The primary goal of the Biomarker Research Group is to identify molecules which can help the diagnosis of different diseases or can serve as therapeutic targets. The Biomarker Research Group focuses on the examination of the molecular mechanisms laying behind diseases affecting mainly the eldelry population such as diabetes, Alzheimer's disease, glaucoma, cardiovascular disease and some forms of cancer. We would like to understand the pathophysiological changes leading to the disease and also to find suitable biomarkers which can help the diagnosis of these diseases. The Biomarker Research Group has good collaboration with the cliniques of the Clinical Center of the University of Debrecen and by using the state-of-the art analytical techniques can analyze the human samples coming to the laboratory. We are mainly focusing on the analysis of body fluids collected by non-invasive means and analyze the protein and lipid profile changes of these human samples. The members of the research group are committed to develop and utilize novel mass spectrometry-related techniques to be able to analyze the alterations of proteins and lipids in the biological samples.

Analysis of tear proteins of patients with Alzheimer’s disease

Alzheimer’s disease is one of the most common age-related dementia affecting millions people worldwide. Multiple studies highlighted the role of amyloid-β peptides and the hyperphosphorilated tau protein in the pathophysiology of the disease. The presence of amyloid plaques was demonstrated in retina and lens of patients with Alzheimer’s disease and according to animal models there is a correlation between the amyloid depositions in the retina and brain. Tear is an easy to collect body fluid containing near 1500 proteins. We are analyzing the tears of patients with Alzheimer’s disease with classical proteomics and targeted mass spectrometry methods in order to identify possible new biomarkers. According to our results the combination of lipocalin-1, dermcidin, lacritin and lysozyme C can be used as biomarker for Alzheimer’s disease. In order to be able to utilize these potential biomarkers more analyses should be performed on larger patient cohorts.

Proteomics analysis of the human sweat

The human skin creates an effective chemical barrier by secreting antimicrobial and immunmodulatory proteins as part of the innate immune system. Some of the antimicrobial peptides were shown to be expressed constitutively while others were found to be inducible upon pathogenic stimuli. Our workgroup has identified the most abundant proteins in the human sweat using state of the art mass spectrometry quantification techniques and have developed SRM-based methods for the analysis of the components of the chemical barrier. Our findings with regard to the proteins forming the chemical barrier of the skin can be further used as a starting point for non-invasive sweat biomarker research.

Identification of salivary biomarkers characteristic for oral squamous cell carcinoma (OSCC)

Hungarian population occupies the top places of statistics regarding oral squamous cell carcinoma incidence, thus the identification of new biomarkers is essential in order to increase the survival rate of the patients. Our workgroup examined saliva samples of patients with oral squamous cell carcinoma by targeted mass spectrometry method and Luminex-based multiplex assay in order to identify possible new biomarkers for the Hungarian population. According to our data, the level of IL-6, S100A9 and thioredoxin changed significantly in the saliva of patients with OSCC.

Multimodal examination of neurodegenerative eye diseases

Glaucoma and diabetic retinopathy are neurodegenerative conditions which can be considered as leading causes of blindness worldwide. Our research group analyses tear samples of patients with different stages of diabetic retinopathy and of patients with glaucoma underwent trabeculectomy. The results of the clinical examination, corneal confocal microscopy and retinal photography examinations are combined with proteomic data to achieve a more comprehensive understanding of the pathopysiological condition present and also to find suitable markers which can help the diagnosis. Databanks of patient data, results of clinical examinations and proteomics analyses are generated permitting the further examination of data coming from different modalities.

Oncoproteomics from systems biology point of view

The analysis of protein profile changes in biological samples originating from patiens having different forms of brain cancers, breast cancer, oral cancer or malignant melanoma and the combination of proteomic data with lipidomic, transcriptomic and microbiota data is the major goal of this project. A system biology approach along with network analysis will be used to evaluate data coming from different omics approaches in order to get a clearer picture of the pathological change and response to therapy.

Tear and serum analysis to decifer patomechanisms laying behind obesity and type 2 diabetes

Obesity and the type 2 diabetes (T2D) are major health impairing conditions affecting millions of people worldwide. The disease itself or the disease-related complications put a heavy burden on the society. In this project our aim is to digitalize the tear and serum proteomes and to carry out an unbiased data-driven proteomics study to identify pathways and proteins characteristic to the obesity – early T2D – advanced diabetes with diabetic complications axis and to follow the appearance of complications at the level of serum and/or tear proteomes. Our aim is to examine the digitalized tear and serum proteomes along with metabolites, lipid mediators and proteins having role in immune response, and to correlate the obtained data with the clinical and ophthalmological parameters. We would like to identify tear and/or serum proteins which can be potential biomarkers to help the prediction of obesity-diabetes transition, the diagnosis of diabetes-related complications, such as diabetic retinopathy or can be used as potential therapeutic targets. The results of the unbiased approach will be verified in cell culture experiments. At the same time, we would like to deposit to publicly available databases the digitalized tear and serum proteomes allowing further examinations by the scientific community and possibly speeding up the translation of research data into clinically usable diagnostic or therapeutic modalities.

