Hematopoiesis and cancer

The primary goal of our research is to understand how the production and differentiation of hematopoietic and immune cells are normally regulated and how defects in this regulation can lead to leukemia and lymphoma and other hematopoietic diseases including rare blood disorders. Our projects are:

The RNA helicase DDX3X is vital in RNA metabolism, transcription, and translation regulation. It is frequently mutated in B cell lymphomas such as diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma. We are interested to understand how loss of function (LOF) mutations in DDX3X that impair its helicase activity, disrupting RNA metabolism and gene expression contribute to lymphomagenesis by promoting malignant transformation and cell proliferation, often in cooperation with the oncogene MYC. For reviews see here: 

The transcription factor GFI1 (Growth Factor Independence 1) and LSD1 (Lysine-Specific Demethylase 1) form a complex to regulate gene expression by modifying histones, maintaining the undifferentiated state of myeloid cells or lymphoid cells. Inhibitors targeting LSD1 can disrupt this complex, activating genes involved in myeloid differentiation and suppressing leukemia cell proliferation. We are exploring  the role of the GFI1/LSD1 complex in the differentiation of myeloid cells as well as in B and T lymphocytes. We are interested how targeting the GFI1/LSD1 axis can be translated into promising therapeutic strategies for leukemia and lymphoma by reactivating suppressed differentiation pathways. For a review see here: 

The BTB/POZ domain protein MIZ-1 (ZBTB17) is essential in lymphocyte differentiation and acts as an interaction partner and co-factor of the oncoprotein c-MYC. MIZ-1 forms complexes with c-MYC to regulate gene expression, influencing cell proliferation and differentiation. We have shown that disruption of the MIZ-1/c-MYC interaction impairs lymphocyte differentiation and the development of lymphoma and leukemia. We are investigating how targeting MIZ-1 can be used as a therapeutic strategy against c-MYC-dependent lymphomas and leukemias by inducing differentiation and apoptosis of cancerous lymphocytes. For reviews see here: 

lncRNAs, which do not encode proteins, play significant roles in the pathogenesis and progression of leukemia and lymphoma by regulating gene expression at various levels, including chromatin modification, transcription, and post-transcriptional processing. lncRNAs can function as oncogenes or tumor suppressors, influencing cell proliferation, apoptosis, and differentiation. We have undertaken several projects to better understand how lncRNA work in leukemia and lymphoma and whether their targeting can be beneficial against acute myeloid leukemia and B cell lymphoma. For a review see here: