Group Leader (Innovation Investigator track) in A-TAP Data Science
Deciphering the genetic architecture of Tertiary Lymphoid Structures formation
My research primarily concentrates on the genetic underpinnings of Tertiary Lymphoid Structures (TLS) formation. These structures are highly organised aggregates of immune cells that spontaneously form within non-lymphoid tissues, intriguingly similar to secondary lymphoid organs. While their significant role in adaptive immunity has been well established, their prevalence varies remarkably among individuals. This variation is associated with diverse clinical outcomes in numerous malignancies and immune-mediated diseases.
In cancer, for example, TLS have been linked to favorable prognosis in various malignancies, including melanoma, renal, and lung cancers. An increased abundance of TLS also correlates with enhanced responsiveness to immune checkpoint inhibitors. Conversely, in Immune-Mediated Inflammatory Diseases, the development of TLS can amplify immune responses and promote tissue damage, contributing to disease progression.
The aim of my research team is to elucidate the biological pathways that drive TLS formation. We hypothesize that germline genetic variations may account for some of the variability observed in TLS formation. We believe that understanding these pathways could lead to targeted interventions to modulate the formation and function of TLS, thereby influencing the immune response in the context of specific diseases.
Our approach involves leveraging existing large datasets of paired RNA/DNA sequencing data, generated by notable cancer genomics projects. Through this approach, we aim to scrutinize gene expression patterns indicative of TLS formation within the tumor microenvironment, while simultaneously seeking genetic variants linked to these profiles.
Ultimately, our research endeavors to uncover the genetic determinants influencing TLS development and maintenance. We anticipate that our findings will contribute to the development of innovative therapeutic targets and biomarkers, thereby enhancing the management of diseases where TLS play a crucial role.