Epigenetics and Human Disease Laboratory

pedrocastelobranco

Location

Building 8, Laboratory 3.29

Department of Biomedical Sciences and Medicine.

University of Algarve

Phone: +351 289 800 100 (ext.7056)

pjbranco@ualg.pt

 

Team Members

Pedro Castelo-Branco, DPhil (Oxon) (Principal Investigator)

Phyllis Alexandra Binnie (MD PhD)

Ricardo Leão, MD (PhD student)

Joana Apolónio (PhD student)

Gabriela Carrasqueiro (Master student)

Inês Faleiro (Master student)

Sara Ramalhete (Master student)

Vânia Roberto (Post-Doc)

João Dias (MD, PhD student)

About Epi Group

Epigenetics is known as “science of change”. Epigenetic regulation is involved in the development of several diseases like cancer, autoimmune diseases and other chronic diseases.
The overall objectives of the Epigenetics and Human Disease are to analyze epigenetic signatures and explore their potential diagnostic and prognostic value in order to help designing therapeutic approaches in an era of personalized medicine.

Selected publications since 2010

Castelo-Branco, P., Passer, B.J., Buhrman J., Rabkin, S., and Martuza R.L. (2010). An Oncolytic virus armed with a Xenogeneic homolog of Prostatic Acid Phosphatase enhances anti-tumor efficacy in Prostate Cancer. Mar;11. Gene Ther.

Castelo-Branco, P., Zhang, C., Lipman, T., Fujitani, M., Hansford, L., Clarke, I., Harley, C., Tressler, R., Malkin , D., Walker, E., Kaplan, D., Dirks, P. and Tabori U. (2011). Neural Tumor Initiating Cells have distinct telomere maintenance and can be safely targeted for telomerase inhibition. Jan 1;17(1):111-21. Clinical Cancer Res.

Walker EJ, Zhang C, Castelo-Branco P., Hawkins C, Wilson W, Zhukova N, Alon N, Novokmet A, Baskin B, Ray P, Knobbe C, Dirks P, Taylor MD, Croul S, Malkin D, Tabori U. (2012). Monoallelic Expression Determines Oncogenic Progression and Outcome in Benign and Malignant Brain Tumors. 2012 Feb 1;72(3):636-44. Cancer Res.

Schwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E, Jacob K, Sturm D, Fontebasso AM, Quang DA, Tönjes M, Hovestadt V, Albrecht S, Kool M, Nantel A, Konermann C, Lindroth A, Jäger N, Rausch T, Ryzhova M, Korbel JO, Hielscher T, Hauser P, Garami M, Klekner A, Bognar L, Ebinger M, Schuhmann MU, Scheurlen W, Pekrun A, Frühwald MC, Roggendorf W, Kramm C, Dürken M, Atkinson J, Lepage P, Montpetit A, Zakrzewska M, Zakrzewski K, Liberski PP, Dong Z, Siegel P, Kulozik AE, Zapatka M, Guha A, Malkin D, Felsberg J, Reifenberger G, von Deimling A, Ichimura K, Collins VP, Witt H, Milde T, Witt O, Zhang C, Castelo-Branco P, Lichter P, Faury D, Tabori U, Plass C, Majewski J, Pfister SM, Jabado N. (2012). Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. 2012 Jan 29;482(7384):226-31. Nature.

Castelo-Branco, P. and Tabori, U.Promises and challenges of exhausting pediatric neural cancer stem cells. (2012). doi:10.1038/pr.2011.63. Pediatric Research.

Pedro Castelo-Branco, Sanaa Choufani, Stephen Mack, Denis Gallagher, Cindy Zhang, Tatiana Lipman, Nataliya Zhukova, Dianna Martin, Diana Merino, Jonathan Wasserman, Cynthia Samuel, Noa Alon, Johann Hitzler, Jean C.Y. Wang, David Malkin, Peter B. Dirks, Stefan Pfister, Michael D. Taylor, Rosanna Weksberg and Uri Tabori. Differentially methylated region of the hTERT promoter and risk stratification of childhood brain tumors: An integrative genomic and molecular study. (2013). May;14(6):534-42. doi: 10.1016/S1470-2045(13)70110-4. The Lancet Oncol.

