PBRM1 is the second most commonly mutated gene in clear cell renal cell carcinoma (the most common type of kidney cancer) and was first identified in 2011.  Despite this, little is known about what the role of PBRM1 loss is in kidney cancer.  We are currently exploring changes in chromatin modification that occur after it is lost and identifying potential avenues for personalized treatment strategies in advance cases of kidney cancer.

When patients have muscle-invasive bladder cancer, the standard of care is to be treated with cisplatin-based chemotherapy before surgery to remove the entire bladder. At the time of bladder removal, about 30-40% of patients will not have residual cancer left in their bladder.  Patients and doctors alike wonder if bladder removal is necessary if there is no tumor left.  The answer at this point in time is “yes” because we do not have a way to reliably identify patients who will respond to chemotherapy (prospectively), or patients who actually did respond to chemotherapy (retrospectively).  We are currently using next generation sequencing to prospectively and retrospectively identify responders, with the aim to safely avoid bladder removal in responders in the future.

Lastly, bladder cancer sequencing efforts have revealed a large number of potentially therapeutically tractable targets, but how to target them is still unknown.  These genetic alterations can be modeled in mice using the exciting new genome editing tool CRISPR.  Using this technology, we are making many new bladder cancer models by introducing combinations of mutations into the mouse bladder to try to model the human disease more accurately in mice. This will hopefully allow us to marry individual mutations to therapeutic strategies in anticipation of personalized medicine algorithms in humans.