Systems Biology Ireland
Tel: +353 1 7166982
I studied Applied Mathematics and Computer Science at undergraduate at Lincoln University in Christchurch, New Zealand. Soon after, I was introduced to the wonderful and mysterious world of cell biology and became deeply interested in the idea of working in an interdisciplinary field that integrates cell biology and mathematical modelling. I went on to complete my Ph.D degree in Computational Systems Biology in late 2009 under the supervision of Prof. Don Kulasiri at Lincoln. In early 2010, I joined Systems Biology Ireland as a postdoctoral research fellow and work under the mentorship of Prof. Boris Kholodenko and Prof. Walter Kolch.
My doctoral research explored the intricate connection between cellular systems behaviour and feedback regulation, focusing on systems governed by multiple negative feedback loops. This work showed that the multiple negative feedback motifs boost systems stability and provide enhanced robustness in response to various perturbations. Furthermore, such coupled-loops architecture was found to generate greater dynamical complexity with richer temporal dynamics repertoires compared to single-loop systems. Another aspect of my thesis looked at effects of molecular noise on dynamics of regulatory networks. Since noise is an inherent property of cellular systems, whose function is context-specific, stochastic investigations are essential in gaining a complete understanding of the cell.
My current research at Systems Biology Ireland focuses on using mathematical and computational modelling to analyse the network structure and regulation of cell signalling networks, particularly in cancer-related contexts. My main aim is to develop accurate and predictive models using multi-disciplinary tools from experimental biology and computational sciences to predict responses to perturbations (such as drugs), define the most sensitive points for interference (targets identification), and analyse the specificity of signalling and adaptation processes.
Name Lan K. Nguyen
Address Systems Biology Ireland, Conway Institute for Biomedical and Biomolecular Research, University College Dublin, Belfield, Dublin 4, Ireland
Phone +353 1716 6326
Nationality New Zealand
2014-present Research Fellow, Junior Group Leader - Systems Biology Ireland, UCD.
2010-2013 Postdoctoral Researcher (L2) - Systems Biology Ireland, UCD, Dublin.
2006-2009 Ph.D in Computational Systems Biology - Lincoln University, New Zealand
2005-2006 Postgraduate Degree in Mathematical Modelling of Biological Systems (with Distinction) - Lincoln University, New Zealand
2001-2004 B. Applied Comp & Maths - Lincoln University, New Zealand
ACADEMIC PRIZES AND AWARDS
2013 Project Grant (3 years, ~ £200K) - Breast Cancer Campaign (Co-Applicant)
2013 UCD Seed Funding Career Development Award (PI), University College Dublin
2013 Travel grant, ICYSB 2013 course, Gothenburg, Sweden
2010 Research Writing Scholarship, Department of Biosciences, Lincoln University
2009 Poster prize at Cancer Systems Biology Summer School - Rostock, Germany
2009 Royal Society of New Zealand Travel Grant
2006-2009 Top Doctoral Achiever Scholar - prestigious NZ Tertiary Education Commission award for doctoral study
2005-2006 Postgraduate Scholarship - Lincoln University
2003 HP Awards for Excellence in Software Engineering - Hewlett Packard
2001- 2003 New Zealand Study Award scholar (prestigious award for undergraduate study)
