Research

Polish Registry of Congenital Malformations (Polski Rejestr Wrodzonych Wad Rozwojowych - PRWWR)

Since 1997, at the initiative of the team of the Chair and Department of Medical Genetics (KiZGM) of PUMS, there has been kept the Polish Registry of Congenital Malformations (PRWWR) which is the only registry of this kind in Poland and the largest one in Europe. The Central Team and Database of PRWWR are located in KiZGM PUMS in Poznan. PRWWR is an original Polish achievement thanks to organizational solutions and numerous and important practical goals. Many organizational solutions are unique and internationally recognized. Thanks to its goals and contact with health care units throughout the country, the role of PRWWR in Poland is equivalent to those played by special government programs in other countries. PRWWR, which is on the official list of registers of the Ministry of Health and has been kept since March 1, 1997, has covered the entire country since 2007, monitoring 100% of births in Poland. Since 2001, PRWWR belongs to the EUROCAT consortium and is its largest registry. Thanks to the membership of PRWWR in EUROCAT, Poland actively participates in the implementation of common goals for monitoring and prevention of congenital malformations in Europe. The chairperson of PRWWR –  Professor A. Latos-Bieleńska, was a member of EUROCAT Steering Committee in the period 2002-2007. A.Materna-Kiryluk, MD, PhD is the Organizational Coordinator of PRWWR. Professor A. Latos-Bieleńska, MD, PhD and  A. Materna-Kiryluk, MD, PhD are members of EUROCAT Registry Leaders and EUROCAT working groups. PRWWR keeps a record of children who have been diagnosed with a developmental defect from the moment of birth until the age of two, as well as stillborn children with developmental defects.  The most important recent publications which confirm the importance of PRWWR include: Sanna-Cherchi S et al. (N Engl J Med. 2013; 369(7):621-9.  IF=54.420); Khoshnood B et al. (BMJ 2015; 351:h5949. doi: 10.1136/bmj.h 5949. IF=19.697).

The first Genome Wide Association Study in Poland for a nonsyndromic cleft lip with or without cleft palate (NSCL/P)

The Chair and Department of Biochemistry and Molecular Biology has made the first and only such an extensive analysis of genetic factors responsible for the development of facial defects in Poland. The GWAS analysis together with the replication analysis allowed the identification of four new chromosomal loci and new candidate genes (DLG1, CHD1 and CDKAL1) for NSCL/P. These results provide an extremely important contribution to the understanding of the complex etiology of these defects and to deepen the fundamental knowledge about the embryonic development of this facial part of the human skull. In the future, the obtained results may directly contribute to the creation of a program of primary prevention of craniofacial malformations which may have serious clinical implications, as the treatment of these developmental anomalies is difficult, long-lasting and multistage. The conducted genomic analysis is an invaluable source of preliminary results for further scientific projects, including advanced statistical and functional analyzes. It allowed the identification of numerous regions in the genome that are significantly related to NSCL/P risk in the Polish population. The identification of these chromosomal loci would be impossible using classical methods of candidate gene analyzes. The obtained results can be used not only for further research on the etiology of NSCL/P, but also other genetically determined diseases. Thanks to the above mentioned GWAS analysis, we also have genotyping results of over 600,000 polymorphisms for a unique control group consisting of 576 healthy people, with no malformations.

Early hearing prosthesis in children using cochlear implants and hearing aids

The Chair and Clinic of Otolaryngology and Laryngological Oncology of Medical Faculty I of Poznan University of Medical Sciences is a pioneering center for the introduction and coordination of the program “Universal Newborn Hearing Research” in the country. The program involves 498 centers, and the medical coordinator is Professor Witold Szyfter, MD, PhD, from the Clinic of Otolaryngology and Laryngological Oncology. The program shortened the detection time of the child's hearing disorders and led to the adoption of prosthesis and early rehabilitation. Early audiological intervention gives the child with a hearing loss a chance to develop speech. In cases of bilateral hearing loss, children need to receive hearing aids early to provide acoustically appropriate sound stimuli. Prosthesis of hearing using hearing aids can therefore take place already in children who are 2-3 months old. However, in some children, especially with bilateral deep hearing loss, such strengthening is not enough. In these cases, it is necessary to implant the cochlear implant. About 100 children who are annually diagnosed as a part of the Program require such highly specialized treatment. It is early cochlear implants in children with bilateral deep hearing that allow them to create the ability to deliver sound stimuli to the developing auditory system which, in turn, gives then the chance for speech development. Early audiological intervention enables proper child development and school education. Szyfter W., Wróbel M., Karlik M., Greczka G.: Polish Universal Neonatal Hearing Screening Program - 10 Years of Experience: Early Intervention - The Benefits and Why ‘Early’ Is Still Not a Standard Practice. Audiol Neurotol 2013;18 (suppl 1):3–5.

