Blerta Xhemalçe, PhD Associate Professor Department of Molecular Biosciences & Institute for Cellular and Molecular Biology, University of Texas at Austin 2500 Speedway Stop A4800, Austin, Texas 78712 Tel: +1 512 471 0461, [email protected]; http://www.BXhemalceLab.com
EDUCATION
PhD, Molecular Biology of the Cell Program, Pasteur Institute, Paris, France, 2/2006 MSc, Molecular Biology of the Cell Program, Paris VII University, France, including Molecular Biology of the Cell Pasteur Institute Course, 9/2002 Bachelor degree, Magister of Genetics, Paris VII University, France, 9/2001
PROFESSIONAL EXPERIENCE
2006-2011 Postdoctoral Fellow, with Prof. Tony Kouzarides, Gurdon Institute, University of Cambridge, Cambridge, UK 2002-2006 Graduate Student, with Dr. Benoit Arcangioli and Dr. Jacob Seeler (Dejean lab), Pasteur Institute, Paris, France 2001 Undergraduate trainee, Institute of Molecular and Cellular Genetics, Orsay, France 2000 Undergraduate trainee, with Prof. Claudine Junien, INSERM U781, Genetics and Epigenetics of Metabolic Diseases, Neurosensorial Diseases and Development, Hôpital Necker-Enfants Malades, Paris, France
ACADEMIC APPOINTMENT
From 09/2019 Associate Professor with Tenure, Department of Molecular Biosciences, University of Texas at Austin, USA 9/2013-8/2019 Tenure-track Assistant Professor, Department of Molecular Biosciences, University of Texas at Austin, USA 9/2011-8/2013 Independent Research Fellow, Institute for Cellular and Molecular Biology, University of Texas at Austin, USA
RESEARCH STATEMENT:
The Xhemalçe lab aims to decipher how epigenetic modifications regulate the expression of genetic information from DNA to RNA to proteins, with a particular focus on RNA methylation pathways. We use a combination of cellular and molecular biology, RNA biochemistry, next generation sequencing and quantitative mass spectrometry to identify and characterize novel "writers", "erasers" and "readers" of RNA modifications. Our objective is to identify fundamental biological mechanisms of gene regulation, as well as potential therapeutic targets for cancer and metabolic diseases.
1 HONORS AND AWARDS
2016 Department of Defense Breast Cancer Research Program, Breakthrough Award 2014 Protégé of The Academy of Medicine, Engineering and Science of Texas (TAMEST) 2014 Best selected talk award, “Crossing Boundaries: Linking Metabolism to Epigenetics” inaugural meeting, Cambridge MA, USA 2010-2011 Project Grant from Cancer Research UK “Role of a novel RNA methyltransferase in miRNA function and cell proliferation”, £185,961 (~$290,000) 2005-2006 Doctoral fellowship from ARC (Cancer Research Association), France 2005-2006 Doctoral fellowship from LCC (League Against Cancer), France (declined) 2002-2005 Doctoral fellowship from MENRT (Ministry of Higher Education, Research and Technology), France 2001-2002 Master fellowship from Paris VII University, France 2001 UNESCO (United Nations Educational, Scientific and Cultural Organization) fellowship
PROFESSIONAL SERVICE
2015-2016 Scientific Consultant for ICENI Therapeutics Ltd, UK (now called STORM) 2015-2016 Co-organizer (with Dr. Sharon Dent), Abcam Symposium, “Chromatin, Non- coding RNAs and RNAP II Regulation in Development and Disease” 2018 Early Career Reviewer, ACE study section, March 13th-14th USA 2018 Grant Reviewer, Israeli Science Foundation 2018 Grant Reviewer, Cancer Research UK 2017 Grant Reviewer, Wellcome Trust UK 2014-2015 Grant Reviewer, Biotechnology and Biological Sciences Research Council (BBSRC) UK 2015-now Grant Reviewer, Italian Association for Cancer Research (AIRC) Italy 2016-now Post-doctoral Fellowship Reviewer, AIRC Italy 2013-now Ad hoc reviewer, Biochemistry and Cell Biology, Nature Communications, Cellular Physiology and Biochemistry, Nature Methods, Cell Reports 2016 Best Poster Award Judge, FASEB Conference, “Biological Methylation: Fundamental Mechanisms in Health and Disease, 19-24 June, Lisbon, Portugal 2013 Judge, 15th Region 2 Siemens competition in Math: Science: Technology
