Ageliki Gerovassili

EDUCATION
2003 – 2006 • King’s College London, London, UK
PhD in Non Invasive Prenatal Diagnosis
Investigation of non-invasive and invasive prenatal diagnosis methods for the detection of chromosomal abnormalities and sickle cell disease. The project involved detection of free fetal DNA in maternal circulation (plasma or serum) and coelomic and amniotic fluid in qualitative or quantitative ways. The funding body of this research was the Fetal Medicine Foundation and the research was carried out under the supervision of Dr David Rees, Prof Swee Lay Thein and Prof Kypros Nicolaides.
Valuable scientific communication skills were gained during patient blood sample collection which entailed working closely with research fellows and patients. The project was explained both in layman’s terms for volunteers consent forms, and in greater detail when applying for ethical approval. High managerial skills were required to effectively organise the protocols, train staff and order all the laboratory consumables for this and other projects. Regular oral presentations were given to an audience ranging from students to clinicians and professors.

2004 – 2006 • King’s College London, London, UK
Associate of King’s College London (AKC)
Courses included: Ethics (medical and social), Different religious experiences, The Bible and the Christian doctrine. This degree improved my understanding of the ethics as seen by people with different religious backgrounds.

2001 – 2002 • University College London, London, UK
MSc in Prenatal Genetics and Fetal Medicine
Courses included: Genetics, Fetal Medicine, Prenatal Diagnosis, Human Embryonic Development, Preimplantation Genetic Diagnosis MSc. Project on “Preimplantation genetic diagnosis for α thalassaemia patients” under the supervision of Dr Mary Petrou.

1998 – 2001 • King’s College London, London, UK
BSc (Hons) in Molecular Genetics, 2.1
Courses included: Molecular genetics, genetic engineering, bioinformatics, gene cloning, human and biochemical genetics, biochemistry of gene expression, medical microbiology, human immunology, regulation of mammalian metabolism, reproduction growth and development, biotechnology, chemistry etc.
Final year project on “Use of bioinformatics to screen the peripheral benzodiazepine receptor for polymorphisms in schizophrenia” under the supervion of Dr David Collier in Institute of Psychiatry (75%)

EMPLOYMENT EXPERIENCE
Oct 2006 – ongoing • Medical Laboratories, Technological Educational Institute of Larissa
Scientific and laboratory collaborator
• Teaching Medical Biotechnology-Molecular Basis of Genetic Diseases lab session (2007-ongoing)
• Elements of Biology-Genetics lab session (2010-2011)
• Research Methodology theory session (2008-2009)
• Medical Microbiology lab session (2006-2007)

Oct 2007 – ongoing • Nursing School, Technological Educational Institute of Larissa
Scientific and laboratory collaborator
• Human Physiology (2008-ongoing)
• General Microbiology theory session (2007-2008)

Sep 2007 – ongoing • Medical School, University of Thessaly, Larissa
Visiting lecturer in MSc Reproduction Biology (Gynaecological Dept)
• Teaching Diagnostic Methodology laboratory sessions
• Teaching Prenatal diagnosis theory sessions

Sep 2007 – Feb 2011 • Medical School, University of Thessaly, Larissa
Full-time scientific collaborator
• Teaching Biology-Genetics lab session to medical students.

2002 – 2003 • Molecular Haematology, King’s College Hospital, London
Research Assistant
• Investigation of the HPFH (hereditary persistence of Hb F) major QTL in order to discover any variations.
• PCR, Sequencing, RACE, cloning.

Summer 1999 • Dr. A. Salgami Microbiology Laboratory, Larissa, Greece
Microbiologist Assistant
• Hematological, Immunological, Biochemical and Hormonal analysis.
• Liasing with patients.

MEMBER IN SOCIETIES
• Member of ESHRE (European society of Human Reproduction)
• Member of Greek society of Molecular Biologists and Geneticists
• Member of the Greek society of Care, Health and Education

Abstract: Individual variation in fetal hemoglobin (HbF, alpha(2)gamma(2)) response underlies the remarkable diversity in phenotypic severity of sickle cell disease and beta thalassemia. HbF levels and HbF-associated quantitative traits (e.g., F cell levels) are highly heritable. We have previously mapped a major quantitative trait locus (QTL) controlling F cell levels in an extended Asian-Indian kindred with beta thalassemia to a 1.5-Mb interval on chromosome 6q23, but the causative gene(s) are not known. The QTL encompasses several genes including HBS1L, a member of the GTP-binding protein family that is expressed in erythroid progenitor cells. In this high-resolution association study, we have identified multiple genetic variants within and 5' to HBS1L at 6q23 that are strongly associated with F cell levels in families of Northern European ancestry (P = 10(-75)). The region accounts for 17.6% of the F cell variance in northern Europeans. Although mRNA levels of HBS1L and MYB in erythroid precursors grown in vitro are positively correlated, only HBS1L expression correlates with high F cell alleles. The results support a key role for the HBS1L-related genetic variants in HbF control and illustrate the biological complexity of the mechanism of 6q QTL as a modifier of fetal hemoglobin levels in the beta hemoglobinopathies.

