User:Orsolya Kiraly

From OpenWetWare

(Difference between revisions)
Jump to: navigation, search
m
(14 intermediate revisions not shown.)
Line 2: Line 2:
[[Image:Profile_picture_OrsiKiraly.JPG|thumb|right|]]
[[Image:Profile_picture_OrsiKiraly.JPG|thumb|right|]]
-
*Orsolya Kiraly
 
*Postdoctoral Associate, Engelward laboratory
*Postdoctoral Associate, Engelward laboratory
*Department of Biological Engineering
*Department of Biological Engineering
Line 8: Line 7:
*77 Massachusetts Ave, Cambridge, MA
*77 Massachusetts Ave, Cambridge, MA
*Lab: 617-750-7335 (Room 16-760)
*Lab: 617-750-7335 (Room 16-760)
-
*[[Special:Emailuser/Orsolya Kiraly|Email me through OpenWetWare]]
+
*okiraly AT mit DOT edu
==Education==
==Education==
<!--Include info about your educational background-->
<!--Include info about your educational background-->
* Ph.D., Pathobiochemistry,  [http://english.sote.hu/ Semmelweis University], [http://en.wikipedia.org/wiki/Budapest Budapest], Hungary, 2008
* Ph.D., Pathobiochemistry,  [http://english.sote.hu/ Semmelweis University], [http://en.wikipedia.org/wiki/Budapest Budapest], Hungary, 2008
-
* B.S., Molecular Biology, [http://www.elte.hu/en Eötvös Loránd University], Budapest, Hungary, 2002
+
* B.S., Biology, [http://www.elte.hu/en ELTE], Budapest, Hungary, 2002
 +
* I was shaped greatly by the education at [http://www.apaczai.elte.hu/ Apaczai Grammar School of ELTE]
==Research interests==
==Research interests==
Line 20: Line 20:
I received my PhD for work on how rare mutations in [http://www.uniprot.org/uniprot/P00995 pancreatic trypsin inhibitor] contribute to chronic pancreatic inflammation.  In the [http://web.mit.edu/engelward-lab/ Engelward lab], my current work is aimed at [http://en.wikipedia.org/wiki/Homologous_recombination homologous recombination] in the pancreas in vivo.
I received my PhD for work on how rare mutations in [http://www.uniprot.org/uniprot/P00995 pancreatic trypsin inhibitor] contribute to chronic pancreatic inflammation.  In the [http://web.mit.edu/engelward-lab/ Engelward lab], my current work is aimed at [http://en.wikipedia.org/wiki/Homologous_recombination homologous recombination] in the pancreas in vivo.
-
While mitotic homologous  recombination is [http://web.mit.edu/engelward-lab/hr_intro.htm 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.  
+
While mitotic homologous  recombination is [http://web.mit.edu/engelward-lab/hr_intro.htm an important DNA repair/tolerance mechanism], it can result in sequence rearrangements that can contribute to cancer. We are 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, [http://carcin.oxfordjournals.org/content/30/7/1073.long which is a major risk factor for cancer].
The next question in my project is whether homologous recombination is induced by inflammation, [http://carcin.oxfordjournals.org/content/30/7/1073.long which is a major risk factor for cancer].
Line 27: Line 27:
'''Functional effects of sequence variants in promoters, introns, and protein-coding regions'''
'''Functional effects of sequence variants in promoters, introns, and protein-coding regions'''
-
In the lab of [http://dentalschool.bu.edu/research/molecular/sahin-toth.htm 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.
+
*In the lab of [http://dentalschool.bu.edu/research/molecular/sahin-toth.htm Miklos Sahin-Toth] at Boston University, I was investigating the functional effects of mutations in [http://www.ihop-net.org/UniPub/iHOP/gs/92355.html 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 [http://digestive.niddk.nih.gov/ddiseases/pubs/pancreatitis/ pancreatic inflammation]. We found that signal peptide mutations [http://www.ncbi.nlm.nih.gov/pubmed/17274009 abolish the secretion of SPINK1] into pancreatic juice, and coding region mutations cause misfolding of the protein which is [http://www.ncbi.nlm.nih.gov/pubmed/17525091 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.
-
We found that signal peptide mutations [http://www.ncbi.nlm.nih.gov/pubmed/17274009 abolish the secretion of SPINK1] into pancreatic juice, and coding region mutations cause misfolding of the protein which is [http://www.ncbi.nlm.nih.gov/pubmed/17525091 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 [http://english.sote.hu/ Semmelweis University] I was working in a team 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 and disorders such as ADHD. However, the functional effects of promoter polymorphisms (and thus the molecular basis of these associations) were not clear. With a reporter gene assay, we found that [http://www.ncbi.nlm.nih.gov/pubmed/17171658 a duplication in the promoter decreases transcriptional efficiency], potentially influencing the number of receptor molecules and neurotransmission. However, the most widely studied SNP in the gene [http://www.ncbi.nlm.nih.gov/pubmed/16723017 had no effect on gene expression in our assay].  The apparent effect of this SNP in association studies is thus probably due to another variant which is in [http://en.wikipedia.org/wiki/Linkage_disequilibrium linkage disequilibrium] with the candidate SNP.
-
At [http://english.sote.hu/ Semmelweis University] I was working in a team 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 and disorders such as ADHD. 
+
*My undergraduate thesis project at the [http://www.abc.hu/index.php?lang=en Agricultural Biotechnology Research Center] (in [http://en.wikipedia.org/wiki/G%C3%B6d%C3%B6ll%C5%91 Gödöllő], Hungary) was aimed at generating host factor independent mutants of the 16-3 phage integrase by protein engineering.  [http://www.biomedsearch.com/nih/Phage-integrases-biology-applications/14687564.html Integrases] catalyze [http://www.web-books.com/MoBio/Free/Ch8D7.htm site-specific recombination] which is harnessed in gene targeting. The excellent mentoring I received at ABC gave me strong foundations in the laboratory techniques of molecular biology and this project raised my interest in DNA metabolism and recombination.
-
However, the functional effects of promoter polymorphisms (and thus the molecular basis of these associations) was not clear.  With a reporter gene assay, we found that [http://www.ncbi.nlm.nih.gov/pubmed/17171658 a duplication in the promoter decreases transcriptional efficiency], potentially influencing the number of receptor molecules and neurotransmissionHowever, the most widely studied SNP in the gene [http://www.ncbi.nlm.nih.gov/pubmed/16723017 had no effect on gene expression in our assay].  The apparent effect of this SNP in association studies is thus probably due to another variant which is in [http://en.wikipedia.org/wiki/Linkage_disequilibrium linkage disequilibrium] with the candidate SNP.
+
-
 
