SULT2B1 Rabbit Pab

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Leader in Biomolecular Solutions for Life Science SULT2B1 Rabbit pAb Catalog No.: A7736 Basic Information Background Catalog No. Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, A7736 neurotransmitters, drugs, and xenobiotic compounds. These cytosolic enzymes are different in their tissue distributions and substrate specificities. The gene structure Observed MW (number and length of exons) is similar among family members. This gene sulfates 41kDa dehydroepiandrosterone but not 4-nitrophenol, a typical substrate for the phenol and estrogen sulfotransferase subfamilies. Two alternatively spliced variants that encode Calculated MW different isoforms have been described. 39kDa/41kDa Category Primary antibody Applications WB, IHC, IF Cross-Reactivity Human, Mouse, Rat Recommended Dilutions Immunogen Information WB 1:500 - 1:2000 Gene ID Swiss Prot 6820 O00204 IHC 1:50 - 1:200 Immunogen 1:50 - 1:100 IF Recombinant fusion protein containing a sequence corresponding to amino acids 1-365 of human SULT2B1 (NP_814444.1). Synonyms SULT2B1;HSST2 Contact Product Information www.abclonal.com Source Isotype Purification Rabbit IgG Affinity purification Storage Store at -20℃. Avoid freeze / thaw cycles. Buffer: PBS with 0.02% sodium azide,50% glycerol,pH7.3. Validation Data Western blot analysis of extracts of various cell lines, using SULT2B1 antibody (A7736) at 1:1000 dilution. Secondary antibody: HRP Goat Anti-Rabbit IgG (H+L) (AS014) at 1:10000 dilution. Lysates/proteins: 25ug per lane. Blocking buffer: 3% nonfat dry milk in TBST. Detection: ECL Basic Kit (RM00020). Exposure time: 90s. Immunohistochemistry of paraffin- Immunohistochemistry of paraffin- Immunohistochemistry of paraffin- embedded human liver cancer using embedded human kidney cancer using embedded mouse lung using SULT2B1 SULT2B1 antibody (A7736) at dilution of SULT2B1 antibody (A7736) at dilution of antibody (A7736) at dilution of 1:100 (40x 1:100 (40x lens). 1:100 (40x lens). lens). Immunohistochemistry of paraffin- Immunofluorescence analysis of A549 cells embedded mouse kidney using SULT2B1 using SULT2B1 antibody (A7736). antibody (A7736) at dilution of 1:100 (40x lens). Antibody | Protein | ELISA Kits | Enzyme | NGS | Service For research use only. Not for therapeutic or diagnostic purposes. Please visit http://abclonal.com for a complete listing of recommended products..

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Gene Expression Profiles in Testis of Pigs with Extreme High and Low
BMC Genomics BioMed Central Research article Open Access Gene expression profiles in testis of pigs with extreme high and low levels of androstenone Maren Moe*1,2, Theo Meuwissen2,3, Sigbjørn Lien2,3, Christian Bendixen4, Xuefei Wang4, Lene Nagstrup Conley4, Ingunn Berget3,5, Håvard Tajet1,2 and Eli Grindflek1,3 Address: 1The Norwegian Pig Breeders Association (NORSVIN), Hamar, Norway., 2Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, Ås, Norway., 3Centre for Integrative Genetics (CIGENE), Norwegian University of Life Sciences, Ås, Norway., 4Faculty of Agricultural Sciences, University of Aarhus, Tjele, Denmark. and 5MATFORSK, Osloveien 1, Ås, Norway. Email: Maren Moe* - [email protected]; Theo Meuwissen - [email protected]; Sigbjørn Lien - [email protected]; Christian Bendixen - [email protected]; Xuefei Wang - [email protected]; Lene Nagstrup Conley - [email protected]; Ingunn Berget - [email protected]; Håvard Tajet - [email protected]; Eli Grindflek - [email protected] * Corresponding author Published: 7 November 2007 Received: 3 July 2007 Accepted: 7 November 2007 BMC Genomics 2007, 8:405 doi:10.1186/1471-2164-8-405 This article is available from: http://www.biomedcentral.com/1471-2164/8/405 © 2007 Moe et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Boar taint is a major obstacle when using uncastrated male pigs for swine production. One of the main compounds causing this taint is androstenone, a pheromone produced in porcine testis.
