The laboratory of Molecular Pathology aims to understand the molecular mechanisms of immune tolerance and autoimmunity.
To understand the mechanisms of autoimmunity, we study a human disease, autoimmune polyendocrinopathy syndrome type 1 (APS1) and corresponding mouse model, where mutations in the autoimmune regulator (AIRE) gene cause defective immune tolerance and result in autoantibodies and autoimmune tissue-destruction. The studies by our and other groups on the role of AIRE have been instrumental in understanding how central immune tolerance of T cells is formed and maintained in thymus. During a long-term research period, the group has explored the function of AIRE at molecular and epigenetic level, and made several seminal findings in AIRE role in transcriptional regulation, and how self-antigens are presented to developing T cells, implicating epigenetic mechanisms behind the mechanism how the self-antigens are presented to developing T cells. Among other studies, in collaboration with other groups, we showed that autoantibodies to Th17 cytokines that are indispensable in controlling the yeast growth on skin and mucosal surfaces can cause susceptibility to chronic Candida infection and, more recently revealed a therapeutic potential of autoantibodies reacting with type 1 interferons and other cytokines.
As another research direction to understand molecular mechanisms in immune cells, our group has performed genome-wide epigenetic analyses of immune cells in older individuals as well as in patients with autoimmune diseases. Together with Estonian Genome Bank, we have accumulated large datasets on gene expression and epigenetic changes in immune cells from human population over recent years. Our aim is to identify the role of epigenetic marks, DNA methylation and histone modifications, and transcriptional changes in key human immune cell types, lymphocytes and monocytes, and to correlate these findings with physiological parameters, aging and immune disorders, in particular autoimmune and inflammatory diseases.
The researchers in the group:
Pärt Peterson, PhD, Professor
Kai Kisand, MD, PhD, Senior Researcher
Martti Laan, MD, PhD, Senior Researcher
Mithu Guha, PhD, Researcher
Liina Tserel, PhD, Researcher
Mario Saare, PhD student
Jaanika Kärner, PhD student
Uku Haljasorg, PhD student
Rudolf Bichele, PhD student
Epp Kaleviste, PhD student
Maia Limbach, PhD student
Julia Maslovskaja, PhD student
Maire Pihlap, Technician
Anu Remm, Technician
Link to the web
