New insights into regulation of human T-cells
T –cells are central regulators of proper immune response. They can specialize to functionally distinct subsets and aberrations in their proper function results in inflammatory and autoimmune disorders such as multiple sclerosis, type 1 diabetes and rheumatoid arthritis.
Kartiek Kanduri studied in his doctoral studies carried out at Turku Bioscience Centre what are the gene regulatory pathways T-cells utilize when they become inflammatory.
Using a range of genome-wide omics-methods, deep sequencing and data mining he succeeded to build a holistic picture of a cell when it becomes pathogenic.
– We identified several new factors that mediate differentiation of an inflammatory Th17 cells through a key transcription factor STAT3, Kanduri explains.
Kanduri discovered that STAT3 binds to a number of regulatory regions in the genome that have been associated with autoimmune diseases. The study revealed also several previously unknown long non-coding RNAs, that are specifically expressed early on when a cell differentiates to a particular cell type.
– Many regions that we found to regulate gene activation are in such areas of genome that previously were thought to be ”junk” DNA. We discovered such regions to have autoimmune disease associated genetic variations, single nucleotide polymorphisms or SNPs. Thus such SNPs may contribute to development of immune mediated diseases through regulation of immune response, Kanduri explains.
The results open up new horizons and provide basis for understanding molecular mechanisms of immune mediated diseases.
The papers of the Ph.D. studies have been published in peer-reviewed international journals Genome Medicine (two papers), Cell Reports and Nature Immunology.
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Kartiek Kanduri will have public defense for his doctoral thesis ”Integration of genome-wide datasets to understand regulation of human T-helper cell differentiation” at University of Turku, Friday June 5th, 2020 at 12 noon.
Due to COVID-19 situation dissertation defences are not arranged as open audience events. Disputant, opponent and custos have to be at least in a voice call. Audience can participate via remote connection.
The opponent is professor Garry Wong (University of Macau, China) and custos academy professor Riitta Lahesmaa (University of Turku). The event is in English. The area of doctoral thesis in medical microbiology and immunology.
Doctoral programme: Turku Doctoral Programme of Molecular Medicine (TuDMM)