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Zhiyan Xu

M.D.


DPhil student in Medical Science

Build up a gene filter system to validate candidate biomarkers identified from single-cell RNA seq analysis

Myeloproliferative neoplasms (MPNs) are a group of haematologic diseases characterized by abnormal proliferation of blood cells in the bone marrow. MPN can be divided into 2 subgroups regarding the presence of Philadelphia chromosome t(9;22)(q34.1;q11.2), i.e. BCR-ABL1. Chronic myeloid leukaemia (CML) is diagnosed by the presence of BCR-ABL1. As for BCR-ABL1 negative MPNs, three common driver mutations are recognized by researchers, JAK2 V617F, CALR and MPL. Besides driver mutations, several somatic non-driver mutations present with variable diseases phenotypes and evolution. With the advent and fast progress of the era of sequencing, variable transcriptional signatures within tumors can also be detected by single-cell RNA sequencing (scRNA-seq), demonstrating the functional heterogeneity in tumors as well.

The main objective of my project is to build up a gene filter platform to validate the candidate biomarkers identified from scRNA-seq analysis. This includes selection of the top heat genes, manipulation gene expression via RNAi or CRISPR-Cas9, validation of gene functions through stem cell assays both in-vitro and in-vivo. This helps elucidate potential therapeutic target for the persistent stem cells after the common driver-mutation target therapy.