The Ventura Lab

We are proud to announce that our latest manuscript: “Somatic chromosomal engineering identifies BCAN-NTRK1 as a potent glioma driver and therapeutic target”, has been just published in Nature Communications. This work was the result of a truly collaborative effort  between our lab and the lab ot our neighbors at MSKCC: Robert Benezra and Maurizio Scaltriti. A follow-up to Danilo Maddalo’s work, this project used CRISPR-based somatic genome editing to model a set of rare genomic rearrangements responsible for  brain cancer-associated gene fusions. Peter J. Cook, is the lead author of this paper and is a joint postdoctoral fellow between the Ventura and the Benezra lab, and the project was funded by the Pershing Square Sohn Cancer Foundation and by the Brain Tumor Center at MSKCC.

Peter’s initial goal was to use CRISPR-Cas9 to model a set of uncharacterized, potentially oncogenic chromosomal rearrangements in the brain. Four gene fusions identified from human glioma patient RNA-Seq data were selected and the chromosomal inversions, deletions, and duplications underlying these fusions were modeled in mouse adult neural stem cell primary cultures and directly in the brain using adenovirus-mediated in vivo genome editing. He found that a chromosomal deletion resulting in the fusion between the secreted proteoglycan Bcan and the receptor tyrosine kinase Ntrk1 was capable of  transforming p53-null neuronal stem cells cells, resulting in high grade gliomas by either in-vitro orthotopic stem cell implantation or by direct in-vivo viral induction. Interestingly, we also found that these tumors were  sensitive to a small molecule kinase inhibitor specific to Ntrk1.

We are excited about this work not only because it resulted in a new a clinically relevant genetically-engineered mouse model for human glioma, but also because it provides an experimental pipeline that can be readily adapted to interrogate a wide range of brain cancer associated  mutations of unknown functional significance.

Last Friday was Stephanie Cervino’s last day in our lab. Our fearless admin assistant/lab manager/organizer is going back to school. Needless to say, Stephanie will be missed by us all, but we are comforted by the hope that she will not forget us, and by the certainty that she will do great things! Good luck, Stephanie!

If Friday was a bitter-sweet day, Monday was simply sweet, as Sandra Casseus started her first official day in the lab. In truth, Sandra has been shadowing Stephanie for the past couple of weeks, learning all the tricks to manage our crazy lab, so we already got to know and appreciate her. Welcome, Sandra!

Today is the last (official) day in the lab for Ciro Bonetti (aka Ciruzzo), one of our senior postdocs. Ciro is leaving to begin a new and exciting adventure at Regeneron. To say that Ciro will be missed is a big understatement and while we are happy for him, he leaves a hole that will be very difficult to fill.

Ciro begun his scientific career in the beautiful city of Naples and, as many Italian aspiring scientists do, came to the US for his postdoctoral training. We have been incredibly lucky to have him in the lab;  during the past six years Ciro contributed to many exciting projects. He was the first to work on lncRNAs in our lab, and thanks to his results we were able to obtain NIH funding. As part of this work he generated four different genetically engineered mouse strains, whose characterization will keep us busy for  years to come.
Together with Joana (another postdoc that soon will start her independent career), Ciro also lead  an exciting project on improving CRISPR-based gene replacement efficiency. This work is nearing completion and hopefully you will hear more about it in the not so distant future on this blog!

In addition to his remarkable scientific accomplishments, Ciro has been a generous and friendly lab member, an outstanding volleyball player, an assiduous concert goer, and a truly nice guy. The sadness of seeing him leave is attenuated by the fact that Ciro will remain in NYC, and we are sure he will not forget his friends and colleagues here at MSKCC.
Ad majora, Ciruzzo!