Internal Medicine Laboratory

Background and Overview
The division of Internal Medicine is devoted to the investigation of key pathogenetic events in a variety of metabolic, infectious, and inflammatory diseases. The division consists of the following Sections and Units:

1. Host-defenses unit [D. Kofteridis, (Prof of Internal Medicine and Infectious Diseases), P. Ioannou (Assistant Prof of Internal Medicine), S. Karakonstantis (Assistant Prof of Internal Medicine)]

Infection is one of the leading causes of mortality and morbidity worldwide. Susceptibility to infection arises from the complex interaction of the pathogen environmental and host factors. Our specific areas of research include: Epidemiology of Infectious Diseases, especially those caused by intracellular pathogens, health care associated infections, infections in immunocompromised patients, in patients with type 2 diabetes and Antibiotic policies. Research on the genetic backgrounds predisposing to infections and their severity. Specific areas of research are the prevalence of Single-Nucleotide Polymorphisms (SNPs) of TLR2 and TLR4, C1q, MBL, VDR, and IL-6 in patients with type 2 diabetes.

1. Molecular Pathology and Human Molecular Genetics Section [G.N. Goulielmos (Prof of Human Molecular Genetics), M.I. Zervou (MSc-PhD, Laboratory Teaching Staff of Human Molecular Genetics)]

The bidirectional interaction between basic and clinical sciences in Medicine, have provided the impetus to the rapid development of Molecular Medicine. The nature and extent of the genetic contribution to human variation and disease is the area of interest of a related field, that of Human Genetics. Most of the genes involved in the major monogenic disorders, which follow Mendelian patterns of inheritance, have now been isolated and characterized; however, their overall population incidence in the population is relatively low. On the other hand, complex diseases such as cancer, diabetes, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), endometriosis, acute lymphoblastic leukemia, coronary artery diseases etc result from the interaction of multiple genetic and environmental factors. This group of diseases represents the most common and the least understood human diseases. Identification of genetic factors predisposing individuals to diseases is a powerful tool since offers the opportunity for prevention or treatment of several human diseases. Our specific areas of research include: 1) The multidisciplinary approach of Familial Mediterranean Fever (FMF), the prototype of the recurrent fever syndromes, from the epidemiologic, genetic, pathogenetic, population and structural biological point of view. The ultimate task is to depthen further the existing pathogenic mechanisms and gain insight into new molecular pathways leading to the development of FMF. 2) The study of the genetics of various complex diseases and, mainly, of the autoimmune diseases resulting from the deregulation of the immune system. In particular, we focus on the investigation of genetic polymorphisms of several genes (new or detected through Genome Wide Association Studies – GWAS), such as eNOS, PDCD1, PTPN22, TRAF1/C5, STAT4, TLR-2, TLR-4, MBL-2, CD40, NCOA5, C1q, TGF-beta, IRF8, IRF5, IL-12B, IL-23R, PTPN2, VDR etc playing a role either as predisposing or severity factors for various autoimmune diseases. The ultimate task is to extend the understanding of existing pathogenetic mechanisms by using functional genomics approaches, aiming to understand the functional significance of the detected gene polymorphisms and, finally, gain insight into new molecular pathways leading to the development of these diseases. The autoimmune diseases of our interest refer to SLE, RA, Sjogren's syndrome (SS), ankylosing spondylitis (AS), type-1 diabetes (T1D), juvenile idiopathic arthritis (JIA), Inflammatory Bowel Diseases (IBD) and psoriatic arthritis (PsA). Our group also studies the different patterns of immune system activation that exist between people of different ancestral background with SLE, as this should explain some of the heterogeneity in treatment responses we observe in this disease. 3) The study of the genetic basis of endometriosis. A remarkable progress has been achieved regarding the detection and confirmation of the role of FN1, FSHB, WNT4, VEZT, IL-16, GREB1, UGT2B28 and USP17L2 genes in the development of the disease, by performing gene association as well as whole exome sequencing (WES) studies. Our group participated in the biggest GWAS for endometriosis conducted so far, as a member of the International Endometriosis Genomics Consortium (IEGC), while further research is being conducted currently in the context of the collaboration with IEGC, aiming to the delineation of the mechanisms leading to endometriosis and adenomyosis as well as the role of vitamin D in endometriosis.

1. Metabolic diseases [T. Filippatos (Associate Prof of Internal Medicine)].

Metabolic diseases and cardiovascular diseases are associated with very high modality and mortality. Our laboratory focuses on advancing the understanding and prevention of metabolic diseases, focusing on diabetes, hyperlipidemia, obesity, and cardiovascular disease prevention. We emphasize translational research that aims to delineate the metabolic and inflammatory pathways of these interconnected conditions, as well as the therapeutic effects of pharmacologic agents. Our specific areas of diabetes research include the role of insulin resistance and lipotoxicity on vascular health, as well as the metabolic effects of newer antidiabetic therapies. Our specific areas of research on hyperlipidemias include the mechanisms of lipotoxicity-induced inflammation and its contribution to atherosclerosis, the effects of newer lipid-lowering therapies, as well as the identification of novel biomarkers and therapeutic targets in familial hypercholesterolemia. Our obesity research focuses on the regulation and systemic effects of adipokines on metabolic and cardiovascular health, and the metabolic effects of newer antiobesity drugs.