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10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609
10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 SULT2B1 Purified Mouse Monoclonal Antibody (Mab) Catalog # AM8716b Specification SULT2B1 - Product Information Application WB,E Primary Accession O00204 Reactivity Human Predicted Human Host Mouse Clonality monoclonal Isotype IgG1,κ Calculated MW 41308 SULT2B1 - Additional Information Gene ID 6820 Other Names Sulfotransferase family cytosolic 2B member 1, ST2B1, Sulfotransferase 2B1, All lanes : Anti-SULT2B1 at 1:2000 dilution 2.8.2.2, Alcohol sulfotransferase, Lane 1: MCF-7 whole cell lysate Lane 2: Hydroxysteroid sulfotransferase 2, MDA-MB-468 whole cell lysate SULT2B1, HSST2 Lysates/proteins at 20 µg per lane. Secondary Goat Anti-mouse IgG, (H+L), Target/Specificity Peroxidase conjugated at 1/10000 dilution. This antibody is generated from a mouse Predicted band size : 41 kDa immunized with a reconbinant protein from Blocking/Dilution buffer: 5% NFDM/TBST. human. Dilution WB~~1:8000 Format Purified monoclonal antibody supplied in PBS with 0.09% (W/V) sodium azide. This antibody is purified through a protein G column, followed by dialysis against PBS. Storage Maintain refrigerated at 2-8°C for up to 2 weeks. For long term storage store at -20°C in small aliquots to prevent freeze-thaw cycles. Precautions SULT2B1 is for research use only and not for use in diagnostic or therapeutic Anti-SULT2B1 at 1:8000 dilution + MCF-7 procedures. whole cell lysate Lysates/proteins at 20 µg per lane. Secondary Goat Anti-mouse IgG, Page 1/3 10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 (H+L), Peroxidase conjugated at 1/10000 SULT2B1 - Protein Information dilution.
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Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?
Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement.
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Sulfation Through the Looking Glass—Recent Advances in Sulfotransferase Research for the Curious
The Pharmacogenomics Journal (2002) 2, 297–308 & 2002 Nature Publishing Group All rights reserved 1470-269X/02 $25.00 www.nature.com/tpj REVIEW Sulfation through the looking glass—recent advances in sulfotransferase research for the curious MWH Coughtrie ABSTRACT Members of the cytosolic sulfotransferase (SULT) superfamily catalyse the Department of Molecular & Cellular Pathology, sulfation of a multitude of xenobiotics, hormones and neurotransmitters. University of Dundee, Ninewells Hospital & Humans have at least 10 functional SULT genes, and a number of recent Medical School, Dundee, Scotland, UK advances reviewed here have furthered our understanding of SULT function. Correspondence: Analysis of expression patterns has shown that sulfotransferases are highly MWH Coughtrie, Department of expressed in the fetus, and SULTs may in fact be a major detoxification Molecular & Cellular Pathology, University enzyme system in the developing human. The X-ray crystal structures of of Dundee, Ninewells Hospital and three SULTs have been solved and combined with mutagenesis experiments Medical School, Dundee DD1 9SY, Scotland, UK. and molecular modelling, they have provided the first clues as to the factors Tel: +44 (0)1382 632510 that govern the unique substrate specificities of some of these enzymes. In Fax: +44 (0)1382 640320 the future these and other studies will facilitate prediction of the fate of E-mail: [email protected] chemicals metabolised by sulfation. Variation in sulfation capacity may be important in determining an individual’s response to xenobiotics, and there has been an explosion in information on sulfotransferase polymorphisms and their functional consequences, including the influence of SULT1A1 genotype on susceptibility to colorectal and breast cancer.
