Overview
The goal of the Porter lab is to develop novel therapeutic strategies for leukemia through better understanding of molecular mechanisms of leukemogenesis and treatment resistance. We employ a wide variety of techniques, in vitro and in vivo, for discovery and validation of molecular vulnerabilities in cancer cells.
A major focus of the lab is directed at understanding mechanisms of immune evasion during leukemogenesis, as well as enhancing immune cells’ response to leukemia cells. Specifically, we are studying the role of a newly describe immune checkpoint protein, Siglec15, in leukemia and lymphoma.
Current Projects
Mechanisms of Immune Evasion During Leukemogenesis
While evasion of the immune system is considered one of the defining features of cancer, the mechanisms by which leukemia cells evade immune detection and elimination remain incompletely understood. We have found that leukemia-cell calcineurin is required for immune evasion in a mouse model of leukemia (Rabe et al, Cancer Res, 2019). This work identified IL-12 as a potent stimulator of T cell response to leukemia cells, which we are now trying to exploit as a therapeutic strategy in collaboration with Erik Dreaden, PhD. In addition, we have discovered that Siglec15 is a novel immunomodulatory molecule, which can be inhibited to promote T cell killing of leukemia cells.
Single Cell Transcriptomics
The presence of minimal residual disease (MRD) is one of the most reliable risk factors for relapse in both ALL and AML and has become a routine part of clinical decision making – when present, intensified therapy is indicated. As part of the Aflac Precision Medicine Program Leukemia/Lymphoma Research Team, our lab has approached this phenomenon to study mechanisms of treatment failure with several strategies. One of these strategies includes the use of single-cell mRNA-sequencing (scRNA-seq) to study leukemia cells and non-leukemia cells sorted from children with B cell acute lymphoblastic leukemia, with or without MRD at the end of induction. This includes ongoing collaborations with Gregory Gibson, PhD and Manoj Bhasin, PhD, in projects on ALL and AML, respectively.