Research project

The System Biology of Reproduction Lendület Research Group studies the obstetrical, biological, immunological, pathological, and systemic biological aspects of habitual miscarriages and severe obstetrical syndromes. The importance of the research topic is given by the fact that 50-70% of conceived pregnancies and 10-15% of clinically recognized pregnancies end in miscarriage, and ~25% of pregnant women experience other complications that endanger the health of the mother and/or fetus (e.g. preeclampsia, intrauterine fetal restriction).

In all these pregnancy complications, the failure of the development or functions of the placenta have a central role. The placenta shares common characteristics with solid tumors, including rapid proliferation and growth, evasion of immune surveillance, and invasion. The focus of our research is the characterization of placenta-solid tumor shared signaling pathways which play a central role in the development of miscarriages and obstetrical syndromes, including the systems biology study of complex and interconnected disorders of maternal-fetal immune tolerance, trophoblast invasion and differentiation.

We perform omics (proteomics, transcriptomics, epigenomics) exploratory and validation studies on pregnancy samples collected by our sample collection activities with clinical collaborators and placed in our Perinatal Biobank. For the analysis of “big data”, we use a wide range of bioinformatics and systems biology methods to identify biomarkers and identify molecular disease pathways. The diagnostic characteristics of the identified biomarkers are established on large number of clinical samples from the biobank with validation studies. As a result of our research, it becomes possible to describe the molecular pathways and regulatory networks of disease processes, as well as to identify new biomarkers and drug action points in miscarriages and obstetrical syndromes, enabling early screening and personalized prevention.