Identification of causes of congenital malformations based on arrayCGH technology, next-generation sequencing (NGS) and functional studies

For years, the Chair and Department of Medical Genetics has been conducting pioneer research on the etiology of congenital malformations, especially congenital defects of limbs, ciliaopathy and eye defects. A team led by Professor Aleksander Jamsheer has published several unique papers presenting new mechanisms of genetic determinants of limb defects, both from the group of CNV genome rearrangements, as well as monogenic causes. These publications by Jamsheer A. et al include, among others: BMC Medical Genetics 2013, 14:13; J.Med.Genet. 2013, 50(9):579-584; Gene 2014, 539(1):157-161; Birth Defects Res A Clin Mol Teratol. 2014, 100(4):314-318; Orphanet J. Rare Dis. 2014, 9:108;  J. Hum. Genet. 2016, 61(5):457-461; J. Hum. Genet. 2016, 61(7):577-583. Joanna Walczak-Sztulpa, MD, PhD and Professor  Anna Latos-Bieleńska, MD, PhD, together with their colleagues, have made the world's first identification of the molecular causes of Sensenbrenner syndrome (craniosacral dysplasia). The significance of this discovery is best illustrated by the fact that in recognition of expert knowledge about the clinical and molecular background of the Sensenbrenner syndrome, the above mentioned authors were asked by the publishers to prepare a chapter (Walczak-Sztulpa J, Latos-Bielenska A .: Sensenbrenner Syndrome (Cranioectodermal Dysplasia, CED): A Genetically Heterogenous Ciliopathy) for the third edition of the widely-known academic book „Epstein’s Inborn Errors of Development. The Molecular Basis of Clinical Disorders of Morphogenesis.” 3rd Edition. (ed. RP Erickson, AJ Wynshaw-Boris), Oxford University Press 2016, p. 259-263.

Pharmacoepidemiological research on the effects of using medicines during pregnancy

The Chair and Department of Medical Genetics of Poznan University of Medical Sciences co-founded the EUROmediCAT program which was implemented in 2011-2015 under the 7th. Framework Program of the European Community (EUROmediCAT: Safety of Medication use in Pregnancy in Relation to Risk of Congenital Malformations). The final executor of the program was an international consortium comprising of nine institutions. The EUROmediCAT project was divided into 6 work packages (WP2-WP7) of a scientific and research nature, and WP8 included a task in the dissemination of project results. The Chair and Department of Medical Genetics of Poznan University of Medical Sciences participated in three work packages - WP2, WP4 and WP8, while managing WP8. The EUROmediCAT project created and tested a pharmaceutical surveillance system for the safety of medicines during pregnancy with respect to their teratogenic effects. It tested fetal safety for antiepileptic, anti-asthmatics, antidiabetic (analogue insulin) and antidepressant drugs. The importance of this type of research was appreciated after the thalidomide tragedy in the 1950s and 1960s. It is worth noting that the EUROmediCAT Consortium is still functioning after the completion of the project and has already evaluated a number of medicines belonging to these groups, publishing the results regarding the safety of use of medicines in pregnancy in relation to the risk of congenital malformations and research. Through the participation of the Chair and Department of Medical Genetics in EUROmediCAT, Poland participates in the creation and implementation of an international system for assessing the safety of medicines for the fetus.

