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Linda J. Wykes

Linda Wykes

Director and
Professor

T: 514-398-7843
F: 514-398-7739
linda [dot] wykes [at] mcgill [dot] ca (Email)

Degrees

  • BSc, Nutrition and Food Science, University of Toronto
  • MSc, Nutritional Sciences, University of Toronto
  • PhD, Nutritional Sciences, University of Toronto

Awards and Recognitions

  • William Dawson Scholar Award (2002-07, renewed 2007-12) recognizing “a scholar developing into an outstanding and original researcher of world-class caliber who is poised to become a leader in the field, similar to that of a CRC Tier II.”
  • New Scientist Award, Canadian Society for Nutritional Sciences, 2007: Presented at the Canadian Nutrition Congress in recognition of “outstanding body of research accomplished in the first 15 years after PhD.”
  • Bio-Serv Award for Experimental Animal Nutrition, American Society for Nutrition, 2007: Presented at Experimental Biology 07 in recognition of “meritorious research for developing a piglet model of colitis” and its impact on childhood malnutrition.
  • Researcher of the Month, May 2008, Canadians for Health Research as the result of a student initiative in the WARM SPARK program.
  • “Bravo 2010” McGill’s Research Gala and “Excellence in Research 2010” McGill’s Public Research Exhibition: spotlighted my “piglets helping people” research approach.
  • Canadian Foundation for Innovation Leaders Opportunity Fund $770,000 infrastructure grant to establish the Mass Spectrometry and Molecular Nutriiton Laboratory (Link here). The lab is equipped with a tandem UHPLC-triple quadrupole mass spectrometer to complement the workhorse gas chromatograph mass spectrometer, and also houses molecular biology equipment to promote a more integrative framework for studies involving both kinetic and molecular analyses

Active Affiliations

  • Editorial Board: Journal of Nutrition and Metabolism
  • Professional memberships:
    • American Society of Nutrition
    • Canadian Nutrition Society
    • Sigma Xi

Current Research

Malnutrition and infection/inflammatory stress interact in a vicious cycle. We investigate how innovative nutrition support regimens can decrease the stress of surgery in hospitalized patients, and decrease inflammation in a piglet model of inflammatory bowel disease. Studies use stable isotopically labelled tracers to determine rates of synthesis of proteins and metabolites. Measurement of amino acid kinetics or rate of synthesis of a protein yields information on the mechanisms of how metabolic adaptations take place in much the same way as cash flow reveals information on the financial health of a business.

Targeted metabolomics analysis using mass spectrometry can be applied to many metabolic and physiological interventions. Improved nutrition support with particular attention to the amount and type of protein can prevent a net catabolic response to surgery, and can have anti-inflammatory effects in piglets with colitis. The piglet is the model of choice because of its metabolic similarity to the human, particularly the growing infant and child. These piglet or human studies are quite intensive, requiring development of special diets, surgery in piglets (and peripheral catheters in humans) for intravenous access for stable isotope infusions and repeated blood sampling. Both the clinical studies and extensive analytical work demand major commitments from highly trained personnel – and offer exciting career opportunities for enthusiastic dedicated people.

Success of Research Graduates

Dr Wykes has supervised 30 graduate students (5 anesthesiology fellows/faculty, 1 surgeon), 1 postdoctoral fellow, 1 research associate, 1 research technician, and 15 undergraduates.  In total, 11 graduate student trainees (11 supervised, 3 visiting) and 2 undergraduate trainees have won a total of 19 national or international awards for their meritorious research in her lab. Supervised trainees have advanced as: Assistant Professors (4 at McGill, United Kingdom, Switzerland, China), and Research Associates (U Alberta, U Montreal), leadership positions in industry or NGO’s, or to advanced dietetics practice in tertiary care hospitals.

Research Themes

1) Development of Innovative New Piglet Models of Parenteral Nutrition and Inflammatory Bowel Disease:

The piglet is the premier model to study nutrition and metabolism in the infant and growing child based on specific metabolic similarities, and studies on functional kinetic responses to interventions. This piglet/human synergy is the hallmark of my research.

We developed a model of Inflammatory Bowel Disease (IBD) to investigate mechanisms of growth restriction, hypoalbuminemia and muscle wasting, and the role of nutrition in modulating stress. Malnourished piglets are at a considerable disadvantage compared to their well-nourished counterparts in ways that are evident only with stable isotope kinetic data (J Nutr 2003). Inflammation doubled albumin synthesis without a change in concentration regardless of nutritional status. In protein energy malnourished piglets, this increase compromised muscle protein synthesis and growth. Studying effects of functional foods offers a new direction. Probiotic bacteria specifically and dramatically stimulate synthesis of liver proteins including hepatically-derived plasma albumin (J Nutr 2008). However only provision of adequate nutrition (but not probiotics) is effective in decreasing disease severity and in increasing growth and muscle protein synthesis and initiation of translation (Pediatr Res 2010). More recently we have shown (Piccolomini PhD thesis 2011) that bioprocessed pressurized whey protein isolate is more effective than native whey or skim milk powder in increasing lean body mass in piglets with colitis (although emerging data suggest it slows bone mineralization) and in decreasing histological evidence of colonic inflammation and cleaved caspase-3 (a marker of apoptosis). Moderate restrictions of protein alone and of protein and energy show modest effects on protein metabolism and inflammation; however protein intake at only 15% of requirement dramatically increases inflammatory markers including TNF-a, IL-8, cleaved caspase-3, and increases histological damage in the colon co-incident with decreased protein synthesis and eNOS (Antunes MSc thesis 2011). These new data illustrate new methodological directions of combining stable isotope kinetic data with molecular markers of anabolism and catabolic stress for a more indepth analysis of mechanisms of the interactions among malnutrition and metabolic stress. Secondly new nutritional therapeutic strategies like probiotics and pressurized whey protein may have future clinical and industrial impact.

2) Nutrition Support and Epidural Analgesia Promote Anabolism and Speed Recovery in Patients Undergoing Colorectal Surgery: 

Protein catabolism and insulin resistance are hallmarks of the stress response to surgery. Our core Nutrition-Anesthesia-Surgery Team (NASTe) of Wykes, Carli and Schricker has been funded Canadian Institutes of Health Research (CIHR) for 12 years. We now have 29 publications providing dramatic evidence that hypocaloric parenteral nutrition support with epidural analgesia is effective in achieving a positive protein balance (protein synthesis minus proteolysis) in patients after colorectal surgery while avoiding hyperglycemia. The novel finding that parenteral amino acids even without glucose are effective in stimulating protein synthesis while maintaining normoglycemia raised the provocative question “Do We Need Glucose?” (Metabolism 2007).  Data from all surgical populations to date (cancer, malnourished, diabetic) underscore the importance of nutrition in modulating the stress response. Recent application of concepts and techniques from the piglet colitis model show the importance of avoiding the common practice of pre-operative fasting to maintain plasma protein and albumin synthesis even after surgery (Annals Surgery 2008).

Evidence is growing that improved nutrition support and effective analgesia are critical in speeding patient well-being and recovery in cardiac, orthopedic and liver surgery as well. Pilot data in patients undergoing intraoperative hyperinsulinemic euglyemic clamp studies show that essential (but not non-essential) amino acid concentrations decrease dramatically (Metabolism 2011). We are now conducting stable isotope infusion studies to determine protein synthesis and proteolysis at the whole body and muscle levels. It is a credit to the anesthesiology members of the collaborative team that they conduct these complex studies with isotope infusions during insulin clamps in patients in the operating room on cardiopulmonary bypass and to maintain the infusions in the post-op ICU. We are now poised to make even more innovations by adding a focus on functional outcomes including glutathione synthesis, oxidative stress and molecular regulators of protein metabolism.

Enteral feeding is generally preferred over parenteral nutrition; however colorectal surgery traditionally involves a long period of perioperative fasting. Based in part on the recent piglet model work, we have developed a pressurized whey protein drink that is high in leucine and cysteine, easily digestible and palatable for the patients. Our initial study (Appl Nutr Metab abstract 2011, MSc student Ball received national award) shows a strong anabolic effect compared to feeding glucose alone. More recently (Appl Nutr Metab abstract 2012, MSc student Gillis received national award), we have shown that our pressurized whey protein drink is just as effective in supporting protein balance as our standard parenteral glucose and amino acid regimen in colorectal patients the day following surgery. Our aim is to minimize the perioperative window of fasting with enteral feeding, or to eliminate the fasting altogether with parenteral feeding initiated prior to surgery.

Publications

To view a list of Dr. Wykes' publications, click here.