In honor of our 30th anniversary, we’re catching up with former grant recipients to hear how their work has impacted kidney cancer care and research.
Dr. Phillip Abbosh is an Assistant Professor of Urology at Albert Einstein Medical Center and researcher at Fox Chase Cancer Center in Philadelphia, Pennsylvania. He received the Kidney Cancer Association’s 2017 Young Investigator Award. We spoke to Dr. Phillip about his research project – Evaluation of the role of PBRM1 loss in Polycomb repression and stem cell maintenance.
Since my days as a grad student at the turn of the century, I have always been interested in epigenetics*. I trained in a lab that was and remains deep in DNA methylation, and when the kidney cancer genome started to be described, I thought it was so curious that a chromatin modifier, PBRM1, mutated so frequently. The interest in kidney cancer was amplified by the environment I am in – Fox Chase is a world-renowned place to get kidney cancer care.
Sometimes in science, you make a reasonable hypothesis, but it doesn’t hold up. I made a neat hypothesis based on available data at the time that mutation (loss) of PBRM1 would engender cancer stem cell characteristics to tumors. We explored it pretty thoroughly but didn’t find evidence to support the hypothesis. We then took a different approach and found a nice lead on a connection to the immune microenvironment of clear cell renal cell carcinoma (ccRCC) tumors.
A few months after we found this connection, a pair of high-impact papers were published by really high-powered labs which showed that we were on the right track. One of the senior authors on the paper won the Nobel Prize in 2019, so I don’t feel too bad about getting beat to the punch, and in fact, was reassured. We are still working on this refined idea and now think we have something that is very interesting and worthy of further study.
It is neat to finally have a unique angle on PBRM1-mutated tumors that we have data to support. Our hypotheses keep coming up spades, so we are close to having a nice story to tell. I would tell ccRCC patients that help is on the way! We think we are getting closer to understanding how mutations in the tumor set up the immune system to both ‘forget’ that the tumor is there and finding a way to ‘remind’ the immune system to do its job.
My lab is actually mostly focused on bladder cancer. We are currently working on really accurate urine biomarkers, the bladder cancer microbiome, bladder tumor immunology, and a cool mouse model. However, I am really committed to finishing this kidney cancer project out. I want to give KCA a nice return on their investment and I think we will. If it works out the way we think it will, there’s no reason the project couldn’t expand to the point where we are both a kidney and bladder cancer lab.
* Epigenetics is the study of changes in organisms as a result of how gene expressions are modified rather than as a result of changes in the genetic code itself.