EXIT procedure (ex utero intrapartum treatment)

EXIT is a therapeutic procedure introduced by a team from the Reproduction Clinic, carried out during the caesarean section, which aims to ensure the patency of the fetal airways before cutting the umbilical cord. It was introduced to rescue newborns with developmental defects that prevent the newborn from taking a spontaneous respiratory function, i.e. primary or secondary obstruction of the fetal airways (congenital thickening or extreme narrowing of the upper respiratory tract, neck tumors (oppressing the tracheal wall) and lung adenomatous cyst degeneration (CCAM)). This procedure is carried out in several centers in the world and it had not been described and applied by any center in Poland up to that moment, which makes our center one of the leading centers in the world in this field. The EXIT procedure was carried out during four births: one with a huge fetal goiter, one with a huge lymphatic neck tumor, one with a teratoma neck tumor and one with a fetus atresia of the larynx and atresia of the upper respiratory tract (CHAOS). The procedure turned out to be successful in the first three cases, while in the case of CHAOS, as a result of total atresia of the larynx and trachea, it was not possible to perform this procedure. The most important clinical aspects of EXIT are: 1) an appropriate method of anesthesia in the pregnant patient for the purpose of deep relaxation of the uterus, to maintain the uteroplacental flow for a longer period of time and to perform this procedure on the extracted fetus with preserved fetal circulation; 2) proper incision of the uterine wall with appropriate hemostasis of the wound edges and extraction of the fetus approximately to the level of the diaphragm without cutting the umbilical cord; and 3) ensuring the patency of the fetal airways by a properly trained laryngological team.

Creation of www.nefropedia.pl - image libraries of kidney biopsy in children, being a universal, open and repository hosting and communication platform

Developed as part of the NCBR project (National projects - applied research): PBR X NR13-0033-10/2010 in the period: 01.11.2010 to 31.10.2013. Principal investigator: Professor  Danuta Ostalska-Nowicka, MD, PhD. It is a digital archive of images of kidney and urinary tract biopsies which is the basis and enrichment of the didactic process of students (both Polish and English-speaking) and doctors receiving education in the field of nephrology. Nefropedia contains micrographs documenting histological changes in the pathology of the urinary system. The preparations are prepared on the basis of classic histological staining and standard immunohistochemical incubations using routine and scientific analyzes, and then the most interesting didactic photomicrographs with a complete description are published in Nefropedia. Most of the photos were obtained by scanning histological preparations in the high-resolution technique. Nefropedia has the following applications: NefroScaut, which allows the creation of virtual tissue microarrays consisting of reference images of kidney biopsies and own images of preparations; NefroAtlas contains interactive micrographs depicting the pathology of the urinary system with marked pathognomic histological changes with descriptions; in the NefroAddere application, we have the opportunity to edit scientific texts, add comments and enrich the site with presentations, PDF files, images and charts by other authors with their consent. Therefore, Nefropedia gives great opportunities as a scientific and didactic tool in pre- and post-graduate education. Nefropedia is recommended by the Polish Society of Pediatric Nephrology (PTND) and it can be accessed through PTND websites.

Scientific and clinical development of mechanisms of vacuum therapy and its practical aspects

The Department of General, Endocrine and Gastroenterological Oncology Surgery of Medical Faculty I of Poznan University of Medical Sciences are the pioneers of wound vacuum therapy (NPWT) in surgery, especially in gastrointestinal surgery. The clinic has implemented innovative methods of treatment of gastrointestinal fistula, open abdomen and extensive perirectal fistulas with NPWT, it has introduced endoscopic vacuum therapy in anastomotic leakage (one of the first in the world), as well as techniques for combining NPWT with wound irrigation, also in proprietary, non-commercial self-developed dressing models. In 2014, the experience of the team members resulted in the creation of the world's first magazine on vacuum therapy - the quarterly Negative Pressure Wound Therapy (www.npwtj.com), whose editor-in-chief became Professor  Tomasz Banasiewicz. NPWTJ is a fast-growing open-access magazine with a group of international experts at the Editorial Board. Using their own experience, as well as cooperation with foreign specialists, they developed the first monograph in Poland, which is a unique work as far as other European countries are concerned, entitled "Vacuum Therapy of Wounds" (edited by  Tomasz Banasiewicz and Maciej Zielinski) which is a compendium of knowledge about vacuum therapy and discusses the basic aspects and mechanisms of the treatment of hypotensive therapy, but, above all, it is an invaluable source of practical information. The staff at the Clinic have also organized 3 large international conferences devoted to vacuum therapy and are the authors of over 40 publications related to this issue.

