不良研究所

Degrees

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

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Short Bio

Linda Wykes is a Professor in the School of Human Nutrition. She received her PhD for work at The Hospital for Sick Children studying amino acid metabolism to develop new parenteral nutrition regimens for neonates. During her PDF at the Children's Nutrition Research Center, of Baylor College of Medicine in Houston, she gained expertise in mass spectrometry. While at 不良研究所, she established a mass spectrometry lab and developed a piglet model of inflammatory bowel disease to study how diet and inflammatory stress interact to affect the regulation of protein synthesis, oxidative stress, and gastrointestinal pathophysiology. While at 不良研究所, she has also become NASTY 鈥� that is one of a team of collaborators with expertise in Nutrition Anesthesiology and Surgery and the Team includes EndocrinologY and KinesiologY. Together they conduct stable isotope tracer and insulin clamp studies in patients during and after surgery. They investigate how nutrition, analgesia and exercise interventions can decrease insulin resistance to improve nutrient utilization, promote anabolism, and ultimately speed recovery.

Awards and Recognitions

• William Dawson Scholar Award (2002-12)
• New Scientist Award, Canadian Society for Nutritional Sciences, 2007: Presented at the Canadian Nutrition Congress in recognition of 鈥渙utstanding body of research accomplished in the first 15 years after PhD.鈥�
• Bio-Serv Award for Experimental Animal Nutrition, American Society for Nutrition, 2007: Presented at Experimental Biology 07 in recognition of 鈥渕eritorious research for developing a piglet model of colitis鈥� and its impact on childhood malnutrition.
• Canadian Foundation for Innovation Leaders Opportunity Fund $770,000 infrastructure grant to establish the Mass Spectrometry and Molecular Nutrition 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

• Professional memberships:
  • American Society of Nutrition
  • Canadian Nutrition Society

Research Interests

When Nutrition becomes NASTY: The multidisciplinary NASTY Team (Nutrition and Anesthesia during Surgery Team including endocrinologY) develops new nutrition and metabolic based therapies to help patients recover from the catabolic stress of surgery and critical illness. Dr Wykes specializes in strategies to promote protein synthesis using tracer kinetic analysis by mass spectrometry. Administering glucose or amino acids labelled with stable isotopes in humans and animals allows measurement of flow of nutrients in the body, and how they how they are used. This approach gives more precise information than concentrations alone, in much the same way as cash flow reveals information on the financial health of a business. Dr Wykes鈥� Mass Spectrometry Laboratory is the nexus to link human and animal model research in nutrition. Nutrition strategies include improving protein quality and developing novel substrates to maximize protein synthesis in enteral and parenteral medical nutrition therapy. Matching the composition of nutrition support regimens with metabolic requirements of patients and the limitations of chemistry requires innovative approaches, and clinical studies of nutrient metabolism in patients.

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.

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 鈥� and offer exciting career opportunities for enthusiastic dedicated people.

Success of Research Graduates

Dr Wykes has supervised over 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 不良研究所, United Kingdom, Switzerland, China), and Research Associates (U Alberta, U Montreal), leadership positions in industry or NGO鈥檚, or to advanced dietetics practice in tertiary care hospitals.

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 (NASTY) 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 鈥淒o We Need Glucose?鈥�. 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. 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 whey protein drink that is high in leucine and cysteine, easily digestible and palatable for the patients. This shows a strong anabolic effect compared to feeding glucose alone. We have shown that 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.

Courses

Publications

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

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