Abstract: Current methods for prenatal diagnosis of chromosomal aneuploidies involve the invasive sampling of fetal materials using procedures such as amniocentesis or chorionic villus sampling and constitute a finite risk to the fetus. Here, we outline a strategy for fetal chromosome dosage assessment that can be performed noninvasively through analysis of placental expressed mRNA in maternal plasma. We achieved noninvasive prenatal diagnosis of fetal trisomy 21 by determining the ratio between alleles of a single-nucleotide polymorphism (SNP) in PLAC4 mRNA, which is transcribed from chromosome 21 and expressed by the placenta, in maternal plasma. PLAC4 mRNA in maternal plasma was fetal derived and cleared after delivery. The allelic ratios in maternal plasma correlated with those in the placenta. Fetal trisomy 21 was detected noninvasively in 90% of cases and excluded in 96.5% of controls.

Abstract: Previous studies on the association of fetal cell-free (cf)DNA levels in maternal circulation have produced conflicting results but the sample sizes were small and based on archived material. We aimed to quantify the levels of fetal and total cfDNA on prospectively collected samples, to understand their correlation with other variables and to clarify their diagnostic value.


Books

2011	P Plageras, A Gerovassili, A Papaioannou (2011) Applications of Molecular Diagnostics P.X. Pasxalidis 1st isbn:978-960-489-188-7 Abstract: Notes:
Journal articles

2010	DOI PMID Anastassios C Manolakis, Andreas N Kapsoritakis, Elisavet K Tiaka, Maria Satra, Aggeliki Gerovassili, Ilias Tsiompanidis, Nikolaos Vamvakopoulos, Spyros P Potamianos (2010) Impact of TLR-4 polymorphisms on circulating levels of antibodies against Helicobacter pylori. Helicobacter 15: 5. 481-482 Oct Abstract: Notes:
2008	DOI PMID G Makrydimas, A Gerovassili, A Sotiriadis, A Kavvadias, K H Nicolaides (2008) Cell-free fetal DNA in celomic fluid. Ultrasound Obstet Gynecol 32: 4. 594-595 Sep Abstract: Notes:
2007	DOI PMID Swee Lay Thein, Stephan Menzel, Xu Peng, Steve Best, Jie Jiang, James Close, Nicholas Silver, Ageliki Gerovasilli, Chen Ping, Masao Yamaguchi, Karin Wahlberg, Pinar Ulug, Tim D Spector, Chad Garner, Fumihiko Matsuda, Martin Farrall, Mark Lathrop (2007) Intergenic variants of HBS1L-MYB are responsible for a major quantitative trait locus on chromosome 6q23 influencing fetal hemoglobin levels in adults. Proc Natl Acad Sci U S A 104: 27. 11346-11351 Jul Abstract: Individual variation in fetal hemoglobin (HbF, alpha(2)gamma(2)) response underlies the remarkable diversity in phenotypic severity of sickle cell disease and beta thalassemia. HbF levels and HbF-associated quantitative traits (e.g., F cell levels) are highly heritable. We have previously mapped a major quantitative trait locus (QTL) controlling F cell levels in an extended Asian-Indian kindred with beta thalassemia to a 1.5-Mb interval on chromosome 6q23, but the causative gene(s) are not known. The QTL encompasses several genes including HBS1L, a member of the GTP-binding protein family that is expressed in erythroid progenitor cells. In this high-resolution association study, we have identified multiple genetic variants within and 5' to HBS1L at 6q23 that are strongly associated with F cell levels in families of Northern European ancestry (P = 10(-75)). The region accounts for 17.6% of the F cell variance in northern Europeans. Although mRNA levels of HBS1L and MYB in erythroid precursors grown in vitro are positively correlated, only HBS1L expression correlates with high F cell alleles. The results support a key role for the HBS1L-related genetic variants in HbF control and illustrate the biological complexity of the mechanism of 6q QTL as a modifier of fetal hemoglobin levels in the beta hemoglobinopathies. Notes:
	DOI PMID Y M Dennis Lo, Nancy B Y Tsui, Rossa W K Chiu, Tze K Lau, Tse N Leung, Macy M S Heung, Ageliki Gerovassili, Yongjie Jin, Kypros H Nicolaides, Charles R Cantor, Chunming Ding (2007) Plasma placental RNA allelic ratio permits noninvasive prenatal chromosomal aneuploidy detection. Nat Med 13: 2. 218-223 Feb Abstract: Current methods for prenatal diagnosis of chromosomal aneuploidies involve the invasive sampling of fetal materials using procedures such as amniocentesis or chorionic villus sampling and constitute a finite risk to the fetus. Here, we outline a strategy for fetal chromosome dosage assessment that can be performed noninvasively through analysis of placental expressed mRNA in maternal plasma. We achieved noninvasive prenatal diagnosis of fetal trisomy 21 by determining the ratio between alleles of a single-nucleotide polymorphism (SNP) in PLAC4 mRNA, which is transcribed from chromosome 21 and expressed by the placenta, in maternal plasma. PLAC4 mRNA in maternal plasma was fetal derived and cleared after delivery. The allelic ratios in maternal plasma correlated with those in the placenta. Fetal trisomy 21 was detected noninvasively in 90% of cases and excluded in 96.5% of controls. Notes:
	DOI PMID Ageliki Gerovassili, Chad Garner, Kypros H Nicolaides, Swee Lay Thein, David C Rees (2007) Free fetal DNA in maternal circulation: a potential prognostic marker for chromosomal abnormalities? Prenat Diagn 27: 2. 104-110 Feb Abstract: Previous studies on the association of fetal cell-free (cf)DNA levels in maternal circulation have produced conflicting results but the sample sizes were small and based on archived material. We aimed to quantify the levels of fetal and total cfDNA on prospectively collected samples, to understand their correlation with other variables and to clarify their diagnostic value. Notes:

