Dr. Huacheng Luo’s current studies are focused on cancer/tumor genetics and epigenetics research fields. One of his current projects involves targeting CTCF boundary remodels chromatin domain and reprograms HOX gene transcription in acute myeloid leukemia. In this research, he employed a pooled CRISPR-Cas9 genetic knockout (KO) library screening to interrogate CTCF binding motifs in all HOX loci and identified a critical CTCF boundary (CBS7/9) located at the edge of TAD encompassing the posterior HOXA genes. He found that CBS7/9 chromatin boundary is critical for initiating and maintaining aberrant expression of posterior HOXA genes (HOXA9-HOXA13).
To further investigate the role of CBS7/9 chromatin boundary in HOX gene organization and regulation, he then carried out genome wide ChIP-seq, ATAC-seq, 4C-seq and RNA-seq analysis to examine the global changes in chromatin domain organization and corresponding gene expression patterns between control and CBS7/9 knockout AML cells. Depletion of the CBS7/9 boundary function leads to expansion of repressive chromatin structure into posterior HOXA domain, blocking enhancer/promoter chromatin accessibility and their associated regulatory networks, decreases in HOXA9 associated oncogenic transcription program and eventually prolonged survival of transplanted AML mouse models. The CTCF boundaries in the oncogene loci such as CBS7/9 may serve as novel therapeutic targets for the treatment of myeloid malignancies.
Dr. Luo is also focused on the studies of the HOX loc lncRNAs function in human normal and malignant hematopoiesis, including HOTTIP and HoxBlinc lncRNAs. He found that HOTTIP/HoxBlinc lncRNA preferentially recognizes and binds to noncoding regulatory regions in the AML genome and specifically regulates genes important for hematopoietic and myeloid lineage differentiation.