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Transcriptional Recapitulation and Subversion Of
Open Access Research2007KaiseretVolume al. 8, Issue 7, Article R131 Transcriptional recapitulation and subversion of embryonic colon comment development by mouse colon tumor models and human colon cancer Sergio Kaiser¤*, Young-Kyu Park¤†, Jeffrey L Franklin†, Richard B Halberg‡, Ming Yu§, Walter J Jessen*, Johannes Freudenberg*, Xiaodi Chen‡, Kevin Haigis¶, Anil G Jegga*, Sue Kong*, Bhuvaneswari Sakthivel*, Huan Xu*, Timothy Reichling¥, Mohammad Azhar#, Gregory P Boivin**, reviews Reade B Roberts§, Anika C Bissahoyo§, Fausto Gonzales††, Greg C Bloom††, Steven Eschrich††, Scott L Carter‡‡, Jeremy E Aronow*, John Kleimeyer*, Michael Kleimeyer*, Vivek Ramaswamy*, Stephen H Settle†, Braden Boone†, Shawn Levy†, Jonathan M Graff§§, Thomas Doetschman#, Joanna Groden¥, William F Dove‡, David W Threadgill§, Timothy J Yeatman††, reports Robert J Coffey Jr† and Bruce J Aronow* Addresses: *Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. †Departments of Medicine, and Cell and Developmental Biology, Vanderbilt University and Department of Veterans Affairs Medical Center, Nashville, TN 37232, USA. ‡McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53706, USA. §Department of Genetics and Lineberger Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA. ¶Molecular Pathology Unit and Center for Cancer Research, Massachusetts deposited research General Hospital, Charlestown, MA 02129, USA. ¥Division of Human Cancer Genetics, The Ohio State University College of Medicine, Columbus, Ohio 43210-2207, USA. #Institute for Collaborative BioResearch, University of Arizona, Tucson, AZ 85721-0036, USA. **University of Cincinnati, Department of Pathology and Laboratory Medicine, Cincinnati, OH 45267, USA. ††H Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. ‡‡Children's Hospital Informatics Program at the Harvard-MIT Division of Health Sciences and Technology (CHIP@HST), Harvard Medical School, Boston, Massachusetts 02115, USA.
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SULT2B1 (NM 177973) Human Mass Spec Standard Product Data
OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for PH304478 SULT2B1 (NM_177973) Human Mass Spec Standard Product data: Product Type: Mass Spec Standards Description: SULT2B1 MS Standard C13 and N15-labeled recombinant protein (NP_814444) Species: Human Expression Host: HEK293 Expression cDNA Clone RC204478 or AA Sequence: Predicted MW: 41.3 kDa Protein Sequence: >RC204478 protein sequence Red=Cloning site Green=Tags(s) MDGPAEPQIPGLWDTYEDDISEISQKLPGEYFRYKGVPFPVGLYSLESISLAENTQDVRDDDIFIITYPK SGTTWMIEIICLILKEGDPSWIRSVPIWERAPWCETIVGAFSLPDQYSPRLMSSHLPIQIFTKAFFSSKA KVIYMGRNPRDVVVSLYHYSKIAGQLKDPGTPDQFLRDFLKGEVQFGSWFDHIKGWLRMKGKDNFLFITY EELQQDLQGSVERICGFLGRPLGKEALGSVVAHSTFSAMKANTMSNYTLLPPSLLDHRRGAFLRKGVCGD WKNHFTVAQSEAFDRAYRKQMRGMPTFPWDEDPEEDGSPDPEPSPEPEPKPSLEPNTSLEREPRPNSSPS PSPGQASETPHPRPS TRTRPLEQKLISEEDLAANDILDYKDDDDKV Tag: C-Myc/DDK Purity: > 80% as determined by SDS-PAGE and Coomassie blue staining Concentration: 50 ug/ml as determined by BCA Labeling Method: Labeled with [U- 13C6, 15N4]-L-Arginine and [U- 13C6, 15N2]-L-Lysine Buffer: 100 mM glycine, 25 mM Tris-HCl, pH 7.3. Store at -80°C. Avoid repeated freeze-thaw cycles. Stable for 3 months from receipt of products under proper storage and handling conditions. RefSeq: NP_814444 RefSeq Size: 1228 RefSeq ORF: 1095 Synonyms: ARCI14; HSST2 Locus ID: 6820 UniProt ID: O00204 This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 2 SULT2B1 (NM_177973) Human Mass Spec Standard – PH304478 Cytogenetics: 19q13.33 Summary: Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These cytosolic enzymes are different in their tissue distributions and substrate specificities. The gene structure (number and length of exons) is similar among family members.