Perinatal Biobank

Selected recent publications

Research papers

N.G. Than, R. Romero, A.L. Tarca, K.A. Kekesi, Y. Xu, Z. Xu, K. Juhasz, G. Bhatti, R.J. Leavitt, Zs. Gelencser, J. Palhalmi, T.H. Chung, B.A. Gyorffy, L. Orosz, A. Demeter, A. Szecsi, E. Hunyadi-Gulyas, Zs. Darula, A. Simor, K. Eder, Sz. Szabo, V. Topping, H. El-Azzamy, C. LaJeunesse, A. Balogh, G. Szalai, S. Land, O. Torok, Z. Dong, I. Kovalszky, A. Falus, H. Meiri, S. Draghici, S.S. Hassan, T. Chaiworapongsa, M. Krispin, M. Knöfler, O. Erez, G.J. Burton, C.J. Kim, G. Juhasz, Z. Papp: Integrated systems biology approach identifies novel maternal and placental pathways of preeclampsia. Frontiers in Immunology, 9, 1661, 2018.
A. Balogh, E. Toth, R. Romero, K. Parej, D. Csala, N.L. Szenasi, I. Hajdu, K. Juhasz, A.F. Kovacs, H. Meiri, P. Hupuczi, A.L. Tarca, S.S. Hassan, O. Erez, P. Zavodszky, J. Matko, Z. Papp, S.W. Rossi, S. Hahn, E. Pallinger, N.G. Than: Placental galectins are key players in regulating the maternal adaptive immune response. Frontiers in Immunology, 10, 1240, 2019.
A. Szilagyi, Zs. Gelencser, R. Romero, Y. Xu, P. Kiraly, A. Demeter, J. Palhalmi, B.A. Gyorffy, K. Juhasz, P. Hupuczi, K.A. Kekesi, G. Meinhardt, Z. Papp, S. Draghici, O. Erez, A.L. Tarca, M. Knöfler, N.G. Than: Placenta-specific genes, their regulation during villous trophoblast differentiation and dysregulation in preterm preeclampsia. International Journal of Molecular Sciences, 21, 628, 2020.
G. Meinhardt, S. Haider, V. Kunihs, L. Saleh, J. Pollheimer,C. Fiala, Sz. Hetey, Zs. Feher, A. Szilagyi, N.G. Than, M. Knöfler: Pivotal role of the transcriptional co-activator YAP in trophoblast stemness of the developing human placenta. Proceedings of the National Academy of Sciences of the USA, 117, 13562-13570, 2020.
Z. Szabolcsi, A. Demeter, P. Kiraly, A. Balogh, M.L. Wilson, J.R. King, Sz. Hetey, Zs. Gelencser, K. Matsuo, B. Hargitai, P. Mhawech-Fauceglia, P. Hupuczi, A. Szilagyi, Z. Papp, L.D. Roman, V.K. Cortessis, N.G. Than: Epigenetic dysregulation of trophoblastic gene expression in gestational trophoblastic disease. Biomedicines, 9, 1935, 2021.
A.L. Tarca, A. Taran, R. Romero, E.J. Jung, C. Paredes, G. Bhatti, C. Ghita, T. Chaiworapongsa, N.G. Than, C.D. Hsu: Prediction of preeclampsia throughout gestation with maternal characteristics and biophysical and biochemical markers: a longitudinal study. American Journal of Obstetrics and Gynecology, 226(1):126.e1-126.e22., 2022.
N.G. Than, M. Posta, D. Györffy, L. Orosz, G. Orosz, S.W. Rossi, G. Ambrus-Aikelin, A. Szilágyi, S. Nagy, P. Hupuczi, O. Török, A.L. Tarca, O. Erez, Z. Papp, R. Romero: Early pathways, biomarkers and four distinct molecular subclasses of preeclampsia: the intersection of clinical, pathological and high dimensional biology studies. Placenta (Trophoblast Research) 125, 10-19, 2022.
N.G. Than, R. Romero, D. Györffy, M. Posta, G. Bhatti, B. Done, P. Chaemsaithong, E. Jung, M. Suksai, F. Gotsch, D.M. Gallo, M. Bosco, B. Kim, Y.M. Kim, T. Chaiworapongsa, S.W. Rossi, A. Szilágyi, O. Erez, A.L. Tarca, Z. Papp: Molecular subclasses of preeclampsia characterized by a longitudinal maternal proteomics study: distinct biomarkers, disease pathways and options for prevention. Journal of Perinatal Medicine, 51(1), 51-68, 2022.
O. Oravecz, R. Romero, E. Tóth, J. Kapitány, M. Posta, D.M. Gallo, S.W. Rossi, A.L. Tarca, O. Erez, Z. Papp, J. Matkó, N.G. Than, A. Balogh: Placental galectins regulate innate and adaptive immune responses in pregnancy. Frontiers in Immunology, 13, 1088024, 2022.
O. Erez, F. Gotsch, E. Jung, T. Chaiworapongsa, D.W. Gudicha, M. Suksai, D.M. Gallo, P. Chaemsaithong, M. Bosco, M. Al Qasem, A. Meyyazhagan, N.G. Than, R. Romero: Perturbations in kinetics of the thrombin generation assay identify women at risk of preeclampsia in the first trimester and provide the rationale for a preventive approach. American Journal of Obstetrics and Gynecology, 228(5):580.e1-580.e17, 2023.

Reviews

N.G. Than, A. Balogh, R. Romero, E. Karpati, O. Erez, A. Szilagyi, I. Kovalszky, M. Sammar, S. Gizurarson, J. Matko, P. Zavodszky, Z. Papp, H. Meiri: Placental Protein 13 (PP13) – a placental immunoregulatory galectin protecting pregnancy. Frontiers in Immunology, 5, Article 348, 1-25, 2014.
N.G. Than, R. Romero, M. Posta, D. Györffy, G. Szalai, S.W. Rossi, A. Szilágyi, P. Hupuczi, S. Nagy, O. Török, A.L. Tarca, O. Erez, N. Ács, Z. Papp: Classification of preeclampsia according to molecular clusters with the goal of achieving personalized prevention. Journal of Reproductive Immunology, 2023 Nov 30;161:104172. doi: 10.1016/j.jri.2023.104172.

eBook

Fetal-Maternal Immune Interactions in Pregnancy. Frontiers in Immunology, Eds. N.G. Than, S. Hahn, S.W. Rossi, J. Szekeres-Bartho, 2019. ISBN 978-2-88963-242-8

