About
Research
Overview
Cancer cells hijack a variety of normal biological functions to grow and survive. Our research explores this topic in the context of mature B cell malignancies, which are highly heterogeneous. These cancers originate from B cells having experienced the germinal center reaction as part of the adaptive immune response, where they must survive an intense competitive selection process.
Our lab focuses on Diffuse Large B Cell Lymphoma (DLBCL), the most common and aggressive B cell malignancy, of which 40% cases relapse or are refractory to treatment. A major challenge in the field has been to gain a mechanistic understanding of how incurable forms develop and what makes them treatment-resistant.
We discovered that aberrant competitive fitness in germinal center B cells represents a novel mechanism of malignant transformation, yielding aggressive and disseminated lymphomas that recapitulate relapsed/refractory human DLBCLs. We are now investigating how cell-cell communication signals, metabolic fitness gain and biochemical adaptation function as key determinants of germinal center B cell competitiveness and aggressive transformation. Questions we are asking include:
1. Which extracellular signals provide competitive fitness to B cells and drive dissemination of malignant B cells outside of their lymphoid niche, including at immune-privileged sites?
2. How do competitive B cells and derived lymphomas satisfy their metabolic needs to sustain intense growth and proliferation?
3. Which biochemical mechanisms underly elevated biosynthetic potential in competitive B cells and aggressive lymphomas?
Our research program will provide knowledge about essential processes that support successful immune responses and a mechanistic understanding of clinically unfavorable DLBCLs from several major biological angles. This will allow identifying new dependencies that can be harnessed to design novel rational therapies for DLBCL patients.
We are dedicated to characterizing the delicate evolutionary trade-off between defending vertebrate organisms from infections and the risk of developing cancer and we expect our findings to be applicable to additional cell types, where superior competitiveness for growth signals and metabolic resources can drive expansion of abnormally fit cells at a high-risk of transformation.