Plenary and Platform Abstracts
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(ALDH1A3) for the Maintenance of Non-Small Cell Lung Cancer Stem Cells Is Associated with the STAT3 Pathway
Author Manuscript Published OnlineFirst on June 6, 2014; DOI: 10.1158/1078-0432.CCR-13-3292 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Essential role of aldehyde dehydrogenase 1A3 (ALDH1A3) for the maintenance of non-small cell lung cancer stem cells is associated with the STAT3 pathway Chunli Shao1,2, James P. Sullivan3, Luc Girard1,2, Alexander Augustyn1,2, Paul Yenerall1,2, Jaime Rodriguez4, Hui Liu4, Carmen Behrens4, Jerry W. Shay5, Ignacio I. Wistuba4, John D. Minna 1,2,6,7 1Hamon Center for Therapeutic Oncology Research, 2Simmons Comprehensive Cancer Center, 3Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, 02114, 4Department of Translational Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, 77054, 5Department of Cell Biology, 6Department of Pharmacology, 7Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, USA. Running Title: ALDH1A3 in non-small cell lung cancer stem cells Keywords: Lung cancer, cancer stem cells, ALDH1A3, STAT3, Stattic Financial Support This project was supported by CPRIT, NCI SPORE P50CA70907, UTSW Cancer Center Support Grant 5P30-CA142543, and the Gillson-Longenbaugh Foundation. Address Correspondence: John D. Minna, M.D. 6000 Harry Hines Blvd Dallas, TX 75390-8593 Hamon Center for Therapeutic Oncology Research UT Southwestern Medical Center Phone: 214-648-4900; Fax: 214-648-4940 [email protected] Disclosure of Potential Conflict of Interest The authors indicate no potential conflicts of interest. Word count: 4583 Total number of figures and tables: 6 figures Downloaded from clincancerres.aacrjournals.org on September 28, 2021. © 2014 American Association for Cancer Research. -
Integrative Genomic and Epigenomic Analyses Identified IRAK1 As a Novel Target for Chronic Inflammation-Driven Prostate Tumorigenesis
bioRxiv preprint doi: https://doi.org/10.1101/2021.06.16.447920; this version posted June 16, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Integrative genomic and epigenomic analyses identified IRAK1 as a novel target for chronic inflammation-driven prostate tumorigenesis Saheed Oluwasina Oseni1,*, Olayinka Adebayo2, Adeyinka Adebayo3, Alexander Kwakye4, Mirjana Pavlovic5, Waseem Asghar5, James Hartmann1, Gregg B. Fields6, and James Kumi-Diaka1 Affiliations 1 Department of Biological Sciences, Florida Atlantic University, Florida, USA 2 Morehouse School of Medicine, Atlanta, Georgia, USA 3 Georgia Institute of Technology, Atlanta, Georgia, USA 4 College of Medicine, Florida Atlantic University, Florida, USA 5 Department of Computer and Electrical Engineering, Florida Atlantic University, Florida, USA 6 Department of Chemistry & Biochemistry and I-HEALTH, Florida Atlantic University, Florida, USA Corresponding Author: [email protected] (S.O.O) Running Title: Chronic inflammation signaling in prostate tumorigenesis bioRxiv preprint doi: https://doi.org/10.1101/2021.06.16.447920; this version posted June 16, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract The impacts of many inflammatory genes in prostate tumorigenesis remain understudied despite the increasing evidence that associates chronic inflammation with prostate cancer (PCa) initiation, progression, and therapy resistance. -
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bioRxiv preprint doi: https://doi.org/10.1101/850776; this version posted January 19, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Intramembrane protease RHBDL4 cleaves oligosaccharyltransferase subunits to target them for ER-associated degradation Julia D. Knopf1, Nina Landscheidt1, Cassandra L. Pegg2, Benjamin L. Schulz2, Nathalie Kühnle1, Chao-Wei Chao1, Simon Huck1 and Marius K. Lemberg1, # 1Centre for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany. 2School of Chemistry and Molecular Biosciences, ARC Training Centre for Biopharmaceutical Innovation, The University of Queensland, St Lucia QLD 4072, Australia. #Corresponding author: [email protected] Running title: RHBDL4 triggers ERAD of OST subunits Key words: Rhomboid serine protease, Rhbdd1, ubiquitin-dependent proteolysis, post- translational protein abundance control, N-linked glycosylation. Abbreviations ERAD, ER-associated degradation; OST, oligosacharyltransferase; TM, transmembrane; UIM, ubiquitin-interacting motif. Abstract The Endoplasmic Reticulum (ER)-resident intramembrane rhomboid protease RHBDL4 generates metastable protein fragments and together with the ER-associated degradation (ERAD) machinery provides a clearance mechanism for aberrant and surplus proteins. However, the endogenous substrate spectrum and with that the role of RHBDL4 in physiological ERAD is mainly unknown. Here, we use a substrate trapping approach in combination with quantitative proteomics to identify physiological RHBDL4 substrates. This revealed oligosacharyltransferase (OST) complex subunits such as the catalytic active subunit STT3A as substrates for the RHBDL4-dependent ERAD pathway. RHBDL4-catalyzed cleavage inactivates OST subunits by triggering dislocation into the cytoplasm and subsequent proteasomal degradation. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Identify Distinct Prognostic Impact of ALDH1 Family Members by TCGA Database in Acute Myeloid Leukemia
