December 2012

Curriculum Vitae

Pilar Blancafort

Associate Professor

Breast Cancer Biology & Epigenetics

School of Anatomy, Physiology, and Human Biology M309

The University of Western Australia

35 Stirling Highway

Crawley, WA

Australia

Phone: +61 8 64883293

Fax: +61 8 6488 1051

Education:

·Ph.D. in Biochemistry, Universite de Montreal (Canada) supervised by Robert Cedergren. August 5th, 1999.

·B.Sc., Molecular Biology and Biochemistry, Universitat de Barcelona (Spain), September 1993.

Languages:

·Catalan

·Spanish

·French

·English

·Portuguese (reading only)

Professional Experience:

·Associate Professor, Cancer Biology, School of Anatomy, Physiology and Human Biology, The University of Western Australia, September 2012-present

·Associate Professor of Pharmacology, University of North Carolina at Chapel Hill, January 2010-September 2012

·Assistant Professor of Pharmacology, University of North Carolina at Chapel Hill, January 2005-January 2010

·Senior Research Associate in Dr. Carlos Barbas III laboratory. Department of Molecular Biology, The Scripps Research Institute, January 2004

·Research Associate in Dr. Carlos Barbas III laboratory. Department of Molecular Biology, The Scripps Research Institute, August 1999

·Editor in Chief, Natural Products against cancer (Versita & Springer), January 2012-present

·Member, Center for stem cell therapy and regenerative medicine, UWA, September 2012-present

·Member, American Association for Cancer Research, AACR, January 2007

·Member, Lineberger Comprehensive Cancer Center, January 2005

Honors and Awards:

·Provocative question NCI PQ18 R01 award, August 2012, Epigenetic silencing of oncogenic transcription factors in breast cancer.

·Susan Swerling invited Lecture, “Targeted Therapy for Cancer: Moving Beyond Kinase Inhibitors.” Dana Farber Cancer Institute, Harvard Medical School, May 16, 2013.

·Winner Research Competition at UWA “Novel anti-cancer peptides for the treatment of basal-like breast cancers”, November 2012

·Department of Defense Breast Cancer Idea Award, 2010

·UCRF Cancer Research Pilot Core Award, 2009

·UCRF Innovation Research Award, 2008

·Golfers Against Cancer Research Award, 2008

·Carolina Center of Cancer Nanotechnology Excellence (C-CCNE) Pilot Grant Award, 2007

·Department of Defense Breast Cancer Idea Award, 2006

·University Research Council Award, UNC-CH, 2005

·American Lung Discovery Award, 2005

·GI SPORE Research Award, 2005

·V-Foundation Award for Cancer Research (breast cancer fellowship in honor of Julie Stewart), 2005

·Winner, Simon-Pierre Noel Price for the best graduate student presentation in the department of Biochemistry, University of Montreal, 1998

· FES (Faculté des Études Supérieures) fellowship to support foreign students in the University of Montreal, 1994

·Fellowship from Foundation Jean Branchet (ULB, Bruxelles) to support foreign students at the ULB (Universite libre de Bruxelles), Belgium, 1993.

·EU ERASMUS fellowship to finish last year of B.Sc. in ULB (Universite libre de Bruxelles), Belgium, 1992. Personal project with Dr. Alain Ghysen

Bibliography:

Books and Chapters:

Blancafort P, Juárez-Moreno K, Stolzenburg S, Beltran AS (2011) Engineering Transcription Factors in Breast Cancer Stem Cells. Breast Cancer - Carcinogenesis, Cell Growth and Signalling Pathways ISBN 978-953-307-714-7, InTech, Available from: http://wwwintechopencom/articles/show/title/engineering-transcription-factors-in-breast-cancer-stem-cells

Hassiotou F., Geddes D., Blancafort P., Filgueira L., Hartmann P.E. (2013). Breastmilk stem cells: Recent advances and future prospects. IN: Regenerative medicine using redundant abdominal fat and menstrual blood. Niranjan Bhattacharya, Phillip Stubblefield (eds.), Springer Verlag International (In press - expected publication date: September 2013).

Submitted/in review:

Beltran A.S., Graves, L.M., Blancafort, P. Interference peptides (iPeps): novel synthetic interfaces to target “undruggable” oncogenic transcription factors. Current Biology (2013).

Significance: This paper describes a novel technology that uses small synthetic peptides (interference peptides), ipeps, to block epitopes necessary for protein-protein interactions, which maintain cooperativity between oncogenic transcription factors in breast cancer. We show that delivery of ipeps with cell penetrating peptide against oncogenes overexpressed in triple negative breast cancer cells results in potent and selective apoptosis of breast cancer cells.

