BRFAA - Biomedical Research Foundation Academy Of Athens
Biomedical Research Foundation Academy Of AthensAcademy Of Athens

Inflammation & Autoimmunity

Inflammation and autoimmunity represent two distinct, yet overlapping, aspects of the activation of the immune system in response to external or internal danger signals.  We study medical inflammation in the context of inflammatory/autoimmune rheumatic diseases (systemic lupus erythematosus-SLE and rheumatoid arthritis-RA) by the use of animal models and tissues from large, well characterized patient cohorts.


Ongoing Research Projects

1. Identification of Novel Molecular Targets of Therapy:
Using high throughput techniques such as DNA arrays and miRNA profiling, we have identified biological processes (autophagy, NETosis and apoptosis), cells (neutrophils and mononuclear cells) and molecules (PDCD4, kinases and kallikrein 4) involved in the pathogenesis of these diseases. 

2. Resolution of Inflammation and Restoration of Ιmmune tolerance:
We collaborate with the Immune Regulation & Tolerance Group (P. Verginis, Group Leader), to identify novel subsets of immune cells that suppress innate and adaptive immune responses, restore immune tolerance and expedite the resolution of inflammation.

3. Tissue Injury and Repair:
Understanding the response of these tissues to injury and mechanisms for repair represents an unmet need. We study immune injury in the lung and the mechanisms of its repair in RA in collaboration with Dr Sideras group. We also address the role of neutrophils and autophagy in tissue injury.

4. Genetics-Transcriptomics and Precision Care:
In collaboration with the Systems Biology Group (Dr Dermitzakis, Group Leader), Dr Sanoudou Group and  & G. Bertsias (Systemic Autoimmunity Genomics Group, UoC), we have performed transcriptomic analysis of relevant tissues and cells  (peripheral blood mononuclear cells, kidney and hematopoietic stem cells) from patients with SLE seeking to understand the gene-environment interactions and their contribution to disease pathogenesis and detect biomarkers for disease activity and response to therapy. We seek to define the core molecular signatures for a) disease susceptibility, b) activity and d) severity,and reprogram the disease by epigenome editing experiments..

5. Clinical Research & Patient Care:
The Rheumatology and Clinical Immunology Clinic, at the Attikon University Hospital is a national referral center for autoimmune diseases. Our group at Attikon consisting from P. Katsimbri (MD, staff Rheumatologist NHS), A. Fanouriakis (MD, Clinical Investigator) and the research associates T. Karagiorgas MD, D. Kassara MD and D. Tseronis MD, is involved in studies of SLE pathogenesis and in phase II- IV clinical studies of novel immunomodulatory agents in autoimmune rheumatic diseases.

 

Fig 1. miR-422a regulated Kallikrein 4 (KLK4) protects the kidneys in SLE from immune injury. Fig 2. Neutrophil NETosis and autophagy-dependent TF-decorated NET release contribute in tissue damage in lupus nephritis.
Fig 3. Deregulated autophagy and increased accumulation of mitochondria in monocytes from SLE patients. Fig 4. Hematopoietic Stem Cell (HSCs) Gene Networks in SLE.
 
Fig 5. RNA-seq differentiates SLE versus healthy individuals and active/severe versus inactive/mildy active SLE.