INTRAMURAL SERVICE
2019-now Chair of the Biology BS curriculum redesign committee 2016-now Committee member for Institute for Cellular and Molecular Biology Seminars 2014-now Co-organizer (with Dr. Arlen Johnson) of the monthly RNA & DNA Club 2013-now Organizer of Student Exchange Program with the European Magistere of Genetics 2019-2020 Member of the Biochemistry BS curriculum redesign committee 2016-2018 Senior Faculty search committee for Department of Molecular Biosciences 2015-2016 Faculty search committee member for Department of Molecular Biosciences
2 2014-2015 Faculty search committee member for Center for Systems and Synthetic Biology 2016-2018 Organizer of the Assistant Professor Society bimonthly meetings 2016-now Q15 qualifying exam committee for Cellular and Molecular Biology Graduate Program 2014-now Selection committee member for Cellular and Molecular Biology Graduate Program 2013-2015 Selection committee member for Cellular and Molecular Biology Graduate Program – International Students 2014 Selection committee member for Named Continuing Fellowship Nominees for Cellular and Molecular Biology Graduate Program 2014 Judge for the best poster award at the 2nd annual Big Data in Biology symposium organized by the Center for Systems and Synthetic Biology
CURRENT GRANT SUPPORT
NIH/NIGMS, “Elucidating mechanisms of microRNA pathway deregulation in human cells”, GM127802, 5/01/2018-04/30/2023, $210,000 direct costs per annum (1,643,250.00 total costs).
STORM Therapeutics Ltd, “Role of BCDIN3D methyltransferase in cancer”, 10/01/2017- 03/31/2020, $68,000 direct costs per annum ($244,372 total costs), B Xhemalce, PI.
Allocation from Cancer Prevention Research Institute of Texas (CPRIT) Core Facility Support Grants RP120348 and RP170002 from MD Anderson Cancer Center Science Park ($63,000 since April 2014).
COMPLETED GRANT SUPPORT
Department of Defense Breast Cancer Research Program, Breakthrough Award, BC151608, “Role of RNA methylation in microRNA processing and breast cancer tumorigenesis and metastasis”, 7/15/2016-7/14/2019, $125,000 direct costs per annum ($568,230 total costs), B Xhemalce, PI. – Invited to submit a DoD CDMRP BCRP Expansion Award.
Welch Foundation, Project Grant F1859, “Regulation of Gene Expression Through Chemical Modifications of RNA”, 06/01/2014-05/31/2017, $180,000 total direct costs, B Xhemalce, PI.
CONFERENCE PRESENTATIONS
2020 Invited speaker, Keystone Symposium on RNA Editing and Modifications: From Biology to Therapy, October 1-5, Denver, CO, USA 2020 Invited speaker, Texas Conference on Genome Repair 2020, March 8-10, San Antonio, TX 2019 Invited speaker, Texas Chemical Biology Conference, 23-24 May 2018 Invited speaker, Symposium on "Understanding the Epitranscriptome", 25-28 Sept, Iqueque, Chile
3 2018 Talk, EMBO Workshop " piRNAs and PIWI proteins", 12-15 Sept, Montpellier, France 2017 Talk, Cold Spring Harbor Asia, RNA modifications & Epitranscriptomics, 13- 17 Nov, Suzhou, China 2017 Gordon Research Conference, Nucleic Acids, June 4-9, Biddeford, Maine 2016 Keynote speaker, Asilomar Chromatin and Chromosomes Conference, 8-11 Dec, Monterey Bay CA, USA 2016 Invited speaker, FASEB Conference, Biological Methylation: Fundamental Mechanisms in Health and Disease”, 19-24 June, Lisbon, Portugal 2016 Invited speaker, Abcam Conference, Chromatin, Non-coding RNAs and RNAP II Regulation in Development and Disease, 29 March, Austin, Texas 2016 Invited