Richard you Wu, Laboratory Medicine and Pathobiology
Student’s full name: Richard You Wu
Supervisor’s full name and title: Dr. Philip Sherman (Senior scientist, Cell Biology Program, SickKids Hospital)
PhD thesis (title and brief overview)
Thesis title: Characterizing effects of prebiotics and human milk oligosaccharides on the intestinal epithelial barrier
Using cellular and animal models, we investigated the biological effects of microbiome-targeted agents including prebiotics and human milk oligosaccharides to test their effects on the intestinal barrier function – a question that is crucial for several inflammatory gastrointestinal disorders spanning from adults to infants such as Inflammatory Bowel Disease and in particularly preterm infants, Necrotizing Enterocolitis - currently one of the leading causes of death in premature infants. Our goal in the future is to ultimately use dietary oligosaccharides to understand both the pathophysiology of these illnesses and develop dietary agents to prevent these devastating diseases from occurring.
A few paragraphs about the student’s PhD research, scholarship and/or awards, publications; current position; future education plans and/or career goals.
During my PhD training with Dr. Philip Sherman, we made several increments in the way we understand prebiotic agents. While these agents were initially thought as inert to the host intestinal mucosa, we showed that in addition to their effects on the microbiota, they also directly exert host cell signaling effects to impact intestinal cell inflammatory responses, barrier function and mucus barrier. We showed that these cellular effects directly altered how the host deals with inflammatory insults in models of infectious colitis and endotoxin-injury. The clinical relevance of these mechanistic studies inform us of the potential roles of oligosaccharides in foodstuffs for inflammatory GI disorders and infant formulas.
April 2018 CREMS MD/PhD Research Scholarship
Feb 2018 Dina Gordon Malkin Award for Top MD/PhD Research Scholar
Aug 2017 James Hosinec Scholarship for Clinician-Scientists
July 2017 R.O. Torrance Conference Bursary award
June 2017 Department of LMP travel bursary for national CIHR competition
June 2017 Microbiology and Infectious Diseases oral competition 1st place
June 2017 CIHR Canadian Student National Research Forum poster competition 1st place
June 2017 Ferring medical student research grant
April 2017 SickKids Cell Biology retreat 2017 oral competition 1st place
April 2017 LMP Graduate Research Conference 2017 poster competition 1st place
April 2017 Hospital for Sick Children Exceptional Trainee 2017
Nov 2016 Clinician-investigator association of Canada oral competition 2nd place
Jun 2016 Sickkids Trainee Travel Grant
Jan 2016 International Society of Prebiotics and Probiotics Travel Grant
April 2016 LMP Graduate Research Conference 2016 poster competition 2nd place
April 2015 LMP Graduate Research Conference 2015 poster competition 1st place
March 2015 School of Graduate Studies conference grant
May 2014 Vanier CIHR Canada Graduate Scholarship
May 2014 Canada Graduate Scholarship Master’s Program (declined)
Sept 2013 University of Toronto Fellowship
May 2013 NASPGHAN Medical Student Summer Research Fellowship
May 2013 Laboratory Medicine and Pathobiology Summer Research Studentship
Jan 2013 MD/PhD CIHR Studentship
- Li B, Hock A, Wu RY, Minich A, Botts SR, Lee C, Antounians L, Miyake H, Koike Y, Chen Y, Zani A, Sherman PM, Pierro A. Bovine mik-derived exosomes enhance goblet cell activity and prevent the development of experimental necrotizing enterocolitis. Plos ONE, 2019. [accepted for publication Jan 15, 2019]
- Wu RY, Li B, Koike Y, Määttänen P, Miyake H, Cadete M, Johnson-Henry KC, Botts SR, Lee C, Abrahamsson TR, Landberg E, Pierro A, Sherman PM. Human Milk Oligosaccharides Increase Mucin Expression in Experimental Necrotizing Enterocolitis. Mol Nutr Food Res. 2018. doi: 10.1002/mnfr.201800658. [Epub ahead of print]
- Meng X, Dunsmore G, Koleva P, Elloumi Y, Wu RY, Sutton RT, Ambrosio L, Hotte N, Nyugen V, Madsen K, Dieleman LA, Chen H, Huang V, Elahi S. The profile of human milk metabolome, cytokines and antibodies in inflammatory bowel diseases versus healthy mothers and potential impacts on the newborn, J Crohn Colitis. 2018. doi: 10.1093/ecco-jcc/jjy186. [Epub ahead of print]
- Määttänen P, Lurz E, Botts SR, Wu RY, Yeung CW, Li B, Abiff S, Johnson-Henry KC, Lepp D, Power KA, Pierro A, Surette ME, Sherman P. Ground flaxseed reverses protection of a reduced fat diet against Citrobacter rodentium-induced colitis. Am J Physiol Gastrointest Liver Physiol, 2018; doi: 10.1152.
