Peter Eck

 

Position: Canada Research Chair in Nutrigenomics

Office:
Human Nutritional Sciences
Room 207, Richardson Centre for Functional Foods and Nutraceuticals
University of Manitoba
196 Innovation Drive
Winnipeg, MB R3T 6C5 Canada

Phone No.: (204) 474-1506

E-mail: peter.eck@ad.umanitoba.ca

 

Education:

Diploma (M.Sc.) in Nutritional Sciences, the Justus-Liebig-University Giessen, Germany
Ph.D. in Nutritional Biochemistry and Physiology, the University of Justus-Liebig-University Giessen, Germany

Research Interests: 

  • Gene-Nutrient Interactions
  • Genetic Variation causing Common Complex Diseases
  • Nutrient related Common and Complex Diseases
  • Nutrient Membrane Transporter
  • Vitamin C Transport, Pharmacokinetics, Recommendations
  • Ascorbic Acid Transporters
  • Organic Cation Transporters
  • Bioactive food components in regard to transporter inhibition and metabolic function
  • Role of dietary components in Health and Chronic Diseases

Research Outcomes:

  • Gene-Specific Dietary Recommendations
  • Development of Functional Food
  • Development of Nutraceuticals

Research Description:

Nutrigenomics. Many common chronic diseases with adult onset are caused by interactions of multiple genes with various environmental factors including the diet. Nutrigenomics investigates the interactions between the genome and nutrients in causing a health outcome. This involves the study of how genetic polymorphisms affect dietary requirements by impacting metabolic pathways. My research investigates how variations in membrane transporter genes impact on the protein’s functions. I seek to determine what role these functional changes play in disease development and outcome, with the resulting ability to develop individualized nutritional recommendations and dietary interventions. The societal health and welfare benefits of this research are significant. Dietary factors play a key role in the disease development and outcome of obesity, type 2 diabetes, some cancers, cardiovascular, and inflammatory diseases.

Membrane transporters are of great physiological importance as they are the major determinants for the absorption, distribution, and elimination of a large number of dietary components. Therefore they are prime candidates to study how genetic variations alter nutrient pharmacokinetics and increase susceptibility to diseases. To date some polymorphisms in membrane transporter genes have been associated with detrimental human phenotypes, and there is evidence that altered nutrient pharmacokinetics leads to diseases in human patients. However, very few genetic variations have been characterized with respect to how they change the proteins’ function. Moreover, there is a profound lack of understanding about the molecular mechanisms of functional changes in membrane proteins. My research program addresses this lack of understanding by characterizing variations of two types of nutrient membrane transporters -- one transporting Vitamin C and the other transporting organic cations. Variations in both of these transporter types have been genetically associated to birth complications, cancers (prostate, lymphoma), or inflammatory bowel diseases (e.g. Crohn’s disease). The research addresses the molecular mechanisms causing the adverse health effects.

Vitamin C Transporter Genes. L-ascorbic acid is directly transported across cell membranes by two sodium-dependent Vitamin C transporter proteins: SLC23A1 and SLC23A2. Drawing on my prior work, in which I and collaborators determined polymorphisms in these Vitamin C transporter genes enable me to study their functional impact. If a human genetic variation alters the Vitamin C transporters functions, ascorbic acid pharmacokinetics can be changed. Changed pharmacokinetics might result in lowered systemic Vitamin C concentrations elevating an individual’s disease risk. Suboptimal Vitamin C concentrations are linked to cardiovascular diseases, some cancers, diabetes, inflammation, infections, and birth complications.
To determine the impact of genetic variation on transport functions I use the Xenopus laevis oocyte expression system as well as a variety of human cell lines. In addition I was involved in the creation of the Slc23a1-/- knock out mouse. Preliminary data show that the Slc23a1-/- mice have disrupted systemic control of ascorbate concentrations. For example, female Slc23a1-/- mice had an 18 fold increase in fractional excretion of ascorbate in urine, and a 70% decrease in plasma ascorbate concentrations compared to wildtype counterparts. Pups born to Slc23a1-/- mothers had 45% perinatal mortality that was prevented with ascorbate supplementation to the mothers. Despite their renal leak, Slc23a1-/- animals do not develop scurvy, demonstrating their usefulness as genetic models for marginal Vitamin C concentrations. Therefore we now have a model to characterize the physiologically adverse effects of marginal ascorbate concentrations and to establish disease mechanisms.
Current Vitamin C recommendations are based on pharmacokinetics studies in a limited number of individuals. The influence of the individual’s genotype had not been considered in these original pharmacokinetic studies, and my ultimate goal is to determine an individual’s requirement based on their genotypes. To realize this goal, my molecular findings will be translated into clinical studies at the National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) of the US NIH. Under the clinical leadership of Drs. Mark Levine and Sebastian Padayatty of the NIDDKs Molecular and Clinical Nutrition Section, several clinical trials are now being designed on Vitamin C pharmacokinetics in relation to human transporter genotypes. I am currently participating as the genetics collaborator in the studies. Ultimately, human Vitamin C transporters genotypes’ influence on pharmacokinetics will be determined. The clinical trials will serve as the basis to establish genotype-specific individualized Vitamin C recommendations.

