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Hematopoietic stem cells give rise to all circulating blood cells throughout life. Complex signaling pathways lie at the heart of regulating the maintenance of stem cell self-renewal, proliferation, and differentiation. Leukemia often arises in cases of aberrant regulation of signaling transduction, ubiquitination, and DNA damage repair. Genome integrity therefore plays a critical role in the prevention of leukemia, but in aging and blood development as well.
The Tong lab focuses on studying the mechanisms that safeguard the genome during DNA replication and proper control of cytokine signaling transduction to maintain stem cell fitness. In addition, the lab investigates how failures in these processes impact hematopoietic stem cell function that leads to bone marrow failure and/or leukemia.
- Dissecting CBL E3 ubiquitin ligase signaling network in myeloid leukemia through proteomics approaches, identifying novel targets of the protein CBL through CRISPR/Cas9 screens, and exploring their therapeutic potentials in treating murine and human myeloid leukemia such as chronic myelomonocytic leukemia.
- Determining mechanisms by which Lnk deficiency alleviates replication stress in hematopoietic stem cells to restore stem cell functions in bone marrow failure syndromes.
- Developing novel mouse models of precursor B-Acute Lymphoblastic Leukemia (B-ALLs) that are highly aggressive and transplantable as well as amenable for downstream applications. The lab performs CRISPR/Cas9 screens for genes whose inactivation abrogate B-ALL development in vivo as well as those confer resistance to therapies.
Dr. Tong investigates cytokine receptor signaling in normal and neoplastic hematopoietic development. She uses integrated approaches encompassing biochemistry, molecular biology, mouse models, and primary human samples to understand signaling events emanating from cytokine receptors that regulate the development of hematopoietic stem/progenitor cells.