Curriculum Vitae

NAME:  CRISTINA AL-KHALILI SZIGYARTO, Ph.D.

EDUCATION/TRAINING

INSTITUTION AND LOCATION	DEGREE	Completion Date MM/YYYY	FIELD OF STUDY
Stockholm University, Stockholm, Sweden	MS	06/1994	Biochemistry
Stockholm University, Stockholm, Sweden	PhD	06/2001	Proteomics, protein purification and characterization
Amsterdam University, AMC, The Nederland	Postdoc	2001-2002	Transcriptomic analysis in peroxisomal function
KTH-Royal Institute of Technology, Stockholm, Sweden	Postdoc	2002-2004	Bioinformatics, protein sequence analysis

 

A.      Personal Statement

The research activities I am involved in aim to promote protein biomarker discovery and validation for different diseases through the development of proteomics methods.  During my research carrier I have moved from basic research to applied research and acquired expertise in the field of proteomics, biotechnology and bioinformatics and aiming to develop methods for molecular characterization of biological systems. I received her Ph.D. at Stockholm University with specialization in protein degradation contributing to development of methods for isolation and characterization of proteins and their involvement in mitochondrial biogenesis and energy production.  In 2001 I was awarded a Postdoctoral Fellowship by the Swedish Research Council for a position at the Amsterdam Medical Center to developed DNA microarray techniques for gene expression analysis. After the postdoc I was recruited to the Royal Institute of Technology by Prof. Mathias Uhlén for the initiation of the Human Protein Atlas project as a group leader for the bioinformatics team involved in protein sequence analysis and antigen design. Subsequently I have been involved in the development of a pipeline for production of antigens and antibodies to be used a tools for proteomics studies. I have used these tools to develop methods for molecular characterization of human tissues both healthy and diseased eg. colorectal cancer, Duchenne muscular Dystrophy, etc. As Scientific coordinator of the Human Protein Atlas research collaborations have been in involved in several EU-FP7 projects AFFINOMICS; ENGAGE, BIO-NMD, CAGEKID, EURATRANS, PRIMES.

During the past 5 years I have focused on development of biomarkers for rare disorders using both transcriptomics and proteomics methods. My goal is to use developed tools, knowledge and expertise to aid translation of research results to clinical practice in particular discovery and validation of biomarkers.

 

B.      Positions and Honors

Positions and Employment

2001-2002       Postdoc, Amsterdam University, Amsterdam Medical Center, The Nederland      

2002-2004       Postdoc, Department for Biotechnology, KTH–Royal Institute of Technology, Stockholm, Sweden,

2005-2008       Group leader PrEST design – The Human Protein Atlas, School of Biotechnology, KTH – Royal Institute of Technology, Stockholm,

2008-               Scientific coordinator - The Human Protein Atlas, School of Biotechnology, KTH – Royal Institute of Technology, Stockholm,

2013- 2016     Director of studies Biotechnology program (20%), School of Biotechnology, KTH – Royal Institute of Technology, Stockholm,

2016-               Master program director (30%) School of Chemistry, Biotechnology and Health, KTH – Royal Institute of Technology, Stockholm,

2021-               Engineering program director (30%) School of Chemistry, Biotechnology and Health, KTH – Royal Institute of Technology, Stockholm,

 

C.      Contributions to Science

C.1. Development of antibodies as research tools

I have used bioinformatic and proteomics methods to develop a pipeline for systematic production of antibodies against human proteins. In the initial phase a new approach for selection of immune-potentiating protein fragments suitable for production of antigens and subsequently antibodies was developed.  I have used the methods to design antigens for 80% of the human genes within the Human Protein Atlas. The antigens were produced in a bacterial system and subsequently used to generate antibodies. A high-throughput procedure for production of antibodies was developed together with data regarding their performance and specificity. The antibodies were used for protein expression profiling in tissues and cells and the development and public release of the Human Protein.

1.     Edfors F, Hober A, Linderbäck C, Maddalo G, Azimi A, Sivertsson Å, Tegel H, Hober S, Al-Khalili Szigyarto C, Fagerberg L, von Feilitzen K, Oksvold P, Lindskog C, Forsström B and Uhlen M (2018) Enhanced validation of antibodies for research applications. Nature Comm. 9:4130.

2.     Uhlén M, Fagerberg L, Hallström B, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson A, Kampf C, Sjöstedt E, Asplund A, Olsson IM, Edlund K, Lundberg E, Navani S, Al-Khalili Szigyarto C, Odeberg J, Djureinovic D, Ottosson Takanen J, Hober S, Alm T, Edqvist P-H, Berling H, Tegel H, Mulder J, Rockberg J, Nilsson P, Schwenk JM, Hamsten M, von Feilitzen K, Forsberg M, Persson L, Johansson F, Zwahlen M, von Heijne G, Nielsen J, Pontén P (2015) Proteomics. Tissue-based map of the human proteome. Science. 23; 347:1260419. doi: 10.1126/science.1260419.