Stolzenburg, S., Beltran, AS, Rivenbark, AG, Rots, MG, Scanlan-Swift, T, Strahl, BS, Ford, E. Lister R, Blancafort P. Hereditable oncogenic silencing in breast tumors by programmable sequence specific methyltransferases. Submitted to Letters to Nature.

Significance: This paper uses inducible Zinc-finger methyltransferases in animal models of breast cancer to show inherited, stable propagation of DNA methylation in targeted oncogenes. The transmission of DNA methylation originally nucleated by artificial methyltransferases is propagated in vivo in the breast cancers implants even in absence of expression of the zinc finger methyltrasferase. This paper proofs the concept that targeted methylation in oncogenic promoters results in long-lasting tumor suppression and provides an opportunity to target cancers for which no cure is available.

In Press:

Juárez-Moreno K, Erices R, Beltran AS, Stolzenburg S, Cuello-Fredes M, Owen, GI, Qian H, Blancafort P (2013). Breaking through an epigenetic wall: Re-activation of OCT4 by KRAB-containing designer zinc finger transcription factors. Epigenetics. In Press.

Van der Gun BTF, Huisman C., Stolzenburg S., Kazemier HG, Ruiters, MHJ., Blancafort, P. Rots MG (2013), Bidirectional modulation of endogenous EpCAM expression to unravel its function in ovarian cancer.BJC. In Press.

Refereed papers and articles

Original research:

Wang Y, Su H-h, Yang Y, Zhang L, Blancafort P, Huang L. Systemic Delivery of Modified mRNA Encoding Herpes Simplex Virus 1 Thymidine Kinase for Targeted Cancer Gene Therapy. Molecular Therapy. (2012); Dec 11. doi: 10.1038/mt.2012.250. [Epub ahead of print]

Blancafort P, Jin J, Frye S (2012). Writing and re-writing the epigenetic code of cancer cells: from engineered proteins to small molecules. Mol Pharmacology Minireview. Available on line http://molpharm.aspetjournals.org

Hassiotou F, Beltran A, Chetwynd E, Stuebe AM, Twigger AJ, Metzger P, Trengove N, Tat Lai C, Filgueira L, Blancafort P, Hartmann PE. Breastmilk is a Novel Source of Stem Cells with Multi-Lineage Differentiation Potential. Stem Cells. (2012) Aug 3. doi: 10.1002/stem.1188. [Epub ahead of print]

Stolzenburg S, Rots MG, Beltran AS, Rivenbark AS, Yuan X, Strahl BS, Blancafort P (2012) Targeted silencing of the oncogenic transcription factor SOX2 in breast cancer. Nucleic Acids Research. (2012); 40:6725-40.

Significance: This paper was selected for the Highlights of the Journal (and the cover), which comprises 5% of the papers based on innovation and scientific excellence.

Lara H, Wang Y, Beltran AS, Juarez-Moreno K, Yuan X, Kato S, Leisewitz AV, Cuello-Fredes M, Licea AF, Connolly DC, Huang L, Blancafort P. Targeting serous epithelial ovarian cancer with designer zinc finger transcription factors. J Biol Chem. (2012); 287:29873-86.

Rivenbark AG, Beltran AS, Yuan X, Rots MG, Strahl BD, Blancafort P. Epigenetic Reprogramming of Cancer Cells via Targeted DNA Methylation. Epigenetics (2012); 7:350-60.

Huang X, Narayanaswamy R, Fenn K, Szpakowski S, Sasaki C, Costa J, Blancafort P, Lizardi PM. Sequence-Specific Biosensors Report Drug-Induced Changes in Epigenetic Silencing in Living Cells. DNA Cell Biol. (2012) Feb 7.

Beltran, A and Blancafort, P. Reactivation of Maspin in Non-Small Cell Lung Carcinoma cells (NSCLC) by Artificial Transcription Factors (ATFs). Epigenetics. 2011 Feb 20;6(2). [EPub ahead of Print]

Beltran, A. S., Russo, A, Lara, H, Fan, C, Lizardi, P. M, Blancafort, P. Suppression of breast tumor growth and metastasis by an engineered transcription factor. PLoS One. 2011. 6: 9 e24595

Beltran AS, Rivenbark AG, Richardson BT, Yuan X, Quian H, Hunt JP, Zimmerman E, Graves LM, Blancafort P. Generation of tumor-initiating cells by exogenous delivery of OCT4 transcription factor. Breast Cancer Res. 2011 Sep 27;13(5):R94

Beltran, A., Blancafort, P. Remodeling genomes with Artificial Transcription Factors and chromatin remodeling drugs. Zinc Finger Protocols. Humana Press. Methods Mol Biol. 2010;649: 163-82.

