Praveen Sethupathy Explores the Fibrolamellar Space
Praveen Sethupathy, PhD, is an Associate Professor at Cornell University.
At the Fibrolamellar Cancer Foundation (FCF) Summit, he sat down with Rare Disease Report to discuss the data he presented, as well as information shared with him from other doctors. In the video below, he discusses why it’s worth being excited about the new breakthroughs being made in the fibrolamellar carcinoma space.
Sethupathy: Right now, we are very excited about mapping at the transcriptional level with the activity in fibrolamellar cancer. We are working very closely with the foundation to acquire as many fibrolamellar tissue samples as we can. The pro-sec technology has advanced to a state where we’re able to work with frozen tissue whereas, previously, in the last 5-6 years, we’ve needed fresh cells. We’re very excited by this advance because it allows us to work with a lot of the tissue that has been bioarchived from fibrolamellar patients. That’s one major area of focus for us.
The other theme that has been coming across in talks at the Symposium is trying to understand what is downstream of DNA HAB1PRKCA. John Gordan spoke about kinome profiling; what are the kinases that are immediately downstream of PRKCA that are getting activated in fibrolamellar, and are any of those potential therapeutic targets? We, too, are interested in kinome profiling, and there may be a really wonderful opportunity to collaborate with them, given that we’ve been pursuing some of those questions, as well.
Another major point of interest for us is that, while it’s still getting established that the fusion – the kimeric protein – is a critical initiator of tumor regenesis in fibrolamellar carcinoma, we don’t know what it is exactly about the fusion? How much does the DNA JB1 contribute? How much does the PKA contribute? What parts of the PKA are most relevant? So, there’s some genetic dissection that needs to occur here, and that’s something we’re very keen on.
Finally, and I’ve alluded to this in a talk, our primary area of expertise is gene regulation and non-coding RNAs. There’s been a growing interest in the role of non-coding RNAs in tumor maintenance. We’ve got some preliminary data to suggest that there is a non-coding RNA profile, both within the cell, and in these little micro-particles that get spit out by the cells that might be conferring some of the rather unique properties of fibrolamellar. It will remain to be seen, and I think that we’ll uncover whether that’s really the case over the next couple of years, but that’s another key question that we’re interested in.
For more from the Fibrolamellar Cancer Foundation, visit the organization’s website: fibrofoundation.org.