prof. dr. A. (Alain) de Bruin
A.deBruin@uu.nl
Gegenereerd op 2017-11-20 07:08:54


Leeropdracht
Hoogleraar Pathobiologie
Benoemingsdatum 01-12-2005
Oratiedatum 30-05-2008
Profiel

Alain de Bruin obtained  his DVM degree in 1994 at University of Hannover, Germany. He performed his PhD research in the field of cancer biology and graduated in 1999 at the University of Berne, Switzerland. From 1999-2002, he was a veterinary anatomic pathology resident at the Ohio State University, USA and received the board-certification by the American College of Veterinary Pathologists. His postdoctoral work was done with Gustavo Leone at the Human Cancer Genetic Institute of the Ohio State University, USA. He received a postdoctoral cancer research award by the US Department of Defense in 2003. In 2005 he was appointed as full Professor in Pathobiology at Utrecht University, Netherlands.

He has developed a powerful combination of techniques and in vivo models to understand the pathobiology of  ageing and cancer. His research is focused on the Rb/E2F pathway, which is altered in almost all types of cancers. He discovered new members of the family E2F transcription factors and studies their impact on controlling the cell cycle, development, regeneration, ageing and cancer. He was awarded with several grants from the Dutch Cancer Foundation (KWF),  Netherlands Organization for Scientific Research (NWO) and the Worldwide Cancer Research Foundation  (AICR). In 2010, he established the Dutch Molecular Pathology Center, an expertise center for the pathological analysis of transgenic animals. In 2013 he was named as program coordinator of the research program “Regenerative Medicine, Stem cells, and Cancer” of the Faculty of Veterinary Medicine at Utrecht University. In 2014, he was awared with the Honorary Professorship for the pathological and molecular analysis of experimental animals at the University Medical Center Gronigen, Netherlands. In 2015, he estabilsed the Single Cell Analysis Center for the genomic and transcriptomic analysis of single cells at Utrecht University. In 2017 he was appointed as chairman of the Research Council of the Faculty of Veterinary Medicine.

 

Strategische thema's / focusgebieden
Betrokken bij de opleiding(en)
Wetenschappelijke expertises
Cancer, Aging, Pathology, Tumor suppressor gene, Rb/E2F, Liver, Polyploidization, In vivo models
Vaardigheden
Pathological analysis of animal models of human diseases
Analysis of the cell cycle
Single cell transcriptomics
Generation of transgenic mouse models

Gegenereerd op 2017-11-20 07:08:54
Curriculum vitae

Education

1999-2002         Residency in Veterinary Pathology, OSU, USA

1999                   PhD, University of Berne, Switzerland

1997                   MSc, University of Berne, Switzerland

1994                   DVM, University of Hannover, Germany

 

Current positions

2017-present     Chairman Research Council Faculty Vet. Med.

2014-present     Honorary Professor, UMCG

2013-present     Coordinator, Research program 'One Medicine' 

2010-present     Director, Dutch Molecular Pathology Center

2005-present    Full Professor in Pathobiology, UU

 

                                                  

Previous positions

2002-2005        Postdoctoral Fellow, OSU, USA

1999-2002        Resident in Anat. Vet. Pathology, OSU, USA 

1994-1999        Graduate Research Associate, Univ. Bern, CH

 

Fellowships and Awards:

2014-2019         Honorary Professorship, UMCG

2003-2005        Postdoctoral Award, U.S. Depart of Defense  

2002                  Human Cancer Genetic Fellowship 

2002                  Diplomate Americ. College of Vet. Pathology 

 

Gegenereerd op 2017-11-20 07:08:54
Sleutelpublicaties

Thurlings, I, Martínez-López, L M, Westendorp, B, Zijp, M, Kuiper, R, Tooten, P, Kent, L N, Leone, G, Vos, H J, Burgering, B & de Bruin, A (2017). Synergistic functions of E2F7 and E2F8 are critical to suppress stress-induced skin cancer. Oncogene, 36, (pp. 829-839).

Kent, Lindsey N., Rakijas, Jessica B., Pandit, Shusil K., Westendorp, Bart, Chen, Hui Zi, Huntington, Justin T., Tang, Xing, Bae, Sooin, Srivastava, Arunima, Senapati, Shantibhusan, Koivisto, Christopher, Martin, Chelsea K., Cuitino, Maria C., Perez, Miguel, Clouse, Julian M., Chokshi, Veda, Shinde, Neelam, Kladney, Raleigh, Sun, Daokun, Perez-Castro, Antonio, Matondo, Ramadhan B., Nantasanti, Sathidpak, Mokry, Michal, Huang, Kun, Machiraju, Raghu, Fernandez, Soledad, Rosol, Thomas J., Coppola, Vincenzo, Pohar, Kamal S., Pipas, James M., Schmidt, Carl R., De Bruin, Alain & Leone, Gustavo (01-08-2016). E2f8 mediates tumor suppression in postnatal liver development. Journal of Clinical Investigation, 126 (8), (pp. 2955-2969) (15 p.).

Weijts, B.G.M.W., Bakker, W.J., Cornelissen, P.W.A., Liang, K.A., Schaftenaar, F.A., Westendorp, B., Wolf, C.A., Paciejewska, M., Scheele, C.L., Kent, L., Leone, G., Schulte-Merker, S. & de Bruin, A. (2012). E2F7 and E2F8 promote angiogenesis through transcriptional activation of VEGFA in cooperation with HIF1. EMBO Journal, 19, (pp. 3871-3884) (14 p.).

Pandit, Shusil K, Westendorp, Bart, Nantasanti, Sathidpak, van Liere, Elsbeth, Tooten, Peter C J, Cornelissen, Peter W A, Toussaint, Mathilda J M, Lamers, Wouter H & de Bruin, Alain (2012). E2F8 is essential for polyploidization in mammalian cells. Nature Cell Biology, 14 (11), (pp. 1181-1191) (11 p.).

Li, J., Ran, C., Li, E., Gordon, F., Comstock, G., Siddiqui, H., Cleghorn, W., Chen, H., Kornacker, K., Pandit, S.K., Khanizadeh, M., Weinstein, M., Leone, G. & de Bruin, A. (2008). Synergistic function of E2F7 and E2F8 is essential for cell survival and embryonic development. Developmental Cell, 14, (pp. 62-75) (15 p.).

Alle publicaties
  Artikelen - 2017
De Cian, M-C, Pauper, E, Bandiera, R, Vidal, V P I, Sacco, S, Gregoire, E P, Chassot, A-A, Panzolini, C, Wilhelm, D, Pailhoux, E, Youssef, S A, de Bruin, A, de Teerds, K, Schedl, A, Gillot, I & Chaboissier, M-C (2017). Amplification of R-spondin1 signaling induces granulosa cell fate defects and cancers in mouse adult ovary. Oncogene, 36, (pp. 208–218).
Kent, Lindsey N., Bae, Sooin, Tsai, Shih Yin, Tang, Xing, Srivastava, Arunima, Koivisto, Christopher, Martin, Chelsea K., Ridolfi, Elisa, Miller, Grace C., Zorko, Sarah M., Plevris, Emilia, Hadjiyannis, Yannis, Perez, Miguel, Nolan, Eric, Kladney, Raleigh, Westendorp, Bart, De Bruin, Alain, Fernandez, Soledad, Rosol, Thomas J., Pohar, Kamal S., Pipas, James M. & Leone, Gustavo (01-03-2017). Dosage-dependent copy number gains in E2f1 and E2f3 drive hepatocellular carcinoma. Journal of Clinical Investigation, 127 (3), (pp. 830-842) (13 p.).
Pedone, Elisa, Olteanu, Vlad-Aris, Marucci, Lucia, Muñoz-Martin, Maria Isabel, Youssef, Sameh A, de Bruin, Alain & Cosma, Maria Pia (03-01-2017). Modeling Dynamics and Function of Bone Marrow Cells in Mouse Liver Regeneration. Cell Reports, 18 (1), (pp. 107-121) (15 p.). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved..
Thurlings, I, Martínez-López, L M, Westendorp, B, Zijp, M, Kuiper, R, Tooten, P, Kent, L N, Leone, G, Vos, H J, Burgering, B & de Bruin, A (2017). Synergistic functions of E2F7 and E2F8 are critical to suppress stress-induced skin cancer. Oncogene, 36, (pp. 829-839).
  Artikelen - 2016
Catrysse, L, Farhang Ghahremani, M, Vereecke, L, Youssef, S A, Mc Guire, C, Sze, M, Weber, A, Heikenwalder, M, de Bruin, A, Beyaert, R & van Loo, G (2016). A20 prevents chronic liver inflammation and cancer by protecting hepatocytes from death. Cell Death and Disease, 7 (6).
Demaria, Marco, O'Leary, Monique N, Chang, Jianhui, Shao, Lijian, Liu, Su, Alimirah, Fatouma, Koenig, Kristin, Le, Catherine, Mitin, Natalia, Deal, Allison M, Alston, Shani, Academia, Emmeline C, Kilmarx, Sumner, Valdovinos, Alexis, Wang, Boshi, de Bruin, Alain, Kennedy, Brian K, Melov, Simon, Zhou, Daohong, Sharpless, Norman E, Muss, Hyman & Campisi, Judith (15-12-2016). Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse. Cancer Discovery Copyright ©2016, American Association for Cancer Research..
Nantasanti, Sathidpak, de Bruin, Alain, Rothuizen, Jan, Penning, Louis C & Schotanus, Baukje A (2016). Concise Review - Organoids Are a Powerful Tool for the Study of Liver Disease and Personalized Treatment Design in Humans and Animals. Stem cells translational medicine, 5 (3), (pp. 325–330). ©AlphaMed Press..
Thurlings, Ingrid & de Bruin, Alain (2016). E2F Transcription Factors Control the Roller Coaster Ride of Cell Cycle Gene Expression. Methods in Molecular Biology, 1342, (pp. 71-88) (18 p.).
Kent, Lindsey N., Rakijas, Jessica B., Pandit, Shusil K., Westendorp, Bart, Chen, Hui Zi, Huntington, Justin T., Tang, Xing, Bae, Sooin, Srivastava, Arunima, Senapati, Shantibhusan, Koivisto, Christopher, Martin, Chelsea K., Cuitino, Maria C., Perez, Miguel, Clouse, Julian M., Chokshi, Veda, Shinde, Neelam, Kladney, Raleigh, Sun, Daokun, Perez-Castro, Antonio, Matondo, Ramadhan B., Nantasanti, Sathidpak, Mokry, Michal, Huang, Kun, Machiraju, Raghu, Fernandez, Soledad, Rosol, Thomas J., Coppola, Vincenzo, Pohar, Kamal S., Pipas, James M., Schmidt, Carl R., De Bruin, Alain & Leone, Gustavo (01-08-2016). E2f8 mediates tumor suppression in postnatal liver development. Journal of Clinical Investigation, 126 (8), (pp. 2955-2969) (15 p.).
Liu, Weilin, Struik, Dicky, Nies, Vera J M, Jurdzinski, Angelika, Harkema, Liesbeth, de Bruin, Alain, Verkade, Henkjan J, Downes, Michael, Evans, Ronald M, van Zutphen, Tim & Jonker, Johan W (23-02-2016). Effective treatment of steatosis and steatohepatitis by fibroblast growth factor 1 in mouse models of nonalcoholic fatty liver disease. Proceedings of the National Academy of Sciences of the United States of America, 113 (8), (pp. 2288-93) (6 p.).
Boekhout, Michiel, Yuan, Ruixue, Wondergem, Annelotte P, Segeren, Hendrika A, Van Liere, Elsbeth A, Awol, Nesibu, Jansen, Imke, Wolthuis, Rob Mf, De Bruin, Alain & Westendorp, Bart (2016). Feedback regulation between atypical E2Fs and APC/C Cdh1 coordinates cell cycle progression. EMBO Reports, 17 (3), (pp. 414-427) (14 p.).
Sudria-Lopez, Emma, Koppers, Max, de Wit, Marina, van der Meer, Christiaan, Westeneng, Henk-Jan, Zundel, Caroline A C, Youssef, Sameh A, Harkema, Liesbeth, de Bruin, Alain, Veldink, Jan H, van den Berg, Leonard H & Pasterkamp, R Jeroen (2016). Full ablation of C9orf72 in mice causes immune system-related pathology and neoplastic events but no motor neuron defects. Acta Neuropathologica, 132 (1), (pp. 145-7) (3 p.).
Mohs, Antje, Kuttkat, Nadine, Reißing, Johanna, Wolfgang Zimmermann, Henning, Sonntag, Roland, Proudfoot, Amanda, Youssef, Sameh A, de Bruin, Alain, Javier Cubero, Francisco & Trautwein, Christian (20-12-2016). Functional role of CCL5/RANTES for HCC progression during chronic liver disease. Journal of Hepatology Copyright © 2016. Published by Elsevier B.V..
Terré, Berta, Piergiovanni, Gabriele, Segura-Bayona, Sandra, Gil-Gómez, Gabriel, Youssef, Sameh A, Attolini, Camille Stephan-Otto, Wilsch-Bräuninger, Michaela, Jung, Carole, Rojas, Ana M, Marjanović, Marko, Knobel, Philip A, Palenzuela, Lluís, López-Rovira, Teresa, Forrow, Stephen, Huttner, Wieland B, Valverde, Miguel A, de Bruin, Alain, Costanzo, Vincenzo & Stracker, Travis H (2016). GEMC1 is a critical regulator of multiciliated cell differentiation. EMBO Journal, 35 (9), (pp. 942-960). © 2016 The Authors..
