Professor Dean Nižetić, M.D., Ph.D.

Profile

Professor Dean Nizetic was born in Split, Croatia in 1959. He obtained his M.D. at the Faculty of Medicine, University of Zagreb, Croatia, in 1982. He performed the experimental work used for his PhD thesis in Molecular Biology at the Max-Planck-Institute for Biology in Tuebingen , Germany. He was a postdoc at the ICRF Genome Analysis Department in London (1987-1994). From 1994, he is an independent research group leader at Centre for Applied Molecular Biology, School of Pharmacy , University of London (today UCL) where he becomes a Reader in 2000. From July 2001, he obtained a Chair in Cellular and Molecular Biology at Barts and The London School of Medicine, Queen Mary, University of London where he remains continuously and at present. Between February2014-April2020, he had reduced his engagement to part-time, to hold also the position of Professor of Molecular Medicine at Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.

Members of the Nizetic team:
-  Dr Ana Muňiz-Garcia, Ph.D.,  Postdoctoral Res. Fellow
-  Dr. Aoife Murray, Ph.D., Jerome Lejeune Postdoctoral Res. Fellow
-  Dr. Ivan Alic, D.V.M., Ph.D., Visiting Res. Fellow
-  Dr. Jurgen Groet, Ph.D., Ph.D. Reader in Molecular and Cellular Biology
-  Mr. Drazen Petrovic, Visiting PhD student, University of Zagreb School of Medicine
-  Ms. Ana Cindric,  Visiting PhD student, University of Zagreb School of Pharmacology and Biochemistry
-  Ms. Gillian Gough, MRes, PhD student at LKCMedicine,  NTU, Singapore
-  Ms. Yeap Yee Jie, MRes, part time PhD student at LKCMedicine, NTU, Singapore

Teaching

Research

Research Interests:

Several results by Professor Nizetic’s group have produced paradigm shifts in the definition of key pathogenic molecules and therapeutic targets in Down Syndrome (DS)-associated childhood leukaemia, (Lancet 2003, BJH 2004, Blood 2005, Oncogene 2010, Blood 2013, Nature Comm 2014, Oncogene 2020). His team also discovered the earliest molecular changes of DS in embryonic stem cells causing the deregulation embryonic stem cell fate (Am J Hum Genet 2008, Mol Cell Proteomics 2009). This work attracted media-attention including Press, live TV and Radio interviews, and support from the UK National DS Association (see http://news.bbc.co.uk/1/hi/health/7597761.stm ). Professor Nizetic coordinated a work package on embryonic stem cell modelling within the €12 million EU-FP6-Integrated Project "AnEUploidy” and on human iPSC modelling within The Wellcome Trust (UK) Strategic Funding Award winning “LonDownS Consortium”.   His team has recently generated an isogenic induced pluripotent stem cell (iPSC) model of DS (Stem Cells 2015) from skin cells of a person with mosaic DS, and successfully used it to model accelerated ageing and Alzheimer’s disease (AD) using a cerebral organoids platform. This enabled the discovery of BACE2 as a physiological dose-sensitive AD-suppressor gene, and a generation of a potential screening approach for AD-primary preventative drugs. These results have been published in the Nature group journal (Mol. Psychiatry 2020), and elicited wide-spread media interest, including a live interview on BBC4 Radio “Today” programme. Prof. Nizetic currently holds a co-investigator role on the project “Protein glycosylation in ageing-related diseases through study of Down syndrome as accelerated ageing condition” (acronym: GlycoDown; “Research Cooperability” Programme of the Croatian Science Foundation), as well as the project “Synaptic, Cellular and Neural Circuit Dysfunction in Down Syndrome”, a £3.8M Collaborative Award in Science by the Wellcome Trust.

Research Group

• Aoife Murray
• Ana Muniz Garcia

Publications

Key Publications

Aoife Murray, Gillian Gough, Ana Cindrić, Frano Vučković, David Koschut, Vincenzo Borelli, Dražen Petrović, Ana Bekavac, Ante Plećaš, Valentina Hribljan, Reinhard Brunmeir, Julija Jurić, Maja Pučić-Baković, Anita Slana, Helena Deriš, Azra Frkatović, Jűrgen Groet, Niamh L. O’Brien, Hong Yu Chen, Yee Jie Yeap, Frederic Delom, Steven Havlicek, Luke Gammon, Sarah Hamburg, Carla Startin, Hana D’Souza, Dinko Mitrečić, Mijana Kero, Ljubica Odak, Božo Krušlin, Željka Krsnik, Ivica Kostović, Jia Nee Foo, Yuin-Han Loh, Norris R Dunn, Susana de la Luna, Tim Spector, Ingeborg Barišić, Michael Thomas, Andre Strydom, Claudio Franceschi, Gordan Lauc, Jasminka Krištić, Ivan Alić & Dean Nižetić. 
“Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels”
eBioMedicine (a Lancet Discovery journal), 2023 Jul 5:104692. doi: 10.1016/j.ebiom.2023.104692. 
PMID: 37451904  In top 10% of the field of Exp Medicine

Fertan E, Böken D, Murray A, Danial JSH, Lam JYL, Wu Y, Goh PA, Alić I, Cheetham MR, Lobanova E, Zhang YP, Nižetić D*, Klenerman D.*
*Shared last authors (equal contribution)
“Cerebral organoids with chromosome 21 trisomy secrete Alzheimer's disease-related soluble aggregates detectable by single-molecule-fluorescence and super-resolution microscopy” 
Molecular Psychiatry (a Nature journal), 
2023 Dec; DOI: 10.1038/s41380-023-02333-3;  PMID: 38102482 
In top 5% of the field of Neurosciences.

Ivan Alić*, Pollyanna A Goh*, Aoife Murray*, Erik Portelius*, Eleni Gkanatsiou, Gillian Gough, Kin Y Mok, David Koschut, Reinhard Brunmeir, Yee Jie Yeap, Niamh L O’Brien, Jurgen Groet, Xiaowei Shao, Steven Havlicek, N Ray Dunn, Hlin Kvartsberg, Gunnar Brinkmalm, Rosalyn Hithersay, Carla Startin Sarah Hamburg, Margaret Phillips, Konstantin Pervushin, Mark Turmaine, David Wallon, Anne Rovelet-Lecrux, Hilkka Soininen, Emanuela Volpi, Joanne E Martin, Jia Nee Foo, David L Becker, Agueda Rostagno, Jorge Ghiso, Željka Krsnik, Goran Šimić, Ivica Kostović, Dinko Mitrečić, LonDownS Consortium, Paul T Francis, Kaj Blennow, Andre Strydom, John Hardy*, Henrik Zetterberg* & Dean Nižetić.*
“Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene-dose-sensitive AD-suppressor in human brain”
Molecular Psychiatry (a Nature journal), 
2021 Oct;26(10):5766-5788. Article, PMID: 32647257
In top 5% of the field of Neurosciences
[Wide media coverage, including live interview on BBC Radio4 “Today” program.]

Aoife Murray, Audrey Letourneau, Claudia Canzonetta, Elisavet Stathaki, Stefania Gimelli, Frederique Sloan-Bena, Robert Abrehart, Pollyanna Goh, Shuhui Lim, Chiara Baldo, Franca Dagna-Bricarelli, Saad Hannan, Martin Mortensen, David Ballard, Denise Syndercombe Court, Noemi Fusaki, Mamoru Hasegawa, Trevor G. Smart, Cleo Bishop, Stylianos E. Antonarakis, Jürgen Groet, and Dean Nizetic.
“Isogenic induced pluripotent stem cell lines from an adult with mosaic Down Syndrome model accelerated neuronal ageing and neurodegeneration”
Stem Cells Jun;33(6):2077-84. (2015) PMID: 25694335  

Dean Nizetic and Jurgen Groet.
“Tumorigenesis in Down’s syndrome: big lessons from a small chromosome”
Nature Reviews Cancer – 2012 Oct;12(10):721-32. doi: 10.1038/nrc3355. Epub 2012 Sep 21.
Top 5% in the field of Oncology.

Claudia Canzonetta*, Claire Mulligan*, Samuel Deutsch, Sandra Ruf, Aideen O’Doherty, Robert Lyle, Christelle Borel, Nathalie Lin-Marq, Frederic Delom, Jürgen Groet, Felix Schnappauf, Serena De Vita, Sharon Averill, John V. Priestley, Joanne E Martin, Janet Shipley, Gareth Denyer, Charles J. Epstein, Cristina Fillat, Xavier Estivill, Victor L. J. Tybulewicz, Elizabeth M. Fisher, Stylianos E. Antonarakis & Dean Nizetic.
"DYRK1A dosage imbalance perturbs NRSF/REST levels de-regulating pluripotency and embryonic stem cell fate in Down syndrome"
American Journal of Human Genetics  Volume 83, Issue 3, 388-400, 04 September 2008
Top 10% in the field of Genetics and Heredity
[Multiple interviews and articles in the media, (see http://news.bbc.co.uk/1/hi/health/7597761.stm )]

Jürgen Groet, Suzanne McElwaine, Monica Spinelli, Andrea Rinaldi, Ingo Burtscher, Claire Mulligan, Afua Mensah, Simona Cavani, Franca Dagna-Bricarelli, Giuseppe Basso, Finbarr E Cotter, Dean Nizetic.
"Acquired mutations in GATA1 in neonates with Down syndrome with Transient Myeloid Disorder"
Lancet, 361:1617-1620 (2003). 

All Publications

Supervision

• Ms. Gillian Gough, MRes, PhD student at LKCMedicine,  NTU, Singapore
• Ms. Yeap Yee Jie, MRes, part time PhD student at LKCMedicine, NTU, Singapore
• Mr. Drazen Petrovic, Visiting PhD student, University of Zagreb School of Medicine
• Ms. Ana Cindric,  Visiting PhD student, University of Zagreb School of Pharm/Biochemistry