Nataliya Zhukova, Vijay Ramaswamy, Marc Remke, Elke Pfaff, David J.H. Shih, Dianna C. Martin, Pedro Castelo-Branco, Berivan Baskin, Peter N. Ray, Eric Bouffet, Andre O. von Bueren, David T. W. Jones, Paul A. Northcott, Marcel Kool, Dominick Sturm, Trevor Pugh, Scott L. Pomeroy, Yoon-Jae Cho, Torsten Pietsch, Marco Gessi, Stefan Rutkowski, Laszlo Bognar, Almos Klekner, Byung-Kyu Cho, Seung-Ki Kim, Kyu-Chang Wang, Charles G. Eberhart, Michelle Fevre-Montange, Maryam Fouladi, Pim J. French, Max Kros, Wieslawa A. Grajkowska, Nalin Gupta, William A. Weiss, Peter Hauser, Nada Jabado, Anne Jouvet, Shin Jung, Toshihiro Kumabe, Boleslaw Lach, Jeffrey R. Leonard, Joshua B. Rubin, Linda M. Liau, Luca Massimi, Ian F. Pollack, Young Shin Ra, Erwin G. van Meir, Karel Zitterbart, Ulrich Schüller, Rebecca M. Hill, Janet C. Lindsey, Ed C. Schwalbe, Simon Bailey, David Ellison, Cynthia Hawkins, Andrey Korshunov, David Malkin, Steven C. Clifford, Stefan Pfister, Michael D. Taylor, and Uri Tabori. Subgroup Specific Prognostic Implications of TP53 Mutation in Medulloblastoma (2013). 2013 Aug 10;31(23):2927-35. doi: 10.1200/JCO. 2012.48.5052. Journal of Clinical Oncology.

Mack SC, Witt H, Piro RM, Gu L, Zuyderduyn S, Stütz AM, Wang X, Gallo M, Garzia L, Zayne K, Zhang X, Ramaswamy V, Jäger N, Jones DT, Sill M, Pugh TJ, Ryzhova M, Wani KM, Shih DJ, Head R, Remke M, Bailey SD, Zichner T, Faria CC, Barszczyk M, Stark S, Seker-Cin H, Hutter S, Johann P, Bender S, Hovestadt V, Tzaridis T, Dubuc AM, Northcott PA, Peacock J, Bertrand KC, Agnihotri S, Cavalli FM, Clarke I, Nethery-Brokx K, Creasy CL, Verma SK, Koster J, Wu X, Yao Y, Milde T, Sin-Chan P, Zuccaro J, Lau L, Pereira S, Castelo-Branco P, Hirst M, Marra MA, Roberts SS, Fults D, Massimi L, Cho YJ, Van Meter T, Grajkowska W, Lach B, Kulozik AE, von Deimling A, Witt O, Scherer SW, Fan X, Muraszko KM, Kool M, Pomeroy SL, Gupta N, Phillips J, Huang A, Tabori U, Hawkins C, Malkin D, Kongkham PN, Weiss WA, Jabado N, Rutka JT, Bouffet E, Korbel JO, Lupien M, Aldape KD, Bader GD, Eils R, Lichter P, Dirks PB, Pfister SM, Korshunov A, Taylor MD. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy (2014). Feb 27;506(7489):445-50. 10.1038/nature13108. Nature.

Pawel Buczkowicz, Christine Hoeman, Patricia Rakopoulos, Sanja Pajovic, Louis Letourneau, Misko Dzamba, Andrew Morrison, Peter Lewis, Eric Bouffet, Ute Bartels, Jennifer Zuccaro, Sameer Agnihotri, Scott Ryall, Mark Barszczyk, Yevgen Chornenkyy, Mathieu Bourgey, Guillaume Bourque, Alexandre Montpetit, Francisco Cordero, Pedro Castelo-Branco, Joshua Mangerel, Uri Tabori, Polly K.C. Ho, Annie Huang, Kathryn R. Taylor, Alan Mackay, Anne E Bendel, Javad Nazarian, Jason R Fangusaro, Matthias Karajannis, David Zagzag, Nicholas K. Foreman, Andrew Donson, Julia V. Hegert, Amy Smith, Jennifer Chan, Lucy Lafay-Cousin, Sandra Dunn, Juliette Hukin, Chris Dunham, Katrin Scheinemann, Jean Michaud, Shayna Zelcer, David Ramsay, Jason Cain, Cameron Brennan, Mark M. Souweidane, Chris Jones, C. David Allis, Michael Brudno, Oren Becher and  Cynthia Hawkins. Comprehensive genomic analysis of diffuse intrinsic pontine gliomas unravels three molecular subgroups and a novel cancer driver (2014). May;46(5):451-6. Nature Genetics.