1. Scholtz B, Vo Minh D, Kiss C, Tar I, Kumar A, Tőzsér J, Csősz É, Márton I. (2020) Examination of Oral Squamous Cell Carcinoma and Precancerous Lesions Using Proximity Extension Assay and Salivary RNA Quantification. BIOMEDICINES. 8:610.

2. Posta, Niké ; Csősz, Éva ; Oros, Melinda ; Pethő, Dávid ; Potor, László ; Kalló, Gergő ; Hendrik, Zoltán ; Sikura, Katalin Éva ; Méhes, Gábor ; Tóth, Csaba et al. (2020) Hemoglobin oxidation generates globin-derived peptides in atherosclerotic lesions and intraventricular hemorrhage of the brain, provoking endothelial dysfunction. LABORATORY INVESTIGATION 100 :7,  986-1002. , 17 p.

3. Márton IJ, Horváth J, Lábiscsák P, Márkus B, Dezső B, Szabó A, Tar I, Piffkó J, Jakus P, Barabás J, Barabás P, Olasz L, Kövér Z, Tőzsér J, Sándor J, Csősz É, Scholtz B, Kiss C. (2019) Salivary IL-6 mRNA is a Robust Biomarker in Oral Squamous Cell Carcinoma. J CLIN MED. 8:1958.

4. Csosz, Eva; Toth, Ferenc; Mahdi, Mohamed; Tsaprailis, George; Emri, Miklos; Tozser, Jozsef (2019) Analysis of networks of host proteins in the early time points following HIV transduction. BMC BIOINFORMATICS  20, 398.
5. Csősz, Éva ; Deák, Eszter ; Tóth, Noémi ; Traverso, Carlo Enrico ; Csutak, Adrienne (2019) Tőzsér, József: Comparative analysis of cytokine profiles of glaucomatous tears and aqueous humour reveals potential biomarkers for trabeculectomy complications. FEBS OPEN BIO 9: 5 pp. 1020-1028. 9 p.
6. Csősz, É ; Márkus, B ; Darula, Z ; Medzihradszky, K ; Nemes, J ; Tőzsér, J ; Kiss, C ; Márton, I (2018) Salivary proteome profiling of oral squamous cell carcinoma in a Hungarian population. FEBS OPEN BIO 8 pp. 556-569. , 14 p.
7. Csősz, Éva ; Tóth, Noémi ; Deák, Eszter ; Csutak, Adrienne ; Tőzsér, József (2018) Wound-Healing Markers Revealed by Proximity Extension Assay in Tears of Patients following Glaucoma Surgery. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 19 : 12 Paper: 4096 , 19 p.
8. Virga, J ; Bognár, L ; Hortobágyi, T ; Zahuczky, G ; Csősz, É ; Kalló, G ; Tóth, J ; Hutóczki, G ; Reményi-Puskár, J ; Steiner, L et al. (2018) Tumor Grade versus Expression of Invasion-Related Molecules in Astrocytoma. PATHOLOGY AND ONCOLOGY RESEARCH 24 : 1 pp. 35-43. , 9 p.
9. Virga, Jozsef ; Bognar, Laszlo ; Hortobagyi, Tibor ; Csosz, Eva ; Kallo, Gergo ; Zahuczki, Gabor ; Steiner, Laszlo ; Hutoczki, Gabor ; Remenyi-Puskar, Judit ; Klekner, Almos (2018) The Expressional Pattern of Invasion-Related Extracellular Matrix Molecules in CNS Tumors. CANCER INVESTIGATION 36 : 9-10 pp. 492-503. , 12 p.
10. Márkus B, Szabó K, Pfliegler WP, Petrényi K, Boros E, Pócsi I, Tőzsér J, Csősz É, Dombrádi V (2017) Proteomic analysis of protein phosphatase Z1 from Candida albicans. PLoS One. 12:e0183176.
11. Márkus B, Pató Z, Sarang Z, Albert R, Tőzsér J, Petrovski G, Csősz É. (2017) The proteomic profile of a mouse model of proliferative vitreoretinopathy. FEBS Open Bio. 7:1166-1177.
12. Csősz É, Lábiscsák P, Kalló G, Márkus B, Emri M, Szabó A, Tar I, Tőzsér J, Kiss C, Márton I. (2017) Proteomics investigation of OSCC-specific salivary biomarkers in a Hungarian population highlights the importance of identification of population-tailored biomarkers. PLoS One. 12:e0177282.
13. Virga J, Bognár L, Hortobágyi T, Zahuczky G, Csősz É, Kalló G, Tóth J, Hutóczki G, Reményi-Puskár J, Steiner L, Klekner A. (2017) Tumor Grade versus Expression of Invasion-Related Molecules in Astrocytoma. Pathol Oncol Res. 2017 Feb 4. [Epub ahead of print]
14. Csősz É, Kalló G, Jakob B, Deák E, Csutak A, Tőzsér J. (2017) Quantitative body fluid proteomics in medicine - A focus on minimal invasiveness. J Proteomics. 153:30-43.
15. Virga J, Bognár L, Hortobágyi T, Zahuczky G, Csősz É, Kalló G, Tóth J, Hutóczki G, Reményi-Puskár J, Steiner L, Klekner A. (2017) Prognostic Role of the Expression of Invasion-Related Molecules in Glioblastoma. J Neurol Surg A Cent Eur Neurosurg. 78:12-19.
16. Csomós K, Kristóf E, Jakob B, Csomós I, Kovács G, Rotem O, Hodrea J, Bagoly Z, Muszbek L, Balajthy Z, Csősz É, Fésüs L. (2017) Protein cross-linking by chlorinated polyamines and transglutamylation stabilizes neutrophil extracellular traps. Cell Death Dis. 7:e2332.
17. Csősz É, Deák E, Kalló G, Csutak A, Tőzsér J. (2017) Diabetic retinopathy: Proteomic approaches to help the differential diagnosis and to understand the underlying molecular mechanisms. J Proteomics. 150:351-358.
18. Gergő Kalló, Miklós Emri, Zsófia Varga, Bernadett Ujhelyi, József Tőzsér, Adrienne Csutak and Éva Csősz (2016) Changes in the chemical barrier composition of tears in Alzheimer's disease reveal potential tear diagnostic biomarkers. PLoS One. 11(6):e0158000.
19. Gábor Hutóczki, László Bognár, Judit Tóth, Beáta Scholtz, Gábor Zahuczky, Zoltán Hanzély, Éva Csősz, Judit Reményi-Puskár, Gergő Kalló, Tibor Hortobágyi, Almos Klekner (2016) Effect of concomitant radiochemotherapy on invasion potential of glioblastoma, Pathol Oncol Res. 22:155-60.
20. Álmos Klekner, Gábor Hutóczki, József Virga, Judit Reményi-Puskár, Judit Tóth, Beáta Scholtz, Éva Csősz, Gergő Kalló, László Steiner, Tibor Hortobágyi, László Bognár (2015) Expression pattern of invasion-related molecules in the peritumoral brain, Clin Neurol Neurosurg. 139:138-43.
21. Gerardo Alvarado, Viktória Jeney, Attila Tóth, Éva Csősz, Gergő Kalló, Thanh An Huynh, Csaba Hajnal, Judit Kalász, Enikő T. Pásztor, István Édes, Magnus Gram, Bo Akerström, Ann Smith, John W. Eaton, György Balla, Zoltán Papp, József Balla (2015) Heme-induced contractile dysfunction in human cardiomyocytes caused by oxidant damage to thick filament proteins, Free Radical Biology and Medicine 89:248-62.
22. Gergő Kalló, Arunima Chatterjee, Márta Tóth, Éva Rajnavölgyi, Adrienne Csutak, József Tőzsér, Éva Csősz (2015) Relative quantification of human β-defensins by an SRM-based proteomics approach, Rapid Communications in Mass Spectrometry, 29:1623–1631.
23. Eva Csosz, Gabriella Emri, Gergő Kalló, George Tsaprailis, József Tőzsér (2015) Highly abundant defense proteins in human sweat as revealed by targeted proteomics and label free quantification mass spectrometry. Journal of the European Academy of Dermatology and Venereology, 29(10):2024-2031.
24. Zsolt Torok, Tunde Peto, Eva Csosz, Edit Tukacs, Agnes M Molnar, Andras Berta, Jozsef Tozser, Andras Hajdu, Valeria Nagy, Balint Domokos, Adrienne Csutak (2014) Combined Methods for Diabetic Retinopathy Screening, Using Retina Photographs and Tear Fluid Proteomics Biomarkers. Journal of Diabetes Research. 501.
25. Csutak A., Török Z., Csősz É., Pető T. (2014) Látásmentő új szűrés. Term. Vil. 145, 207-210.
26. Torok Z, Peto T, Csosz E, Tukacs E, Molnar A, Maros-Szabo Z, Berta A, Tozser J, Hajdu A, Nagy V, Domokos B, Csutak A. (2013) Tear fluid proteomics multimarkers for diabetic retinopathy screening. BMC Ophthalmol. 13:40.
27. Palicz Z, Jenes A, Gáll T, Miszti-Blasius K, Kollár S, Kovács I, Emri M, Márián T, Leiter E, Pócsi I, Csősz E, Kalló G, Hegedűs C, Virág L, Csernoch L, Szentesi P. (2013) In vivo application of a small molecular weight antifungal protein of Penicillium chrysogenum (PAF). Toxicol Appl Pharmacol. 269:8-16.
28. Csősz E, Boross P, Csutak A, Berta A, Tóth F, Póliska S, Török Z, Tőzsér J. (2012) Quantitative analysis of proteins in the tear fluid of patients with diabetic retinopathy. J Proteomics. 75:2196-2204.