Organic Cation Transporters. Several genetic studies have shown associations between mutations in the organic cation transporters OCTN1 and OCTN2 and a propensity to develop Crohn’s disease but the disease causing mechanisms are not understood. OCTN2 transports mainly carnitine, by contrast, the molecular and physiologic functions of OCTN1 are poorly understood and the protein is proposed to be a multi-specific organic cations transporter. I aim to determine how genetic variation in organic cation transporters leads to intestinal inflammation and how it can be counteracted using nutritional intervention.

Glucose Transporters. I and co-workers have previously proven the concept of using plant flavonoids to inhibit intestinal sugar transporter proteins. Therefore the glucose transporters have become attractive targets of this novel class of phenolic bioactives, which delayed or inhibit glucose absorption. Complementary studies show slowed carbohydrate absorption when consuming phenolics rich plant products. However, the full breadth of dietary components responsible for these effects and their molecular actions has not been characterized well. I investigate the inhibition of the dominant intestinal transporter proteins, SGLT1 and GLUT2, by plant fractions and isolates. SGLT1 and GLUT2 will be overexpressed in Xenopus oocytes and suitable mammalian cells. The uptake of radiolabeled glucose into the overexpressing cells will be determined in the presence and absence of the plant fractions. This will lead to the identification of the bioactive fractions inhibiting intestinal glucose transport. Once identified, bioactives will be tested for their ability to dampen or inhibit intestinal glucose absorption in vivo. The project aims to determine functional food or nutraceuticals helping in glycemic control.

Interested in my Research? 

If you are interested in my research I will be working with you to create opportunities to join my research group. Please consider the following advice:

POST-GRADUATE POSITIONS.
Post-doctoral Fellows and to a lesser extend Ph.D. applicants should have significant experience in molecular biology and protein biochemistry. Eligibility for external funding opportunities is also important. Please submit a letter describing your research background and interests, and include names and contact information for 3 referees.

Graduate Students. I am always glad to hear from potential grad students interested in my research areas. Students expecting a BSc in Nutritional Sciences, Biochemistry, Pharmacology, Biology or Life Sciences, and who anticipate graduating with at least an 80% average (or close to!) are encouraged to apply. Some of the criteria I consider are: (i) a strong background and interest in biochemistry or genomics and genetics; (ii) lab courses in biochemistry; (iii) reference letters from professors; (iv) completion of an undergraduate (lab-based) research project and/or summer position. Preference is given to students who are interested in going on to complete a PhD, and are eligible for external funding opportunities.
To be considered for graduate studies in my lab, please send brief letter/email describing your research interests. Also include the names and contact information for 3 referees and if available, a copy of your academic transcripts; unofficial is fine at this point. Later, a formal application will also have to be submitted to the Department of Human Nutritional Sciences. Information on how to do so can be found on the websites of the Department of Human Nutritional Sciences.

Publications:

Publications in scientific peer reviewed journals:
Corpe C., Tu H., Eck P., Wang Y., Faulhaber-Walter R., Schnermann J., Margolis S., Padayatty S., Sun H., Wang Y., Nussbaum R., Espey M.G., Levine M. (2010). Vitamin C transporter slc23a1 links renal reabsorption, control of vitamin C concentrations, and perinatal survival. Accepted Journal of Clinical Investigation.
Levine M.A., Eck P. (2009) Vitamin C: working on the x-axis. Editorial, American Journal of Clinical Nutrition. 90: 1121-1122. 