2006	DOI PMID O Falcon, M Auer, A Gerovassili, K Spencer, K H Nicolaides (2006) Screening for trisomy 21 by fetal tricuspid regurgitation, nuchal translucency and maternal serum free beta-hCG and PAPP-A at 11 + 0 to 13 + 6 weeks. Ultrasound Obstet Gynecol 27: 2. 151-155 Feb Abstract: To examine whether in pregnancies with fetal trisomy 21 the level of maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks' gestation is independent of the presence or absence of tricuspid regurgitation and to estimate the performance of a screening test that combines tricuspid regurgitation with fetal nuchal translucency (NT) thickness and serum free beta-hCG and PAPP-A. Notes:
	DOI PMID Ageliki Gerovassili, Kypros H Nicolaides, Swee Lay Thein, David C Rees (2006) Cell-free DNA levels in pregnancies at risk of sickle-cell disease and significant ethnic variation. Br J Haematol 135: 5. 738-741 Dec Abstract: Cell-free (cf) DNA in maternal circulation is increasingly investigated in pregnancy. This study aimed to determine whether sickle-cell trait women had quantitative differences of cf-DNA to controls and if there was an ethnic difference between the cf-DNA levels of Northern European and African/African-Caribbean populations. Non-invasive prenatal diagnosis, through quantification of fetal and total cf-DNA, was tested in 33 pregnant women at risk of carrying a fetus affected with sickle-cell disease and 124 control pregnancies. A significant variation in cf-DNA was found between ethnic groups, which should be taken into consideration in future studies measuring cf-DNA. Notes:
	DOI PMID Yu K Tong, Chunming Ding, Rossa W K Chiu, Ageliki Gerovassili, Stephen S C Chim, Tak Y Leung, Tse N Leung, Tze K Lau, Kypros H Nicolaides, Y M Dennis Lo (2006) Noninvasive prenatal detection of fetal trisomy 18 by epigenetic allelic ratio analysis in maternal plasma: Theoretical and empirical considerations. Clin Chem 52: 12. 2194-2202 Dec Abstract: The discovery of cell-free fetal DNA in maternal plasma has opened up new possibilities for noninvasive prenatal diagnosis. However, the use of maternal plasma fetal DNA for the direct detection of fetal chromosomal aneuploidies has not been reported. We postulate that the aneuploidy status of a fetus could be revealed by an epigenetic allelic ratio approach, i.e., by analyzing the allelic ratio of a single-base variation present within DNA molecules exhibiting a placental-specific epigenetic signature in maternal plasma. Notes:
	DOI PMID K C Allen Chan, Chunming Ding, Ageliki Gerovassili, Sze W Yeung, Rossa W K Chiu, Tse N Leung, Tze K Lau, Stephen S C Chim, Grace T Y Chung, Kypros H Nicolaides, Y M Dennis Lo (2006) Hypermethylated RASSF1A in maternal plasma: A universal fetal DNA marker that improves the reliability of noninvasive prenatal diagnosis. Clin Chem 52: 12. 2211-2218 Dec Abstract: We recently demonstrated that the promoter of the RASSF1A gene is hypermethylated in the placenta and hypomethylated in maternal blood cells. This methylation pattern allows the use of methylation-sensitive restriction enzyme digestion for detecting the placental-derived hypermethylated RASSF1A sequences in maternal plasma. Notes:
2004	DOI PMID James Close, Laurence Game, Barnaby Clark, Jean Bergounioux, Ageliki Gerovassili, Swee Lay Thein (2004) Genome annotation of a 1.5 Mb region of human chromosome 6q23 encompassing a quantitative trait locus for fetal hemoglobin expression in adults. BMC Genomics 5: 1. May Abstract: Heterocellular hereditary persistence of fetal hemoglobin (HPFH) is a common multifactorial trait characterized by a modest increase of fetal hemoglobin levels in adults. We previously localized a Quantitative Trait Locus for HPFH in an extensive Asian-Indian kindred to chromosome 6q23. As part of the strategy of positional cloning and a means towards identification of the specific genetic alteration in this family, a thorough annotation of the candidate interval based on a strategy of in silico / wet biology approach with comparative genomics was conducted. Notes:

Books

Journal articles