Research Overview

The overarching goal of the DiuNguyen laboratory is to understand the control of stem cells in normal development and human diseases. Our research program focuses on uncovering the role of post-transcriptional regulation (PTR) by RNA binding proteins (RBPs) in normal and malignant stem cells using hematopoiesis as a model system. While somatic alterations in genetic and epigenetic mechanisms in tumorigenesis have been intensively studied, little is known about how processes that affect PTR of gene expression impact cancer development. We aim (1) to identify novel RBPs required for normal blood development and leukemogenesis, and (2) to understand the molecular mechanisms for how altered activities of RBPs contribute to malignant transformation, with the ultimate goal of developing innovative targeted therapies for cancer.

Long term vision

Key questions that we will address in our lab are:

• Despite their relevance in diseases and great therapeutic potential, the function of majority of RBPs (of >1700 RBPs in the cells), including non-canonical RBPs lacking RNA binding domains (RBD) in normal and cancer stem cells, has not been studied.
• Although some RBPs have been demonstrated to be critical for stem cell behavior, the molecular basis for their function in PTR, in particular translational regulation, and how it alters during malignant transformation is poorly understood.
• How the cell-context dependent activity of RBPs play role in determining heterogeneity of stem cell population and cell fate decision.

To answer these questions, we will undertake a multidisciplinary approach integrating hematopoietic assays, RNA-editing based technology, proteomics and molecular biology in cell lines, mouse genetic models and patient primary cells and -derived xenografts.

We aim to build a strong team of curious and highly motivated scientists who are driven to study RNA biology in normal development and cancer and to identify new therapeutic opportunities. We support and help our team members to achieve their career goals and personal development.