Harkema, L, Youssef, S A & de Bruin, A (01-03-2016). Pathology of Mouse Models of Accelerated Aging. Veterinary Pathology, 53 (2), (pp. 366-389). © The Author(s) 2016..
Nantasanti, Sathidpak, Toussaint, Mathilda J M, Youssef , Sameh A, Tooten, Peter C J & de Bruin, Alain (2016). Rb and p53 Liver Functions Are Essential for Xenobiotic Metabolism and Tumor Suppression. PLoS One, 11 (3).
Matondo, Ramadhan B, Toussaint, Mathilda Jm, Govaert, Klaas M, van Vuuren, Luciel D, Nantasanti, Sathidpak, Nijkamp, Maarten W, Pandit, Shusil K, Tooten, Peter Cj, Koster, Mirjam H, Holleman, Kaylee, Schot, Arend, Gu, Guoqiang, Spee, Bart, Roskams, Tania, Rinkes, Inne Borel, Schotanus, Baukje, Kranenburg, Onno & de Bruin, Alain (13-06-2016). Surgical resection and radiofrequency ablation initiate cancer in cytokeratin-19+- liver cells deficient for p53 and Rb. Oncotarget, 7 (34), (pp. 54662-54675).
  Artikelen - 2015
Donega, Vanessa, Nijboer, Cora H, van Velthoven, Cindy T J, Youssef, Sameh A, de Bruin, Alain, van Bel, Frank, Kavelaars, Annemieke & Heijnen, Cobi J (13-08-2015). Assessment of long-term safety and efficacy of intranasal mesenchymal stem cell treatment for neonatal brain injury in the mouse. Pediatric Research
White, Ryan R, Milholland, Brandon, de Bruin, Alain, Curran, Samuel, Laberge, Remi-Martin, van Steeg, Harry, Campisi, Judith, Maslov, Alexander Y & Vijg, Jan (2015). Controlled induction of DNA double-strand breaks in the mouse liver induces features of tissue ageing. Nature Communications, 6.
Nantasanti, Sathidpak, Spee, Bart, Kruitwagen, Hedwig S, Chen, Chen, Geijsen, Niels, Oosterhoff, Loes A, van Wolferen, Monique E, Pelaez, Nicolas, Fieten, Hille, Wubbolts, Richard W, Grinwis, Guy C, Chan, Jefferson, Huch, Meritxell, Vries, Robert R G, Clevers, Hans, de Bruin, Alain, Rothuizen, Jan, Penning, Louis C & Schotanus, Baukje A (2015). Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids. Stem Cell Reports, 5 (5), (pp. 895-907) (13 p.).
de Bruin, Alain, Cornelissen, Peter W A, Kirchmaier, Bettina C, Mokry, Michal, Iich, Elhadi, Nirmala, Ella, Liang, Kuo-Hsuan, Végh, Anna M D, Scholman, Koen T, Groot Koerkamp, Marian J, Holstege, Frank C, Cuppen, Edwin, Schulte-Merker, Stefan & Bakker, Walbert J (17-12-2015). Genome-wide analysis reveals NRP1 as a direct HIF1α-E2F7 target in the regulation of motorneuron guidance in vivo. Nucleic Acids Research © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research..
van der Heijden, Roel A, Sheedfar, Fareeba, Morrison, Martine C, Hommelberg, Pascal H, Kor, Danny, Kloosterhuis, Niels J, Gruben, Nanda, Youssef, Sameh A, de Bruin, Alain, Hofker, Marten H, Kleemann, Robert, Koonen, Debby Y & Heeringa, Peter (2015). High-fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL/6j mice. Aging, 7 (4), (pp. 256-68) (13 p.).
Hermsen, Roel, Toonen, Pim, Kuijk, Ewart, Youssef, Sameh A, Kuiper, Raoul, van Heesch, Sebastiaan, de Bruin, Alain, Cuppen, Edwin & Simonis, Marieke (2015). Lack of Major Genome Instability in Tumors of p53 Null Rats. PLoS One, 10 (3).
Deng, Lei, Ibañez, Lorena Itatí, Van den Bossche, Veronique, Roose, Kenny, Youssef, Sameh A, de Bruin, Alain, Fiers, Walter & Saelens, Xavier (14-05-2015). Protection against Influenza A Virus Challenge with M2e-Displaying Filamentous Escherichia coli Phages. PLoS One, 10 (5), (pp. 1-21).
Wu, L, de Bruin, A, Wang, H, Simmons, T, Cleghorn, W, Goldenberg, L E, Sites, E, Sandy, A, Trimboli, A, Fernandez, S A, Eng, C, Shapiro, C & Leone, G (02-01-2015). Selective roles of E2Fs for ErbB2- and Myc-mediated mammary tumorigenesis. Oncogene, 34 (1), (pp. 119-28) (10 p.).
  Artikelen - 2014
Bartuzi, Paulina, Wijshake, Tobias, Dekker, Daphne C, Fedoseienko, Alina, Kloosterhuis, Niels J, Youssef, Sameh A, Li, Haiying, Shiri-Sverdlov, Ronit, Kuivenhoven, Jan-Albert, de Bruin, Alain, Burstein, Ezra, Hofker, Marten H & van de Sluis, Bart (2014). A cell-type-specific role for murine Commd1 in liver inflammation. Biochimica et Biophysica Acta, 1842 (11), (pp. 2257-65) (9 p.). Copyright © 2014 Elsevier B.V. All rights reserved..
Demaria, Marco, Ohtani, Naoko, Youssef Hassan, Sameh, Rodier, Francis, Toussaint, Wendy, Mitchell, James R, Laberge, Remi-Martin, Vijg, Jan, Van Steeg, Harry, Dollé, Martijn E T, Hoeijmakers, Jan H J, de Bruin, Alain, Hara, Eiji & Campisi, Judith (22-12-2014). An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA. Developmental Cell, 31 (6), (pp. 722-33) (12 p.). Copyright © 2014 Elsevier Inc. All rights reserved..
Gruben, Nanda, Vergara, Marcela Aparicio, Kloosterhuis, Niels J., Van Der Molen, Henk, Stoelwinder, Stefan, Youssef, Sameh, De Bruin, Alain, Delsing, Dianne J., Kuivenhoven, Jan Albert, Van De Sluis, Bart, Hofker, Marten H. & Koonen, Debby P Y (29-04-2014). Chemokine-like receptor 1 deficiency does not affect the development of insulin resistance and nonalcoholic fatty liver disease in mice. PLoS One, 9 (4).
Sheedfar, Fareeba, Sung, Miranda My, Aparicio-Vergara, Marcela, Kloosterhuis, Niels J, Miquilena-Colina, Maria Eugenia, Vargas-Castrillón, Javier, Febbraio, Maria, Jacobs, René L, de Bruin, Alain, Vinciguerra, Manlio, García-Monzón, Carmelo, Hofker, Marten H, Dyck, Jason Rb & Koonen, Debby P Y (2014). Increased hepatic CD36 expression with age is associated with enhanced susceptibility to nonalcoholic fatty liver disease. Aging, 6 (4), (pp. 281-95) (15 p.).
Pruis, M G M, Lendvai, A, Bloks, V W, Zwier, M V, Baller, J F W, de Bruin, A, Groen, A K & Plösch, T (2014). Maternal western diet primes non-alcoholic fatty liver disease in adult mouse offspring. Acta Physiologica, 210 (1), (pp. 215-27) (13 p.).
Van Leeuwen, Lisanne M., Van Der Kuip, Martijn, Youssef, Sameh A., De Bruin, Alain, Bitter, Wilbert, Marceline Van Furth, A. & Van Der Sar, Astrid M. (01-01-2014). Modeling tuberculous meningitis in zebrafish using Mycobacterium marinum. DMM Disease Models and Mechanisms, 7 (9), (pp. 1111-1122) (12 p.).
