Khalid Al-Zahrani

The Al-Zahrani Lab aims to develop and apply new high throughput in vivo functional genomics tools. We study how large-scale chromosomal alterations drive tumorigenesis and can be leveraged as a therapeutic vulnerability in cancer. While chromosomal instability is a hallmark of cancer, identifying which genes drive tumorigenesis is complicated by the fact that these unstable regions span hundreds-to-thousands of genes which can be lost, gained and/or re-arranged.

To overcome this challenge, we perform multiplexed CRISPR screens in mouse models of disease to simultaneously assess the tumorigenic potential of all affected genes to identify cancer-specific drivers and vulnerabilities within the context of a native tumor microenvironment.

Creating New Functional Genomics Tools

We strive to create new functional genomics approaches to investigate disease biology at scale. Our previous work developed new tools for CRISPR-based multiplexing and we are currently adapting these types of approaches to study the causes and consequences of both genetic and transcriptional heterogeneity in cancer.

Developing Mouse Models of Disease

We aim to develop new mouse models of cancer and disease that are amenable to functional interrogation through direct in vivo genetic manipulation. Currently our lab focuses on identifying the earliest drivers of brain, breast, and ovarian cancers by genetically manipulating cells within their native environment.

Investigating How Aneuploidy Drives Cancer

Our previous work identified that chromosomal arm-level gains and losses harbor distinct cancer-driving events. One of our major goals is to combine our new functional genomics tools with mouse models of cancer to investigate how other types of common chromosomal and transcriptional heterogeneities drive cancer and can be targeted therapeutically.