Archive for category: News

A proteogenomic surfaceome study identifies DLK1 as an immunotherapeutic target in neuroblastoma

Amber K. Hamilton, Alexander B. Radaoui, Matthew Tsang, Daniel Martinez, Karina L. Conkrite, Khushbu Patel, Simone Sidoli, Alberto Delaidelli, Apexa Modi, Jo Lynne Rokita, Maria V. Lane, Nicholas Hartnett, Raphael D. Lopez, Bo Zhang, Chuwei Zhong, Brian Ennis, Daniel P. Miller, Miguel A. Brown, Komal S. Rathi, Pichai Raman, Jennifer Pogoriler, Tricia Bhatti, Bruce Pawel, Tina Glisovic-Aplenc, Beverly Teicher, Stephen W.Erickson, Eric J. Earley, Kristopher R. Bosse, Poul H. Sorensen, Kateryna Krytska, Yael P. Mosse, Karin E. Havenith, Francesca Zammarch, Patrick H. van Berkel, Malcolm A. Smith, Benjamin A. Garcia, John M. Maris, and Sharon J. Diskin

https://doi.org/10.1016/j.ccell.2024.10.003

Cancer immunotherapies produce remarkable results in B cell malignancies; however, optimal cell surface targets for many solid cancers remain elusive. Here, we present an integrative proteomic, transcriptomic, and epigenomic analysis of tumor and normal tissues to identify biologically relevant cell surface immunotherapeutic targets for neuroblastoma, an often-fatal childhood cancer. Proteogenomic analyses reveal sixty high-confidence candidate immunotherapeutic targets, and we prioritize delta-like canonical notch ligand 1 (DLK1) for further study. High expression of DLK1 directly correlates with a super-enhancer. Immunofluorescence, flow cytometry, and immunohistochemistry show robust cell surface expression of DLK1. Short hairpin RNA mediated silencing of DLK1 in neuroblastoma cells results in increased cellular differentiation. ADCT-701, a DLK1-targeting antibody-drug conjugate (ADC), shows potent and specific cytotoxicity in DLK1-expressing neuroblastoma xenograft models. Since high DLK1 expression is found in several adult and pediatric cancers, our study demonstrates the utility of a proteogenomic approach and credentials DLK1 as an immunotherapeutic target.

Diskin Lab hangs another tassle!

     On June 5, 2024, Diskin lab was thrilled to present another student for their successful thesis defense. Rawan Shraim joined the lab in July 2020, amidst all the pandemic turmoil and restrictions on personnel sharing space. She came to us through a unique program at Drexel University School of Biomedical Engineering, Science and Health Systems which allows individuals with full-time employment to pursue their doctorate degree in a part-time setting. Rawan was already working at CHOP, in a clinical research coordinator position with GI.  She then transitioned to the CCCR Bioinformatics Core supporting other research groups while simultaneously conducting her own research, combining in silico data analysis with wet bench validation of proposed targets. Her work, titled Proteogenomic Discovery Of Immunotherapeutic Targets in Cancer: Focus on Rhabdomyosarcoma was completed in record time, especially considering her efforts in unrelated research for other groups.

Rawan will be remaining at CHOP in her role as a Bioinformatics Scientist II and working with the Teachey lab while the targets she identified continue to be worked up into potential cures. Great work, Rawan!

As things are ever-changing here at CHOP and in the CCCR, so too in the Diskin Lab. Dr. Diskin is overseeing the newly formed Center for Childhood Cancer Research Bioinformatics Core, a resource to be used by Cancer Center researchers to help analyze data sets. This is a collaborative effort between CCCR and the Department for Biomedical and Health Informatics (DBHI), and is aimed at supporting the bioinformatics research needs of CCCR investigators.

We are pleased to announce that Rebecca Kaufman, MS will be the first member of this newly formed team as a Bioinformatics Scientist.  Welcome, Rebecca! We hope to expand the team soon.