-
My undergraduate thesis project at the [http://www.abc.hu/index.php?lang=en Agricultural Biotechnology Research Center] (in [http://en.wikipedia.org/wiki/G%C3%B6d%C3%B6ll%C5%91 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.
 
==Publications==
==Publications==
Line 46: Line 42:
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
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
-
 
==Bookmarks==
==Bookmarks==
===Laboratory tools and resources===
===Laboratory tools and resources===
-
[http://www.qiagen.com/literature/benchguide/bg_pls_lit.aspx Qiagen bench guide]
+
*[http://www.qiagen.com/literature/benchguide/bg_pls_lit.aspx Qiagen bench guide]
-
[http://www.djblabcare.co.uk/djb/info/6/User_Tools Centrifuge calculator]
+
*[http://www.djblabcare.co.uk/djb/info/6/User_Tools Centrifuge calculator]
-
[[Berglund:PCR_Additives]] A good list of PCR additives
+
*[[Berglund:PCR_Additives]] A good list of PCR additives
-
[http://www.genecards.org/ GeneCards]
+
*[http://www.genecards.org/ GeneCards]
-
[http://www.ihop-net.org/UniPub/iHOP/ Information Hyperlinked over Proteins]
+
*[http://www.ihop-net.org/UniPub/iHOP/ Information Hyperlinked over Proteins]
===Useful links===
===Useful links===
-
[http://monographs.iarc.fr/ENG/Classification/index.php Classification of carcinogens] according to the [http://www.iarc.fr/ International Agency for Research on Cancer]
+
*[http://monographs.iarc.fr/ENG/Classification/index.php Classification of carcinogens] according to the [http://www.iarc.fr/ International Agency for Research on Cancer]
-
[http://www.ewg.org/search Environmental Working Group]
+
*[http://www.ewg.org/search Environmental Working Group]
-
[http://ctd.mdibl.org/ The Comparative Toxicogenomics Database]
+
*[http://ctd.mdibl.org/ The Comparative Toxicogenomics Database]
-
[http://www.aacr.org/ American Association for Cancer Research]
+
*[http://www.aacr.org/ American Association for Cancer Research]
===Good books===
===Good books===
-
[http://books.google.com/books?id=WYCJBzTxPywC&printsec=frontcover&dq=suffering+gene&hl=en&ei=0ciBTL3nG4P98Ab2vb2aAg&sa=X&oi=book_result&ct=result&resnum=1&ved=0CCUQ6AEwAA#v=onepage&q&f=false The Suffering Gene] is a very readable book about the various environmental exposures that can damage DNA
+
*[http://books.google.com/books?id=WYCJBzTxPywC&printsec=frontcover&dq=suffering+gene&hl=en&ei=0ciBTL3nG4P98Ab2vb2aAg&sa=X&oi=book_result&ct=result&resnum=1&ved=0CCUQ6AEwAA#v=onepage&q&f=false The Suffering Gene] is a very readable book about the various environmental exposures that can damage DNA
 +
 