Open Access Annals of Hematology & Oncology Research Article Identify Distinct Prognostic Impact of ALDH1 Family Members by TCGA Database in Acute Myeloid Leukemia Yi H, Deng R, Fan F, Sun H, He G, Lai S and Su Y* Department of Hematology, General Hospital of Chengdu Abstract Military Region, China Background: Acute myeloid leukemia is a heterogeneous disease. Identify *Corresponding author: Su Y, Department of the prognostic biomarker is important to guide stratification and therapeutic Hematology, General Hospital of Chengdu Military strategies. Region, Chengdu, 610083, China Method: We detected the expression level and the prognostic impact of Received: November 25, 2017; Accepted: January 18, each ALDH1 family members in AML by The Cancer Genome Atlas (TCGA) 2018; Published: February 06, 2018 database. Results: Upon 168 patients whose expression level of ALDH1 family members were available. We found that the level of ALDH1A1correlated to the prognosis of AML by the National Comprehensive Cancer Network (NCCN) stratification but not in other ALDH1 members. Moreover, we got survival data from 160 AML patients in TCGA database. We found that high ALDH1A1 expression correlated to poor Overall Survival (OS), mostly in Fms-like Tyrosine Kinase-3 (FLT3) mutated group. HighALDH1A2 expression significantly correlated to poor OS in FLT3 wild type population but not in FLT3 mutated group. High ALDH1A3 expression significantly correlated to poor OS in FLT3 mutated group but not in FLT3 wild type group. There was no relationship between the OS of AML with the level of ALDH1B1, ALDH1L1 and ALDH1L2. Conclusion: The prognostic impacts were different in each ALDH1 family members, which needs further investigation. -
Targeting Non-Oncogene Addiction for Cancer Therapy
biomolecules Review Targeting Non-Oncogene Addiction for Cancer Therapy Hae Ryung Chang 1,*,†, Eunyoung Jung 1,†, Soobin Cho 1, Young-Jun Jeon 2 and Yonghwan Kim 1,* 1 Department of Biological Sciences and Research Institute of Women’s Health, Sookmyung Women’s University, Seoul 04310, Korea; [email protected] (E.J.); [email protected] (S.C.) 2 Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea; [email protected] * Correspondence: [email protected] (H.R.C.); [email protected] (Y.K.); Tel.: +82-2-710-9552 (H.R.C.); +82-2-710-9552 (Y.K.) † These authors contributed equally. Abstract: While Next-Generation Sequencing (NGS) and technological advances have been useful in identifying genetic profiles of tumorigenesis, novel target proteins and various clinical biomarkers, cancer continues to be a major global health threat. DNA replication, DNA damage response (DDR) and repair, and cell cycle regulation continue to be essential systems in targeted cancer therapies. Although many genes involved in DDR are known to be tumor suppressor genes, cancer cells are often dependent and addicted to these genes, making them excellent therapeutic targets. In this review, genes implicated in DNA replication, DDR, DNA repair, cell cycle regulation are discussed with reference to peptide or small molecule inhibitors which may prove therapeutic in cancer patients. Additionally, the potential of utilizing novel synthetic lethal genes in these pathways is examined, providing possible new targets for future therapeutics. Specifically, we evaluate the potential of TONSL as a novel gene for targeted therapy. Although it is a scaffold protein with no known enzymatic activity, the strategy used for developing PCNA inhibitors can also be utilized to target TONSL. -
1 Canonical BAF Complex in Regulatory T Cells 2 3 Chin
bioRxiv preprint doi: https://doi.org/10.1101/2020.02.26.964981; this version posted February 27, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 A genome-wide CRISPR screen reveals a role for the BRD9-containing non- 2 canonical BAF complex in regulatory T cells 3 4 Chin-San Loo1,3,#, Jovylyn Gatchalian2,#, Yuqiong Liang1, Mathias Leblanc1, Mingjun 5 Xie1, Josephine Ho2, Bhargav Venkatraghavan1, Diana C. Hargreaves2*, and Ye 6 Zheng1* 7 8 1. NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for 9 Biological Studies 10 2. Molecular and Cellular Biology Laboratory, Salk Institute for Biological Studies 11 3. Division of Biological Sciences, University of California, San Diego 12 # Co-first authors 13 * Co-corresponding authors 14 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.02.26.964981; this version posted February 27, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 15 Summary 16 Regulatory T cells (Tregs) play a pivotal role in suppressing auto-reactive T cells 17 and maintaining immune homeostasis. Treg development and function are 18 dependent on the transcription factor Foxp3. Here we performed a genome-wide 19 CRISPR/Cas9 knockout screen to identify the regulators of Foxp3 in mouse 20 primary Tregs. The results showed that Foxp3 regulators are highly enriched in 21 genes encoding SWI/SNF and SAGA complex subunits. Among the three 22 SWI/SNF-related complexes, the non-canonical or ncBAF (also called GBAF or 23 BRD9-containing BAF) complex promoted the expression of Foxp3, whereas the 24 PBAF complex repressed its expression. -
Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’S Biological Network Based on Systematic Pharmacology
ORIGINAL RESEARCH published: 25 June 2021 doi: 10.3389/fphar.2021.601846 Exploring the Regulatory Mechanism of Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’s Biological Network Based on Systematic Pharmacology Kailin Yang 1†, Liuting Zeng 1†, Anqi Ge 2†, Yi Chen 1†, Shanshan Wang 1†, Xiaofei Zhu 1,3† and Jinwen Ge 1,4* Edited by: 1 Takashi Sato, Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of 2 Tokyo University of Pharmacy and Life Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China, Galactophore Department, The First 3 Sciences, Japan Hospital of Hunan University of Chinese Medicine, Changsha, China, School of Graduate, Central South University, Changsha, China, 4Shaoyang University, Shaoyang, China Reviewed by: Hui Zhao, Capital Medical University, China Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Maria Luisa Del Moral, fi University of Jaén, Spain Rhizoma Compound (HCC) has de nite curative effect on cerebral ischemic diseases, *Correspondence: such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its Jinwen Ge mechanism for treating cerebral ischemia is still not fully explained. [email protected] †These authors share first authorship Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. Specialty section: The CIR genes were obtained from Genecards and OMIM and the protein-protein This article was submitted to interaction (PPI) data of HCC’s targets and IS genes were obtained from String Ethnopharmacology, a section of the journal database. -
CD29 Identifies IFN-Γ–Producing Human CD8+ T Cells With
+ CD29 identifies IFN-γ–producing human CD8 T cells with an increased cytotoxic potential Benoît P. Nicoleta,b, Aurélie Guislaina,b, Floris P. J. van Alphenc, Raquel Gomez-Eerlandd, Ton N. M. Schumacherd, Maartje van den Biggelaarc,e, and Monika C. Wolkersa,b,1 aDepartment of Hematopoiesis, Sanquin Research, 1066 CX Amsterdam, The Netherlands; bLandsteiner Laboratory, Oncode Institute, Amsterdam University Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; cDepartment of Research Facilities, Sanquin Research, 1066 CX Amsterdam, The Netherlands; dDivision of Molecular Oncology and Immunology, Oncode Institute, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; and eDepartment of Molecular and Cellular Haemostasis, Sanquin Research, 1066 CX Amsterdam, The Netherlands Edited by Anjana Rao, La Jolla Institute for Allergy and Immunology, La Jolla, CA, and approved February 12, 2020 (received for review August 12, 2019) Cytotoxic CD8+ T cells can effectively kill target cells by producing therefore developed a protocol that allowed for efficient iso- cytokines, chemokines, and granzymes. Expression of these effector lation of RNA and protein from fluorescence-activated cell molecules is however highly divergent, and tools that identify and sorting (FACS)-sorted fixed T cells after intracellular cytokine + preselect CD8 T cells with a cytotoxic expression profile are lacking. staining. With this top-down approach, we performed an un- + Human CD8 T cells can be divided into IFN-γ– and IL-2–producing biased RNA-sequencing (RNA-seq) and mass spectrometry cells. Unbiased transcriptomics and proteomics analysis on cytokine- γ– – + + (MS) analyses on IFN- and IL-2 producing primary human producing fixed CD8 T cells revealed that IL-2 cells produce helper + + + CD8 Tcells. -
High Expression of an Unknown Long Noncoding RNA RP11-290L1.3 from GDM Macrosomia and Its Effect on Preadipocyte Differentiation