3.     Fagerberg L, Hallstrom BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, Habuka M, Tahmasebpoor S, Danielsson A, Edlund K, Asplund A, Sjostedt E, Lundberg E, Szigyarto Al-Khalili C, Skogs M, Takanen O J, Berling H, Tegel H, Mulder J, Nilsson P, Schwenk J M, Lindskog C, Danielsson F, Mardinoglu A, Sivertsson A, von Feilitzen K, Forsberg M, Zwahlen, Olsson I, Navani S, Huss M, Nielsen J, Ponten F, and Uhlen M. (2014) Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics. Mol. Cell. Prot. 13:397-406.

4.     Berglund L, Björling E, Jonasson K, Rockberg J, Fagerberg L, Al-Khalili Szigyarto C, Sivertsson A, Uhlén M.(2008) A whole-genome bioinformatics approach to selection of antigens for systematic antibody generation. Proteomics. 8:2832-9. 


5.     Berglund L, Björling E, Oksvold P, Fagerberg L, Asplund A, Al-Khalili Szigyarto C, Persson A, Ottosson J, Wernérus H, Nilsson P, Lundberg E, Sivertsson A, Navani S, Wester K, Kampf C, Hober S, Ponten F, and Uhlen M. (2008) A gene centric Human Protein Atlas for expression profiles based on antibodies. Mol Cell Proteomics. 7:2019-27. 


C2. Molecular characterization of human biology on transcript and protein level

Proteome analysis was employed on a whole anatomic level and published through the Human Protein Atlas portal (www.proteinatlas). Until today more than 17,000 proteins have been profiled to describe the human proteome. Expression of genes was mapped on transcript level using RNA-seq and on protein level using  Immunohistochemical staining of 66 different cell types, immunofluorescent microscopy of cell lines for detection of 16 subcellular localizations. Aiming to confirm and complement the proteomics data I have developed RNA-seq analysis methods for characterization of the human proteome. In addition I have contributed to the design of an  interactive database for exploration of the human proteome from single proteins to tissue composition as a research resource.

1.     Kennedy SA, Jarboui MA, Srihari S, Raso C, Bryan K, Dernayka L, Charitou T, Bernal-Llinares M, Herrera-Montavez C, Krstic A, Matallanas D, Kotlyar M, Jurisica I, Curak J, Wong V, Stagljar I, LeBihan T, Imrie L, Pillai P, Lynn MA, Fasterius E, Al-Khalili Szigyarto C, Breen J, Kiel C, Serrano L, Rauch N, Rukhlenko O, Kholodenko BN, Iglesias-Martinez LF, Ryan CJ, Pilkington R, Cammareri P, Sansom O, Shave S, Manfred Auer, Horn N, Klose F, Ueffing M, Boldt F, Lynn Dj, Kolch W. Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS G13D. (2020) Nature Communications 11 (1), 1-14.

2.     Charitou T, Srihari S, Lynn MA, Jarboui MA, Fasterius E, Moldovan M, Shirasawa S,  Tsunoda T, Ueffing M, Xie J, Xin J, Wang X, Proud CG, Boldt K, Al-Khalili Szigyarto C, Kolch W & Lynn DJ (2019) Transcriptional and metabolic rewiring of colorectal cancer cells expressing the oncogenic KRASG13D mutation. British J Cancer. 521:1.

3.     Fasterius E and Al-Khalili Szigyarto C (2018) Analysis of public RNA-sequencing data reveals biological consequences of genetic heterogeneity in cell line populations. Sci Rep, 8: 11226.

4.     Fasterius E, Raso C, Kennedy S, Rauch N, Lundin P, Kolch W, Uhlén M, Al-Khalili Szigyarto C. (2017) RNA-sequencing data analysis for cell line authentication. PLoS One. 12(2): e0171435, DOI: 10.1371/journal.pone.0171435.


5.     Wein N, Vulin A, Falzarano MS, Szigyarto Al-Khalili C, Maiti B, Findlay A, Heller KN, Uhlén M, Bakthavachalu B, Messina S, Vita G, Passarelli C, Gualandi F, Wilton SD, Rodino-Klapac LR, Yang L, Dunn DM, Schoenberg DR, Weiss RB, Howard MT, Ferlini A, Flanigan KM. Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice. (2014) Nat Med. doi: 10.1038/nm.3628.

