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Bägli Lab
Paediatric Regenerative Medicine (PRM) Program

Brief Biography

Dr. Bägli was recruited back to Canada from the United States to initiate a new direction in the evolution of the Urology Division at The Hospital for Sick Children (SickKids) and to create a basic research sphere of activity within the division.

Dr. Bägli became a member of the surgical staff at SickKids and the Department of Surgery, University of Toronto, in 1995. He is certified in Urologic Surgery by both the Royal College of Physicians and Surgeons of Canada, and the American Board of Urology and is a Fellow of the American Academy of Pediatrics.

He directs a laboratory in the Developmental & Stem Cell Biology research program at the SickKids Research Institute, as well as oversees a busy clinical practice in paediatric urology and reconstructive surgery. He is currently one of only three paediatric urologists with an independent cell and molecular biology program in North America and the only one in Canada.

Dr. Bägli is currently investigating extracellular matrix biology as it pertains to wound healing and biomechanically-mediated injury in the lower urinary tract. He continues to pursue innovative collaborations with clinicians and investigators at University of Toronto, in Canada and the United States. He has been principal author and co-author of many papers and book chapters in both clinical paediatric urology as well as basic research. 

Dr. Bägli holds peer–reviewed funding from CIHR for his research and is actively involved in both the basic science and clinical training of graduate and undergraduate students, paediatric urology fellows, and medical students. 

Research Interests

The urinary bladder is the organ which stores and empties urine. From a scientific point of view, focus on the bladder has generally been in cancer or urine control problems of aging. However, a great deal remains to be learned about bladder dysfunction and disease in children. Children's bladder disorders can be quite far ranging. Our lab is studying the bladder disease which arises when the bladder is unable or unwilling to store or empty properly. This leads to tissue changes in the bladder wall which resemble overgrowth and scarring.

We are attempting to understand the molecular components most responsible for these changes. We are using bladder muscle cells as well as the whole bladder removed from its host animal, as models. We are testing these models using various stimuli of mechanical stretching or decreased oxygen levels to stress the bladder and observe how specific genes and proteins are affected. Once we unravel the key components which regulate the undesirable changes in the bladder, we can target these components for prevention of specific bladder diseases in children. As it happens, several of these pediatric bladder ailments affect adults. It is anticipated that our search will have useful implications for the treatment ad prevention of similar bladder dysfunction later in life.

We have determined that mechanical stretching of the bladder, as well as very recently decreased oxygen tension is a potent stimulus for the activation of erk MAP kinase. This signalling pathway may be involved in physiologic fibroproliferative bladder response to excessive pressureand tension. We have also demonstrated that damaged extracellular
matrix, proteolysed collagen, is a powerful growth stimulus for bladder smooth muscle cells, and that this growth response is also mediated by erk1/2. Since matrix remodeling in vivo involves a cascade of enzymes which proteolyse the collagen matrix, we have gone on to determine that the matrix metalloproteinases (MMP) are involved both directly in erk1/2 activation as well as indirectly in generating a damaged extracellular environment in vivo. Our goal is to elucidate the functional cell-matrix relationships between MMPs and signaling in the bladder and to target these responses to prevent tension/pressure induced fibrosis and bladder wall hypertrophy associated with bladder failure. These investigations will also provide a basis for rational design of tissue engineering strategies for bladder and other organ replacement.

External Funding

• CIHR (2009-2014). Team Grant Co-PI. Effects of brominated flame retardants on reproductive health.
• CIHR (2009-2013). PI. Bladder smooth muscle novel molecular targets for therapy.
• Kidney Foundation of Canada (2008-2010). PI. Bladder smooth muscle signaling.
• Sickkids Research Institute New Ideas Grant Program: (2007). PI. Epigenetics of urinary tract infection.

Achievements

• 1st prize Basic Science-Robson Research Day for Stat 3 Kinase in Bladder Stretch Injury (Sarel Halachmi presented). 2003
• 2nd Prize Basic Science-Robson Research Day for Dissociated autologous urolthelial grafting for bladder augmentation in a porcine model (John Hodapp presented). 2003
• 2nd Prize Clinical Research-Robson Research Day for The role of bacterial infection in pediatric acute epidydimo-orchitis (Sarel Halachmi presented). 2003
• Service Award- Society for Basic Urologic Research received at the Spring 2004 annual meeting in recognition of your tremendous efforts, valuable service and insight in structuring and expanding the SBUR website and maintaining its function at a professional level. 2004

Publications

• A selected list of publications can be found on Dr. Bägli's lab website
• A detailed list is also available on PubMed