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Profile of Brent Derry

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Dr. Brent Derry

Dr. Brent Derry, PhD

  • Senior Scientist, Developmental & Stem Cell Biology
  • Assistant Professor, Molecular Genetics, University of Toronto

1. Where are you from? /Where did you study?
I was born in Belleville and raised in Madoc, Ontario (a little town just north of Belleville).

I did my undergraduate studies at Carleton University in Ottawa where I started out studying chemistry and finished with a B.Sc. in biochemistry.  In Hamilton, I worked on a Master’s degree in biochemistry at McMaster University where I first got interested in cancer therapy working on the design of chemotherapy drugs.  This in turn led me to the University of California, Santa Barbara where I pursued my PhD under the supervision of Dr. Leslie Wilson.We were researching the mechanism action of the front-line chemotherapeutic drug Taxol®, which led to a better understanding of how this drug kills cancer cells.

After I completed my PhD I got really interested in understanding how cells die, and it was fortuitous that Dr. Joel Rothman had just relocated his lab from the University of Wisconsin to UC Santa Barbara.  I stayed in California to undertake post-doctoral research with Dr. Rothman and switched fields from biochemistry to genetics.  My work focused on how an organism orchestrates the suicide of the cells that it doesn’t need during development or reproductive stem cells damaged by stresses such as radiation or chemotherapeutic drugs.  It was in Dr. Rothman’s lab that I was introduced to the worm (C. elegans) as a model system which I still use in my research today.

2. What are you researching right now?
My research is primarily focused on using C. elegans to understand the function of genes that are deregulated in human diseases, such as cancer.  At the moment we are focused on discovering new genes and deciphering the mechanisms by which they regulate a cellular suicide process called apoptosis.

One of the genetic diseases we are interested in is Li-Fraumeni syndrome.  In this condition, patients inherit a mutation in the tumour suppressor gene called p53.  When that gene is mutated, two things happen: patients acquire cancer at a very high frequency early in life and the tumour cells are resistant to chemotherapy.  Essentially, p53 functions in two ways: (i) to protect the genome from acquiring mutations that eventually transform a normal cell into a cancer cell, and (ii) to act as a cellular executioner to kill cells by apoptosis if they are subjected to stresses that mutate DNA.  Thus, if a patient is missing p53 dangerous cells survive and can develop into tumors that are resistant to most therapies.  We use the powerful genetic toolkit of the worm to find new ways to try to trick cells into committing suicide independent of p53. 

Related to our interests in p53-independent apoptosis, we recently discovered that neighbouring cells assist in killing cells damaged by radiation. Interestingly, the first gene we found to be responsible for this “assisted suicide” (kri-1) is a homologue of the human CCM1 gene, which is frequently mutated in a disease called cerebral cavernous malformations (CCM).  This disease is manifested by angiomas that form in the brain and superficially appear to be unrelated to cancer. We are now developing a model of CCM disease in C. elegans to sort out whether cell death plays as important a role in this disease as it does in cancer.

3. Who is your all-time favourite scientist, and why?
For me it is a tie between Dr. Francis Crick (http://nobelprize.org/nobel_prizes/medicine/laureates/1962/crick-bio.html) and Dr. Sydney Brenner (http://nobelprize.org/nobel_prizes/medicine/laureates/2002/brenner-autobio.html). I like them both because they were brilliant and yet both were underdogs in many ways.

I think Francis Crick was an absolutely remarkable individual.  Crick and Dr. James Watson proposed that DNA is a double helix, which essentially gave birth to the field of molecular biology.  Crick is fascinating to me as an underdog because he got a late start in his career and still accomplished so much.  Not only did he work out the structure of DNA with Watson, but he went on to work with Brenner to propose the genetic code – that a triplet of bases in DNA encodes a single amino acid.  That was a huge breakthrough that influences every aspect of my work.  Later Crick proposed the ‘central dogma’ of molecular biology, in which DNA provides the template for mRNA to synthesize protein.  This has been altered over time with new discoveries, but he really was the father of molecular biology.  Later in life he became interested in consciousness and neurobiology.