 

C.3. Application of proteomics and transcriptomics methods in preclinical and translational research

I have produced and used antibodies as proteomics reagents for the analysis of biomarkers within the context of Duchenne and Becker muscular dystrophy. Protocols were developed and optimized to lower the use of rare and scarce samples to few microliters using multiplex suspension bead arrays. 19 potential protein biomarkers associated with disease severity and disease progression in blood were identified and 2 of them subsequently confirmed in the analyzed of longitudinal sample collections. In addition, I developed methods for protein analysis, both antibody-based and mass spectrometry based to explore and characterize functional dystrophin protein isoform expressed in intermediate forms of Duchenne and Becker muscular dystrophy.

1.     Passarelli C, Selvatici R, Carrieri A, Di Raimo F R, Falzarano MS, Fortunato F, Rossi R, Straub V, Bushby K, Reza M, Zharaieva I, D’Amico A, Bertini E, Merlini L, Sabatelli P, Borgiani P, Novelli G, Messina S, Pane M, Mercuri E, Claustres M, Tuffery-Giraud S, Aartsma-Rus A, Spitali P, T’Hoen PAC, Lochmüller H, Strandberg K, Al-Khalili Szigyarto C, Kotelnikova E, Lebowitz M, Schwartz E, Muntoni F, Scapoli C, Ferlini A (2020) Tumor Necrosis Factor Receptor SF10A (TNFRSF10A) SNPs Correlate With Corticosteroid Response in Duchenne Muscular Dystrophy. Front Genet 11:605.

2.     Signorelli M, Ayoglu B, Johansson C, Lochmüller H, Straub V, Muntoni F, Niks E, Tsonaka R, Persson A, Aartsma‐Rus A, Nilsson P, Al‐Khalili Szigyarto C, Spitali P (2019) Longitudinal serum biomarker screening identifies malate dehydrogenase 2 as candidate prognostic biomarker for Duchenne muscular dystrophy J Cachexia, Sarcopenia and Muscle DOI: 10.1002/jcsm.12517

3.     Spitali P, Hettne K, Tsonaka R, Charrout M, van den Bergen J, Koeks Z, Kan HE, Hooijmans MT, Roos A, Straub V, Muntoni F, Al‐Khalili‐Szigyarto C, Koel‐Simmelink MJA, Teunissen CE, Lochmüller H, Niks EH, Aartsma‐Rus A, (2018) Tracking disease progression non‐invasively in Duchenne and Becker muscular dystrophies. J. Cachexia, Sarcopenia and Muscle. 9:715–726, DOI:10.1002/jcsm.12304

4.     A. Lourbakos, N. Yau, P. de Bruijn, M. Hiller, K. Kozaczynska, R. Jean-Baptiste, M. Reza, R. Wolterbeek, Z. Koeks, B. Ayoglu, D. de Klerk, G. Campion, I. Zaharieva, V. D. Nadarajah, P. Nilsson, C. Al-Khalili Szigyarto, F. Muntoni, H. Lochmüller, J. J. Verschuuren, N. Goemans, M. Tulinius, E. H. Niks, S. de Kimpe, A. Aartsma-Rus, Peter A. C. ’t Hoen, P. Spitali (2017) Evaluation of serum MMP-9 as predictive biomarker for antisense therapy in Duchenne, Sci Rep. 2017; 7: 17888, doi: 10.1038/s41598-017-17982-y.

5.     Ayoglu B, Chaouch A, Lochmüller H, Politano L, Bertini E, Spitali P, Hiller M, Niks E, Gualandi F, Pontén F, Bushby K, Aartsma-Rus A, Schwartz E, Le Priol Y, Straub V,  Uhlén M, Cirak S, ’t ‘t Hoen AC, Muntoni F, Ferlini A, Schwenk JM, Nilsson P, Al-Khalili Szigyarto C. (2014) Profiling geographically dispersed cohorts reveals protein markers in blood for Duchenne muscular dystrophies. (2014) EMBO Mol. Med. 6:918-936.

Complete publications list can be found at Publication list

 

D.             Research Support

European Union

BIO-NMD (Grant agreement no: 241665) 2010 - 2013, Identifying and validating pre-clinical biomarkers for diagnostics,

AFFINOMICS (Grant agreement no: 241481) 2010 - 2015, Protein Binders for characterisation of Human Proteome Function: Generation, Validation,

CAGEKID (Grant agreement no: 241669) 2010 - 2014, Cancer Genomics of the Kidney,

PRIMES (Grant agreement no: 278568) 2011 - 2017, Protein Interaction Machines in Oncogenic EGF signaling,

The French Muscular Dystrophy Association,                             

Mark-MD (Grant reference number 17724),  2014 - 2016

Industrial collaboration - Biomarker assay development