Barszczyk M, Buczkowicz P, Castelo-Branco P, Mack SC, Ramaswamy V, Mangerel J, Agnihotri S, Remke M, Golbourn B, Pajovic S, Elizabeth C, Yu M, Luu B, Morrison A, Adamski J, Nethery-Brokx K, Li XN, Van Meter T, Dirks PB, Rutka JT, Taylor MD, Tabori U, Hawkins C. Telomerase inhibition abolishes the tumorigenicity of pediatric ependymoma tumor-initiating cells (2014).  Aug 6. Acta Neuropathol.

Mangerel J, Price A, Castelo-Branco P, Brzezinski J, Buczkowicz P, Rakopoulos P, Merino D, Baskin B, Wasserman J, Mistry M, Barszczyk M, Picard D, Mack S, Remke M, Starkman H, Elizabeth C, Zhang C, Alon N, Lees J, Andrulis IL, Wunder JS, Jabado N, Johnston DL, Rutka JT, Dirks PB, Bouffet E, Taylor MD, Huang A, Malkin D, Hawkins C, Tabori U.Alternative lengthening of telomeres is enriched in, and impacts survival of TP53 mutant pediatric malignant brain tumors (2014). Oct 15. Acta Neuropathol.

Zhukova N, Ramaswamy V, Remke M, Martin DC, Castelo-Branco P, Zhang CH, Fraser M, Tse K, Poon R,  Shih DJH, Baskin B, Ray PN, Bouffet E, Dirks P, von Bueren AO, Pfaff E, Korshunov A, Jones DTW, Northcott PA, Kool M, Pugh T, Pomeroy SL, Cho YJ, Pietsch T, Gessi M, Rutkowski S, Bognr L, Cho BK, Eberhart CG, Fävre-Montange M, Fouladi M, French PJ, Grajkowska WA, Gupta N, Hauser P, Jabado N, Jouvet A, Jung S, Kim SK, Klekner A, Kumabe T, Lach B, Leonard JR36, Liau LM38, Massimi L, Pollack IF, Ra YS, Rubin JB, Van Meir EG, Wang KC, Weiss WA, Zitterbart K, Bristow R, Alman B, Hawkins CE, Malkin D, Clifford SC, Pfister SM ,Taylor MD  and Tabori U. WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma (2014). Dec 24;2:174. Acta Neuropathol Communications.

Matthew Mistry, Nataliya Zhukova, Daniele Merico,Patricia Rakopoulos, Rahul Krishnatry, Mary Shago, Jim Stavropoulos, Noa Alon, Jason Pole, Peter N. Ray,Vilma Navickiene, Joshua Mangerel, Marc Remke, Pawel Buczkowicz, Vijay Ramaswamy, Martin Li, Ted Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzzane Laughlin, Adam Shlien, Jennifer Chan, Keith L.Ligon, James T. Rutka, Peter B. Dirks, Michael D.Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins and Uri Tabori. BRAF mutation and CDKN2A deletion define a clinically distinct subgroup of childhood secondary high grade glioma (2015). Mar 20;33(9):1015-22. doi: 10.1200/JCO.2014.58.3922. Journal of Clinical Oncology.

Ernst A, Jones DT, Maass KK, Rode A, Deeg KI, Michael Chelliah Jebaraj B, Korshunov A, Hovestadt V, Tainsky MA, Pajtler KW, Bender S, Brabetz S, Gröbner S, Kool M, Devens F, Edelmann J, Zhang C, Castelo-Branco P, Tabori U, Malkin D, Rippe K, Stilgenbauer S, Pfister SM, Zapatka M, Lichter P. Telomere dysfunction and chromothripsis (2016). Feb 9. doi: 10.1002/ijc.30033. International Journal of Cancer.

