Kan, Ryan

Ryan is in the Cell & Developmental Biology (CDB) home area of the MBIDP, and joined the CMB Training Program in 2022.

Mentor: Dr. Aparna Bhaduri

Research project:

     Glioblastoma (GBM) is the most common malignant brain and CNS tumor. It is classified as a grade IV tumor, which makes it one of the deadliest and fastest-growing tumors. Despite decades of research, the prognosis for GBM patients remains poor, with a median survival rate of 15 months. The current standard of care is limited to surgical resection and chemotherapy. Due to the highly invasive and heterogeneous nature of the tumor, recurrence is practically inevitable. Single-cell RNA sequencing of patient tumors has identified a population of cells resembling the transcriptomes of outer radial glia (oRG), which act as stem cells and are only expressed in the developing human brain. One of the genes that define this population of cells and is highly upregulated in the sequenced GBM tumors is PTPRZ1, a receptor-type protein tyrosine phosphatase. In the developing brain, PTPRZ1-expressing oRG exhibit a unique behavior known as mitotic somal translocation, in which the cells travel a certain distance before they divide; this has been proposed to be the mechanism of migration for these oRG-like cells in GBM. My research aims to dissect the role of PTPRZ1 in driving tumor progression and migration.

     In my research project, I aim to investigate the roles of enzymatic activity and dimerization of PTPRZ1 in the tumor. To accomplish this, I will express different isoforms and mutants of PTPRZ1 in a GBM cell line using lentiviral transduction methods. The GBM cell line will also have endogenous PTPRZ1 knocked out with CRISPR/cas9 mutagenesis. I will then interrogate the transcriptomes of these cell lines using bulk RNA sequencing, phospho-proteomes using mass spectrometry, migration capabilities using invasion assays, and proliferation rates using viability assays. All of these pieces will lend insight into the mechanism of this protein and warrant the targeting of PTPRZ1 catalytic activity and/or dimerization as novel therapeutics.