 +
*[http://books.google.com/books?id=5ziWNCqD7OEC&printsec=frontcover&dq=cancer+evolutionary&hl=en&ei=I8mBTPKHGoOC8gbav6H3AQ&sa=X&oi=book_result&ct=result&resnum=5&ved=0CEIQ6AEwBA Cancer, the Evolutionary Legacy] describes why we are susceptible to cancer even without environmental exposures
-
[http://books.google.com/books?id=5ziWNCqD7OEC&printsec=frontcover&dq=cancer+evolutionary&hl=en&ei=I8mBTPKHGoOC8gbav6H3AQ&sa=X&oi=book_result&ct=result&resnum=5&ved=0CEIQ6AEwBA Cancer, the Evolutionary Legacy] describes why we are susceptible to cancer even without environmental exposures
+
*[http://books.google.com/books?id=WGmVPGh7AOMC&printsec=frontcover&dq=correcting+the+blueprint+of+life&source=bl&ots=6XcQhpeXhL&sig=6B-9fzLtn4vZO6swtR-WTc8TgnA&hl=en&ei=IjmCTNCRJ8P-8Aa_hPWBAg&sa=X&oi=book_result&ct=result&resnum=1&ved=0CBIQ6AEwAA#v=onepage&q&f=false Correcting the Blueprint of Life: An Historical Account of the Discovery of DNA Repair Mechanisms] by [http://en.wikipedia.org/wiki/Errol_Friedberg Errol C. Friedberg] is a fascinating story of scientific discovery, great scientist personalities and the unpredictability of research
-
[http://books.google.com/books?id=WGmVPGh7AOMC&printsec=frontcover&dq=correcting+the+blueprint+of+life&source=bl&ots=6XcQhpeXhL&sig=6B-9fzLtn4vZO6swtR-WTc8TgnA&hl=en&ei=IjmCTNCRJ8P-8Aa_hPWBAg&sa=X&oi=book_result&ct=result&resnum=1&ved=0CBIQ6AEwAA#v=onepage&q&f=false Correcting the Blueprint of Life: An Historical Account of the Discovery of DNA Repair Mechanisms] by [http://en.wikipedia.org/wiki/Errol_Friedberg Errol C. Friedberg] is a fascinating story of scientific discovery, great scientist personalities and the unpredictability of research
+
*[http://books.google.com/books?id=8dSSt6Mrn6sC&printsec=frontcover&dq=at+the+end+of+an+age&source=bl&ots=QynHJAmmSs&sig=6TM1lalB77xQB69lGqQ7leewnU8&hl=en&ei=5jqCTMmMGYSclgfD_Yn5Dw&sa=X&oi=book_result&ct=result&resnum=2&sqi=2&ved=0CCIQ6AEwAQ#v=onepage&q&f=false At the End of an Age] by historian [http://en.wikipedia.org/wiki/John_Lukacs John Lukacs] is not a scientific book, but it contains a deeply informed reflection on the nature of historical and scientific knowledge. Read a shorter essay on this [http://www.theamericanscholar.org/putting-man-before-descartes/ here]
-
[http://books.google.com/books?id=8dSSt6Mrn6sC&printsec=frontcover&dq=at+the+end+of+an+age&source=bl&ots=QynHJAmmSs&sig=6TM1lalB77xQB69lGqQ7leewnU8&hl=en&ei=5jqCTMmMGYSclgfD_Yn5Dw&sa=X&oi=book_result&ct=result&resnum=2&sqi=2&ved=0CCIQ6AEwAQ#v=onepage&q&f=false At the End of an Age] by historian [http://en.wikipedia.org/wiki/John_Lukacs John Lukacs] is not a scientific book, but it contains a deeply informed reflection on the nature of historical and scientific knowledge. Read a shorter essay on this [http://www.theamericanscholar.org/putting-man-before-descartes/ here]
+
*Also by Lukacs, [http://www.staugustine.net/Confessions%20of%20an%20original%20sinner.htm Confessions of an Original Sinner] is a rich account of a journey through very different places and times, full of sharp observations
===Miscellaneous===
===Miscellaneous===
-
[http://www.sciencedaily.com/news/plants_animals/new_species/ New animal species] are being discovered to this day, the latest being [http://news.nationalgeographic.com/news/2010/09/100901-tarzan-chameleon-tarzanville-forest-science-environment/ the Tarzan chameleon]
+
*[http://www.sciencedaily.com/news/plants_animals/new_species/ New animal species] are being discovered to this day, the latest being [http://news.nationalgeographic.com/news/2010/09/100901-tarzan-chameleon-tarzanville-forest-science-environment/ the Tarzan chameleon]
-
Read about which [http://en.wikipedia.org/wiki/List_of_Hungarians#Scientists_and_inventors Hungarian or Hungarian-born scientists] gave the world the [http://en.wikipedia.org/wiki/L%C3%A1szl%C3%B3_B%C3%ADr%C3%B3 ballpoint pen], [http://en.wikipedia.org/wiki/Dennis_Gabor holography], [http://en.wikipedia.org/wiki/Andrew_Grove Intel], [http://en.wikipedia.org/wiki/Ern%C5%91_Rubik Rubik’s cube], [http://en.wikipedia.org/wiki/Albert_Szent-Gy%C3%B6rgyi vitamin C], [http://en.wikipedia.org/wiki/Hans_Selye stress], and the [http://en.wikipedia.org/wiki/Le%C3%B3_Szil%C3%A1rd nuclear chain reaction]
+
*Read about which [http://en.wikipedia.org/wiki/List_of_Hungarians#Scientists_and_inventors Hungarian or Hungarian-born scientists] gave the world the [http://en.wikipedia.org/wiki/L%C3%A1szl%C3%B3_B%C3%ADr%C3%B3 ballpoint pen], [http://en.wikipedia.org/wiki/Dennis_Gabor holography], [http://en.wikipedia.org/wiki/Andrew_Grove Intel], [http://en.wikipedia.org/wiki/Ern%C5%91_Rubik Rubik’s cube], [http://en.wikipedia.org/wiki/Albert_Szent-Gy%C3%B6rgyi vitamin C], [http://en.wikipedia.org/wiki/Hans_Selye stress], and the [http://en.wikipedia.org/wiki/Le%C3%B3_Szil%C3%A1rd nuclear chain reaction]