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2971.Full-Text.Pdf
Published OnlineFirst March 28, 2014; DOI: 10.1158/1078-0432.CCR-13-2567 Clinical Cancer Imaging, Diagnosis, Prognosis Research Steroidogenic Germline Polymorphism Predictors of Prostate Cancer Progression in the Estradiol Pathway Eric Levesque 1,2, Isabelle Laverdiere 1, Etienne Audet-Walsh1, Patrick Caron1,Melanie Rouleau1, Yves Fradet2, Louis Lacombe2, and Chantal Guillemette1 Abstract Purpose: Reliable biomarkers that predict prostate cancer outcomes are urgently needed to improve and personalize treatment approaches. With this goal in mind, we individually and collectively appraised common genetic polymorphisms related to estradiol metabolic pathways to find prostate cancer prognostic markers. Methods: The genetic profiles of 526 men with organ-confined prostate cancer were examined to find common genetic polymorphisms related to estradiol metabolic pathways and these findings were replicated in a cohort of 213 men with more advanced disease (follow-up time for both cohorts, >7.4 years). Specifically, we examined 71 single-nucleotide polymorphisms (SNP) in SULT2A1, SULT2B1, CYP1B1, COMT, CYP3A4, CYP3A5, CYP3A43, NQO1, and NQO2 and assessed the impact of the SNPs alone and in combination on prostate cancer progression and on circulating hormone levels. Results: According to a multivariate analysis, CYP1B1 (rs1800440), COMT (rs16982844), and SULT2B1 (rs12460535, rs2665582, rs10426628) were significantly associated with prostate cancer progression and hormone levels. Remarkably, by combining the SNP information with previously identified HSD17B2
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Intratumoral Estrogen Sulfotransferase Induction Contributes to the Anti-Breast Cancer Effects of the Dithiocarbamate Derivative TM208
npg Acta Pharmacologica Sinica (2015) 36: 1246–1255 © 2015 CPS and SIMM All rights reserved 1671-4083/15 www.nature.com/aps Original Article Intratumoral estrogen sulfotransferase induction contributes to the anti-breast cancer effects of the dithiocarbamate derivative TM208 Xi-wei JI 1, 2, Guang-ping CHEN4, Yan SONG5, Ming HUA1, Li-jie WANG1, Liang LI1, Yin YUAN1, Si-yuan WANG1, Tian-yan ZHOU1, 3, *, Wei LU1, 3 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; 2Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100191, China; 3State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China; 4Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA; 5Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China Aim: Sulfotransferase-catalyzed sulfation is the most important pathway for inactivating estrogens. Thus, activation of estrogen sulfotransferase (EST) may be an alternative approach for the treatment of estrogen-dependent breast cancer. In this study we investigated the involvement of EST in anti-breast cancer effects of the dithiocarbamate derivative TM208 in vitro and in vivo. Methods: The viability of human breast cancer MCF-7 cells was determined using a SBB assay. Nude mice bearing MCF-7 cells were orally administered TM208 (50 and 150 mg·kg-1·d-1) for 18 days. The xenograft tumors and uteri were collected. The mRNA expression of EST was examined with real-time PCR. EST protein was detected with Western blot, ELISA or immunohistochemical staining assays. A radioactive assay was used to measure the EST activity.
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A Grainyhead-Like 2/Ovo-Like 2 Pathway Regulates Renal Epithelial Barrier Function and Lumen Expansion
BASIC RESEARCH www.jasn.org A Grainyhead-Like 2/Ovo-Like 2 Pathway Regulates Renal Epithelial Barrier Function and Lumen Expansion † ‡ | Annekatrin Aue,* Christian Hinze,* Katharina Walentin,* Janett Ruffert,* Yesim Yurtdas,*§ | Max Werth,* Wei Chen,* Anja Rabien,§ Ergin Kilic,¶ Jörg-Dieter Schulzke,** †‡ Michael Schumann,** and Kai M. Schmidt-Ott* *Max Delbrueck Center for Molecular Medicine, Berlin, Germany; †Experimental and Clinical Research Center, and Departments of ‡Nephrology, §Urology, ¶Pathology, and **Gastroenterology, Charité Medical University, Berlin, Germany; and |Berlin Institute of Urologic Research, Berlin, Germany ABSTRACT Grainyhead transcription factors control epithelial barriers, tissue morphogenesis, and differentiation, but their role in the kidney is poorly understood. Here, we report that nephric duct, ureteric bud, and collecting duct epithelia express high levels of grainyhead-like homolog 2 (Grhl2) and that nephric duct lumen expansion is defective in Grhl2-deficient mice. In collecting duct epithelial cells, Grhl2 inactivation impaired epithelial barrier formation and inhibited lumen expansion. Molecular analyses showed that GRHL2 acts as a transcrip- tional activator and strongly associates with histone H3 lysine 4 trimethylation. Integrating genome-wide GRHL2 binding as well as H3 lysine 4 trimethylation chromatin immunoprecipitation sequencing and gene expression data allowed us to derive a high-confidence GRHL2 target set. GRHL2 transactivated a group of genes including Ovol2, encoding the ovo-like 2 zinc finger transcription factor, as well as E-cadherin, claudin 4 (Cldn4), and the small GTPase Rab25. Ovol2 induction alone was sufficient to bypass the requirement of Grhl2 for E-cadherin, Cldn4,andRab25 expression. Re-expression of either Ovol2 or a combination of Cldn4 and Rab25 was sufficient to rescue lumen expansion and barrier formation in Grhl2-deficient collecting duct cells.
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Characterization of Cytosolic Sulfotransferase Expression and Regulation in Human Liver and Intestine
Wayne State University Wayne State University Dissertations January 2019 Characterization Of Cytosolic Sulfotransferase Expression And Regulation In Human Liver And Intestine Sarah Talal Dubaisi Wayne State University, [email protected] Follow this and additional works at: https://digitalcommons.wayne.edu/oa_dissertations Part of the Molecular Biology Commons, and the Pharmacology Commons Recommended Citation Dubaisi, Sarah Talal, "Characterization Of Cytosolic Sulfotransferase Expression And Regulation In Human Liver And Intestine" (2019). Wayne State University Dissertations. 2158. https://digitalcommons.wayne.edu/oa_dissertations/2158 This Open Access Dissertation is brought to you for free and open access by DigitalCommons@WayneState. It has been accepted for inclusion in Wayne State University Dissertations by an authorized administrator of DigitalCommons@WayneState. CHARACTERIZATION OF CYTOSOLIC SULFOTRANSFERASE EXPRESSION AND REGULATION IN HUMAN LIVER AND INTESTINE by SARAH DUBAISI DISSERTATION Submitted to the Graduate School of Wayne State University, Detroit, Michigan in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY 2018 MAJOR: PHARMACOLOGY Approved By: ________________________________________ Advisor Date ________________________________________ ________________________________________ ________________________________________ ________________________________________ DEDICATION To Mom and Dad for their love, support, and guidance To my husband for being by my side and motivating me during this journey ii ACKNOWLEDGEMENTS I would like to thank my mentors, Dr. Melissa Runge-Morris and Dr. Thomas Kocarek, for their tremendous support, guidance, and patience and for helping me develop or improve the skills that I will need to be an independent researcher. I also want to thank them for allowing me to explore new ideas and present my work at national conferences. I am very grateful to my committee members: Dr.
