David Dominguez-Sola, MD, PhD

Invisible to the human eye, cancer initiation is believed to shape the molecular and cellular landscape of all cancers. Although we have been able to probe these pre-malignant stages in a handful of tumor types, our knowledge remains exceptionally limited for other malignancies like B-cell lymphomas.

B cell lymphomas occur both in adult and children, being one of the most common cancers in the latter group. Notably, an importantfraction of lymphomas rely on the activation of oncogenes through particular genetic rearrangements (e.g. translocations). These genetic events are known to drive lymphomagenesis in animal models, and constitute a useful system to study the basic mechanisms of cancer initiation and progression.

 

Most human B-cell lymphomas arise from B-lymphocytes (B cells) recruited to transient microanatomic structures known as Germinal Centers. Germinal centers are highly organized and dynamic compartments where B cells are trained and selected for their ability to efficiently recognize antigens, a process that is essential to sustain efficient immune responses. However, the molecular and cellular events driving the germinal center also impose a high risk for cellular transformation and lymphomagenesis.

 

Our laboratory is particularly interested in understanding the early steps of B cell lymphomagenesis, and in deciphering how the tissue and cellular contexts affect how oncogenes drive lymphoma initiation and shape the genetic landscape of lymphoma cells, with a particular interest in B-cell lymphomas driven by deregulation of the c-Myc protooncogene. To address these questions we use a multiplicity of in vitro and in vivo methodologies that combine strategies borrowed from both the cancer biology and immunology fields. Using this approach we are refining our knowledge on the cellular origin of B-cell lymphomas and the basic mechanisms of cancer initiation.

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