Source: SOUTH DAKOTA STATE UNIVERSITY submitted to
DIETARY INFLUENCES ON INFLAMMATION AT GENETIC AND EPIGENETIC LEVELS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
HATCH
Reporting Frequency
Annual
Accession No.
0221536
Grant No.
(N/A)
Project No.
SD00H360-09
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
Dec 1, 2009
Project End Date
Sep 30, 2014
Grant Year
(N/A)
Project Director
Dey, MO.
Recipient Organization
SOUTH DAKOTA STATE UNIVERSITY
PO BOX 2275A
BROOKINGS,SD 57007
Performing Department
College of Education & Human Sciences
Non Technical Summary
OBJECTIVES: Two sub-projects are proposed within the scope of this proposal. The aim of the first one is to investigate the epigenetic mechanism of suppression of STAT1 transcription factor gene and its downstream signaling by phenethylisothyocyanate (PEITC), a known dietary anti-inflammatory/anti-cancer compound. The goal of the second sub-project is to study the effects of complex diets on multiple genes (several hundred) along the inflammation signaling pathway (mainly TLR and cytokines) that plays a key role in various diseases starting from cardiovascular to T2DM to chronic arthritis and cancer. The gene expression changes will be investigated in a tissue/organ-specific manner to shed light specific to individual diseases that may be associated with general low-grade inflammation and influenced by dietary intake. Already known biomarkers of inflammation such as CRP levels in blood will be evaluated as a positive control. APPROACH: With the unraveling of the human genome and the linking of its variability to a multitude of phenotypes from ``healthy'' to an enormously complex range of predispositions, the dietary modulation of these propensities has become an area of active research. The new era of nutrition recognizes the complex relation between the health of the individual, its genome, and the life-long dietary exposure, and has lead to the realization that nutrition is essentially a gene-environment interaction science. The overall long-term goal of my research is to understand nutrient-gene interactions and the cellular mechanisms of action of dietary components (i.e., bioactive food components, vitamin, minerals and synergistic effects of complex diet) contributing to their health-promoting and/or-degrading properties. Understanding of these interactions and mechanisms involved are crucial to scientifically refine healthy personal dietary requirements. Here, using model systems, we are examining the biochemical, molecular and physiological basis for changes in gene expression, in response to diets and dietary chemicals under diseased and non-diseased circumstances. This work identifies novel and known mammalian genes that are differentially regulated in different tissues/organs that are involved in common diseases.
Animal Health Component
(N/A)
Research Effort Categories
Basic
(N/A)
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
7023840104030%
7023840108010%
7027010109010%
7027010104030%
7027410104020%
Knowledge Area
702 - Requirements and Function of Nutrients and Other Food Components;

Subject Of Investigation
3840 - Laboratory animals; 7010 - Biological Cell Systems; 7410 - General technology;

Field Of Science
1040 - Molecular biology; 1090 - Immunology; 1080 - Genetics;
Goals / Objectives
The primary and long-term goal of my research is to understand nutrient-gene interactions and the cellular mechanisms of action of dietary components (i.e., bioactive food components, vitamins and minerals) contributing to their health-promoting and/or-degrading properties. This is an immensely complex subject, given the complexity of genetic and epigenetic regulatory switches that are turned on and off during one's life span as well as the complexity of the genotype, diet and their interactions. However, understanding of these mechanisms is crucial to scientifically determine healthy personal dietary requirements. Subsequent improvements in health should lead to improved economic costs, such as decreased medical costs associated with treatment for obesity, heart disease, diabetes or bone loss, all of which are in one way or other consequences of chronic inflammation. Available genome information made it possible to attempt such study goals only in recent years. Three general approaches will be undertaken to accomplish the primary research goal: 1. In-depth study of cellular mechanisms for compounds that have known health benefits in animals and/or human. The established health effects could be from my previous research or based on published data. 2. To evaluate the efficacy (in vivo)/ biological activity (in vitro gene-expression based screens/assays) of various dietary components in attenuating production of proinflammatory mediators. 3. Link epidemiologic findings (from literature) to genetic mechanisms. The data that will emerge from the research proposed here will provide for preliminary data for future grant applications to NIH (NCCAM, NIEHS or NCI, NIGMS), non-federal foundations etc.
Project Methods
SUB-PROJECT A: The mechanism of STAT1 regulation by PEITC will be investigate in vitro in mouse and human cell lines. It is only reasonable and ethical to use in vitro systems for such in-depth mechanism study over in vivo systems which are also typically more expensive. A significant portion of ongoing epigenetic research involves the investigation of DNA methylation and chromatin modification patterns seen throughout many biological processes. Over the last few years, epigenetic research has undergone a gradual shift and recent studies have been directed toward a genome-wide assessment. DNA methylation and chromatin modifications are essential components of the regulation of gene activity. DNA methylation effectively down-regulates gene activity by addition of a methyl group to the five-carbon of a cytosine base. Less specifically, modification of the chromatin structure can be carried out by multiple mechanisms leading to either the upregulation or down-regulation of the associated gene. Of the many assays used to assess the effects of epigenetic modifications, chromatin immunoprecipitation (ChIP), which serves to monitor changes in chromatin structure, and bisulfite modification, which tracks changes in DNA methylation, are the two most commonly used techniques (DeAngelis and Farrington 2008). Bisulfite treatment of DNA changes unmethylated cytosine residues to uracil, but leaves methylated cytosines unchanged. Quantitative PCR, can then be used to compare the sequences of treated and untreated DNA to determine which bases were methylated. However given the inconvenience of bisulphate conversion, I will use enzyme-based Methyl Profiler PCR system kits from SA Bioscience as alternate methodology. To probe into histone modification, chromatin immunoprecipitation, or ChIP will be used followed by Q-PCR. Commercially available antibodies and kits will be used. As appropriate and when necessary immunoblotting will be used for validation of obtained results. Specific kits to test each of the known epigenetic mechanisms are available from Epigentek Inc (Brooklyn, NY). SUB PROJECT B: IN VIVO ANIMAL MODELS AND/OR IN VITRO HUMAN CELL ASAYS WILL BE USED. AMONG THE MOLECULAR METHODS, QPCR WILL BE EXTENSIVELY USED. DIET PREPARATION, PELLET EXTRUSION ETC WILL BE DONE BY USING A THIRD PARTY AND NUTRITIONAL EVALUATION OF CUTOM PREPARADE DIET WILL BE DONE USING ANALYTICAL METHODS. Protein expression and immunocytochemistry may be carried out to validate any significant finding.

