So my group focuses on developing novel, faithful mouse models of chronic lymphocytic leukemia and transformation into Richter’s. We know Richter’s syndrome remains a very big challenge in CLL patient management, and so far there’s been very limited mouse models that could be explored to understand more about the biology and also the treatment opportunities for Richter’s. So what I did was to employ CRISPR-Cas9 gene editing to introduce multiple combinatorial genetic drivers typical of Richter’s syndrome in the animals and these, to our surprise, were very nicely modeling disease biology in vivo...
So my group focuses on developing novel, faithful mouse models of chronic lymphocytic leukemia and transformation into Richter’s. We know Richter’s syndrome remains a very big challenge in CLL patient management, and so far there’s been very limited mouse models that could be explored to understand more about the biology and also the treatment opportunities for Richter’s. So what I did was to employ CRISPR-Cas9 gene editing to introduce multiple combinatorial genetic drivers typical of Richter’s syndrome in the animals and these, to our surprise, were very nicely modeling disease biology in vivo.
So we now have platforms that we’ve been able to explore in the context of immunotherapy with anti-PD-1, for example, I will show some results about that tomorrow. We’re able to explore changes in tumor microenvironment with focus, with single cell sequencing technologies we’ve been able to see very broad changes in both T-cells and monocytes. And we’re now even further increasing the complexity of our models to more faithfully recapitulate Richter’s syndrome disease heterogeneity that has emerged in recent human studies employing cytosine base editing technology.
So we hope to have platforms that, on one hand, can allow us to really define vulnerabilities of patients with selected molecular alterations so we could potentially target in a personalized fashion. And on the other hand, we still need to know more about the biology of Richter’s. We still need to know more about the individual function of selected driver lesions. So we are also focused very much on the mechanistic understanding of the function of these drivers in our current studies.