Pedro Castelo-Branco, Ricardo Leão, Tatiana Lipman, Brittany Campbell, Donghyun Lee, Aryeh Price, Cindy Zhang, Abolfazl Heidari, Derek Stephens, Stefan Boerno, Hugo Coelho, Ana Gomes, Celia Domingos, Joana D Apolonio, Georg Schäfer, Robert G Bristow, Michal R Schweiger, Robert Hamilton, Alexandre Zlotta, Arnaldo Figueiredo, Helmut Klocker, Holger Sültmann and Uri Tabori. A cancer specific hypermethylation signature of the TERT promoter predicts biochemical relapse in prostate cancer (2016). Jul 16. doi: 10.18632. Oncotarget.

Ricardo Leão, Célia Domingos, Arnaldo Figueiredo, Robert Hamilton, Uri Tabori and Pedro Castelo Branco. Cancer Stem Cells in Prostate Cancer: Implications for Targeted Therapy (2016). In press. Urologia Internationalis.

Inês Faleiro, Ricardo Leão, Alexandra Binnie, Ramon Andrade de Mello, Ana-Teresa Maia and Pedro Castelo-Branco (2016). Epigenetic therapy in urologic cancers: an update on clinical trials. In press. Oncotarget.

Full link of publications:

https://www.ncbi.nlm.nih.gov/pubmed/?term=Castelo+Branco+P

Team Members

castelobranco_team

Highlights

Picture1

Grants

2016-2017 – Bolsa de Investigação Liga Portuguesa Contra o Cancro/FUNDAÇÃO PT, Portugal. “Uncovering novel therapeutic targets that regulate the self-renewal capacity of colorectal cancer”. – Supervisor.

2015-2016 – Bolsa de Investigação APU/Tecnimede, Portugal. “miRNAs marcadores séricos de doença testicular ativa.” – Co-applicant.

2015-2016 – Maratonas da Saude, Portugal. “Diagnostic, prognostic and therapeutic implications of THOR – Tert Hypermethylated Oncologic Region in breast cancer.” – PI.

2015-2020 – McLaughlin Centre Accelerator Grants in Genomic Medicine and Health Informatics. Epigenetic Profiling in Severe Sepsis (EPSIS).”– Co-applicant.

2015-2020 – Canadian Cancer Society – Impact Grant, Canada. “Targeting the telomere maintenance pathway for cancer diagnostics and therapeutics.” – Co-applicant.

2015-2020 – Canadian Institutes of Health Research, Canada. “Novel implications of THOR hypermethylation in telomere maintenance and gliomagenesis.” – Co-applicant.

2015-2017 – Canadian Cancer Society Research Institute. “Utilization of THOR hypermethylation for stratification and noninvasive detection of cancer.” – Co-applicant.

2010-2015 – Canadian Institutes of Health Research, Canada. “Prediction and Prevention of glioma recurrence by targeting telomere dependent self-renewal capacity of tumor initiating cells.”  – Team member.

2012-2014 – ASTELLAS grant, Portugal. “O papel da leptina no microambiente e oncogenese do carcinoma da prostata.”– Co-applicant.

Collaborators

Dr Uri Tabori, The Hospital for Sick Children (Toronto, Canada)

Dr Samuel Rabkin, Harvard Medical School (Boston, USA)

Claudia dos Santos (MS, MSc, BSc, St.Michael´s Hospital, researcher at Li Ka Shing Knowledge Institute)

PCB

Lab Members

PCB_group_nova

Member mails

Members mails:

Prof. Pedro Castelo-Branco: mailto:castelobranco.pedro@gmail.com

Joana Apolónio: mailto:joanadias_a@hotmail.com

Vânia Roberto: mailto:roberto.vania@gmail.com

Inês Faleiro: mailto:inesfaleiro.9@gmail.com

Gabriela Carrasqueiro: mailto:gabrielacarrasqueiro@gmail.com

Ricardo Leão: mailto:romaoleao@gmail.com

Leave a Reply

Your email address will not be published. Required fields are marked *