Jongbloed, Franny, De Bruin, Ron W F, Pennings, Jeroen L A, Payán-Gómez, César, Van Den Engel, Sandra, Van Oostrom, Conny T., De Bruin, Alain, Hoeijmakers, Jan H J, Van Steeg, Harry, IJzermans, Jan N M & Dollé, Martijn E T (24-06-2014). Preoperative fasting protects against renal ischemia-reperfusion injury in aged and overweight mice. PLoS One, 9 (6).
Bach, Frances C, Rutten, Kirsten, Hendriks, Kristyanne, Riemers, Frank M, Cornelissen, Peter, de Bruin, Alain, Arkesteijn, Ger J, Wubbolts, Richard, Horton, William A, Penning, Louis C & Tryfonidou, Marianna A (2014). The paracrine feedback loop between vitamin D₃ (1,25(OH)₂D₃) and PTHrP in prehypertrophic chondrocytes. Journal of Cellular Physiology, 229 (12), (pp. 1999-2014) (16 p.).
Reiling, Erwin, Dollé, Martijn E T, Youssef, Sameh A, Lee, Moonsook, Nagarajah, Bhawani, Roodbergen, Marianne, de With, Piet, de Bruin, Alain, Hoeijmakers, Jan H, Vijg, Jan, van Steeg, Harry & Hasty, Paul (2014). The progeroid phenotype of Ku80 deficiency is dominant over DNA-PKCS deficiency. PLoS One, 9 (4).
  Artikelen - 2013
Tulinski, P., Fluit, A.C., van Putten, J.P.M., de Bruin, A., Glorieux, S., Wagenaar, J.A. & Duim, B. (2013). An Ex Vivo Porcine Nasal Mucosa Explants Model to Study MRSA Colonization. PLoS One, 8 (1), (pp. e53783) (1 p.).
Weijts, B.G.M.W., van Impel, A. & de Bruin, A. (2013). Atypical E2fs control lymphangiogenesis through transcriptional regulation of Ccbe1 and Flt4. PLoS One, 8 (9), (pp. e73693) (1 p.).
Magliozzi, R., Low, T.Y., Weijts, B.G.M.W., Cheng, T., Spanjaard, E., Mohammed, S., van Veen, A., Ovaa, H., de Rooij, J., Zwartkruis, G.J.T., Bos, J.L., de Bruin, A. & Heck, A.J.R. (2013). Control of Epithelial Cell Migration and Invasion by the IKKβ- and CK1α-Mediated Degradation of RAPGEF2. Developmental Cell, 27, (pp. 574-585) (12 p.).
Bakker, W.J., Weijts, B.G.M.W., Westendorp, B. & de Bruin, A. (2013). HIF proteins connect the RB-E2F factors to angiogenesis. Transcription, 4, (pp. 62-66) (5 p.).
Choorapoikayil, S., Weijts, B.G.M.W., Kers, R. & de Bruin, A. (2013). Loss of Pten promotes angiogenesis and enhanced vegfaa expression in zebrafish. DMM Disease Models and Mechanisms, 6 (5), (pp. 1159-1166) (8 p.).
Slim, C.L., Lazaro-Dieguez, F., Bijlard, M., Toussaint, M.J.M., de Bruin, A., Du, Q., Musch, A. & IJzendoorn, S.C. (2013). Par1b induces asymmetric inheritance of plasma membrane domains via LGN-dependent mitotic spindle orientation in proliferating hepatocytes. PLoS Biology, (pp. e1001739) (1 p.).
Pandit, S.K., Westendorp, B. & de Bruin, A. (2013). Physiological significance of polyploidization in mammalian cells. Trends in Cell Biology, 23 (11), (pp. 556-566) (11 p.).
Mans, D.A., Vermaat, J.S.P., Weijts, B.G.M.W., van Rooijen, E., van Reeuwijk, J., Boldt, K., Daenen, L.G.M., van der Groep, P., Rowland, B., Jans, J.J.M., Roepman, R., Voest, E.E., van Diest, P.J., Verhaar, M.C., de Bruin, A. & Giles, R.H. (2013). Regulation of E2F1 by the von Hippel-Lindau tumour suppressor protein predicts survival in renal cell cancer patients. Journal of Pathology, 231 (1), (pp. 117-129) (13 p.).
de Bruin, A. (2013). Subsidie studie foute celdeling. Het Financiële Dagblad; AD/Utrechts Nieuwsblad; AD/Amersfoortse Courant;
Aparacio-Vergara, M., Hommelberg, P.P.H., Schreurs, Marijke, Gruben, N., Stienstra, R., Shiri-Sverdlov, R., Kloosterhuis, N.J., de Bruin, A., van de Sluis, B., Koonen, D.P.Y. & Hofker, M.H. (2013). Tumor Necrosis Factor Receptor 1 Gain-of-Function Mutation Aggravates Nonalcoholic Fatty Liver Disease but Does Not Cause Insulin Resistance in a Murine Model. Hepatology, 57 (2), (pp. 566-576) (11 p.).
  Artikelen - 2012
Ouseph, M.M., Li, J., Chen, H., Pecot, T., Wenzel, P., Thompson, J., Comstock, G., Chokshi, V., Byrne, M., Forde, B., Chong, J., Huang, K., Machiraju, R., de Bruin, A. & Leone, G. (2012). Atypical E2F Repressors and Activators Coordinate Placental Development. Developmental Cell, 22 (4), (pp. 849-862) (13 p.).
Weijts, B.G.M.W., Bakker, W.J., Cornelissen, P.W.A., Liang, K.A., Schaftenaar, F.A., Westendorp, B., Wolf, C.A., Paciejewska, M., Scheele, C.L., Kent, L., Leone, G., Schulte-Merker, S. & de Bruin, A. (2012). E2F7 and E2F8 promote angiogenesis through transcriptional activation of VEGFA in cooperation with HIF1. EMBO Journal, 19, (pp. 3871-3884) (14 p.).
Westendorp, B., Mokry, M., Groot Koerkamp, M.J., Holstege, F.C.P., Cuppen, E.P.J.G. & de Bruin, A. (2012). E2F7 represses a network of oscillating cell cycle genes to control S-phase progression. Nucleic Acids Research, 40 (8), (pp. 3511-3523) (13 p.).
Pandit, Shusil K, Westendorp, Bart, Nantasanti, Sathidpak, van Liere, Elsbeth, Tooten, Peter C J, Cornelissen, Peter W A, Toussaint, Mathilda J M, Lamers, Wouter H & de Bruin, Alain (2012). E2F8 is essential for polyploidization in mammalian cells. Nature Cell Biology, 14 (11), (pp. 1181-1191) (11 p.).
Pandit, S.K., Westendorp, B., Nantasanti, S., van Liere, E., Tooten, P.C.J., Cornelissen, P.W.A., Toussaint, M.J.M., Lamers, W.H. & de Bruin, A. (14-10-2012). E2F8 is essential for polyploidization in mammalian cells. Nature Cell Biology
Choorapoikayil, S., Kuiper, R.V. & de Bruin, A. (2012). Haploinsufficiency of the genes encoding the tumor suppressor Pten predisposes zebrafish to hemangiosarcoma. DMM Disease Models and Mechanisms, 5 (2), (pp. 241-247) (7 p.).
Seyednejad, S.H., Gawlitta, D., Kuiper, R.V., de Bruin, A., van Nostrum, C.F., Vermonden, T., Dhert, W.J.A. & Hennink, W.E. (2012). In vivo biocompatibility and biodegradation of 3D-printed porous scaffolds based on a hydroxyl-functionalized poly(epsilon-caprolactone). Biomaterials, 33 (17), (pp. 4309-4318) (10 p.).
Seyednejad, Hajar, Gawlitta, Debby, Kuiper, Raoul V, de Bruin, Alain, van Nostrum, Cornelus F, Vermonden, Tina, Dhert, Wouter J A & Hennink, Wim E (2012). In vivo biocompatibility and biodegradation of 3D-printed porous scaffolds based on a hydroxyl-functionalized poly(ε-caprolactone). Biomaterials, 33 (17), (pp. 4309-18) (10 p.). Copyright © 2012 Elsevier Ltd. All rights reserved..
Aranzamendi Esteban, C.R., de Bruin, A., Kuiper, R.V., Boog, C.J.P., van Eden, W., Rutten, V.P.M.G. & Pinelli, E. (2012). Protection against allergic airway inflammation during the chronic and acute phases of Trichinella spiralis infections. Clinical and Experimental Allergy, 43 (1), (pp. 103-115) (13 p.).
van Essen, V.J., Uilenreef, J.J., Szatmari, V., Veldhuis - Kroeze, E.J.B., Kuiper, R.V., Rothuizen, J. & de Bruin, A. (2012). Ultrasound-guided serial transabdominal cardiac biopsies in cats. Veterinary Journal, 191 (3), (pp. 341-346) (6 p.).
  Artikelen - 2011
Mul, J.D., Nadra, K., Jagalur, N.B., Nijman, I.J., Toonen, P.W., Médard, J., Grès, S., de Bruin, A., Han, G., Brouwers, J.F.H.M., Carman, G.M., Salnier-Blanche, J., Meijer, D., Chrast, R. & Cuppen, E.P.J.G. (2011). A hypomorphic mutation in Lpin1 induces progressively improving neuropathy and lipodsytrophy in the rat. Journal of Biological Chemistry, 286 (30), (pp. 26781-26793) (13 p.).
van Boxtel, R., Kuiper, R.V., Toonen, P.W., van Heesch, S., de Bruin, A. & Cuppen, E.P.J.G. (2011). Homozygous and Heterozygous p53 Knockout Rats Develop Metastasizing Sarcomas with High Frequency. American Journal of Pathology, 179 (4), (pp. 1616-1622) (7 p.).
  Artikelen - 2010
de Keizer, P.L.J., Packer, L.M., Szypowska, A.A., Riedl-Polderman, P.E., van den Broek, N.J.F., de Bruin, A., Dansen, T.B., Marais, R., Brenkman, A.B. & Burgering, B.M.T. (2010). Activation of forkhead box O transcription factors by oncogenic BRAF promotes p21cip1-dependent senescence. Cancer Research, 70 (21), (pp. 8526-8536) (11 p.).
da Costa Martins, P.A., Salic, K., Gladka, M., Armand, A.S., Leptidis, S., el Azzouzi, H., Hansen, A., Coenen-de Roo, C.J., Bierhuizen, M.F.A., van der Nagel, R., van Kuik, J., de Weger, R.A., de Bruin, A., Condorelli, G., Arbones, M.L., Eschenhagen, T. & de Windt, L.J. (2010). MicroRNA-199b targets the nuclear kinase Dyrk1a in an auto-amplification loop promoting calcineurin/NFAT signalling. Nature Cell Biology, 12, (pp. 1220-1227) (8 p.).
van Dijk-Ottens, M., Vos, I.H.C., Cornelissen, P.W.A., de Bruin, A. & Everts, M.E. (2010). Thyroid hormone-induced cardiac mechano growth factor expression depends on beating activity. Endocrinology, 151 (2), (pp. 830-838) (9 p.).
  Artikelen - 2009
Matondo, R., Punt, C., Homberg, J.R., Toussaint, M.J.M., Kisjes, R., Korporaal, S.J.A., Akkerman, J.W.N., Cuppen, E. & de Bruin, A. (2009). Deletion of the serotonin transporter in rats disturbs serotonin homeostasis without impairing liver regeneration. American Journal of Physiology - Gastrointestinal and Liver Physiology, 296, (pp. G963-G968) (6 p.).
Kester, M.H., Toussaint, M.J.M., Punt, A.C., Matondo, R., Aarnio, A.M., Darras, V.M., Everts, M.E., de Bruin, A. & Visser, T.J. (2009). Large induction of type III deiodinase (D3) expression after partial hepatectomy in the regenerating mouse and rat liver. Endocrinology, 150, (pp. 540-545) (6 p.).
Aqeilan, R.I., Hagan, J.P., de Bruin, A., Rawahneh, M., Salah, Z., Gaudio, E., Siddiqui, H., Volinia, S., Adler, H., Lian, J.B., Stein, G. & Croce, C.M. (2009). Targeted ablation of the Wwox tumor suppressor leads to impaired steroidogenesis. Endocrinology, 150, (pp. 1530-1535) (6 p.).
  Artikelen - 2008
Mosaliganti, K., Pan, T., Ridgway, R., Sharp, R., Cooper, L., Gulacy, A., Sharma, A., Irfanoglu, O., Machiraju, R., Kurc, T., de Bruin, A., Wenzel, P., Leone, G., Saltz, J. & Huang, K. (2008). An imaging workflow for characterizing phenotypical change in large histological mouse model datasets. Journal of Biomedical Informatics, 41, (pp. 863-873) (11 p.).
Trimboli, A.J., Fukino, F., de Bruin, A., Wei, G., Shen, L., Tanner, S.M., Creasap, N., Rosol, T.J., Robinson, M.L., Eng, C., Ostrowski, M.C. & Leone, G. (2008). Direct evidence for Epithelial-Mesenchymal transitions in breast cancer. Cancer Research, 68, (pp. 937-945) (9 p.).
van Boxtel, R., Toonen, P., van Roekel, H., Verheul, M., Smits, B.M., Korving, J., de Bruin, A. & Cuppen, E. (2008). Lack of DNA mismatch repair protein MSH6 in the rat results in hereditary non-polyposis colorectal cancer-like tumorigenesis. Carcinogenesis, 29, (pp. 1290-1297) (8 p.).
Tsai, S.Y., Opavsky, R., Sharma, N., Wu, L., Naidu, S, Nolan, E., Feria-Arias, E., Timmers, C., Opavska, J., de Bruin, A., Chong, J., Trikha, P., Fernandez, S., Stromberg, P., Rosol, T.J. & Leone, G. (2008). Mouse development with a single E2F activator. Nature, 454, (pp. 1137-1141) (5 p.).
Li, J., Ran, C., Li, E., Gordon, F., Comstock, G., Siddiqui, H., Cleghorn, W., Chen, H., Kornacker, K., Pandit, S.K., Khanizadeh, M., Weinstein, M., Leone, G. & de Bruin, A. (2008). Synergistic function of E2F7 and E2F8 is essential for cell survival and embryonic development. Developmental Cell, 14, (pp. 62-75) (15 p.).
Aqeilan, R.I., Hassan, M.Q., de Bruin, A., Hagan, J.P., Volinia, S., Palumbo, T., Hussain, S., Lee, S., Gaur, T., Stein, G., Lian, J.B. & Croce, C.M. (2008). The WWOX tumor suppressor is essential for postnatal survival and normal bone metabolism. Journal of Biological Chemistry, 283, (pp. 21629-21639) (11 p.).
  Artikelen - 2007
Mosaliganti, K., Janoos, F., Sharp, R., Ridgway, R., Machiraju, R., Huang, K., Wenzel, P.L., de Bruin, A., Leone, G. & Saltz, J. (2007). Detection and visualization of surface-pockets to enable phenotyping studies. IEEE Transactions on Medical Imaging, 26 (9), (pp. 1283-1290) (7 p.).
de Bruin, A., Caldelari, R., Williamson, L., Suter, M.M., Hunziker, T., Wyder, M. & Muller, E.J. (2007). Plakoglobin-dependent disruption of the desmosomal plaque in pemphigus vulgaris. Experimental Dermatology, 6, (pp. 468-475) (8 p.).
