Dr. Salil Garg

The Garg Lab aims to define the molecular drivers in mutationally bland cancers to develop new diagnostics and therapies. Next-generation sequencing has led to an explosion in understanding the DNA changes that lead to malignancy and led to new diagnostic tests in the clinic. Yet, not all malignancies have been impacted equally. Many pediatric malignancies such as ependymoma and subclasses of leukemia show no or few recurrent DNA changes, complicating attempts at personalized therapy. Interestingly, these mutationally bland cancers and many others show extensive tumor heterogeneity arising spontaneously from single cells.

Understanding this intrinsic heterogeneity arising at a single cell level is key to unlocking the pathogenesis of cancers that may have epigenetic drivers. These malignancies often involve de-differentiation with inappropriate expression of embryonic developmental programs. An embryonic cell model system has been developed that shows intrinsic heterogeneity in generating different functional cell states. The states transition in part through coordinated expression changes of many genes in functional networks that depend on microRNAs, post-transcriptional regulatory small RNAs that bind gene products.

The Garg Lab is interested in how microRNAs stabilize gene networks in embryonic cells and in the malignant cell state. Their hypothesis is that transitions in microRNA expression generate changes in cell behavior and can drive the malignant cell state in mutationally bland cancers. The lab is testing these ideas using techniques from cell biology, systems biology, and genomics. Additionally, the Garg Lab is working closely with the Anderson and Sharp Labs to develop single cell microRNA sequencing. This platform technology will allow researchers to test whether changes in microRNA expression precede changes in cell behavior and will provide a new diagnostic for early cancer detection.