Epigenetic regulation of cytotoxic lymphocyte
- Reference number
- FFL12-0188
- Start and end dates
- 140101-191231
- Amount granted
- 9 700 000 SEK
- Administrative organization
- Karolinska Institutet
- Research area
- Life Sciences
Summary
Deciphering of the human genome will transform medical practice in numerous ways. However, much still remains to be elucidated, particularly in how non-coding DNA supports cellular differentiation and homeostasis. My lab studies how cytotoxic lymphocytes contribute to human health. Genetic defects in the function of such cells can cause life-threatening diseases, ranging from hyperinflammatory syndromes to haematological malignancies and systemic autoimmunity. In this proposal, to better understand how non-coding DNA regulates cytotoxic lymphocyte function, I seek support for studies aimed at performing genome-wide characterization of epigenetic regulation upon differentiation in human cytotoxic lymphocyte subsets. Moreover, using high-throughput sequencing technologies as well as insights from epigenetic studies, we aim to identify potentially novel mutations causative of disease in patients suffering early-onset hyperinflammatory, autoinflammatory, and autoimmune disorders. Furthermore, cells from these patients will be used to understand how specific inflammatory circuits can affect cytotoxic lymphocyte differentiation, providing insights into epigenetic plasticity of immune function. Gaining insights into such regulatory circuits can provide important insights into inflammatory diseases, which represent a large health burden in developed societies. Our work promises to aid the rapid diagnoses of patients and may unravel new biomarkers, drug targets, as well as treatments.
Popular science description
The deciphering of the human genome can improve medical practice in numerous ways. However, much still remains to be elucidated, particularly in how non-coding DNA regulate the expression of genes encoding proteins that are vital for generating cells. Our laboratory studies how a particular subsets of white blood cells, that can kill infected and malignant target cells, contribute to human health. Genetic defects in the function of such cells can cause life-threatening diseases, ranging from hyperinflammatory syndromes to blood malignancies and very severe autoimmunity. In this proposal, to better understand how non-coding DNA regulates cytotoxic lymphocyte function, we seek support for studies aimed at performing genome-wide characterization of marks signifying regulation and activity of the genome upon development of human immune cell subsets. Moreover, using high-throughput sequencing technologies to assess the genome, as well as insights from our studies of genome markers of activity, we aim to identify potentially novel mutations causative of disease in patients suffering early-onset hyperinflammatory, autoinflammatory, and autoimmune disorders. Furthermore, cells from these patients will be used to understand how specific inflammatory cascades can affect immune cell function in different ways. Gaining insights into such regulatory circuits can provide important insights into inflammatory diseases, which represent a large health burden in developed societies. Our work promises to aid the rapid diagnoses of patients and may unravel new biomarkers, drug targets, as well as treatments.