Brenner blows my mind because not only did he help uncover the genetic code with Crick, he also discovered messenger RNA (mRNA) with François Jacob and Matthew Meselson. Brenner went on to introduce a genetically tractable organism to study how an organism develops.  This organism is C. elegans, the little round worm that I use in my lab to study cell death. Brenner essentially founded the C. elegans community that I am now a part.  Crick laid the foundations for molecular biology and Brenner introduced a genetically tractable organism to understand how genes regulate development of a multicellular organsim.  So far, three Nobel Prizes have been awarded to six C. elegans researchers for work that has had a profound impact on basic biology and medicine.  People like Crick and Brenner were mavericks in many ways, fearless thinkers who did it their own way.  The magnitude of their influence in modern biology is unbelievable and that has benefited us all.

4. What in your opinion is the single most important scientific breakthrough, and why?
There are so many, but I’ve come to the conclusion that to me the most important breakthrough was the discovery by Canadian-born Dr. Oswald Avery and his colleagues that the heritable material which makes genes and chromosomes is DNA.  This goes full circle back to Watson, Crick and Brenner - the discovery that provided the foundation upon which the field of molecular biology was built.

5. What are your major interests outside the lab?
First and foremost, spending quality time with my family is important to me.  My kids are really fun right now and they are at an age where they still think I am cool, so I am taking full advantage of this narrow window of time!  My son is nine and my daughter is seven.  We play a lot of sports together, laugh a lot and I involve them in my music.

I have been playing in all kinds of bands since I was young and today I am part of a band in Toronto called the Grindstone Cowboys.  The band started as a casual jam session with my neighbour and his brother and has sort of taken off from there.  Sometimes we even play in front of strangers.

For the kids and myself, music is a really great outlet and a creative way to express oneself.  I think it is important to balance the demands of a career in science with the joy of expression through art and music.  It is just something that I have to do, it’s in my DNA.

I also play ice hockey and that is one of the sports that I enjoy playing with my son.  Sports are important – healthy body, healthy mind.

6. Why science?
Why not? Science allows you the freedom to work on questions that are fascinating to you and may be beneficial to others.  It provides endless intellectual stimulation by combining the power of imagination with self-discipline in order to answer that difficult question.  If you are doing the right science, you have to use your imagination but you also have to be rigorous and have a foot in reality.  It’s a great job and I can’t imagine working in anything else, for my particular personality type.

7. Why SickKids?
I had a lot of options when I was looking for a position and for me SickKids stood out for a couple of major reasons.  First of all, the quality of research here is fantastic and it’s an exceptional institution across a wide range of disciplines.  The other thing I liked about SickKids was the openness and collegiality between basic and clinical scientists.  I think it is second to none.  Other places I looked at which were medical school-based seemed to have a less than ideal environment between clinical and basic scientists.  Ultimately, those of us that work on basic questions hope and dream that our discoveries will someday impact human society in a positive way.  The people that do the clinical research are the ones that are going to make that happen and so if you have a positive rapport with colleagues on both sides then I think good things can happen much more quickly, and a lot of good things have happened at SickKids. This synergy will be even more productive after the new Research and Education Tower is completed in 2013.

8. What is the most controversial question in your field right now?
The p53 protein which is known as the guardian of the genome is central to this controversy.  Scientists are trying to figure out the mechanism by which this protein kills cells.  The dogma, or accepted way by which p53 works, is that it binds to a segment of DNA that increases or decreases the expression of a gene near it.  In other words, it controls the levels of genes that dictate whether cells live or die.  Now there is evidence to suggest that p53 doesn’t just activate the expression of genes that encode killer proteins but also physically interacts with these proteins to form a complex that kills the doomed cell.  If this is the case, p53 has both a transcriptional function and also a transcriptionally independent role in apoptosis – it is both aiding and abetting in the killing of cells.  It’s going to be fun to see how this plays out in the next few years.This is probably the most controversial question in my field right now and I think it’s going to be fun to see how it all plays out.

9. What are you reading right now?
At present, I am reading the theses of two of my PhD students.

In my spare time, I am reading John Lennon: The Life, a biography by Philip Norman. Being a musician on the side, I find it really interesting. John Lennon is a lot like Francis Crick to me, a maverick who did things his own way and succeeded.

10. If you could give one piece of advice to someone considering a research career, what would it be?
Follow your heart. Science is a passion, not a nine-to-five job. You’ve gotta love it.

August 2010

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