Xu H, Eck PK, Baidoo KE, Choyke PL, Brechbiel MW (2009). Toward preparation of antibody-based imaging probe libraries for dual-modality positron emission tomography and fluorescence imaging. Bioorganic Medical Chemistry 17(14): 5176-5181.

Boswell C.A., Eck P., Regino A.S.C., Xu H., Bernardo M., Wong J.K., Milenic E.D., Choyke L.P., Brechbiel W.M. (2008). Synthesis, Characterization, and Biological Evaluation of Integrin alphavbeta3-Targeted PAMAM Dendrimers. Molecular Pharmacology 5(4):527-539.

Erichsen H.C., Peters U., Eck P., Welch R., Yeager M., Levin M., Hayes R.B., Chanock S. (2008). Genetic variation in sodium-dependent vitamin C transporters SLC23A1 and SLC23A2 and the risk of advanced colorectal adenoma, Nutrition and Cancer, 60(5) 652-659

Eck P., Erichsen H.C., Taylor, J., Corpe P.C., Chanock S., Levine, M. (2007). Genomic and functional analysis of the sodium-dependent vitamin C transporter SLC23A1 –SVCT1. Genes & Nutrition 2 (1) 143-145.

Kwon, O.; Eck, P.; Chen, S.; Corpe, P.C.; Lee, J-H.; Kruhlak, M.; Levine, M. (2007). Inhibition of the intestinal glucose transporter GLUT 2 by flavonoids. FASEB Journal 21: 366-377. Epub. 2006 Dec 16. 2006

Erichsen, H.C.; Engel, S.A.; Eck, P.K.; Welch, R.; Yeager, M.; Levine, M.; Siega-Riz, A.M.; Olshan, A.F.; Chanock, S.J. (2006).  Genetic variation in the sodium-dependent vitamin C transporters, SLC23A1 and SLC23A2 and risk for preterm delivery. American Journal of Epidemiology 163(3): 245-254. 

Corpe, C.P.; Lee, J.; Kwon, O.; Eck, P.; Narayanan, J.; Kirk, K.L.; Levine, M.A. (2005). 6-bromo-6-deoxy-L-ascorbic acid: an ascorbate analog specific for Na+-dependent vitamin C transporter but not glucose transporter pathways. Journal of Biological Chemistry, 280 (7): 5211-5220.

Eck, P., Erichsen, H. C., Taylor, J., Yeager, M., Hughes, A., Levine, M. & Chanock, S. (2004).  Comparison of the genomic structure and variation in the two human sodium-dependent vitamin C transporters, SLC23A1 and SLC23A2. Human Genetics, 115 (4): 285-294

Padayatty, S, Katz, A., Wang, Y., Eck, P., Kwon, O., Lee, J. -H., Chen, S., Corpe, C., Dutta, S. & Levine, M. (2003).  Vitamin C as an antioxidant: does it have a role in disease prevention?  Journal of the American College of Nutrition.  22 (1): 18-35. 

Song, J., Kwon, O., Chen, S., Daruwala, R., Eck, P., Park, J., Levine M. (2002).  Flavonoid inhibition of sodium-dependent Vitamin C transporter 1 (SVCT1) and glucose transporter isoform 2 (GLUT2), intestinal transporters for Vitamin C and glucose.  Journal of Biological Chemistry 277 (18): 15252-15260.

Eck, P., Erichsen, H. C., Levine, M. & Chanock, S. (2001).  Characterization of the genomic structure of the human Vitamin C transporter SVCT1 (SLC23A2).  Journal of Nutrition 131: 2623-2627.

Levine, M., Wang, Y., Katz, A., Eck, P., Kwon, O., Chen, S., Lee, J. & Padayatty, S. (2001).  Ideal Vitamin C intake.  Biofactors 15 (2-4): 71-74.