2002 Summer Research Scholarship - Lincoln University
2001 Summer Research Scholarship - Lincoln University
2001 Bruce Robson Memorial Prize - Lincoln University
2000 Second Prize of Vietnamese National Student Mathematics Olympiad in Algebra and Calculus.
1999 2nd Medal of the Asian Pacific Mathematics Olympiad (APMO)
2013 Completion of UCD Commercialisation Bootcamp, NOVA UCD, May
2013 Completion of UCD Learning to Teach, Teaching to Learn course (IS50060), April
2011 Completion of the module Fundamental Biological Imaging, Conway Institute, UCD
| Year 2009 Institution: Lincoln University, Christchurch, NZ
Qualification: PhD Subject: Computational Systems Biology
Peer Reviewed Journals
|Editor's Choice: Romano D, Nguyen LK*, Matallanas D, Halasz M, Doherty C, Kholodenko BN, Kolch W. (*Lead modelling author) (2014) 'Switching Partners by Phosphorylation'. Science signaling, 7 (335). [DOI] [Details]|
|Tai Kiuchi#, Elena Ortiz-Zapater#, James Monypenny#, Daniel R. Matthews, Lan K. Nguyen*, Jody Barbeau, Oana Coban, Katherine Lawler, Brian Burford, Daniel Rolfe, Emanuele de Rinaldis, Dimitra Dafou, Michael A. Simpson, Natalie Woodman, Sarah Pinder, Cheryl E. Gillett, Viviane Devauges, Simon P. Poland, Gilbert Fruhwirth, Pierfrancesco Marra, Ykelien L. Boersma, Andreas Plückthun, William J Gullick, Yosef Yarden, George Santis, Martyn Winn, Boris N. Kholodenko, Marisa Martin-Fernandez, Peter Parker, Andrew Tutt, Simon M. Ameer-Beg, Tony Ng (*Lead computational author.) (2014) 'The ErbB4 CYT2 variant protects EGFR from ligand-induced degradation to enhance cancer cell motility'. Science signaling, . [Details]|
|Romano D, Nguyen LK*, Matallanas D, Halasz M, Doherty C, Kholodenko BN, Kolch W. (*Lead modelling author.) (2014) 'Protein interaction switches coordinate Raf-1 and MST2/Hippo signalling'. Nature Cell Biology, 16 (7):673-684. [DOI] [Details]|
|Maciej Dobrzyn ́ski, Lan K. Nguyen, Marc R. Birtwistle, Alexander von Kriegsheim, Alfonso Blanco-Ferna ́ndez, Alex Cheong, Walter Kolch, Boris N. Kholodenko (2014) 'Nonlinear signalling networks and cell-to-cell variability transform external signals into broadly distributed or bimodal responses'. Journal of the Royal Society Interface, . [Details]|
|Lan K. Nguyen1,*, Maciej Dobrzyński1, Dirk Fey1, Boris N. Kholodenko1,2,3,* (2014) 'Polyubiquitin chain assembly and organisation determine the dynamics of protein activation and degradation'. Frontiers in physiology, . [Details]|
|Nguyen, L.K., & Kulasiri, D. (2009) 'On the functional diversity of dynamical behaviour in genetic and metabolic feedback systems'. BMC systems biology, 3 (51). [Details]|
|Nguyen, L.K., & Kulasiri, D. (2011) 'Distinct noise-controlling roles of multiple negative feedback mechanisms in a prokaryotic operon system'. IET systems biology, 5 (2):145-56. [Details]|
|Nguyen, L.K., Muñoz-García, J., Maccario, H., Ciechanover, A., Kolch W., & Kholodenko, B.K. (2011) 'Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system'. PLoS Computational Biology, 7 (12). [Details]|
|Nguyen, L. K. (2012) 'Regulation of oscillation dynamics in biochemical systems with dual negative feedback loops'. Journal of the Royal Society, Interface / the Royal Society, 9 (73):1998-2010. [DOI] Link to full text [Details]|
|Dobrzynski, M.*, Fey, D.*, Nguyen, L.K.*, Kholodenko, B.N. (*co-first author) (2012) 'Bimodal Protein Distribution in Heterogeneous Oscillating Systems'. Lecture Notes in Computer Science, (7605):17-28. [Details]|
|Nguyen, L.K., Matallanas, D., Croucher, D.R., von Kriegsheim, A, Kholodenko, B.N. (2013) 'Signalling by protein phosphatases and drug development: a systems-centred view'. FEBS Journal, 280 (2):751-65. [DOI] [Details]|
|Nguyen, L.K., Cavadas, M.A.S., Scholz, C.C., Fitzpatrick, S.F., Bruning, U., Cummins, E.P., Tambuwala, M.T., Manresa, M.C., Kholodenko, B.N., Taylor, C.T., & Cheong, A. (2013) 'A dynamic model of the hypoxia-inducible factor (HIF) network'. Journal of Cell Science, 126 (Pt 6):1454-63. [DOI] [Details]|
|Cavadas, M.A.S., Nguyen, L.K., Cheong, A. (2013) 'Hypoxia-inducible factor (HIF) signalling: Molecular mechanisms and mathematical models'. Cell communication and signaling : CCS, 11 (42). [DOI] Link to full text [Details]|
|Nguyen, L.K., Kolch, W., Kholodenko, B.N. (2013) 'When ubiquitinylation meets phosphorylation: the systems biology of MAP kinase'. Cell Communication and Signaling, 11 (52). [DOI] [Details]|
|Kulasiri, D., Nguyen, L.K., Samarasinghe, S., & Xie, Z. (2008) 'A review of systems biology perspective on genetic regulatory networks with examples' Current Bioinformatics (3) :197-225. [Details]|
|Nguyen, L.K., & Kulasiri, D. (2008) 'On multiple regulatory mechanisms in the tryptophan operon system in Escherichia coli: in silico study of perturbation dynamics' In Silico Biology (8) :485-510. [Details]|
|Nguyen, L.K., & Kulasiri, D. (2007) Effect of Molecular Noise on the Dynamics of Tryptophan Operon System in Escherichia coli . In: Oxley, L and Kulasiri, D eds. Proceedings of International Congress of Modelling and Simulation [Details]|
|Verwoerd, W., & Nguyen, L.K. (2003) Dynamic Modelling of Pest Control Using a Pesticide. Lincoln University, New Zealand, Applied Computing, Mathematics and Statistics group. [Details]|
|Nguyen, L.K., &Verwoerd, W. (2004) A Review of Horizontal Gene Transfer in Bacteria. Lincoln University, New Zealand, Mathematics and Statistics group. [Details]|
The overwhelming complexity of biochemical networks requires quantitative frameworks for efficient analysis of their behaviours. My current research focuses on using mathematical and computational modelling to analyse the network structure and regulation of cell signalling, particularly in cancer-related contexts. The main aim is to develop accurate and predictive models using multi-disciplinary tools from experimental biology and mathematical, computational sciences to predict responses to perturbations (such as drugs), define the most sensitive points for interference (targets identification), and analyse the specificity of signalling and adaptation processes.
