Jack Calder

 
Will Lockwood
Comox
Canada
CIHR Graduate Scholarships
 

Research Topic

Transformation induced dependency of the normally non-vital RNA helicase DDX3X provides a novel therapeutic strategy in lung cancer

Research Description

Recently, our collaborators screened a panel of 189,290 diverse chemical compounds in search of new agents to treat lung tumors. One compound, designated LCS3, was found to be a broad-spectrum inhibitor of cancer cells while not being toxic to normal cells. Early indications from affinity approaches using LCS3-linked beads and gene knockout cell lines indicate that the primary target of LCS3 is DDX3X, an ATP dependent RNA helicase. First, using loss-of-function and cDNA overexpression "rescue" experiments, I look to confirm DDX3X as the target of LCS3 drug. Second, I look to identify DDX3X’s role in tumorigenesis through measuring differences in DDX3X knockouts and normal LC cells in such things as apoptosis, cell cycle, senescence, anchorage independent growth and migration, and observing if overexpression of DDX3X makes immortalized LC cells more tumorigenic. Lastly, I look to determine what underlying pathways DDX3X helps regulate in LC cells to better fully understand its role in the cell. This can be achieved through genome-wide expression pattern analysis of sensitive cell lines treated with LCS3, in parallel using DDX3X knockdowns, and in reciprocal experiments overexpressing DDX3X in normal lung cells. Those pathways that are affected across all sensitive cell lines will have a fundamental role in mediating the biological effect of LCS3 treatment – and therefore DDX3X inhibition – and these pathways are likely to function in lung tumorigenesis. Together, this work will lead to a better understanding of the underlying mechanisms that lead to lung tumorigenesis and the molecular mechanisms of LCS3.

What aspect of your graduate program do you enjoy the most or are looking forward to with the greatest curiosity?

I am most excited about getting some papers out, as I've done a lot of lab work and am now just getting some data back that I hope will contain relevant and print-worthy results.

What was the best surprise about UBC or life in Vancouver?

Life in Vancouver is very busy, and there is always something going on or something to do in and around the town. West coast weather is pretty amazing, and I really enjoy being able to easily leave Vancouver to go hiking or camping. I've also really enjoyed the number of sports leagues and especially like the number of bike routes that make it easy for me to bike to and from work and everyday and around town year-round. The city is definitely a great place to be young, athletic, and adventurous.

Why did you decide to study at UBC?

I chose to study at UBC for two reasons. One, because I'm from Comox and enjoy the west coast and being somewhat close to my family. Two, because the BC Cancer Agency is highly touted and there are very impressive researchers working on amazing projects.

What is it specifically, that your program offers, that attracted you?

The program offers me the ability to focus primarily on working on my research projects and not on having to take too many classes or TA undergrad labs. It does require certain classes, which I found for the most part to be very relevant for not only my research but also in helping me make a more informed decision on my future plans.

 

Why did you decide to pursue a graduate degree?

I was always interested in genetics and specifically human genetics, and not in things like med school or pharmacy or any other of those type of programs. Doing a graduate degree seemed to be the next logical step in opening up opportunities in this kind of field.

What do you see as your biggest challenge(s) in your future career?

For me my biggest challenge is still trying to figure out what kind of job and what kind of lifestyle I want ten years down the road. There are many different options and paths for me as of right now, all with their own positives and negatives, so it's just trying to figure out what I think is best for future me.

How do you feel your program is preparing you for those challenges?

The program provides countless opportunities to meet with people of different professions with different career paths and opens up a lot of opportunities to see all the different types of careers that are out there.

What aspects of your life or career before now have best prepared you for your UBC graduate program?

I had a co-op job at Environment Canada in Ontario after my third year where I ended up working for 16 months. As I wasn't really an environmental science student, it prepared and showed me that if you are committed, work hard, and put the time in, even if you start out knowing hardly anything about the specific field, you can overcome this and do a great job.

What do you like to do for fun or relaxation?

I don't do too much relaxation, and most of my free time is taken up playing a lot of different sports including soccer, volleyball, tennis and softball, which for me is tons of fun.

What advice do you have for new graduate students?

I would advise new graduate students to take some time to really think and try to figure out what they want to do and if a graduate degree would help in achieving that goal. I would also advise any new graduate student to look into projects they are interested in, but most importantly to find a supervisor who you like and think you could work well with as you will be working with them for at least two years, if not more.