- Wu RY, Määttänen P, Napper S, Scruten, Li B, Koike Y, Johnson-Henry KC, Pierro A, Rossi L, Botts S, Surette MG, Sherman P. Non-digestible oligosaccharides directly modulate host kinome to modulate host inflammatory responses without alterations in the gut microbiota. Microbiome, 2017; 5(10): 135.
- Wu RY, Abdullah M, Määttänen P, Pilar AV, Scruten E, Johnson-Henry KC, Napper S, O’Brien C, Jones NL, Sherman P. Protein kinase C δ signaling is required for dietary prebiotic-induced strengthening of intestinal epithelial barrier function. Scientific Reports, 2017; 18(7): 40820.
- Li B, Lee C, Filler T, Hock A, Wu RY, Li Q, Chen S, Koike Y, Ip W, Chi L, Zani-Ruttenstock E, Määttänen P, Gonska T, Delgado Olguin P, Zani A, Sherman P, Pierro A. Inhibition of corticotropin-releasing hormone receptor 1 and activation of receptor 2 protect against colonic injury and promote epithelium repair. Scientific Reports, 2017; accepted publication.
- Wu RY, Jeffrey M, Johnson-Henry KC, Green-Johnson J, Sherman P. Impact of prebiotics, probiotics and gut derived metabolites on host immunity. LymphoSign Journal, 2017; 4(1): 1-24.
- Johnson-Henry KC, Abrahamsson T, Wu RY, Sherman P. Probiotics, prebiotics, and synbiotics for the prevention of necrotizing enterocolitis. Advances in Nutrition, 2016;15:928-937.
- C. West, Wu RY, Wong A, Stanisz AM, Yan R, Min KK, Pasyk M, McVey Neufeld K-A, Foster JA, Bienenstock J, Forsythe P, Kunze WA. Lactobacillus rhamnosus strain JB-1 reverses restrain stress-induced gut dysmotility. Neurogastroenterology and Motility. 2016; 1-11.
- Wu RY, Sherman P. Host-intestinal microbe interactions in human health and disease. University of Toronto Medical Journal. 2015; 92(3): 30-34.
- Abrahamsson TR, Wu RY, Jenmalm MC. Gut Microbiota and allergy: the importance of the pregnancy period. Pediatric Research. 2015; 77(1-2): 214-219.
- Koike Y, Li B, Chen Y, Miyake H, Lee C, Chi L, Wu RY, Inoue M, Uchida K, Kusunoki M, Delgado-Olguin P, Pierro A. Live imaging of fetal intra-abdominal organs using two-photo laser-scanning microscopy. Methods in Molecular Biology, 2018; 1752: 63-69.
- Abrahamsson T, Wu RY, Sherman P. Microbiota in functional gastrointestinal disorders in infancy: implications for management. Nestlé Nutrition Institute Workshop series, 2017; 88, 107-115.
- Wu RY. “Human milk oligosaccharides prevent experimental NEC by inducing mucus” Medical Student Research Day 2018, Toronto, Ontario, Canada (Feb 2018).
- Wu RY. Oral presentation “The role of dietary prebiotics on host intestinal barrier and inflammation” Department of Gastroenterology and Hepatology Research Seminar, Hospital for Sick Children, Toronto, Ontario, Canada (Dec 2017).
- Wu RY. Oral presentation “HMO: role in NEC and mechanisms of action” CIHR NEC Symposium 2017. Hospital for Sick Children, Toronto, Ontario, Canada (June 2017).
- Wu RY. Oral presentation “Human milk oligosaccharides prevent experimental Necrotizing Enterocolitis by inducing mucus production”. Microbiology and Infectious Diseases Research Days. University of Toronto, Toronto, Ontario, Canada (June 2017).
- Koike Y, Wu RY, Li B, Määttänen P, Sherman P, Pierro A. Oral presentation “Human milk oligosaccharides protect the intestinal epithelium”. American Pediatric Surgery Association 2017, Hollywood, FL, USA (May 2017).
- Hock A, Li B, Wu RY, Lee C, Miyake H, Koike Y, Chen Y, Zani A, Sherman P, Pierro A. Invited oral presentation “Milk-derived exosomes promote goblet cell function and prevent the development of experimental necrotizing enterocolitis”. Pacific Association of Pediatric Surgeons conference 2017. Seattle, USA (March 2017).
- Wu RY. Oral presentation “Dietary human milk oligosaccharides protect experimental necrotizing enterocolitis by inducing mucin production”. SickKids Cell Biology Retreat 2017, Toronto, Ontario, Canada (April 2017).
- Wu RY. Oral presentation “Prebiotics: more than foods for bugs?” University of Toronto, Lawson Family Nutrition Microbiome Seminar, Toronto, Ontario, Canada (Jan 2017)
- Koike Y, Wu RY, Li B, Määttänen P, Sherman P, Pierro A. Oral presentation “Human milk oligosaccharides protect the intestinal epithelium and prevent experimental necrotizing enterocolitis” American Pediatric Surgery Association 2017, Hollywood, Florida, USA (May 2017)
- Wu RY, Li B, Koike Y, Määttänen P, Pierro A, Sherman P. Oral presentation “Human milk oligosaccharides in the prevention of necrotizing enterocolitis through mucus production” Clinician-Investigator Trainee Association of Canada annual meeting, Toronto, Ontario, Canada (Nov 2016)
- Wu RY, Määttänen P, Napper S, Scruten E, Li B, Koike Y, Johnson-Henry K, Pierro A, Sherman P. Oral presentation “Prebiotic modulation of inflammatory processes by modulation of host kinome”. International Society of Prebiotics and Probiotics 2016, Turku, Finland (June 2016)
- Wu RY, Li B, Koike Y, Määttänen P, Johnson-Henry K, Sherman P. Oral presentation “Human milk oligosaccharides in the protection of necrotizing enterocolitis”. Department of Pediatrics Research Seminar, University of Linköping, Linköping, Sweden. (June 2016)
- Wu RY, Li B, Koike Y, Määttänen P, Johnson-Henry K, Sherman P. Oral presentation “Impact of dietary human milk oligosaccharides on gut epithelial barrier in necrotizing enterocolitis”. Lallemand Health Solutions Scientific Exchange 2016, Montreal, Quebec, Canada (June 2016)
- Wu RY, Määttänen P, Pilar A, Johnson-Henry K, Sherman P. Oral presentation “Dietary prebiotics activate protein kinase C delta isoform to impact intestinal epithelial barrier”. SickKids Cell Biology Retreat 2015, Toronto, ON. (May 2015)
- Wu RY, Määttänen P, Pilar A, Johnson-Henry K, Sherman P. Oral presentation “Prebiotics enhance intestinal epithelial barrier function via activation of protein kinase C”. Canadian Digestive Disease Week 2015, Banff, Alberta, Canada (Feb 2015)
Current position: Combined MD/PhD Training (Year 7) at University of Toronto, expected graduation 2020
Future education plans/goals: My training at LMP for my PhD studies was monumental in shaping my identity as a clinician-scientist. The questions, conversations, and fantastic colleagues I had the pleasure to meet continue to develop my passion and curiosity for basic discovery, and it was through my training with Phil and rest of the team that helped me link these questions to both answerable experiments and draw important clinical correlates to our patients. I am currently back in medical school at UofT in clinical rotations to complete my MD/PhD training. I remain curious about the various unanswered questions underlying my patients’ illnesses. My goal is to pursue a clinician-investigator residency program, and continue my training for becoming clinician-scientist with an interest in gastrointestinal disorders. Thank you LMP for helping me further in this goal, and being a big part of my journey.