Pharmaceutical research

The effective development of Faculty of Pharmacy in 2013-2016 resulted in a significant increase in the number of publications in renowned international journals (90 scientific papers from this period are among the highest-ranked quartile qualitative category of magazines from the Q1 Philadelphia list). This success reflects excellent conditions enabling the development of academic staff and genuine internal cooperation within the Faculty. An important area of interest for scientists at the Faculty is the issue of cancer, including the study of cellular and molecular mechanisms of carcinogenesis, DNA damage and the role of epigenetics in the diagnosis, prevention and therapy of cancer. The research also includes the mechanisms of chemoprevention, especially in the aspect of the use of natural plant materials and food ingredients. The priority is to modify existing drugs and to receive more and more new active compounds, candidates for innovative medicines with a favorable therapeutic index, with particular emphasis on porphyriaids, stilbene derivatives and triterpenes. The current issue investigated by cooperating faculty units are toxic xenobiotics, especially the components of tobacco smoke which are evaluated in terms of pharmacological action, metabolism and harmfulness. The common technological and analytical interests of the Faculty's researchers are focused on the development of new, therapeutically useful forms of the drug (including those based on nanoparticles) and on the evaluation of the durability of medicinal substances and drug stability studies. The Faculty staff also conduct practical research of clinical significance in the form of pharmacokinetic analyzes as part of monitoring of immunosuppressive and antifungal therapy, as well as pharmacogenetic work.

The employees of Faculty of Pharmacy effectively cooperate with business entities directly and through the University Center for Transfer of Medical Technology, often using the faculty Promoter of Academic Entrepreneurship operating within the Wielkopolska Innovation Platform. Extensive research and development cooperation with companies from the pharmaceutical, cosmetics, veterinary and energy sectors is provided by the Chair and the Department of Drug Form Technology. Since 2016, together with the company Biofarm, it has implemented Measure 1.2 "Strengthening the innovative potential of Wielkopolska's enterprises". The scope of work carried out in the Chair also allowed the implementation of "ordered" research in the form of master's theses (2), an ongoing doctoral dissertation (1), and also resulted in the presentation of results at conferences and publications in scientific journals. The Chair and Department of Natural Medicinal and Cosmetic Raw Materials  effectively cooperates with companies in the field of launching new cosmetic preparations. Certified laboratories of the Chair and Department of Genetics and Pharmaceutical Microbiology perform analyzes commissioned by 12 pharmaceutical companies in the field of microbiological purity of medicinal products, pharmaceutical raw materials, semi-finished products, purified water, dietary supplements, medical materials and drug manufacturing environment. During the parameterization period, these analyzes covered 3242 studies. The implementation of the NCN project entitled Strengthening professional competences of students of pharmacy at Poznan University of Medical Sciences in the period 01.10.2014-30.06.2015, during which 100 students developed their professional practical skills at trainings, workshops and internships in 37 companies, was of great importance for the stimulation of the Faculty's cooperation with the economy.

Genetics in psychiatry

Research conducted at the Department of Genetics in Psychiatry at Medical Faculty II is unique as far as our country is concerned. In the association studies on interleukins genes and their receptors in schizophrenia, there was observed a relationship between schizophrenia and autoimmune diseases. As a result of research on the polymorphism of genes related to the body's response to stress and the risk of developing depression and bipolar disorder, there was described the association of FKBP5 gene polymorphisms with unipolar disease, while there was demonstrated no association of these compounds with the bipolar disorder. Genetic tests were conducted to identify risk factors of a suicide attempt in people diagnosed with bipolar disorder and depression. An innovative approach was a look at suicide attempts in the context of rhythm disorders as a symptom of bipolar disorder and the mechanisms of the molecular biological clock. The observed differences in the results of association studies between men and women correspond to the tendency to combine the functions of neurotransmitter systems with the endocrine system. A continuation of the research was an analysis of candidate genes of the central biological clock in unipolar and bipolar disorder, including circadian rhythm disorders and the assessment of the quality of sleep. An important achievement was the confirmation of the relationship of the analyzed clock genes with mood disorders. The application of "data mining" methods is the first step in determining genes and their polymorphisms that can be used as biological markers in the genetic screening panel of diagnostic and predictive importance. The results of research carried out in the period 2013-2016 were published in 78 papers, mainly international, with a total IF value of 237.889.

Laser microdissection and expression microarrays

The Department of Histology and Embryology of Medical Faculty II is a thriving research center with modern research equipment. Since 2013, Affymetrix GeneAtlas equipment system has been used to analyze the expression of the entire transcriptome. The applied technology together with advanced methods of bioinformatic analysis of the obtained results allowed to carry out many innovative experiments that are important also for the selection of new markers of the processes of carcinogenesis and pathogenesis mechanisms of the examined disease entities. In this context, there were carried out experiments in order to understand the mechanisms of drug resistance of ovarian cancer cells. The research works resulting from the implementation of these studies are often quoted (Januchowski 2013,2014). The presented transcriptomic analyzes were strengthened by the use of a modern laser microdissection system - PALM MicroBeam by Zeiss. Thanks to the use of this method, it is possible to select pure populations of the examined cells, e.g. tumor cells and normal cells, and then compare their profiles of gene expression. It should be emphasized that the employees of the unit are recognized experts in the field of complex bioinformatic analysis of microarray results. Their experience in this area is used by, among others: Laboratory of Radiobiology, Laboratory of Gene Therapy of the Wielkopolska Center of Oncology, Department of General Pathology of Pomeranian Medical University in Szczecin, Department of Histology and Embryology of Medical University of Wroclaw. Up to this day, there have been published 16 papers based on the results and analyzes obtained from microarray experiments, and the total value of the IF coefficient is 30, while the IF for the publication of the whole unit in the years 2013-2016 amounts to 198.780.

Sonoelastography in the diagnosis of thyroid diseases

Department of Endocrinology, Metabolism and Internal Diseases of Medical Faculty II is a leading center of diagnosis and treatment of endocrine diseases. The unit conducts pioneering research using the AIXPLORER ™ apparatus from SUPERSONIC IMAGINE. The aim of the research is to assess the usefulness of sonoelastography, a new diagnostic imaging method that uses ultrasound to study tissue stiffness in the diagnosis and differentiation, as well as monitoring the treatment of focal lesions and thyroiditis. The research conducted in the Clinic showed particular usefulness of the sonoelastographic examination in the selection of focal lesions eligible for biopsy in multinodular goiter. Foci with reduced flexibility present a greater risk of malignancy. Characteristic changes in the elasticity of the gland parenchyma and the usefulness of the method in the diagnosis and differentiation of various types of thyroiditis, as well as monitoring the course of their treatment, have also been described. The expert knowledge of the unit's employees enabled cooperation with the Otolaryngology Clinic and endocrinology centers throughout Poland. The accumulated IF score of works published in 2013-2016 amounted to 47.373. Extensive experience in the application of classic and most recent methods of thyroid gland imaging has enabled the team to publish the "Atlas of Thyroid Ultrasound in a Practical Aspect"  (published by Termedia) which obtained the Minister of Health's didactic award. The book which archives numerous, often very unique clinical units, has been recognized as an innovative and professional, and at the same time accessible source of knowledge in the field of thyroid ultrasound, which is a valuable and real help in the daily clinical practice of doctors of many specialties.

