This week, Luke Gilbert, PhD, Assistant Professor, Department of Urology, and a Goldberg-Benioff Endowed Professor in Prostate Cancer Translational Biology, was named a member of the 2019 class of the Pew-Stewart Scholars Program for Cancer Research. Gilbert was one of seven early-career scientists working in the US to garner the award.
Below, Gilbert discusses how manipulating bacteria as a teen led him away from a career in espionage, the profound impact of CRISPR, and traveling to Mars.
Congratulations on being named a Pew-Stewart Scholar. What does this award mean for you and your research?
I am delighted to be a Pew-Stewart Scholar. This award lets us pursue a high-risk, high- reward idea that searches for a new way to target tumors driven by loss of a tumor suppressor called p53 (also called TP53).
This blew my mind that we could program living cells to do specific things with relatively simple methods.
Another really important benefit is that I am now part of the Pew Foundation scholar community. This enables a variety of great interactions such as participation in an annual meeting for Pew Scholars which I have heard is a wonderful event.
In terms that are as lay-friendly as possible, explain this project and how the idea came about?
Cancers that have lost the function of a gene called p53 generally have poor prognosis and are difficult to treat. We are looking for new ways to improve survival of patients with p53 mutant tumors. The problem is that we cannot target a gene that is lost. So, we are looking for innovative anti-cancer strategies for targeting p53 mutant cancers using a new tool we have created that we call a CRISPR genetic interaction map.
This method enables us to search through hundreds of thousands of gene relationships in a single experiment and measure how changing gene function enables or blocks the survival of p53 mutant cancer cells.
When did CRISPR come to your attention and what impact has it had on cancer research?
I started working on CRISPR in 2012 in collaboration with Jennifer Doudna, first in yeast and then in human cells. At UCSF, we built the first modified CRISPR system that lets us turn genes on and off in human cells by editing the epigenome to control transcription. CRISPR is an amazingly powerful discovery technology in cancer research enabling us to rapidly reveal genes driving cancer processes such as drug resistance and metastasis. CRISPR is also being used for robust customized anti-cancer cellular therapies in immuno-oncology.
If CRISPR didn’t exist, what would your research look like?
If CRISPR didn’t exist, then none of my lab’s current research program would be possible. Every single one of the projects in lab is using CRISPR in multiple ways to edit the genome or epigenome. Older technologies such as RNA interference can serve a somewhat similar role enabling us to experimentally identify genes driving cancer progression, but CRISPR lets us do so much more that I can’t imagine my lab without these tools.
When did you decide to go into science; what put you on the path to biosciences? Did you love science as a kid? Why urology?
As a kid I wanted to be a spy or diplomat. I loved history and really didn’t care much for science. I fell in love with science, and more specifically biology, in high school when I was allowed to do simple experiments to manipulate bacteria. This blew my mind that we could program living cells to do specific things with relatively simple methods.
Prostate cancer is a leading killer of men. The urology department and the HDFCCC are wonderful environments for research. My lab works on building new CRISPR tools and applying them to pressing problems in cancer such as drug resistance and metastasis. We are excited to be working on prostate cancer but also other cancers. For example, my Pew-Stewart award is to work on high risk acute myeloid leukemia driven by loss of p53 which historically has an extremely poor prognosis.
If you weren’t a scientist, what career would you have?
I can’t imagine not being a scientist at this point, but if forced to choose I guess I probably would have ended up as a lawyer.
What do you do in your spare time that is not related to work?
Deal with my monster of a dog. Just kidding! She is great. I enjoy running with my dog and exploring northern California with my wife, Laralynne.
What is the best advice you ever received?
Relax! Also, not to take setbacks or being told no too personally.
What advice do you have for young future scientists?
Be persistent. Science can be slow and frustrating at times, but is overall a wonderful career.
Last question, and it’s science fiction, so go with it: if you were a mad scientist using CRISPR or CRISPR-like technology, what trait or characteristic would you alter or remove from humans?
I would CRISPR in resistance to space radiation so we can travel to Mars someday without health consequences.
More on Luke Gilbert from UCSF School of Medicine: