorlova, Chao Agnes Hsiung, Christopher I Amos, Hongbing Shen, Stephen J Chanock, Nathaniel Rothman, Takashi Kohno, Qing Lan 2023 The Texas Medical Center Library

Genome-Wide Association Study Of Lung Adenocarcinoma In East Asia And Comparison With A European Population, Jianxin Shi, Kouya Shiraishi, Jiyeon Choi, Keitaro Matsuo, Tzu-Yu Chen, Juncheng Dai, Rayjean J Hung, Kexin Chen, Xiao-Ou Shu, Young Tae Kim, Maria Teresa Landi, Dongxin Lin, Wei Zheng, Zhihua Yin, Baosen Zhou, Bao Song, Jiucun Wang, Wei Jie Seow, Lei Song, I-Shou Chang, Wei Hu, Li-Hsin Chien, Qiuyin Cai, Yun-Chul Hong, Hee Nam Kim, Yi-Long Wu, Maria Pik Wong, Brian Douglas Richardson, Karen M Funderburk, Shilan Li, Tongwu Zhang, Charles Breeze, Zhaoming Wang, Batel Blechter, Bryan A Bassig, Jin Hee Kim, Demetrius Albanes, Jason Y Y Wong, Min-Ho Shin, Lap Ping Chung, Yang Yang, She-Juan An, Hong Zheng, Yasushi Yatabe, Xu-Chao Zhang, Young-Chul Kim, Neil E Caporaso, Jiang Chang, James Chung Man Ho, Michiaki Kubo, Yataro Daigo, Minsun Song, Yukihide Momozawa, Yoichiro Kamatani, Masashi Kobayashi, Kenichi Okubo, Takayuki Honda, Dean H Hosgood, Hideo Kunitoh, Harsh Patel, Shun-Ichi Watanabe, Yohei Miyagi, Haruhiko Nakayama, Shingo Matsumoto, Hidehito Horinouchi, Masahiro Tsuboi, Ryuji Hamamoto, Koichi Goto, Yuichiro Ohe, Atsushi Takahashi, Akiteru Goto, Yoshihiro Minamiya, Megumi Hara, Yuichiro Nishida, Kenji Takeuchi, Kenji Wakai, Koichi Matsuda, Yoshinori Murakami, Kimihiro Shimizu, Hiroyuki Suzuki, Motonobu Saito, Yoichi Ohtaki, Kazumi Tanaka, Tangchun Wu, Fusheng Wei, Hongji Dai, Mitchell J Machiela, Jian Su, Yeul Hong Kim, In-Jae Oh, Victor Ho Fun Lee, Gee-Chen Chang, Ying-Huang Tsai, Kuan-Yu Chen, Ming-Shyan Huang, Wu-Chou Su, Yuh-Min Chen, Adeline Seow, Jae Yong Park, Sun-Seog Kweon, Kun-Chieh Chen, Yu-Tang Gao, Biyun Qian, Chen Wu, Daru Lu, Jianjun Liu, Ann G Schwartz, Richard Houlston, Margaret R Spitz, Ivan P Gorlov, Xifeng Wu, Ping Yang, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, Bu-Tian Ji, H-Erich Wichmann, David C Christiani, Gadi Rennert, Susanne Arnold, Paul Brennan, James Mckay, John K Field, Sanjay S Shete, Loic Le Marchand, Geoffrey Liu, Angeline Andrew, Lambertus A Kiemeney, Shan Zienolddiny-Narui, Kjell Grankvist, Mikael Johansson, Angela Cox, Fiona Taylor, Jian-Min Yuan, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Hyo-Sung Jeon, Shih Sheng Jiang, Jae Sook Sung, Chung-Hsing Chen, Chin-Fu Hsiao, Yoo Jin Jung, Huan Guo, Zhibin Hu, Laurie Burdett, Meredith Yeager, Amy Hutchinson, Belynda Hicks, Jia Liu, Bin Zhu, Sonja I Berndt, Wei Wu, Junwen Wang, Yuqing Li, Jin Eun Choi, Kyong Hwa Park, Sook Whan Sung, Li Liu, Chang Hyun Kang, Wen-Chang Wang, Jun Xu, Peng Guan, Wen Tan, Chong-Jen Yu, Gong Yang, Alan Dart Loon Sihoe, Ying Chen, Yi Young Choi, Jun Suk Kim, Ho-Il Yoon, In Kyu Park, Ping Xu, Qincheng He, Chih-Liang Wang, Hsiao-Han Hung, Roel C H Vermeulen, Iona Cheng, Junjie Wu, Wei-Yen Lim, Fang-Yu Tsai, John K C Chan, Jihua Li, Hongyan Chen, Hsien-Chih Lin, Li Jin, Jie Liu, Norie Sawada, Taiki Yamaji, Kathleen Wyatt, Shengchao A Li, Hongxia Ma, Meng Zhu, Zhehai Wang, Sensen Cheng, Xuelian Li, Yangwu Ren, Ann Chao, Motoki Iwasaki, Junjie Zhu, Gening Jiang, Ke Fei, Guoping Wu, Chih-Yi Chen, Chien-Jen Chen, Pan-Chyr Yang, Jinming Yu, Victoria L Stevens, Joseph F Fraumeni, Nilanjan Chatterjee, Olga Y Gorlova, Chao Agnes Hsiung, Christopher I Amos, Hongbing Shen, Stephen J Chanock, Nathaniel Rothman, Takashi Kohno, Qing Lan

Faculty, Staff and Student Publications

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European …


Mesoporous Silica Nanoparticles As A Gene Delivery Platform For Cancer Therapy, Nisar Ul Khaliq, Juyeon Lee, Joohyeon Kim, Yejin Kim, Sohyeon Yu, Jisu Kim, Sangwoo Kim, Daekyung Sung, Hyungjun Kim 2023 The Texas Medical Center Library

Mesoporous Silica Nanoparticles As A Gene Delivery Platform For Cancer Therapy, Nisar Ul Khaliq, Juyeon Lee, Joohyeon Kim, Yejin Kim, Sohyeon Yu, Jisu Kim, Sangwoo Kim, Daekyung Sung, Hyungjun Kim

Faculty, Staff and Student Publications

Cancer remains a major global health challenge. Traditional chemotherapy often results in side effects and drug resistance, necessitating the development of alternative treatment strategies such as gene therapy. Mesoporous silica nanoparticles (MSNs) offer many advantages as a gene delivery carrier, including high loading capacity, controlled drug release, and easy surface functionalization. MSNs are biodegradable and biocompatible, making them promising candidates for drug delivery applications. Recent studies demonstrating the use of MSNs for the delivery of therapeutic nucleic acids to cancer cells have been reviewed, along with their potential as a tool for cancer therapy. The major challenges and future interventions …


Differential Degeneration Of Neurons In A Mouse Model Of Canavan Disease, Vibha Chauhan, Quy Nguyen, Jeremy Francis, Paola Leone 2023 Rowan University

Differential Degeneration Of Neurons In A Mouse Model Of Canavan Disease, Vibha Chauhan, Quy Nguyen, Jeremy Francis, Paola Leone

Rowan-Virtua Research Day

Canavan disease (CD) is an inherited leukodystrophy caused by inactivating mutations to the glial enzyme aspartoacylase (ASPA). ASPA catabolizes neuronal N-acetylaspartate (NAA) into free acetate and aspartate and loss of this function results in the chronic elevation of non-catabolized NAA and the failure of developmental myelination. Elevated NAA is thought to cause damage to myelin and myelin-producing cells (oligodendrocytes, but the viability of neurons in CD is relatively unexplored. We compare here the progressive degeneration of neurons in two regions of the CD mouse brain, the thalamus and the cortex, distinguished by differing degrees of vacuolation, and show that the …


Orthologs Of The C. Elegans Heterochronic Genes Have Divergent Functions In C. Briggsae, Maria Ivanova, Eric G. Moss 2023 Rowan University

Orthologs Of The C. Elegans Heterochronic Genes Have Divergent Functions In C. Briggsae, Maria Ivanova, Eric G. Moss

Rowan-Virtua Research Day

The heterochronic genes of C. elegans comprise the best-studied pathway controlling the timing of tissue and organ formation in an animal. To begin to understand the evolution of this pathway, the significance of each factor, and the relationships among the components, we characterized 11 C. briggsae orthologs of C. elegans heterochronic genes. Using CRISPR/Cas9, we made a variety of alleles and found that several mutant phenotypes differ in significant ways from those of C. elegans. Although most orthologs displayed defects in developmental timing, those phenotypes could differ in which stages they controlled, the penetrance and expressivity of the phenotypes, or …


The Presence Of Childhood Obesity In Nebraska And The Physiological Repercussions Of The Disease, Madison R. Bezousek 2023 University of Nebraska-Lincoln

The Presence Of Childhood Obesity In Nebraska And The Physiological Repercussions Of The Disease, Madison R. Bezousek

Honors Program: Senior Projects (Public)

Childhood Obesity can cause lifelong repercussions in children and adults. There has been stigma around the causes of obesity and its relation to lifestyle choices, without consideration of the genetic and syndromic causes. In this literature review the causes of obesity were investigated, along with the effect on the physiological systems and the enviornmental factors that are continuing the obesity epidemic. Preventing and treating lifestyle obesity is something that is seen to have the greatest effect on youth, especially with intergenerational obesity. Nebraska schools have implemented programs to encourage healthy living, and ongoing research is being implemented to reduce the …