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Anti-SULT2B1 Antibody (ARG56370)
Product datasheet [email protected] ARG56370 Package: 100 μl anti-SULT2B1 antibody Store at: -20°C Summary Product Description Rabbit Polyclonal antibody recognizes SULT2B1 Tested Reactivity Hu, Ms, Rat Tested Application WB Host Rabbit Clonality Polyclonal Isotype IgG Target Name SULT2B1 Antigen Species Human Immunogen Recombinant protein of Human SULT2B1 Conjugation Un-conjugated Alternate Names Hydroxysteroid sulfotransferase 2; Alcohol sulfotransferase; Sulfotransferase 2B1; EC 2.8.2.2; HSST2; ST2B1; Sulfotransferase family cytosolic 2B member 1 Application Instructions Application table Application Dilution WB 1:500 - 1:2000 Application Note * The dilutions indicate recommended starting dilutions and the optimal dilutions or concentrations should be determined by the scientist. Positive Control BT474 Calculated Mw 41 kDa Properties Form Liquid Purification Affinity purification with immunogen. Buffer PBS (pH 7.3), 0.02% Sodium azide and 50% Glycerol. Preservative 0.02% Sodium azide Stabilizer 50% Glycerol Storage instruction For continuous use, store undiluted antibody at 2-8°C for up to a week. For long-term storage, aliquot and store at -20°C. Storage in frost free freezers is not recommended. Avoid repeated freeze/thaw cycles. Suggest spin the vial prior to opening. The antibody solution should be gently mixed before use. Note For laboratory research only, not for drug, diagnostic or other use. www.arigobio.com 1/2 Bioinformation Gene Symbol SULT2B1 Gene Full Name sulfotransferase family, cytosolic, 2B, member 1 Background Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These cytosolic enzymes are different in their tissue distributions and substrate specificities. The gene structure (number and length of exons) is similar among family members.
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Identification of Novel Regulatory Genes in Acetaminophen
IDENTIFICATION OF NOVEL REGULATORY GENES IN ACETAMINOPHEN INDUCED HEPATOCYTE TOXICITY BY A GENOME-WIDE CRISPR/CAS9 SCREEN A THESIS IN Cell Biology and Biophysics and Bioinformatics Presented to the Faculty of the University of Missouri-Kansas City in partial fulfillment of the requirements for the degree DOCTOR OF PHILOSOPHY By KATHERINE ANNE SHORTT B.S, Indiana University, Bloomington, 2011 M.S, University of Missouri, Kansas City, 2014 Kansas City, Missouri 2018 © 2018 Katherine Shortt All Rights Reserved IDENTIFICATION OF NOVEL REGULATORY GENES IN ACETAMINOPHEN INDUCED HEPATOCYTE TOXICITY BY A GENOME-WIDE CRISPR/CAS9 SCREEN Katherine Anne Shortt, Candidate for the Doctor of Philosophy degree, University of Missouri-Kansas City, 2018 ABSTRACT Acetaminophen (APAP) is a commonly used analgesic responsible for over 56,000 overdose-related emergency room visits annually. A long asymptomatic period and limited treatment options result in a high rate of liver failure, generally resulting in either organ transplant or mortality. The underlying molecular mechanisms of injury are not well understood and effective therapy is limited. Identification of previously unknown genetic risk factors would provide new mechanistic insights and new therapeutic targets for APAP induced hepatocyte toxicity or liver injury. This study used a genome-wide CRISPR/Cas9 screen to evaluate genes that are protective against or cause susceptibility to APAP-induced liver injury. HuH7 human hepatocellular carcinoma cells containing CRISPR/Cas9 gene knockouts were treated with 15mM APAP for 30 minutes to 4 days. A gene expression profile was developed based on the 1) top screening hits, 2) overlap with gene expression data of APAP overdosed human patients, and 3) biological interpretation including assessment of known and suspected iii APAP-associated genes and their therapeutic potential, predicted affected biological pathways, and functionally validated candidate genes.
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