Eck, P. & Pallauf, J. (2001).  Induction of metallothionein by exposure to normobaric 100% oxygen atmosphere in rats with different zinc supply.  Journal of Trace Elements in Medicine and Biology 15 (4): 229-235.

Eck, P. & Pallauf, J. (1999).  Induction of metallothionein by paraquat injection in zinc-deficient rats.  Journal of Animal Physiology and Animal Nutrition 81 (4-5): 203-211.

Publications in Preparation for scientific journals:
Eck, P.; Chen, S.; Kwon, O.; Schnermann, J.; Levine, M.A. (2010). SVCT1 does not mediate cellular Vitamin C release. In preparation.

Eck, P. (2010). Alternative splicing in the SLC22A4 gene locus and its potential relevance in intestinal inflammation. In preparation.

Contributions to scientific books:
Levine, M.; Padayatty, S.; Katz, A.; Kwon, O.; Eck, P.; Corpe, C.; Lee, J-H.; Wang, Y. 2003: Dietary Allowances for Vitamin C: Recommended Dietary Allowances and Optimal Nutrient Ingestion. In Vitamin C Asard H., Smirnoff N., May J. Editors Bios London 

Katz, A.; Padayatty, S.J.; Wang, Y.; Eck, P.; Kwon, O.; Chen, S.; Lee, J-H.; Levine, M. 2003: Vitamin C, in The Encyclopedia of Dietary Supplements . Coates P., Cragg G., Levine M., Moss J.White P. Editors

Padayatty, S.J., Daruwala, R., Wang, Y., Eck, P., Song, J., Koh, W., Levine, M. (2001).  Vitamin C: From Molecular Mechanisms to Optimum Intake. In: Handbook of Antioxidants 2nd edition Chapter 7, pages 117-146. Editors Cadenas, Packer. Published by Marcel Dekker, New York.

Monographic:
Eck P. 1998. Antioxidative properties of metallothionein and zinc in conditions of oxidative stress in vivo and in vitro. PhD Thesis, University of Giessen, Germany.

Contributions to scientific conferences and symposia:
Espey M., Cam M., Wang J., Padayatty M., Eck P., Levine M. (2009). PRECISELY CONTROLLED HUMAN VITAMIN C INTAKE, GENOMIC EXPRESSION PATTERNS AND IMMUNE HOMESTASIS. 3rd Congress of the International Society of Nutrigenetics/Nutrigenomics (ISNN), Natcher Conference Center, the National Institutes of Health, Bethesda, MD, USA

Tu H., Eck P., Corpe C., Wang, J.; Sun H., Espey M., Padayatty M., Levine M. (2008). Role of Sodium Dependent Vitamin C Transporter 1 in Vitamin C Physiology. NATIONAL INSTITUTE of DIABETES, DIGESTIVE and KIDNEY DISESEAS Retreat 2008, USA

Latourette, N.; Choyke, P.; Eck, P. (2008). Identifying the site of galactose-terminated protein binding on the surface of ovarian cancer cells. Howard Hughes Medical Institute Student and Teacher Internship Program Presentation. May 08 2008, Bethesda, MD, USA

Nguyen, H.; Latourette, N.; Choyke, P.; Eck, P. (2007). Expression of Galactose-Terminated Protein Receptor ASGR1 in Cancer Cell Lines.  NIH Summer Student Research Presentation Day.

Corpe, C.; Tu, H.; Wang, J.; Eck, P.; Wang, Y.; Schnermann, J.; Faulhaber-Walter, R.; Nussbaum, R.;Levine, M. (2007). SVCT1 (Slc23a1) knockout mice: Slc23a1 as the vitamin C kidney reabsorptive transporter. FASEB J. 21: lb520

Eck, P., Erichsen, H. C., Taylor, J., Corpe, C., Chanock, S. Levine, M. (2005).  Genomic and Functional Analysis of the Sodium-Dependent Vitamin C Transporter SLC23A1 – SVCT1.  NUGO Personalised Nutrition Conference 2005 - From Nutrigenomics to Personalised Nutrition. Palma de Mallorca, Spain.

Ferguson L., Shelling A., Petermann I., Hübner C., Browning B., Eck, P. (2005). Biodiversity and Gut Health. NUGO Personalised Nutrition Conference 2005 - From Nutrigenomics to Personalised Nutrition. Palma de Mallorca, Spain.

