Understanding the Role of Epigenetics in Multiple Myeloma Progression
Mentor: Irene Ghobrial, M.D. (Dana Farber Cancer Institute)
Multiple myeloma is a cancer of the plasma cells – a type of white blood cell that secretes antibodies and is integral in helping the immune system fight off infections. This disease is characterized by an overgrowth of these rogue plasma cells in the bone marrow which then results in the inhibition of production of other types of blood cells and weakens the bone. This condition is often difficult to diagnose as it is asymptomatic in the initial stages of disease. Unfortunately, multiple myeloma is not curable and has a poor clinical prognosis. Common chromosomal modifications seen in multiple myeloma patients are translocations t(4;14) and t(11;14). The presence of such translocations brings to light the importance epigenetic regulation may have on disease development in multiple myeloma. Studies have shown that the epigenetic downregulation of tumor suppressor genes can influence the progression of a cancer. Certain regulatory elements were defined by the Ghobrial Lab to be associated with multiple myeloma progression. My focus is to identify and validate epigenetic regulatory mechanisms of genes that are important in multiple myeloma. This project will take advantage of CRISPRi technology to analyze how the suppression of certain non-coding regions would affect the expression of target genes. The expression of these genes will then be analyzed using quantitative real-time PCR. Understanding the network behind these enhancers could aid in identifying potential drug targets for the treatment of multiple myeloma.
Photo Caption: This figure demonstrates the components of the CRISPRi technology used in transcriptional repression experiments. Photo Source: https://www.genecopoeia.com/wp-content/uploads/2019/02/CRISPRi-cartoon.jpg Source: