Chromatin factors and transcriptional deregulation in blood malignancies

Ningqing Liu studied biology (natural products) with a support of a Huygens Scholarship at the Leiden University (2007-2009). Afterwards he performed his PhD research in the department of medical oncology at the Erasmus MC (2009-2013), during which he developed a low input quantitative proteomics workflow, and applied this platform to identify the first protein signature that predicts prognosis of triple negative breast cancer patients (Liu et al., Journal of the National Cancer Institute, 2014; Liu et al., Molecular and Cellular Proteomics, 2014). With these works, he was awarded with a “Chinese government award for outstanding self-financed students abroad”. After his PhD, he worked as a postdoc researcher (2013-2016) in the department of molecular biology at the Radboud University Nijmegen. He took a combined proteomics and epigenomics approach to identify the transcription factors interacting with human colorectal cancer risk loci (Liu et al., Nature Communications, 2017).

During 2017 and 2022, He did his second postdoc with a NWO Veni grant in division of gene regulation at the Netherlands Cancer Institute (NKI). At the NKI, his research focused on the functions of two non-sequence-specific chromatin factors, the cohesin and BAF complex, in distal gene regulation in the context of stem cell maintenance and oncogenesis. His works about the cohesin complex revealed the importance of dynamic cohesin cycles in controlling cell type specific genes (Liu et al., Nature Genetics, 2021), and also identified a new principle of 3D genome organization between actively transcribed genes (Liu et al., bioRxiv, 2021). His work on human BAF complex identified three major MYC enhancer modules in malignant rhabdoid tumor of kidney, and revealed the patient specific regulation of these distal enhancers (Liu et al., bioRxiv, 2021, under revision in Nature Communications).

Since March 2023, he became a junior group leader in the department of hematology at the Erasmus MC. Currently, his research aims to understand transcriptional deregulation in human blood malignancies, with a specific focus on elucidating the roles of human BAF complex in acute myeloid leukemia (AML).

Our research

Depending on the protein composition, the BAF complex is classified into three subfamilies, known as canonical BRG1/BRM-associated factor (cBAF), polybromo-associated BAF (pBAF), and noncanonical BAF (ncBAF) complexes (Figure 1). The BAF member genes are frequently mutated in human malignancies, occurring in about 25% of cases. In addition to these mutations, many BAF subunits are overexpressed in human cancers. For instance, a ncBAF subunit called BRD9 is overexpressed in blood cancers such as AML and multiple myeloma.

My lab is interested in understanding the dose-dependent role of different BAF subunits in leukemogenesis. We will combine state-of-the-art acute protein degradation techniques and multi-omics to understand how the expression changes of a BAF subunit lead to disequilibrium of the BAF complex assembly, and consequently drive oncogenic transcriptional program in AML. By understanding the molecular mechanisms of how the BAF complex regulates important leukemic genes, we hope to design more effective epigenetic therapies to treat AML and other blood malignancies.

Our team

Key publications