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About the Institute

Profile of Darius Bägli

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Dr. Darius Bagli

Dr. Darius J. Bägli, MDCM, FRCSC, FAAP, FACS

  • Senior Associate Scientist, Developmental & Stem Cell Biology
  • Associate Surgeon-in-Chief, Urology at SickKids
  • Professor, Department of Surgery, University of Toronto

1. Where are you from? Where did you study?
I was born in USA and moved to Canada, to Montreal, Quebec when I was very young. I am a dual citizen.

I began my education in Montreal, obtaining three degrees from McGill University; one in Science (Physiology), one in Music (Piano-Performance) and a Doctor of Medicine (MDCM) degree. I then moved back to the United States for post-graduate training.

At Harvard University in Boston I pursued a Harvard Surgical NIH Research Fellowship in Immunology/Oncology and the Harvard Program in Urology and then went on to the University of Washington in Seattle for a clinical and research fellowship in Paediatric Urology.

2. What are you researching right now?
My research team and I are currently trying to understand why hollow organs such as the bladder become damaged by excess pressure, tension and outflow obstruction. In scientific terms, we’re studying mechanotransduction.

The hallmark of this phenomenon is excess muscle cell overgrowth and over-accumulation of the surrounding cell scaffold, or cell matrix. Interestingly, pathologic characteristics such as cell overgrowth and tissue thickening can also be considered desirable tissue regeneration goals, especially when the challenges in tissue regeneration are an inability to achieve adequate cell and tissue growth.

For my research, uncovering what drives the ‘overgrowth’ in disease, if harnessed correctly, along with understanding normal early development of the tissue in question, could provide clues that help drive regeneration. Thus, my research question becomes ‘how do mechanical and matrix stimuli (properties of the cellular microenvironment) interact in stem cell fate?’

Part of my research is focused on epigentics, the study of how the development of an organism unfolds. We know that tissue and organ maladaptation to excess pressure are not generally an inherited problem – they are extra-genetic. Through my research we have learned that external stimuli will modify gene function. With this understanding, we are now reasoning that such reactive urologic responses may be epigenetic targets. For example, we obliquely fell into the notion that urinary tract infection (UTI) – an extremely common problem – is an external stimulus. This is an example of a new area we have helped establish in the epigenetics of UTI.

This kind of research won my team and I first place in the Sickkids New Ideas Grant Competition in 2007. This program funds ideas that are ‘nuts’, but possible...but could never be funded conventionally, early on. I like to call it the ‘Crazy Ideas Fund!’

3. Who is your all-time favourite scientist, and why?
The scientist I most admire is Dr. Judah Folkman, MD (1933-2008). He was a paediatric surgeon who was responsible for discovering the awesome importance of angiogensis. This is the process by which a tumour attracts blood vessels to nourish itself and sustain its existence. I admire him for his hard work and dogged determination. He pioneered his new idea of angiogenesis even when those around him thought his ideas were unlikely.

He had a unique way of approaching problems and always urged students to study the important questions and focus on them because those are the questions that make a difference. He had a big white board in his lab at Boston Children’s with research problems that needed addressing: He promised “first-authorship” to the person who could think up HOW to ask the question that could best address that problem. That was all they would have to do to get that honour. I like that about him, that he was more concerned with how to ASK the question than how to answer it

I think of him as the consummate scientist-humanist: I had the great fortune to be a medical student of his (one of four on elective for a month). In his presence, and at the moment you were with him, he made his students and his patients feel like they were the most important person in the world. I recall one experience like that. He was going to teach us how to do a saphenous vein cut-down in a baby to provide urgent intravenous access. This ‘research giant’ personally made arrangements for the all of the resources and materials we needed to learn the procedure and took the time out of his busy schedule to take us down to the pathology lab to teach each one of us this procedure.

4. What in your opinion is the single most important scientific breakthrough, and why?
I think what makes a breakthrough significant depends on what the breakthrough is measured against, and the prevailing times in which it is made.

At this moment, the breakthrough I would point to would be epigenetics, more specifically the relationship between DNA and epigenetics. Epigenetics is the study of the extra-genetic modifications–often simple chemical additions to the individual A-T-C-G nucleotides of DNA– that ultimately will control DNA’s decoding.

Most biologists think DNA is the biggest thing since moldy sliced bread (with apologies to Louis Pasteur!) While I agree that DNA is the consummate pre-requiste to life, I would argue that DNA doesn’t explain everything. Broken genes are frequently not the answer and replacing broken or missing genes doesn’t always fix the problem.

I think the key point to consider is here is the concept of nature versus nurture. DNA is nothing without an environment in which to exist. Consider how the same genetic code manages to respond in a multitude of ways to its environment. How do muscle, fat, immune or nerve cells become so different from each other? They all have the same DNA! It can blow your mind!

Whether it is the microenvironement within a cell, or the microenvironement adjacent to a stem cell, or the environment of the polluted city versus the clean country air, or the food environment in North America versus Africa versus China, it is the environment that can determine an outcome. In other words, if DNA is the piano keyboard, then epigenetics is what produces the music (as a pianist, I love that!)

I think epigenetics is gonna be huge...

5. What are your major interests outside the lab?
I enjoy music and photography.

I am a concert pianist. In 2002 I competed in the Van Cliburn Internatial Piano Competition for Outstanding Amateurs, in Fort Worth TX. There were 74 pianists from all over, all with ‘day-jobs’, playing for and making music with each other. It was a fantastic experience! As I play more these days, I am becoming interested in the health benefits of music.

6. Why science?
As physician, I am interested in science because of the drive to work toward the ultimate good of the single patient. Our attention for the single patient outweighs consideration of the many. However, as a scientist, the attention for the good of the many eclipses that afforded to the single patient. I believe that science is the complementary context to patient care and all physicians, at some place in their hearts, must be scientists.

This question brings to mind a favourite quote of mine by William Osler:
“One of the first duties of the physician is to educate the masses not to take medicine. I am among those who think that science has great beauty. A scientist in his laboratory is not only a technician: he is also a child placed before natural phenomena which impress him like a fairy tale.”

Personally, I find so much in science. Other people’s science can be so very cool, so distracting, so fascinating, and I am always wondering how other scientists’ observations, no matter how far afield, may apply to my questions. And I have so many interests in science beyond just my own field. There are many times I wish I could be so many different types of scientist, depending on the day: neuobiologist, engineer, protein biologist…

7. Why SickKids?
Of all the institutions I visited, Sickkids was the one place that truly embodied the philosophy of science, that truly protected, nurtured, expected and created the conditions to play out the role of scientist and surgeon.

8. What is the most controversial question in your field right now?
Children’s urology is responsible for the integrity of genital structure and function. In children born with disorders of sexual differentiation (i.e., superficially it is unclear whether the baby looks like versus actually is, chromosomally, a boy or a girl), there is significant disagreement as to when and whether such patients should undergo reconstructive surgery of the genital tissues. This controversy cuts across tissue development, wound healing/scarring, gender identity, sexual preference, patient and parental consent, psychological and psychosocial development, cultural and sociological environment and expectations, as well as the often deep-rooted beliefs of the caregiver.

Now THERE’S a tough question!

January 2010

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