Ferguson L., Philpott M., and Shelling A., Eck, P. (2005). Nutrigenomics and Inflammatory Bowel Diseases. Workshop on Systems biology - from genomes to phenomes. Melbourne, Australia.

Petermann I., Hübner C., Eck, P., Philpott M., Ferguson L., and Shelling A. (2005). Nutrigenomics and Inflammatory Bowel Disease (IBD). Queenstown Molecular Biology Meeting.

Hübner C., Petermann I., Eck, P., Philpott M., Ferguson L., and Shelling A. (2005). Genetic studies in Inflammatory Bowel Disease (IBD). Queenstown Molecular Biology Meeting.

Petermann I., Hübner C., Eck, P., Philpott M., Ferguson L., and Shelling A. (2005). Genetic studies in Inflammatory Bowel Disease. New Zealand Molecular Mapping Workshop (25th – 26th May 2006), Crop & Food Research, Lincoln.

Petermann I., Hübner C., Eck, P., Philpott M., Ferguson L., and Shelling A. (2005). SNP analysis in Inflammatory Bowel Disease. New Zealand Molecular Mapping Workshop (25th – 26th May 2006), Crop & Food Research, Lincoln.

Eck, P., Erichsen, H. C., Taylor, J., Corpe, C., Yeager, M., Hughes, A., Levine, M. & Chanock, S. (2004).  Genomic and functional analysis of two sodium dependent Vitamin C transporters, SLC23A1 and SLC23A2. Keystone Symposia 2004, Human Genome Sequence Variation and Inherited Basis of Common Disease, Abstract book, Drawer 1630, page 48, #123

Erichsen H.C., Eck P., Taylor J., Yeager, M., Hughes A., Levine M., Chanock S. (2002). Genetic Analysis of Two Sodium Dependent Vitamin C Transporters, SLC23A1 and SLC23A2. American Journal of Human Genetics 71 (4): 910S.

Eck, P., Erichsen, H. C., Taylor, J., Levine, M. & Chanock, S. (2002).  Genomic analysis of the SLC23A1 locus.   NIH research Festival.

Eck, P., Erichsen, H. C., Taylor, J., Levine, M. & Chanock, S. (2002).  Genomic diversity in the human SLC23A1 locus, which encodes the sodium dependent Vitamin C transporter.  Proceeding of the World Meeting of the Oxygen Society of California, 118.

Eck, P., Erichsen, H. C., Taylor, J., Levine, M. & Chanock, S. (2002).  Genomic diversity in the human SLC23A1 locus, which encodes the sodium dependent Vitamin C transporter.  FARE 2002.

Obermayer, T., Levine, M., Eck, P. (2001). Functional testing of possible alternative translational start points on the SVCT2 RNA.  NIH Summer Student Research Presentation Day.

Eck, P., Daruwala, R., Levine, M. (1999).  Mechanism of dehydroascorbic acid reduction by glutaredoxin (thioltransferase).  Free Radicals in Biology and Medicine 27 (1): S35.

Levine, M., Daruwala, R., Song, J., Rumsey, S. C. & Eck P. (1999).  Ascorbate transport and recycling in human neutrophils: potential role in oxidant defense.  Free Radicals in Biology and Medicine 27 (1): S6.

Eck, P., Pallauf, J., Fischer A (1999). The protective role of zinc or metallothionein supplementation to hepatic homogenates of zinc deficient rats at induced oxidative stress. 1999 Oxygen Club of California World Congress book of abstracts

Eck, P. & Pallauf, J. (1998).  Influence of zinc and metallothionein on lipid peroxidation in liver homogenates.  Proceedings of the Society of Nutritional Physiology 7, 51.

Eck, P. & Pallauf, J. (1997).  Induction of metallothionein under oxidative stress conditions in vivo.  Proceedings of the Society of Nutritional Physiology 6, 170.

Saris, W.H.M.; Eck, P.; Schroeder U.; Cramwinkel B.; Van Mazijk D.; Beckers E.J.; Brouns F. (1992). Taste perception during endurance exercise. Medicine and Science in Sports and Exercise, 24 (5) S71.