Beltran, A., Sun, X., Lizardi,PM, Blancafort, P. Reprogramming epigenetic silencing: Artificial Transcription Factors synergize with chromatin remodeling drugs to re-activate the tumor suppressor mammary serine protease inhibitor maspin. Mol Cancer Ther. 2008;7:1080-90.

Blancafort P, Beltran AS. Rational Design, Selection and Specificity of Artificial Transcription Factors (ATFs): The Influence of Chromatin in Target Gene Regulation. Comb Chem High Throughput Screen. (2008);11:146-58.

Blancafort, P., Tschan, M.P., Edrmann, D., Barbas III, C.F. Modulation of drug resistance by artificial transcription factors. Mol Cancer Ther. (2008); 7:688-97.

Beltran, A., Parikh, S., Liu, Y., Cuevas, BD, Johnson GL, Fustcher, BW and Blancafort, P. Reactivation of a dormant tumor suppressor by designed transcription factors. Oncogene. (2007);26:2791-8.

Beltran, A., Liu, Y., Parikh, S., Brenda, T., and Blancafort, P. Interrogating genomes with combinatorial transcription factor libraries: asking zinc finger questions. Assay Drug Dev Technol. (2006); 4:317-331

Dreier, B., Fuller, R.P, Segal, D.J., Lund, C., Blancafort, P., Huber, A., Koksch, B., and Barbas, C.F.III. Development of zinc finger domains for recognition of the 5’-CNN-3’ family DNA sequences and their use in the construction of artificial transcription factors. J. Biol. Chem. (2005); 280: 35588-97.

Blancafort, P., Chen, E., Gonzalez, B., Bergquist, S., Zijlstra, A., Guthy, D., Brachat, A., Brakenhoff, R., Quigley, J., Edrmann, D., and Barbas C.F.III. Genetic reprogramming of tumor cells by zinc finger transcription factors. Proc. Natl. Acad. Sci. (2005); 102:11716-21.

Magnenat, L., Blancafort, P. and Barbas III, C.F. In vivo library selection and designed affinity manuration of polydactyl zinc finger transcription factors for ICAM–1 gene regulation. J. Mol. Biol. (2004); 341:635-49.

Blancafort, P, Segal, D.J., and Barbas III, C.F. Designing transcription factor architectures for drug design. Mol Pharmacol. (2004); 66:1361-71.

Lund, C.V, Blancafort, P., Popkov, M. and Barbas III, C.F. Promoter-targeted Phage Display Selections with Preassembled Synthetic Zinc Finger Libraries for Endogenous Gene Regulation. J.Mol. Biol. (2004); 340:599-613.

Blancafort,P., Magnenat, L. and Barbas III, C.F. Scanning the human genome with combinatorial transcription factor libraries. Nat Biotechnol. (2003);21:269-74.

Segal, D.J., Beerli R.R, Blancafort, P., Dreider, B., Effertz, K., Huber, A., Koksch, B., Magnenat, L., Valente, D., and Barbas III., C.F. (2003). Evaluation of a modular strategy for the construction of novel polydactyl zinc finger DNA-binding proteins. Biochemistry. 2003; 42:2137-48.

Blancafort, P., Klinck, R., Steinberg, S., Scott, J.K. and Cedergren, R. The recognition of a non-canonical base pair by a zinc finger protein. Chem Biol. (1999); 6:585-97.

Blancafort, P., Ferbeyre, G., Sariol, C., and Cedergren, R. Pol I-driven integrative expression vectors for yeast. Journal of Biotechnology (1997);56:41-7

Published abstracts:

Ferbeyre, G., Bratty, J., Blancafort, P., and Cedergren, R. (1995). Yeast as a model for hammerhead ribozyme action. Yeast, 11:15-48A.

Patents:

Blancafort, P. and Barbas III, C.F. "Zinc finger libraries". International Patent Application Serial No. PCT/US03/03705 (2001).

Blancafort P, Beltran AS. “Interference Peptides, ipeps. Pending patent application.

Conference presentations:

Blancafort P. Susan Swerling invited Lecture, “Targeted Therapy for Cancer: Moving Beyond Kinase Inhibitors.” Dana Farber Cancer Institute, Harvard Medical School, May 16, 2013

Hassiotou F., Trengove N., Tat Lai C., Filgueira L., Blancafort P., Hartmann P.E., (2012). Breastmilk stem cells: An overview of the current knowledge. Breastfeeding and Lactation Symposium, Vienna, Austria, April 2012 (Plenary Speaker).

