Functional genomic approaches to understanding tumorigenesis and treatment resistance in malignant brain tumors.
John Liu, Professor
UC San Francisco
Applications for Spring 2025 are closed for this project.
Glioblastoma (GBM) is the most common primary brain cancer. Despite decades of research to better treat this cancer, most patients unfortunately die within 2 years of diagnosis. Surgery followed by radiation therapy and chemotherapy comprise the standard of care for patients with GBM, but resistant to treatment poses a major problem. These mechanisms of treatment resistance have largely remained unknown partially because our ways of studying GBM have not fully captured the full extent of the heterogeneity and complexity of these tumors in their native environments. CRISPR/Cas9 technologies have the potential to not only reveal new therapeutic targets and molecular pathways, but also to directly edit the genome or epi-genome of tumors. In this project, we will develop CRISPR/Cas9-based genetic screens to better understand pathways that contribute to treatment resistance in fully intact GBM tumors grown in vivo. Importantly, we aim to discover and characterize candidate therapeutic targets for GBM that spare normal brain tissues, by evaluating the consequences of gene inactivation in multiple cell types within GBM tumors, through high-coverage sgRNA libraries combined with single cell RNA-sequencing. As a step beyond target discovery, we will then develop an epigenetic editing strategy using engineered CRISPR/Cas9 derivatives combined with lipid nanoparticles to target GBM epigenetic aberrations, which can drive tumor progression and treatment resistance. The goal of this project is to leverage a platform that can discover new therapeutic targets and then act on them precisely using advanced CRISPR/Cas9 technologies.
Role: The student will take an active role in the design, implementation, and analysis of experiments related to this project, which will include:
(1) studying the mechanisms through which brain tumors develop and become resistant to treatments and
(2) identifying novel therapeutic targets using molecular biology, CRISPR genome and epigenome editing, biochemistry, mouse genetics, bioinformatics, pharmacology, and multidisciplinary collaborations.
In the process, students will be expected to gain proficiency in advanced molecular biology, bioengineering, tumor biology, and bioinformatics. They will have the opportunity to collaborate with basic scientists, computational biologists, and physician-scientists at the UCSF Helen Diller Cancer Center and broadly throughout the UCSF Campuses and beyond.
Students will have the opportunity to be co-authors on publications resulting from this project as well as potentially present at international conferences. Students will receive mentorship from Professor Liu that is tailored toward future career objectives, such as the pursuit of a MD, biomedical PhD, or MD/PhD.
Qualifications: - Strong interest in tumor biology, genomics, and/or molecular biology.
- Strong degree of self-motivation, eagerness to learn and think critically, and enthusiasm for science and/or medicine.
- Attention to detail and problem solving ability.
- Demonstrated reliability and integrity.
- Strong organizational, communication, and documentation skills.
- Initiative to work well as part of a team and also independently.
- Prior laboratory experience a plus but not required.
Hours: to be negotiated
Off-Campus Research Site: University of California, San Francisco Helen Diller Family Cancer Research Building 4th Floor 1450 3rd Street San Francisco, CA 94158
Related website: https://liulab.ucsf.edu
Biological & Health Sciences