ID: 20-0584 10 2 Y Lin, Y Zhand, L Xu et al. RP11 enhanced preadipocyte 10:2 191–204 differentiation RESEARCH High expression of an unknown long noncoding RNA RP11-290L1.3 from GDM macrosomia and its effect on preadipocyte differentiation Yu Lin1,*, Yingying Zhang1,*, Lei Xu2,*, Wei Long1, Chunjian Shan1, Hongjuan Ding1, Lianghui You1, Chun Zhao1 and Zhonghua Shi1 1State Key Laboratory of Reproductive Medicine, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, People’s Republic of China 2Maternal and Child Health Care Hospital of Dongchangfu District, Liaocheng, People’s Republic of China Correspondence should be addressed to C Zhao or Z Shi: [email protected] or [email protected] *(Y Lin, Y Zhang and L Xu contributed equally to this work) Abstract Aims: Gestational diabetes mellitus (GDM)-induced macrosomia is predominantly Key Words characterized by fat accumulation, which is closely related to adipocyte differentiation. f long noncoding RNA An unknown long noncoding RNA RP11-290L1.3, referred to as RP11, was identified to f GDM be dramatically upregulated in the umbilical cord blood of women with GDM-induced f preadipocyte macrosomia in our previous study. We conducted this study to identify the function of differentiation RP11 in GDM-induced macrosomia. f macrosomia Methods: The effects of RP11 gain- and loss-of-function on HPA-v (human preadipocytes- f fat accumulation visceral) adipogenesis were determined with lentivirus mediated cell transduction. The mRNA and protein expression levels of adipogenesis makers were evaluated by qPCR/Western blot. Then, we performed the microarray and pathway analysis to explore the possible mechanisms by which RP11 regulates adipogenesis. -
RNA Editing at Baseline and Following Endoplasmic Reticulum Stress
RNA Editing at Baseline and Following Endoplasmic Reticulum Stress By Allison Leigh Richards A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Human Genetics) in The University of Michigan 2015 Doctoral Committee: Professor Vivian G. Cheung, Chair Assistant Professor Santhi K. Ganesh Professor David Ginsburg Professor Daniel J. Klionsky Dedication To my father, mother, and Matt without whom I would never have made it ii Acknowledgements Thank you first and foremost to my dissertation mentor, Dr. Vivian Cheung. I have learned so much from you over the past several years including presentation skills such as never sighing and never saying “as you can see…” You have taught me how to think outside the box and how to create and explain my story to others. I would not be where I am today without your help and guidance. Thank you to the members of my dissertation committee (Drs. Santhi Ganesh, David Ginsburg and Daniel Klionsky) for all of your advice and support. I would also like to thank the entire Human Genetics Program, and especially JoAnn Sekiguchi and Karen Grahl, for welcoming me to the University of Michigan and making my transition so much easier. Thank you to Michael Boehnke and the Genome Science Training Program for supporting my work. A very special thank you to all of the members of the Cheung lab, past and present. Thank you to Xiaorong Wang for all of your help from the bench to advice on my career. Thank you to Zhengwei Zhu who has helped me immensely throughout my thesis even through my panic. -
The Complex SNP and CNV Genetic Architecture of the Increased Risk of Congenital Heart Defects in Down Syndrome
Downloaded from genome.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Research The complex SNP and CNV genetic architecture of the increased risk of congenital heart defects in Down syndrome M. Reza Sailani,1,2 Periklis Makrythanasis,1 Armand Valsesia,3,4,5 Federico A. Santoni,1 Samuel Deutsch,1 Konstantin Popadin,1 Christelle Borel,1 Eugenia Migliavacca,1 Andrew J. Sharp,1,20 Genevieve Duriaux Sail,1 Emilie Falconnet,1 Kelly Rabionet,6,7,8 Clara Serra-Juhe´,7,9 Stefano Vicari,10 Daniela Laux,11 Yann Grattau,12 Guy Dembour,13 Andre Megarbane,12,14 Renaud Touraine,15 Samantha Stora,12 Sofia Kitsiou,16 Helena Fryssira,16 Chariklia Chatzisevastou-Loukidou,16 Emmanouel Kanavakis,16 Giuseppe Merla,17 Damien Bonnet,11 Luis A. Pe´rez-Jurado,7,9 Xavier Estivill,6,7,8 Jean M. Delabar,18 and Stylianos E. Antonarakis1,2,19,21 1–19[Author affiliations appear at the end of the paper.] Congenital heart defect (CHD) occurs in 40% of Down syndrome (DS) cases. While carrying three copies of chromosome 21 increases the risk for CHD, trisomy 21 itself is not sufficient to cause CHD. Thus, additional genetic variation and/or environmental factors could contribute to the CHD risk. Here we report genomic variations that in concert with trisomy 21, determine the risk for CHD in DS. This case-control GWAS includes 187 DS with CHD (AVSD = 69, ASD = 53, VSD = 65) as cases, and 151 DS without CHD as controls. Chromosome 21–specific association studies revealed rs2832616 and rs1943950 as CHD risk alleles (adjusted genotypic P-values <0.05).