Blancafort, P. Transcriptional regulation of breast cancer stem cell fate. American Society for Investigative Pathology. Breast Cancer Workshop. Washington, DC. April 13th, 2011.

Blancafort, P. Selection of Artificial Transcription Factors modulating breast cancer metastasis. Phage and Yeast Display Conference. Boston, MA. May 9-10 2011.

Stolzenburg, S, Blancafort P. Reprogramming the epigenetic code of breast cancer cells. Era of Hope meeting, Department of defense Breast cancer meeting, Orlando Florida, August 2-5, 2011.

Blancafort P. Reprogramming Epigenetic Silencing with Artificial Transcription Factors. The Chilean Society for Cell Biology meeting. Pucon, Chile. October 29nd –November 2nd 2010.

Blancafort P. Reprogramming Epigenetic Silencing with Artificial Transcription Factors. Department of Pharmacology, UNC. October 5th, 2010.

Blancafort, P. Reprogramming self-renewal in breast cancer. Centre de Regulacio Genetica de Barcelona, CRG, Barcelona, Spain. July 31st, 2009.

Blancafort, P. Epigenetic reprogramming of tumor and stem cells by Artificial Transcription Factors. Molecular therapeutics of Cancer Research Conference. Stanford University July 23-25, 2009.

Blancafort, P. Remodeling genomes of tumor and stem cells by Artificial Transcription Factors. November 5th, 2008. Loyola University. Host: Bruce Cuevas.

Blancafort, P. Reprogramming epigenetic silencing with Artificial Transcription factors. April 15th, 2008. AACR, experimental and molecular cancer therapeutics minisymposium. San Diego, CA. Abstract selected for a 10-min presentation.

Blancafort, P. Targeting breast and lung cancer metastases with zinc finger engines. NIEHS, February 12, 2008. Host: Dr. John Roberts.

Blancafort, P. Reprogramming epigenetic silencing in tumor/stem cells with Artificial Transcription factors. April first, 2008. Department of Biochemistry, The University of North Carolina at Chapel Hill. Host: Dr. L. Parise.

Blancafort, P. Reprogramming epigenetic silencing with Artificial Transcription factors. June 29th, 2007. University of Pennsylvania and Penn Genomic Institute, Summer Mini-Symposium. Host: Dr. Jim Eberwine.

Blancafort, P. Exploring the Dark Side of the human genome with Artificial Transcription Factors (ATFs). June 19th, 2007. University of Montreal, Department of Biochemistry. Host: Dr. Sylvie Mader.

Blancafort, P. Reprogramming breast tumor cells with artificial transcription factors. June 16th, 2006. University of California, Davis Genome Center. Host: Dr. David Segal.

Blancafort, P. Genetic reprogramming of tumor cells by artificial transcription factors. May 24th, 2005. Yale University, dept. of pathology. Host: Dr. Paul Lizardi.

Blancafort, P, Magnenat, L. and Barbas, CF III. Endogenous gene regulation and gene discovery with polydactyl zinc finger transcription factors, Protein Engineering section, the 227th ACS National Meeting, Anaheim, CA March 28th 2004.

Blancafort, P. Zinc finger libraries for gene discovery. Invited speaker. Banting and Best Department of Medical Research. Department of Chemistry, University of Toronto, Toronto, Canada. Host: Dr. C. Boone. May 20, (2003).

Blancafort, P. Scanning the human genome with Zinc finger libraries. Invited speaker. Department of Chemistry, University of California, Irvine. Host: Dr. G. A. Weiss. May 5, (2003).

Blancafort, P. Zinc finger libraries and targeted regulation of endogenous genes. Understanding Phage Display. Morris j. Centre for Dialogue, Simon Fraser University, Vancouver, Canada, January 17, (2003).

Blancafort, P. Making conformation-specific RNA binding zinc fingers. 4th Annual Montreal Joint Center for Structural Biology Workshop. Biotechnology Research Institute, Montreal, Canada. May 22 (1998).

Blancafort, P., Selection in vitro de doigts de zinc liant l’ARN. Concours Simon Pierre Noel, Departement de Biochimie, Universite de montreal, Montreal, Canada (1998).

Blancafort, P., Modeles d'interaction proteine-ARN issus de la selection in vitro de banques aleatoires de proteines. Concours Simon-Pierre Noel, Departement de Biochimie, Universite de montreal, Montreal, Canada (1996).

Posters (most relevant to this work):