Difference between revisions of "User:Orsolya Kiraly"

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==Contact Info==
==Contact Info==
[[Image:OWWEmblem.png|thumb|right|Orsolya Kiraly (an artistic interpretation)]]
*Orsolya Kiraly
*Orsolya Kiraly

Revision as of 08:47, 1 September 2010

Contact Info

  • Orsolya Kiraly
  • Postdoctoral Associate
  • Engelward laboratory
  • Department of Biological Engineering
  • Massachusetts Institute of Technology
  • 77 Massachusetts Ave
  • Lab: 617-750-7335 (Room 16-760)
  • Cambridge, MA
  • Email me through OpenWetWare


Research interests

I received my PhD for work on how rare mutations in pancreatic trypsin inhibitor contribute to chronic pancreatic inflammation. In the Engelward lab, my current work is aimed at homologous recombination in the pancreas in vivo.

While mitotic homologous recombination is an important DNA repair/tolerance mechanism, it can result in sequence rearrangements that can contribute to cancer. I am investigating the effects of DNA damaging chemicals, radiation, cell proliferation and DNA repair on homologous recombination in the pancreas.

The next question in my project is whether homologous recombination is induced by inflammation, which is a major risk factor for cancer.

Past projects

In the lab of Miklos Sahin-Toth at Boston University, I was investigating the functional effects of mutations in SPINK1, the pancreatic secretory trypsin inhibitor. This inhibitor is an important line of defense against trypsin activity in the pancreas. It is important to inhibit any trypsin activity in the pancreas because trypsin activity can result in the activation of other digestive enzymes in a cascade reaction, which can lead to cell damage and pancreatic inflammation. We found that signal peptide mutations abolish the secretion of SPINK1 into pancreatic juice, and coding region mutations cause misfolding of the protein which is degraded intracellularly and is not secreted. In patients with these mutations, spontaneously activated trypsin is thus not inhibited by SPINK1, eventually resulting in autodigestion and inflammation.

At Semmelweis University I was studying the functional effects of polymorphisms in the promoter of the D4 dopamine receptor gene. This gene was the first one to be investigated in psychiatric genetics association studies, and its polymorphisms are associated with several personality traits. The functional effect of promoter polymorphisms was not known, however. With a reporter gene assay, we found that a duplication in the promoter decreases transcriptional efficiency, potentially influencing the number of receptor molecules and neurotransmission. However, the most widely studies SNP in the gene had no effect on gene expression in our assay. The apparent effect of this SNP in association studies is thus propably due to another variant which is in linkage disequilibrium with the candidate SNP.

My undergraduate thesis project at the Agricultural Biotechnology Research Center (in Gödöllő, Hungary) was aimed at generating host factor independent mutants of the 16-3 phage integrase by protein engineering. Integrases catalyze site-specific recombination which is harnessed in gene targeting. This project and the excellent mentoring I received at ABC gave me strong foundations in laboratory techniques in molecular biology and an interest in DNA metabolism and recombination.


Research papers

  1. Kereszturi E, Király O, and Sahin-Tóth M. Minigene analysis of intronic variants in common SPINK1 haplotypes associated with chronic pancreatitis. Gut. 2009 Apr;58(4):545-9. DOI:10.1136/gut.2008.164947 | PubMed ID:18978175 | HubMed [Paper1]
  2. Király O, Wartmann T, and Sahin-Tóth M. Missense mutations in pancreatic secretory trypsin inhibitor (SPINK1) cause intracellular retention and degradation. Gut. 2007 Oct;56(10):1433-8. DOI:10.1136/gut.2006.115725 | PubMed ID:17525091 | HubMed [Paper2]
  3. Király O, Boulling A, Witt H, Le Maréchal C, Chen JM, Rosendahl J, Battaggia C, Wartmann T, Sahin-Tóth M, and Férec C. Signal peptide variants that impair secretion of pancreatic secretory trypsin inhibitor (SPINK1) cause autosomal dominant hereditary pancreatitis. Hum Mutat. 2007 May;28(5):469-76. DOI:10.1002/humu.20471 | PubMed ID:17274009 | HubMed [Paper3]
  4. Kereszturi E, Kiraly O, Csapo Z, Tarnok Z, Gadoros J, Sasvari-Szekely M, and Nemoda Z. Association between the 120-bp duplication of the dopamine D4 receptor gene and attention deficit hyperactivity disorder: genetic and molecular analyses. Am J Med Genet B Neuropsychiatr Genet. 2007 Mar 5;144B(2):231-6. DOI:10.1002/ajmg.b.30444 | PubMed ID:17171658 | HubMed [Paper4]
  5. Kereszturi E, Kiraly O, Barta C, Molnar N, Sasvari-Szekely M, and Csapo Z. No direct effect of the -521 C/T polymorphism in the human dopamine D4 receptor gene promoter on transcriptional activity. BMC Mol Biol. 2006 May 24;7:18. DOI:10.1186/1471-2199-7-18 | PubMed ID:16723017 | HubMed [Paper5]
  6. Király O, Guan L, Szepessy E, Tóth M, Kukor Z, and Sahin-Tóth M. Expression of human cationic trypsinogen with an authentic N terminus using intein-mediated splicing in aminopeptidase P deficient Escherichia coli. Protein Expr Purif. 2006 Jul;48(1):104-11. DOI:10.1016/j.pep.2006.01.023 | PubMed ID:16542853 | HubMed [Paper6]
  7. Szantai E, Kiraly O, Nemoda Z, Kereszturi E, Csapo Z, Sasvari-Szekely M, Gervai J, and Ronai Z. Linkage analysis and molecular haplotyping of the dopamine D4 receptor gene promoter region. Psychiatr Genet. 2005 Dec;15(4):259-70. PubMed ID:16314756 | HubMed [Paper7]

All Medline abstracts: PubMed | HubMed

Book chapters

Nemoda Z, Kiraly O, Barta C, Sasvari-Szekely M. Pharmacogenetic aspects of dopaminergic neurotransmission-related gene polymorphisms. In: Darvas F, Guttman A, Dormán G (eds): Chemical Genomics, Marcel Dekker Inc., New York, 2003, pp. 275-313. isbn=0824754905

Király O, Guan L, Sahin-Tóth M. Expression of recombinant proteins with uniform N termini using intein technology and aminopeptidase deficient Escherichia coli. In: Ming-Qun X, Evans T (eds): Heterologous Protein Expression in E. coli, Methods in Molecular Biology, Springer/Humana Press, in press