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Blizard Institute - Faculty of Medicine and Dentistry

Professor Dean Nižetić, M.D., Ph.D.

Dean

Principal Investigator, Professor of Cell and Molecular Biology

Centre: Genomics and Child Health

Email: d.nizetic@qmul.ac.uk
Telephone: 020 7882 7164

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.

Teaching

  • Graduate School Programme in Genetics (Lecture on “Genetic Basis of Disease”), 2004-2009
  • MSc in Paediatric Oncology. “Childhood tumours in Down syndrome”, 2007
  • FUN-MED LECTURE on “Chromosomal Genetics”, 2010, 2011
  • Problem Based Learning sessions
  • PPD/CPT/PATHOLOGY COURSE Lecture on “Single Gene Disorders”, from 2006 – present
  • SSC2A (Research SSC) supervised eight student projects (2009-2013) Supervised the Intercalated BmedSci project student Amelia E. Fisher, Jan-Jun 2010. Project won an award for the best project and was selected for oral presentation at the “Intercalators Conference"
  • Project skills dissertation mentorship (2019-present)
  • A lecture on Postgraduate taught module “Experimental Neuropathology” (ICM6021/ICM6014), 2020

 

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.

 

 

Members of the Nizetic team:

Publications

Key Publications

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 Pshychiatry (a Nature journal),
In Press, July 2020. Article, PMID: 32647257; doi: 10.1038/s41380-020-0806-5.
IF=12.38;    In top 5% of the field of Neuroscience
[Wide media coverage, including live interview on BBC Radio4 “Today” program.]

David Koschut, Debleena Ray, Zhenhua Li, Emanuela Giarin, Jürgen Groet, Ivan Alić, Shirley Kow-Yin Kham, Wee Joo Chng, Hany Ariffin, David M. Weinstock, Allen Eng-Juh Yeoh, Giuseppe Basso, and Dean Nižetić
“RAS-protein activation but not mutation status is an outcome predictor and unifying therapeutic target for high-risk acute lymphoblastic leukemia"
Oncogene (a Nature journal), In Press, Oct 2020.
PMID: 33247204
I.F.=7.97 [In top 10% of the field of Genetics and Heredity, top 10% of the field of Biochemistry and Mol. Biology]. Invited “Behind the paper” online article published on Nature Research Cancer web portal.

Sergey I Nikolaev, Marco Garieri, Federico Santoni, Emilie Falconnet, Pascale Ribaux, Michel Guipponi, Aoife Murray, Jürgen Groet, Emanuela Giarin, Giuseppe Basso, Dean Nizetic* and Stylianos E Antonarakis*
*co-corresponding, shared senior authors
“Frequent cases of RAS-mutated Down syndrome acute lymphoblastic leukaemia lack JAK2 mutations"
Nature Communications 5, Article No: 4654 doi:10.1038/ncomms5654, 8 Aug 2014.
IF= 12.12     Top 10% in the field of Multi-disciplinary sciences
[Double page interview in the “Straits Times”, main Singapore newspaper]

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.
IF= 53.03    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
IF=10.5;   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, Claire Mulligan, Monica Spinelli, Anna Serra, Suzanne McElwaine, Finbarr E. Cotter, Franca Dagna-Bricarelli, Giuseppe Saglio, Giuseppe Basso and Dean Nizetic.
Independent clones at separable stages of differentiation, bearing different GATA1 mutations in the same TMD patient with Down Syndrome.
Blood, 106(5):1887-1888 September 2005.
IF=17.8,  The top journal in the field of Haematology

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).  IF=60.4.

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