Research Projects and Interests

The Jiang Laboratory studies the molecular mechanisms of RNA and DNA editing in normal and cancer stem cells, how these editase enzymes are regulated in different cellular contexts, and how to target these pathways in pre-clinical models of both solid tumor and blood malignancies. The Jiang lab is pursuing these interests by studying the functions and molecular targets of DNA/RNA editing enzymes that specify normal stem cell development and maintain cancer stem cells (CSCs) in T-cell lymphoblastic leukemia and ovarian cancer models. We employ a variety of bioinformatic, molecular and cell biological tools, as well as patient samples and xenograft mouse models to address these questions surrounding human health and disease.

Project 1: Investigating the role of A-to-I RNA editing in T-cell Acute Lymphoblastic Leukemia stem cells as a therapeutic target

Epitranscriptomic ADARs (adenosine deaminase acting on RNA) are a class of enzymes that catalyze adenosine-to-inosine (A-to-I) changes in RNAs. CSCs often harbor increased adenosine-to-inosine RNA editing, a phenomenon by which a cell can change its RNA to improve survival and expansion. Put simply, RNA editing allows cells to “re-invent” their own RNA to create new proteins that might help the CSCs escape chemotherapy and cause relapse. This aberrant ADAR1 activation is a crucial event in the oncogenic transformation of normal progenitors to CSCs. In this project, we are interested in understanding the roles of ADAR1 in lymphoid progenitor maintenance and cancer derived from lymphoid progenitors such as T-cell lymphoblastic leukemia (T-ALL). We leavage scRNA-sequencing, organoid models, and PDX mouse models to explore the RNA targets and molecuar basis of our finding.

Project 2: Examining the Role of DNA Deaminase APOBEC3 in Regulating Cancer Stem Cell Evolution

We often think of DNA as the stable genetic material that defines and differentiates organisms. It is now clear that biological diversity is governed by complexity created by dynamic changes that occurs within this framework. One such example is the deamination of cytidine to uracil (C-to-U) by APOBEC3 (Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3) family of proteins. This important DNA modification is important in maintaining the genetic integrity of healthy stem cells but is also abundant in a wide array of cancer types. We are interested in understanding if on-going A3 activity and the resulting DNA mutations are necessary to generate new cancer stem cell clones and what are the functional consequences of these APOBEC3-mediated mutations in cancer progression and relapse. High-grade serous ovarian cancer (HGSOC) is an aggressive and often lethal type of ovarian cancer. Because genomic instability and high mutation rates are commonly observed in HGSOC, we will utilize this model to study the dynamic transformations of the genomic landscape by APOBEC3 during CSC evolution.

Our research is currently or has been previously supported by these generous funding organizations: