Chi is a clinician scientist interested in identifying and understanding the genetic and molecular basis of haematological cancers using a combination of genetic model systems, genomics and cell biology. With these tools, he focuses particularly on cancer subtypes associated with poor prognosis to uncover urgently needed, new therapeutic strategies.
The Sanger Institute has played a pivotal role in identifying gene variants that are important in human disease, such as mutations that predispose individuals to developing cancer or are commonly found in sporadic cancers. For example, large-scale analysis of cancer genomes from diverse cancer types uncovered the CUX1 transcription factor as novel cancer gene that was overlooked by previous, smaller sequencing studies.
A key challenge now is to understand the role of CUX1 and other newly identified gene aberrations in cancer development. By harnessing the Institute’s strength in producing genetically tractable model systems, I have generated several genetic, cancer models to recapitulate cancer-associated mutations using CRISPR/Cas9-mediated genome-editing techniques. With these models, I can study the phenotypic consequences of these mutations and decipher the underlying mechanisms underpinning the observed phenotypes. By understanding the mechanistic action of these gene mutations, I aim ultimately to uncover new therapeutic strategies that can specifically target cellular pathways critical for cancer maintenance. As many of genes under investigation confer poor prognosis in patients when mutated, identifying new treatment modalities is a key priority. Beneficially, my findings will be tested in a complementary approach using primary human cancer samples obtained from my clinical work.
Inactivating CUX1 mutations promote tumorigenesis.
Nature genetics 2014;46;1;33-8
Therapy for mitochondrial genetic disease: are we at the thin end of the wedge?
Reproductive biomedicine online 2014;29;2;147-9
Defective ribosome assembly in Shwachman-Diamond syndrome.
The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast.
Nature genetics 2007;39;4;486-95