Some main projects include:
(i) Modelling the Ring1B/Bmi1 ubiquitination system: In collaboration with the group of Nobel laureate Prof. A. Ciechanover who discovered the ubiquitin-proteasome system, I have developed a computational model of the Polycomb Ring1B/Bmi1 system to understand the non-proteolytic roles of ubiquitination in gene silencing. This represents the first mechanistic model of a system dynamically regulated by ubiquitination, and revealed ubiquitination as an important protein modification for the dynamic control of cellular processes. Experimental work was jointly performed between our groups. The work was published in PloS Computational Biology, a top journal in the computational biology field.
(ii) Together with SBI experimental researcher Dr. David Romano, we took a computational-experimental approach to show that competitive protein interactions and phosphorylation effects create functional switches that influence cell fate decisions. Specifically, we study how different feedback loops, protein interactions and phosphorylation enable Raf-1 to differentially control the mitogenic ERK pathway and the pro-apoptotic MST2 pathway. This work, under revision, represents an important conceptual advance in protein-protein networks and is a demonstration of the power of integrating computational and experimental work to gain functional insights into biomolecular networks.
(iii) My collaboration with Prof. Cormac Taylor and Alex Cheong groups at Conway Institute recently led to a first-author paper on understanding the Hypoxia-Inducible Factor signalling pathway using mechanistic mathematical modelling, published in the respected Journal of Cell Science.
(iv) Most recently, I am interested in using modelling to investigate the role of the mTOR signalling pathway in cancers. The mTOR protein is at the hub of a complex, balance-keeping network that controls cellular response to various signals including nutrient and energy. In cancers, this balance is often lost, resulting in aberrant mTOR signalling. Initial work is focusing on characterising the regulatory function of DEPTOR, a new component of the mTOR network. We found theoretically that DEPTOR, through direct interaction with mTOR, can unexpectedly induce complex dynamics including switch-like and oscillatory behaviour. We are doing experiments to validate these predictions, and a manuscript is under preparation for the results.
In addition to research, I am also involved in the supervision and mentorship of two Ph.D students who work on modelling the Rac1/RhoA network controlling cell migration and mTOR signalling pathway in colon cancer. Both projects are closely driven by in-house experimental observations. Beside publishing papers, I have disseminated my research results at various local and international conferences. I have been on various committees responsible for recruiting PhDs and postdocs for SBI. I also contribute to SBI's overall research strategies through involvement in the development of funding proposals, grant writing, report w
| Sponsor : University College Dublin (UCD)
Title : Systems modelling of the mTOR/ERK signalling crosstalk to identify novel drug targets for prostate cancer
Start Date / End Date : 01-MAY-13 / 31-OCT-14
|Please visit http://lanknguyen.wordpress.com for details on my teaching port-folio|
Enhancement of Teaching
| Dr. David Gomez Matallanas, UCD
Dr. Alex von Kriegsheim, Systems Biology Ireland, UCD
Prof. Walter Kolch, Systems Biology Ireland, UCD
Prof. Cormac Taylor, Conway Institute, UCD
Dr. Maria Prencipe, OncoMark & Conway Institute, UCD
| Dr. Alex Cheong, Aston University, UK
Prof. Tony Ng, Kings College London and University College London Comprehensive Cancer Imaging Centre
Prof. Aaron Ciechanover, Nobel Laureate, Technion ¿ Israel Institute of Technology