Wenzel, P.L., Wu, L.L., de Bruin, A., Chong, J., Chen, W., Dureska, G., Sites, E., Pan, T., Sharma, A., Huang, K., Ridgway, R., Mosaliganti, K., Sharp, R., Machiraju, R., Saltz, J., Yamamoto, H., Cross, J.C., Robinson, M.L. & Leone, G. (2007). Rb is critical in a mammalian tissue stem cell population. Genes and Development, 21, (pp. 85-97) (13 p.).
  Artikelen - 2006
Williamson, L., Raess, N.A., Caldelari, R., Zakher, A., de Bruin, A., Posthaus, H., Bolli, R., Hunziker, T., Suter, M.M. & Muller, E.J. (2006). Pemphigus vulgaris identifies plakoglobin as key suppressor of c-Myc in the skin. EMBO Journal, 25 (14), (pp. 3298-3309) (12 p.).
  Artikelen - 2005
Maiti, Baidehi, Li, Jing, de Bruin, Alain, Gordon, Faye, Timmers, Cynthia, Opavsky, Rene, Patil, Kaustubha, Tuttle, John, Cleghorn, Whitney & Leone, Gustavo (2005). Cloning and characterization of mouse E2F8, a novel mammalian E2F family member capable of blocking cellular proliferation. Journal of Biological Chemistry, 280 (18), (pp. 18211-20) (10 p.).
Jiang, Yuying, de Bruin, Alain, Caldas, Hugo, Fangusaro, Jason, Hayes, John, Conway, Edward M, Robinson, Michael L & Altura, Rachel A (27-07-2005). Essential role for survivin in early brain development. Journal of Neuroscience, 25 (30), (pp. 6962-70) (9 p.).
de Bruin, Alain, Wack, Ray & Weisbrode, Steven E (2005). Persistent metanephric ducts in a geriatric white tiger. Journal of Veterinary Diagnostic Investigation, 17 (1), (pp. 91-3) (3 p.).
  Artikelen - 2003
Wu, Lizhao, de Bruin, Alain, Saavedra, Harold I, Starovic, Maja, Trimboli, Anthony, Yang, Ying, Opavska, Jana, Wilson, Pamela, Thompson, John C, Ostrowski, Michael C, Rosol, Thomas J, Woollett, Laura A, Weinstein, Michael, Cross, James C, Robinson, Michael L & Leone, Gustavo (27-02-2003). Extra-embryonic function of Rb is essential for embryonic development and viability. Nature, 421 (6926), (pp. 942-7) (6 p.).
de Bruin, Alain, Maiti, Baidehi, Jakoi, Laszlo, Timmers, Cynthia, Buerki, Robin & Leone, Gustavo (2003). Identification and characterization of E2F7, a novel mammalian E2F family member capable of blocking cellular proliferation. Journal of Biological Chemistry, 278 (43), (pp. 42041-9) (9 p.).
de Bruin, Alain, Wu, Lizhao, Saavedra, Harold I, Wilson, Pamela, Yang, Ying, Rosol, Thomas J, Weinstein, Michael, Robinson, Michael L & Leone, Gustavo (2003). Rb function in extraembryonic lineages suppresses apoptosis in the CNS of Rb-deficient mice. Proceedings of the National Academy of Sciences of the United States of America, 100 (11), (pp. 6546-51) (6 p.).
  Artikelen - 2002
Dahm, A M, de Bruin, A, Linat, A, von Tscharner, C, Wyder, M & Suter, M M (2002). Cultivation and characterisation of primary and subcultured equine keratinocytes. Equine veterinary journal. Supplement, 34 (2), (pp. 114-20) (7 p.).
Saavedra, Harold I, Wu, Lizhao, de Bruin, Alain, Timmers, Cynthia, Rosol, Thomas J, Weinstein, Michael, Robinson, Michael L & Leone, Gustavo (2002). Specificity of E2F1, E2F2, and E2F3 in mediating phenotypes induced by loss of Rb. Cell Growth and Differentiation, 13 (5), (pp. 215-25) (11 p.).
  Artikelen - 2001
Caldelari, R, de Bruin, A, Baumann, D, Suter, M M, Bierkamp, C, Balmer, V & Müller, E (2001). A central role for the armadillo protein plakoglobin in the autoimmune disease pemphigus vulgaris. Journal of Cell Biology, 153 (4), (pp. 823-34) (12 p.).
Köhler, H B, Huchzermeyer, B, Martin, M, De Bruin, A, Meier, B & Nolte, I (2001). TNF-alpha dependent NF-kappa B activation in cultured canine keratinocytes is partly mediated by reactive oxygen species. Veterinary Dermatology, 12 (3), (pp. 129-37) (9 p.).
  Artikelen - 2000
Caldelari, R, Suter, M M, Baumann, D, De Bruin, A & Müller, E (2000). Long-term culture of murine epidermal keratinocytes. Journal of Investigative Dermatology, 114 (5), (pp. 1064-5) (2 p.).
Müller, E, Caldelari, R, de Bruin, A & Suter, M M (2000). Störungen der Zelladhäsion bei autoimmunen bullösen Hautkrankheiten. Schweizer Archiv fur Tierheilkunde, 142 (5), (pp. 241-6) (6 p.).
  Artikelen - 1999
Köhler, H B, Knop, J, Martin, M, de Bruin, A, Huchzermeyer, B, Lehmann, H, Kietzmann, M, Meier, B & Nolte, I (1999). Involvement of reactive oxygen species in TNF-alpha mediated activation of the transcription factor NF-kappaB in canine dermal fibroblasts. Veterinary Immunology and Immunopathology, 71 (2), (pp. 125-42) (18 p.).
De Bruin, A, Müller, E, Wurm, S, Caldelari, R, Wyder, M, Wheelock, M J & Suter, M M (1999). Loss of invasiveness in squamous cell carcinoma cells overexpressing desmosomal cadherins. Cell Adhesion and Communication, 7 (1), (pp. 13-28) (16 p.).
de Bruin, A, Müller, E, Wyder, M, Anhalt, G J, Lemmens, P & Suter, M M (1999). Periplakin and envoplakin are target antigens in canine and human paraneoplastic pemphigus. Journal of the American Academy of Dermatology, 40 (5 Pt 1), (pp. 682-5) (4 p.).
  Voordrachten / lezingen - 0
A. de Bruin () Mouse models of studying liver cell polyploidization an liver cancer
A. de Bruin () Pathology of ageing mice and zebrafish
A. de Bruin () Pathology on genetically modified mice
A. de Bruin () Senescence and angiogenesis in zebrafish
A. de Bruin () Surgical resection and radiofrequency ablation initiate cancer in bile ducts deficient for p53 and Rb
A. de Bruin () Surgical resection and radiofrequency ablation initiate cancer in bile ducts deficient for p53/ Rb
  Contribution to the work of national or international committees and working groups - 0
A. de Bruin () Adhoc Reviewer
A. de Bruin () American College of Veterinary Pathologists
A. de Bruin () Dutch Society for Liver Research
A. de Bruin () Grant review committee
A. de Bruin () Member Review Committee of ZonMw for Clinical Fellows
A. de Bruin () Organizing committee
A. de Bruin () promotor Graduated Ph.D. student Bart Weijts (2013) typical E2Fs, old acquaintances with new faces. A novel role of E2F7 and E2F8 in angiogenesis and lymphoangiogenesis
A. de Bruin () Scientific advisory board member
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Gegenereerd op 2017-11-20 07:08:55