Investigating Gene-Diet Interactions Impacting The Association Between Macronutrient Intake And Glycemic Traits, Kenneth E Westerman, Maura E Walker, Sheila M Gaynor, Jennifer Wessel, Daniel DiCorpo, Jiantao Ma, Alvaro Alonso, Stella Aslibekyan, Abigail S Baldridge, Alain G Bertoni, Mary L Biggs, Jennifer A Brody, Yii-Der Ida Chen, Joseé Dupuis, Mark O Goodarzi, Xiuqing Guo, Natalie R Hasbani, Adam Heath, Bertha Hidalgo, Marguerite R Irvin, W Craig Johnson, Rita R Kalyani, Leslie Lange, Rozenn N Lemaitre, Ching-Ti Liu, Simin Liu, Jee-Young Moon, Rami Nassir, James S Pankow, Mary Pettinger, Laura M Raffield, Laura J Rasmussen-Torvik, Elizabeth Selvin, Mackenzie K Senn, Aladdin H Shadyab, Albert V Smith, Nicholas L Smith, Lyn Steffen, Sameera Talegakwar, Kent D Taylor, Paul S de Vries, James G Wilson, Alexis C Wood, Lisa R Yanek, Jie Yao, Yinan Zheng, Eric Boerwinkle, Alanna C Morrison, Miriam Fornage, Tracy P Russell, Bruce M Psaty, Daniel Levy, Nancy L Heard-Costa, Vasan S Ramachandran, Rasika A Mathias, Donna K Arnett, Robert Kaplan, Kari E North, Adolfo Correa, April Carson, Jerome I Rotter, Stephen S Rich, JoAnn E Manson, Alexander P Reiner, Charles Kooperberg, Jose C Florez, James B Meigs, Jordi Merino, Deirdre K Tobias, Han Chen, Alisa K Manning 2023 The Texas Medical Center Library

Investigating Gene-Diet Interactions Impacting The Association Between Macronutrient Intake And Glycemic Traits, Kenneth E Westerman, Maura E Walker, Sheila M Gaynor, Jennifer Wessel, Daniel Dicorpo, Jiantao Ma, Alvaro Alonso, Stella Aslibekyan, Abigail S Baldridge, Alain G Bertoni, Mary L Biggs, Jennifer A Brody, Yii-Der Ida Chen, Joseé Dupuis, Mark O Goodarzi, Xiuqing Guo, Natalie R Hasbani, Adam Heath, Bertha Hidalgo, Marguerite R Irvin, W Craig Johnson, Rita R Kalyani, Leslie Lange, Rozenn N Lemaitre, Ching-Ti Liu, Simin Liu, Jee-Young Moon, Rami Nassir, James S Pankow, Mary Pettinger, Laura M Raffield, Laura J Rasmussen-Torvik, Elizabeth Selvin, Mackenzie K Senn, Aladdin H Shadyab, Albert V Smith, Nicholas L Smith, Lyn Steffen, Sameera Talegakwar, Kent D Taylor, Paul S De Vries, James G Wilson, Alexis C Wood, Lisa R Yanek, Jie Yao, Yinan Zheng, Eric Boerwinkle, Alanna C Morrison, Miriam Fornage, Tracy P Russell, Bruce M Psaty, Daniel Levy, Nancy L Heard-Costa, Vasan S Ramachandran, Rasika A Mathias, Donna K Arnett, Robert Kaplan, Kari E North, Adolfo Correa, April Carson, Jerome I Rotter, Stephen S Rich, Joann E Manson, Alexander P Reiner, Charles Kooperberg, Jose C Florez, James B Meigs, Jordi Merino, Deirdre K Tobias, Han Chen, Alisa K Manning

Faculty, Staff and Student Publications

Few studies have demonstrated reproducible gene-diet interactions (GDIs) impacting metabolic disease risk factors, likely due in part to measurement error in dietary intake estimation and insufficient capture of rare genetic variation. We aimed to identify GDIs across the genetic frequency spectrum impacting the macronutrient-glycemia relationship in genetically and culturally diverse cohorts. We analyzed 33,187 participants free of diabetes from 10 National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program cohorts with whole-genome sequencing, self-reported diet, and glycemic trait data. We fit cohort-specific, multivariable-adjusted linear mixed models for the effect of diet, modeled as an isocaloric substitution of carbohydrate …