Revision as of 13:20, 4 September 2010

Contents

Contact Info

  • Postdoctoral Associate, Engelward laboratory
  • Department of Biological Engineering
  • Massachusetts Institute of Technology
  • 77 Massachusetts Ave, Cambridge, MA
  • Lab: 617-750-7335 (Room 16-760)
  • okiraly AT mit DOT edu

Education

Research interests

My current work is about DNA damage and homologous recombination

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. We are 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

Functional effects of sequence variants in promoters, introns, and protein-coding regions

  • 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 working in a team 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 and disorders such as ADHD. However, the functional effects of promoter polymorphisms (and thus the molecular basis of these associations) were not clear. 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 studied SNP in the gene had no effect on gene expression in our assay. The apparent effect of this SNP in association studies is thus probably 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. The excellent mentoring I received at ABC gave me strong foundations in the laboratory techniques of molecular biology and this project raised my interest in DNA metabolism and recombination.


Publications

Research papers

See them on PubMed

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.

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

Bookmarks

Laboratory tools and resources

Useful links

Good books

  • The Suffering Gene is a very readable book about the various environmental exposures that can damage DNA
  • At the End of an Age by historian John Lukacs is not a scientific book, but it contains a deeply informed reflection on the nature of historical and scientific knowledge. Read a shorter essay on this here

Miscellaneous

Personal tools