Innovation activity / patent applications

The immunotherapeutical use of placental galectins. Hungarian patent application No. P1900045 (submitted)
Novel biomarkers of recurrent pregnancy loss. (in preparation)
Novel biomarkers of intrauterine growth restriction. (in preparation)

Scientific collaborations

International research groups

Pregnancy Research Branch, National Institutes of Health (Detroit, MI, USA)
Wayne State University (Detroit, MI, USA)
University of Southern California (Los Angeles, CA, USA)
University of Basel (Basel, Switzerland)
Universitätsklinikum Hamburg-Eppendorf (Hamburg, Germany)
Ben Gurion University (Beer Sheva, Israel)
Tampere University (Tampere, Finland)
Medical University of Vienna (Vienna, Austria)
West Midlands Perinatal Pathology Centre, Birmingham Women’s and Children’s NHS FT (Birmingham, United Kingdom)
University of Bologna (Bologna, Italy)
Monash University (Clayton, Australia)

HUN-REN research institutes

HUN-REN Research Centre for Natural Sciences (Budapest)
HUN-REN Biological Research Centre (Szeged)

HUN-REN RCNS research groups

Structural Biophysics Research Group
Gene Regulation Research Group
Oncology Biomarker Research Group
Epigenetic and Genome Editing Research Group
MS Proteomics Research Group

Hungarian Universities / Hospitals

Semmelweis University (Budapest)
Eötvös Loránd University (Budapest)
University of Pécs (Pécs)
University of Debrecen (Debrecen)
Petz Aladár County Teaching Hospital (Győr)
Maternity Clinic (Budapest)

Industrial partners

Zymo Research Corporation (Irvine, CA, USA)
Biognosys AG (Schlieren, Switzerland)
TeleMarpe Ltd (Tel Aviv, Israel)
Richter Gedeon Plc (Budapest)
GraviDiagnostics Ltd. (Budapest)

Current grant support

NKFIH 2020-1.1.2-PIACI-KFI-2021-00273
NKFIH 2019-2.1.7-ERA-NET-2020-00014
Research Centre for Natural Sciences – Lendület Fund

Teaching activity

Postgraduate teaching

Semmelweis University – Chapters from the immunobiology of pregnancy
Eötvös Loránd University – The systems biological view of the immunology of pregnancy

PhD topic

Semmelweis University, Clinical Medicine Doctoral School – Pathomechanisms, early prediction and diagnosis of the Great Obstetrical Syndromes

PhD students

Katalin Karászi, PhD (2021)
Gábor Szalai, MD, PhD (2015)
Szilvia Szabó, PhD (2015)
Emese Vivien Farkas, MSc
Orsolya Oravecz, MSc
Máté Posta, MD

Interviews, presentations

Principal investigator

Nándor Gábor Than, MD PhD, senior research fellow

Our research group on the cover

Members

Name	Status	Phone	Office	Bibliography
Judit Baunoch	laboratory assistant	+36 1 3826 674	É2.07
Emese Vivien Farkas	PhD student	+36 1 3826 674	É2.07
Dániel Györffy, PhD	research fellow	+36 1 3826 717	D3.08B	10019484
Mariann Holczer-Havas	research coordinator	+36 1 3826 788	D3.11A
Irén Horváth
Andor Jelinek	biobank coordinator	+36 1 3826 641	É2.07
Éva Etelka Kiss
János Matko, DSci
Orsolya Oravecz	PhD student	+36 1 3826 641	É2.07	10081331
Andrea Papp-Balogh, PhD	senior research fellow	+36 1 3826 641	É2.07	10019319
Máté Posta, MD	PhD student	+36 1 3826 641	É2.07	10082656
Gábor Szalai, MD, PhD
András Szilágyi, PhD	senior research fellow	+36 1 3826 717	D3.08B	10010376
Ákos Szödényi	research fellow	+36 1 3826 788	D3.11A
Nándor Gábor Than, MD, PhD	group leader	+36 1 3826 788	D3.11A	10011696