speaker, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine/MD Anderson Cancer Center Joint Symposium, DNA Damage Response and Cancer Therapy, 5 Feb, Houston, USA 2016 Kouzarides lab reunion, 20-21 Jan, Claire College, Cambridge, UK 2015 Invited speaker, Epigenetic Methyltransferases; Structure, Mechanism and Inhibition Symposium, 19 Aug, Toronto, Canada 2014 Crossing Boundaries: Linking Metabolism to Epigenetics inaugural meeting, May 1, Cambridge MA, USA 2009 EPITRON (EPIgenetic TReatment Of Neoplastic disease) Annual Meeting, 8 Oct, Lisbon, Portugal 2008 HEROIC (High-throughput Epigenetic Regulatory Organization In Chromatin) Annual Meeting, 8 Oct, Vienna, Austria 2006 HEROIC annual meeting, 30 Oct, Uppsala, Sweden 2004 Chromatin Immunoprecipitation, EMBO Practical Course: Molecular Genetics with the Fission Yeast, 11-21 Jun, Copenhagen, Denmark
INVITED SEMINARS
2018 Invited seminar at the Ohio State University College of Medicine, Columbus, OH 2018 Invited seminar at University of Vermont, Burlington, VT 2018 Gene Regulation and Genomics Seminar Series, UT Southwestern, Dallas, TX 2017 STORM Therapeutics, Babraham Research Campus, Cambridge, United Kingdom 2013 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA 2013 Department of Biochemistry and Microbiology, University of Victoria, Victoria British Columbia, Canada 2011 Epigenetics and Cell Fate Institute, Université Paris VII – Denis Diderot, Paris, France 2005 Department of Dynamics of the Genome, Pasteur Institute, Paris, France 2004 Molecular and Cellular Genetics Institute, Lyon, France
INTRAMURAL PRESENTATIONS
2019 Guest lecture on messenger RNA modifications 2019 ICMB Retreat 2018 LiveStrong Cancer Institute Research Retreat
4 2018 Dean's Scholars Friday lunch 2017 The LIVESTRONG Cancer Institute Basic/Translational Research retreat 2016 The Waggoner Center for Alcohol and Addiction Research Center seminar 2015 Department of Molecular Biosciences, Faculty Discussion Group (FDG) meeting chalk talk 2013, 2017 University of Texas at Austin, Center for Systems and Synthetic Biology 2013 University of Texas at Austin, Institute for Cellular and Molecular Biology retreat
TEACHING
2014-2019 University of Texas at Austin, Molecular Biology, forty course hours, ~70 students Spring 2017 University of Texas at Austin, Genetics, three course hours, 12 graduate students Summer 2016 Dell Medical School, Molecules & Cells Class, three guest lectures Fall 2014 University of Texas at Austin, Current Topics in Microbiology, three course hours, 10 graduate students
PATENT
WO2011154704, Nucleic Acid Methyl Transferase, Blerta Xhemalce and Tony Kouzarides, filed June 2011
PEER-REVIEWED ARTICLES
1. Xhemalce B, Seeler JS, Thon G, Dejean A and Arcangioli B. 2004. Role of the Fission Yeast SUMO E3 Ligase Pli1p in Centromere and Telomere Maintenance. EMBO Journal 23(19):3844-53.
2. Xhemalce B, Madi Riising E, Baumann P, Thon G, Dejean A, Arcangioli B and Seeler JS. 2007. Role of SUMO in the Dynamics of Telomere Maintenance in Fission Yeast. Proc Natl Acad Sci USA 104(3):893-8.
3. Xhemalce B, Miller KM, Driscoll R, Masumoto H, Jackson SP, Kouzarides T, Verreault A and Arcangioli B. 2007. Regulation of histone H3 lysine 56 acetylation in Schizosaccharomyces pombe. J Biol Chem 282(20):15040-7.
4. Xhemalce B and Kouzarides T. 2010. A chromodomain switch mediated by Histone H3 Lysine 4 Acetylation regulates heterochromatin assembly. Genes & Development, 24(7):647-52.
Highlighted article: Kim JH and Workman JL. 2010. Histone acetylation in heterochromatin assembly Genes & Development. 24(7): 738-40.
5. Bartke T, Vermeulen M, Xhemalce B, Robson SC, Mann M, Kouzarides T. 2010. Nucleosome-Interacting Proteins Regulated by DNA and Histone Methylation. Cell 143(3):470-84.
5 6. Xhemalce B, Dawson MA and Bannister AJ. 2011. Histone Modifications. Epigenetic Regulation and Epigenomics, "Encyclopedia of Molecular Cell Biology and Molecular Medicine", John Wiley & Sons. Cover of Epigenetic Regulation and Epigenomics Book
7. Rodriguez R, Miller KM, Forment JV, Bradshaw CR, Nikan M, Xhemalce B, Balasubramanian S and Jackson SP. 2012. Small molecule induced DNA damage identifies druggable, alternatively-structured DNA sites. Nature Chemical Biology 8(3):301-10.
8. Dawson MA, Foster SD, Bannister AJ, Robson SC, Wang X, Xhemalce B, Wood AD, Green AR, Göttgens B and Kouzarides T. 2012. Three distinct patterns of histone H3Y41 phosphorylation mark active genes. Cell Reports 2(3):470-7.
9. Xhemalce B, Robson SC and Kouzarides T. 2012. Human RNA methyltransferase BCDIN3D regulates microRNA processing. Cell 151(2):278-88.
Highlighted article: David R. 2012. Small RNAs: Controlling maturity Nature Reviews Molecular Cell Biology. 13, 752-753
10. Xhemalce B. 2013. From histones to RNA: role of methylation in cancer. Briefings in Functional Genomics 12(3):244-53.
11. Spivey EC, Xhemalce B, Shear JB and Finkelstein IJ. 2014. A 3D-Printed Microfluidic Microdissector for High-Throughput Studies of Cellular Aging. Analytical Chemistry 86(15):7406-12.
12. Chen W, Ebelt ND, Stracker TH, Xhemalce B, Van Der Berg CL and Miller KM. 2015. ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion. eLife, Jun 1;4
13. Shelton SB, Reinsborough CW and Xhemalce B. 2016. Who watches the watchmen: Roles of RNA modifications in the RNA interference Pathway. PLOS Genetics Jul 21;12(7)
14. Abell NS, Mercado M, Caneque T, Rodriguez R and Xhemalce B. 2017. Click- Quantitative Mass Spectrometry Identifies PIWIL3 as a Mechanistic Target of RNA Interference Activator Enoxacin in Cancer Cells. J Am Chem Soc. Jan 17
15. Zacharioudakis E, Agarwal P, Bartoli A, Abell NS, Kunalingam L, Xhemalce B, Miller KM, and Rodriguez, R. 2017. Chromatin regulates genome targeting with cisplatin. Angewandte Chemie, 2017, May 5
16. Shelton SB, Shah NM, Abell NS, Mercado M, and Xhemalce B. 2018. Crosstalk between the RNA methylation and histone binding activities of MePCE regulates pTEFb activation on chromatin. Cell Reports, 2018 Feb 6
17. Bryant JD, Sweeney SR, Sentrandreu E, Shin M, Ipas H, Xhemalce B, Momb J, Tiziani S and Appling DR. 2018. Deletion of the neural tube defect-associated gene Mthfd1l disrupts one-carbon and central energy metabolism in mouse embryos. J Biol Chem, 2018 Apr 20; 293(16):5821-5833.
6 18. Shelton SB and Xhemalce B, 2019. Antibody-free assay for RNA methyltransferase activity analysis. J. Vis. Exp. (149), e59856, doi:10.3791/59856.
19. Reinsborough CW, Ipas H, Abell NS, Nottingham RM, Yao J, Shelton SB, Devanathan SK, Lambowitz AM and Xhemalce B. 2019. BCDIN3D regulates tRNAHis 3’ fragment processing. PLOS Genetics Jul 22;15(7):e1008273, doi: 10.1371/journal.pgen.1008273.
20. Kim JJ, Lee S, Gong F, Battenhouse AM, Boutz DR, Bashyal A, Refvik ST, Chiang CM, Xhemalce B, Paull TT, Brodbelt JS, Marcotte EM and Miller KM. 2019. Systematic Bromodomain Protein Screens Identify Homologous Recombination and R-Loop Suppression Pathways Involved in Genome Integrity, Genes & Development, in press.
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