|Department||Signalling and Gene Expression Research|
|Institution||La Jolla Institute for Allergy and Immunology|
|9420 Athena Circle|
|City, State, Zip||San Diego, CA 92037|
|Research Field||Molecular Biology/Biochemistry|
|Country of Origin||Brazil|
|Mentor||Dr. Anjana Rao|
Our research explores the role that epigenetic modification plays in the development of human leukemia. Our laboratory and others have shown that TET proteins are essential regulators of ES cell pluripotency, and their dysegulation is frequently associated with cancer. Somatic deletions and loss of function mutations in the TET2 gene have been identified in 20-40% of all myeloid malignancies in humans and TET2 mutations observed in leukemia patients caused impaired hydroxymethylation. In hematopoietic stem cells (HSCs), TET2 restrains aberrant self-renewal and expansion, and that the decrease of TET2 activity in stem/progenitor cells skewed their development toward the monocyte/macrophage lineage. However, the mechanisms by which TET2 controls differentiation and function of myeloid cells remain to be discovered. The main objective of this work is to understand the role of TET2 in monocytic cells and, in consequence, how it can be related to myeloid malignancies. We are using the well-characterized human myeloid leukemia cell line U937 to purify and identify TET2 nuclear interacting proteins. We will also perform ChIP assays and identify genome-wide localization of TET2 using high-throughput sequencing. The integration of data obtained for TET2-interacting proteins, genome-wide localization of TET2, and TET2 target genes, will provide important information on the role of TET2 in myeloid cell proliferation, differentiation and function. These data will be essential to understanding the role of this protein in myeloid malignancies and may lead to important therapeutic insights.
- Boechi, Leonardo
- Carreño, Leandro J.
- Criollo, Alfredo C.
- Fuxman Bass, Juan I.
- Giudice, Jimena
- Kahn, Suzana A.
- Martin, Natalia
- Pereira, Renata M.
- Pérez-Cuesta, Luis María
- Silva Manzano, Daniel Adriano