We want to understand the pathobiology of ageing and cancer. Interestingly both processes are caused by DNA damage but with different outcomes. In aged cells, accumulation of DNA double strand breaks results in the activation of proteins that cause a cell cycle arrest thereby preventing the efficient regeneration of damaged tissues. Remarkably these cell cycle-regulating proteins that induce ageing are often mutated in cancer cells. Loss of these so called tumor suppressor genes, such as Retinoblastoma (Rb) or p53, results in uncontrolled cell divisions and tumor formation.  Our research team wants to determine the molecular mechanism that causes ageing and cancer by study the functions of tumor suppressors and their direct downstream effectors, the E2F transcription factors. We use genetic modified mouse models to elucidate the contribution of p53, Rb and E2Fs in ageing and cancer of the liver.

Our long-term goal is to gain mechanistic insights to develop therapeutic strategies delaying ageing and suppressing cancer.  One promising avenue we are currently exploring is whether atypical E2Fs (E2F7 and E2F8) can be used to inhibit liver cancer, because we discovered that these atypical E2Fs function as very potent tumor suppressor proteins. A major obstacle in creating novel anticancer drugs is that many tumor suppressor genes are mutated and therefore cannot be reactivated to block cancer. However atypical E2Fs are very rarely mutated in cancer and therefore represent a novel and promising therapeutic target that be activated in cancer cells to inhibit cell divisions. 

Furthermore we have developed unique expertise in the pathological analysis of genetic modified animals, and established in 2010 the Dutch Molecular Pathology Center (DMPC), which collaborates worldwide with more than 50 different research groups or industry partners to analyze their transgenic animal models of human diseases. In 2016, we created a novel Single Cell Analysis Center (SCAC), which has the unique expertise and innovative equipment to isolate, image, select and analyze single cells for global genomic and transcriptomic alterations. This novel technology platform can be used to identify novel subsets of cell populations in normal or diseased tissues. Moreover it can be used to determine the heterogeneity within tumors or aged tissues.

 

Gegenereerd op 2017-11-20 07:08:55

Teaching activities

 

Veterinary bachelor students:  General pathology on cancer, stem cells, regenerative medicine, inflammation, cell degeneration and cell death

 

PhD, Master, Bachelor students: Animal models for cancer and regeneration, research projects

 

Researchers (academia & industry): Pathological analysis of animal models

 

School kids at primary school: Math challenges 'Rekentijgers'

 

Gegenereerd op 2017-11-20 07:08:55
Nevenfuncties

Commissions of trust

2017-present     Chairman Research Council, Faculty Vet. Med.

2017-present     Full Professor Nomination Advisory committees

2013- present    Scientific Advisory Board, Faculty Vet. Med.

2013- present    Scientific Advisory Board InnoSer, Lelystad

 

Grant review committee member

2013-present      OSU Intramural Research Program, USA

2009-present     NWO (Veni, Rubicon, ALW-open)

 

Organizing committee member

2012-2016          NVVP Dutch Society human and vet. pathologists

2011-2014          European hypoxia network, COST Action TD0901

 

Adhoc Reviewer

for journals:

EMBO Journal, Nuclei Acid Research, Molecular and Cellular Biology, Genes and Cancer, Cancers, Veterinary Pathology, The Veterinary Journal, BMC Veterinary Research, BMC Cancer, BBA Moelcular Basis of Disease, Aging, EMBO Moelcular Medicine, Hepatology, Journal of Clinical Investigation, Nature Communication

for grant agencies:

NWO, Worldwide Cancer Reserach, University of Liege, Polish National Science

Gegenereerd op 2017-11-20 07:08:55
Volledige naam
prof. dr. A. de Bruin Contactgegevens
Androclusgebouw

Yalelaan 1
Kamer O167
3584 CL  UTRECHT

Telefoonnummer direct 030 253 4293
Telefoonnummer afdeling 030 253 4303
Gegenereerd op 2017-11-20 07:08:55
Laatst bijgewerkt op 26-09-2017