Atherosclerosis in a systemic approach

Department of Clinical Biochemistry and Laboratory Medicine of Medical Faculty II conducts unique research in the field of biology and systemic medicine. Since 2015, in the modern interdisciplinary Laboratory of Biology and Systemic Medicine, there has been examined the nature of mutual interactions of genes, cells, organs, organisms and ecosystems, their forces and a network of connections between particular elements. Unique modeling methods have been developed as a part of the Department’s activities. In cooperation with Poznan University of Technology, Petri nets were used and developed as mathematical tools with an intuitive graphical representation and enabling a precise analysis of the properties of a model built with their help. Based on the expert knowledge of the team and the results of research carried out as part of cooperation with other clinical units of PUMS and Institute of Computer Science at Poznan University of Technology, Institute of Bioorganic Chemistry PAS, Bioinformatics Group, Technical University of Applied Sciences  inBerlin, Johann Wolfgang Goethe-University in Frankfurt a.  Main and Victoria University of Wellington, there have been created several models of processes being, among others, the cause of atherosclerosis. As part of the research, differential models of atherosclerotic plaque buildup were created in the context of age-related changes and used medications, taking into account the complex dynamics of the process. In cooperation with the European Center for Bioinformatics and Genomics, the proteome was analyzed for patients with documented atherosclerosis in various stages of chronic kidney disease and without its coexistence. Research was also conducted using machine learning and genetic programming to analyze extensive clinical data. The scientific activity of the Department in 2013-2016 resulted in publications with a total IF of 48.92.

Childhood without caries

The Pediatric Dentistry Department of the Medical Faculty II conducts educational, promotional and preventive activities towards oral health. In the years 2013-2016 it was the leader and coordinator of the nationwide project "Education, promotion and prevention of oral health addressed to young children, their parents, guardians and educators", implemented with the participation of medical universities. This largest national preventive and educational program, which is a part of the Swiss-Polish Cooperation Program, covered all Polish provinces. The total budget was PLN 21 million. The activities were conducted in several, complementary areas: educational activities for children aged 0-2 and 3-5, and meetings with their parents run by educators, training for preschool teachers, pediatricians, nurses and midwives, as well as free dental consultations. The program included 360,000 children from 6,000 kindergartens, 15 thousand preschool teachers and over 700,000 parents, together with almost 1,400 nurses and midwives and 285 pediatricians. Within the framework of the projects, there was also launched a social campaign aimed at 29 million people, including TV spots in the largest stations, advertisements and articles on Internet portals and e-mailings. An innovation was the introduction of the mobile application "Pampiś - tooth adventure" for children aged 3-6 with games that teach oral hygiene principles. There was published a guidebook titled "Oral cavity health of a small child”, covering good practices in shaping pro-health behaviors in education and upbringing institutions, local government bodies and non-governmental organizations in Poland, developed by a team of academic teachers from the unit. The activities were published on an ongoing basis at www.zebymalegodziecka.pl

Hearing prosthetics

In the academic year 2014/2015, as part of the Department of Biophysics operating within the structures of Medical Faculty II, there were created second degree studies in hearing prosthetics based on a general academic profile, being the first and so far the only such program of studies in Poland. This program is distinguished by a modern education concept, a valuable, unique curriculum and practical orientation, corresponding to the needs of the labor market. Studies are characterized by the highest level of education with a strong focus on interdisciplinary skills and competencies of graduates. The inspiration to create the program was a reflection on demographic forecasts for Poland, the shortage of highly qualified personnel in this field and the lack of a development path for people practicing the profession of a hearing aid technician. Studies in hearing prosthetics include scientific disciplines in the field of medicine, biophysics, acoustics, statistics, computer science, electronics and electrical engineering, along with the elements of social and economic sciences. There has been introduced innovative education content and innovative didactic methods based on laboratory techniques and activating methods. While creating the program, potential employers were contacted and involved in the consultations of the Framework Curriculum, and their suggestions regarding the competence of the graduate were included in the curriculum. Classes are conducted by highly  qualified academic staff, and students have access to a specialized laboratory base at the European level. In March 2016, hearing prosthetics, as an innovative and substantially valuable field of study, adapted to the current civilization challenges and needs of the labor market, received  the certificate “Studies with a Future” in the 1st edition of a competition organized by the Foundation for the Development of Education and Higher Education and the PRC Agency.