Gwas And Meta-Analysis Identifies 49 Genetic Variants Underlying Critical Covid-19, Erola Pairo-Castineira, Konrad Rawlik, Andrew D Bretherick, Ting Qi, Yang Wu, Isar Nassiri, Glenn A McConkey, Marie Zechner, Lucija Klaric, Fiona Griffiths, Wilna Oosthuyzen, Athanasios Kousathanas, Anne Richmond, Jonathan Millar, Clark D Russell, Tomas Malinauskas, Ryan Thwaites, Kirstie Morrice, Sean Keating, David Maslove, Alistair Nichol, Malcolm G Semple, Julian Knight, Manu Shankar-Hari, Charlotte Summers, Charles Hinds, Peter Horby, Lowell Ling, Danny McAuley, Hugh Montgomery, Peter J M Openshaw, Colin Begg, Timothy Walsh, Albert Tenesa, Carlos Flores, José A Riancho, Augusto Rojas-Martinez, Pablo Lapunzina, GenOMICC Investigators, SCOURGE Consortium, ISARICC Investigators, 23andMe COVID-19 Team, Jian Yang, Chris P Ponting, James F Wilson, Veronique Vitart, Malak Abedalthagafi, Andre D Luchessi, Esteban J Parra, Raquel Cruz, Angel Carracedo, Angie Fawkes, Lee Murphy, Kathy Rowan, Alexandre C Pereira, Andy Law, Benjamin Fairfax, Sara Clohisey Hendry, J Kenneth Baillie 2023 The Texas Medical Center Library

Gwas And Meta-Analysis Identifies 49 Genetic Variants Underlying Critical Covid-19, Erola Pairo-Castineira, Konrad Rawlik, Andrew D Bretherick, Ting Qi, Yang Wu, Isar Nassiri, Glenn A Mcconkey, Marie Zechner, Lucija Klaric, Fiona Griffiths, Wilna Oosthuyzen, Athanasios Kousathanas, Anne Richmond, Jonathan Millar, Clark D Russell, Tomas Malinauskas, Ryan Thwaites, Kirstie Morrice, Sean Keating, David Maslove, Alistair Nichol, Malcolm G Semple, Julian Knight, Manu Shankar-Hari, Charlotte Summers, Charles Hinds, Peter Horby, Lowell Ling, Danny Mcauley, Hugh Montgomery, Peter J M Openshaw, Colin Begg, Timothy Walsh, Albert Tenesa, Carlos Flores, José A Riancho, Augusto Rojas-Martinez, Pablo Lapunzina, Genomicc Investigators, Scourge Consortium, Isaricc Investigators, 23andme Covid-19 Team, Jian Yang, Chris P Ponting, James F Wilson, Veronique Vitart, Malak Abedalthagafi, Andre D Luchessi, Esteban J Parra, Raquel Cruz, Angel Carracedo, Angie Fawkes, Lee Murphy, Kathy Rowan, Alexandre C Pereira, Andy Law, Benjamin Fairfax, Sara Clohisey Hendry, J Kenneth Baillie

Faculty, Staff and Student Publications

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a …


The Genetic Determinants Of Recurrent Somatic Mutations In 43,693 Blood Genomes, Joshua S. Weinstock, Cecelia A. Laurie, Jai G. Broome, Kent D. Taylor, Xiuqing Guo, Alan R. Shuldiner, Jeffrey R. O'Connell, Ravi Duggirala, Joanne E. Curran, John Blangero 2023 The University of Texas Rio Grande Valley

The Genetic Determinants Of Recurrent Somatic Mutations In 43,693 Blood Genomes, Joshua S. Weinstock, Cecelia A. Laurie, Jai G. Broome, Kent D. Taylor, Xiuqing Guo, Alan R. Shuldiner, Jeffrey R. O'Connell, Ravi Duggirala, Joanne E. Curran, John Blangero

School of Medicine Publications

Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid …


Meta-Narrative Review Of Possible Impacts Of Genetic Screening On Treatment Of Breast Cancer, Toqa Al Alawi, Sheza Khan, Ivey Knebel, Steven Luong, Vilma Sanchez, Kamilah Walker-Charles 2023 The University of Texas MD Anderson Cancer Center

Meta-Narrative Review Of Possible Impacts Of Genetic Screening On Treatment Of Breast Cancer, Toqa Al Alawi, Sheza Khan, Ivey Knebel, Steven Luong, Vilma Sanchez, Kamilah Walker-Charles

Research Methods Poster Session 2023

Objective: To examine the impacts of genetic screening on the treatment of breast cancer, in relation to differences, outcomes and decisions in treatment plans or surgery in patients that performed genetic screening versus those that did not.

Background: Genetic screening technology has become commercially available, yet standard preventative care for breast cancer has no genetic screening involved. Genetic screening in breast cancer treatment is performed, but its usage is not standardized.

Methods: Findings were synthesized using the meta-narrative review style to examine articles retrieved from searches of digital databases PubMed and the M.D. Anderson Scholarly Library.

Discussion: Articles were selected …


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