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Yan Liu, PhD

Email:liu219@iu.edu
Phone: 317-274-4791
Office: R4 121

Yan Liu, PhD

St. Baldrick’s Foundation Scholar

Herman B Wells Center for Pediatric Research

Department of Pediatrics

Assistant Professor of Biochemistry & Molecular Biology

Assistant Professor of Pediatrics

Education

  • PhD:Chinese Academy of Sciences
  • Postdoctoral: Memorial Sloan-Kettering Cancer Center

Research Interest:

Leukemia can be viewed as an aberrant hematopoietic disease initiated by rare leukemia stem cells (LSCs) that have maintained or re-acquired the capacity for indefinite self-renewal through accumulated mutations and/or epigenetic changes. While LSCs are generally malignant versions of hematopoietic stem cells (HSCs), they are largely resistant to chemotherapy or targeted therapies. The development of new therapeutic approaches that can target LSCs, but not HSCs, will have a profound impact on our ability to eradicate leukemia. The long-term goal of our research is to identify novel regulators of hematopoietic stem cells (HSCs), to understand the molecular mechanisms controlling their function and develop novel therapeutic strategies to eliminate leukemia stem cells (LSCs). We are interested in investigating the molecular mechanisms that regulate HSC quiescence and self-renewal in normal and leukemic hematopoiesis.

Current research in my lab is focused on:

  • The role of mutant p53 in leukemia stem cell self-renewal and leukemogenesis. The importance of the p53 protein in the cellular response to DNA damage is well known, but its function during steady-state hematopoiesis has not been established. We have defined a critical role of p53 in regulating hematopoietic stem cell quiescence. The frequency of TP53 mutations in acute myeloid leukemia (AML) is approximately 10%. However, in AML with complex karyotype, the frequency of TP53 mutations and/or deletions is almost 70%. Clinically, TP53 mutations are correlated with shortest survival and drug resistance of AML patients. We will determine the role of mutant p53 in LSC self-renewal and pathogenesis of AML.
  • The role of Polycomb Repressive Complex 1 (PRC1) in regulating hematopoietic stem cell self-renewal. Polycomb group (PcG) proteins are epigenetic gene silencers that have been implicated in stem cell maintenance and cancer development. Genetic and biochemical studies indicate that Polycomb group proteins exist in at least two protein complexes, Polycomb repressive complex 2 (PRC2) and Polycomb repressive complex 1 (PRC1), that act in concert to initiate and maintain stable gene repression. Bmi1 and Mel18 are two major homologs of the PCGF subunit within the PRC1 complex. While Bmi1 is important for leukemia stem cell (LSC) self-renewal and high Bmi1 expression is correlated with poor prognosis, the role of PRC1 complex in leukemogenesis is largely unknown. Therefore, it is important to investigate the role of PRC1 complex in regulating LSC behavior and decipher how PRC1 mediates gene silencing in LSCs.
  • The role of phosphatase PRL2 in leukemia stem cell self-renewal and leukemogenesis. The PRL (phosphatase of regenerating liver) family of phosphatases, consisting of PRL1, PRL2, and PRL3, represents an intriguing group of proteins being validated as biomarkers and therapeutic targets in human cancers. However, the role of PRL2 in hematopoiesis remains elusive. We discovered that phosphatase PRL2 plays an important role in regulating HSC self-renewal and proliferation. We found that PRL2 mediates and sustains SCF/KIT signaling in hematopoietic stem and progenitor cells. Thus, PRL2 plays critical roles in regulating HSC self-renewal and mediating SCF/KIT signaling. In the future, we will determine the role of PRL2 in leukemia stem cell self-renewal and leukemogenesis.