Systemic education of patients with diabetes

Department of Internal Diseases and Diabetology of Medical Faculty II is a thriving scientific unit, providing clinical care to a large group of patients with diabetes from the entire macroregion. For many years, there have been carried out prospective observational studies of cohorts of patients with type 1 diabetes treated with intensive insulin therapy, including systemic education of patients. Research called "PoProStu; PoznanProspectiveStudy "contributed to the identification of factors determining the course of type 1 diabetes, the development of chronic complications of the disease and the determinants of partial clinical remission. In the years 2013-2016, a training program for patients and doctors was launched under the name "Pump week" during which participants raised their knowledge and acquired skills in the treatment using a personal insulin pump and new technologies for glucose monitoring. During the trainings, special attention was paid to physically active patients, recognizing the importance of physical exercise for the patient's well-being, prevention of chronic complications of diabetes or achieving partial clinical remission. There was developed an educational module for people with diabetes practicing sports at a professional or amateur level.  There were launched studies which allowed the parameterization of "athletes with diabetes", including the assessment of physical fitness and sensitivity to insulin. As part of the educational program, a monograph was prepared on practical guidelines for the treatment of diabetes in adults with the use of a personal insulin pump. There has also been launched a website for patients and their families, giving access to numerous popular studies on the subject.

Molecular research in cancer

For many years, the Department of Cancer Immunology of Medical Faculty II has been conducting international research activities as a part of its own projects, financed by the NCN and FNP funds, and as a part of international projects funded by NCI/NIH in the USA. The aim of the research is to analyze the epigenetic mechanisms involved in the reprogramming of human cells to inducible pluripotent cells. The conducted studies have demonstrated the key role of the TRIM28 epigenetic repressor and transcription factors with the KRAB domain in cell reprogramming processes and the differentiation of human pluripotent cells. The research was carried out in collaboration with the MD Anderson Cancer Center in Houston. The result of the research within the international projects  The Cancer Genome Atlas (TCGA), TCGA PanCancer Atlas, as well as Clinical Proteomic Tumor Analysis Consortium (CPTAC), was an analysis of molecular profiles of tumors in order to develop modern methods of diagnosis and treatment. As a result of the performed molecular analyzes, characteristic molecular subtypes of breast cancer, stomach cancer, oesophageal cancer, melanoma, head and neck cancer were isolated. In the further stages of the research, there were demonstrated features of parenthenia and dedifferentiation in 30 types of cancer, and there was performed a correlation analysis of these features with selected biological mechanisms, and pathomorphological and clinical features. The CPTAC project results in an integrated analysis of 10 types of cancer genomes and proteomes, as well as the development of modern methods of cancer diagnostics and treatment using specific biomarkers and personalized therapies. The results of these analyzes were published in Nature, Cell, PNAS and Oncotarget, and the total IF of the Department's publications in the period 2013-2016 is 272.851.

Genetics in endocrinology

For many years, the Laboratory of Molecular Endocrinology at the Clinic of Endocrinology of the Medical Faculty II has performed diagnostics and research in the field of genetic basis of innate endocrine diseases and thyroid cancer. Since 2013, using a next-generation high-throughput sequencing platform and a micro-array platform for genomic screening, there were carried out studies on a globally unique group of patients with thyroid hemiagenesis (THA) (currently over 100 patients), a group of patients with multi-hormonal pituitary insufficiency revealed in childhood, with the diagnosis of Addison's autoimmune disease and in patients with suspected MEN1 and MEN2 syndrome in whom routine genetic diagnosis was implemented. The conducted studies have shown more frequent occurrences of longer variants of the polyalanine tract FOXE1 in familial cases of TSHA, as compared to sporadic patients or healthy people. There has also been discovered a new splicing variant of the PAX8 gene which may consequently significantly reduce the expression of the PAX8 protein, as well as four new defects of the PSMA1, PSMA3 and PSMD3 genes. There has been identified a new mutation of the splice site within the PSMD2, as well as the deletion of the VPS13C and RAD23B gene, which have not been described previously. It has been proven that even a small disturbance of the protein degradation process may affect the functioning of the thyroid genes and thus affect the migration process and division of the thyroid gland into lobes. The results of the study were published in Clinical Thyroidology, a journal published by the American Thyroid Association, and the Yearbook of Pediatric Endocrinology, summarizing groundbreaking scientific publications in the field of endocrinology. The total IF of the publications based on the above mentioned research amounted to 171.284.