Progress 12/01/09 to 09/30/14

Outputs
Target Audience: Results of the project published in various journals and presented at national and international conferences are available to and can be used by the nutrition and food scientists and food/nutraceutical companies for development of new health foods. These findings can also be used by health educators to demonstrate health benefits of bioactive compounds present in Brassicaceae group of vegetables and by using whole grain derived health-promoting food ingredients such as wheat resistant starch or avennathramides from oats. The role of dietary active compounds in human health is one of the most important research areas of nutritional sciences. The findings on this subject have wide-ranging implications for consumers, health-care providers, and nutrition educators as well as the food industry. PI was able to utilize the research data to present to highly motivated graduate students in her class of NFS775. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Graduate Student advising as major advisor 1. Yi Liu (doctoral) 2010-2014 (graduated last summer), currently employed at Mayo Clinic, Jacksonville, FL as postdoctoral scientist; her dissertation research was selected for oral presentation at an international science Congress in 2014. Dissertation title: Mechanistic investigation into the biological activity of Phenethyl isothiocyanate and sodium butyrate in context of IBD and colon cancer; (many scholarship items) 2. Bijaya Upadhyaya (doctoral) 2012 Fall-present, expected graduation 2015 Dissertation title: Effects of dietary phenethyl isothiocyanate on nutri-epigenetic modulation of intestinal inflammation in vivo; (one scholarship item, two more in progress,). Also awarded a prestigious award for graduate research in 2014. 3. Robert Juenemann (masters, option A thesis) 2013 Fall-present, expected graduation 2015 Thesis title: Resistant Starch Type-4 enriched diet impacts human gut microbiome and fecal short chain fatty acid concentrations in Adults with metabolic syndrome (one scholarship item in progress) 4. Thamer Aljutaily (doctoral) 2014 Fall-present, expected graduation and scholarship not decided at this time. Plan of study and committee will be formed in spring 2015, when dissertation title will be decided as well. I allow the first semester for taking courses and for reading and writing a review of scientific literature (one scholarship item in progress). 5. Milton Thomas (doctoral) 2011 Fall-2012 summer, discontinued and wanted to prepare for NAVLE (licensing examination for veterinary practice; Milton had a prior veterinary degree) (one scholarship item) Undergraduate research mentoring: During summer 2014, I advised Chad Novak, a senior at SDSU, on scientific literature review, interpretation, and research design that resulted in a manuscript. Chad intends to apply for M.D/PhD programs at various medical schools in 2015 and this experiential learning on biomedical literature review will help him in his future career. He received a work-study fellowship for this specific training. Post-Graduate Trainees: Sailendra Nichenametla, 2011−2013, currently at Orentreich Foundation for Advancement of Science, as Senior Scientist, NY (worked together on one journal paper). Previously Dr. Sailendra received his Ph.D. from Pennsylvania State University. Dan Wang, 2011−2013, currently in the department of Biology and Microbiology at SD State University, as Research Assistant Professor, SD (worked together on two journal papers). Previously Dr. Wang received her Ph.D. from SDSU. V.G. Premkumar, 2009 (10 months), currently at Cincinnati Children's Hospital Medical Center as Research Faculty, OH (worked together on two journal papers). Previously Dr. Premkumar received his Ph.D. in India. Two short-term (6-12 months each) post-M.S. trainees, 2009-2010: Bing Xia, Chaitanya Doddivenaka finished M.S in China and SDSU respectively prior to working with me. How have the results been disseminated to communities of interest? Results of the project have been disseminated to communities of interest through the following: 1. scientific publications (over a dozen): for professionals 2. popular press articles (over a dozen): for members of general public 3. Public radio network (twice): for general public 4. oral presentations and invited talks at local, regional, national and international conferences (over a dozen): for members of general public and professionals What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? All proposed goals were accomplished and exceeded. In addition, 17 new collaborations were initiated during the project period. Of the 17 selected collaborations listed below, 10 are within SDSU and 7 outside of SDSU of which one abroad and remaining in the USA.

Publications

  • Type: Book Chapters Status: Published Year Published: 2012 Citation: Thomas, M., and Dey, M. (2011) Gastroprotective effects of bioactive foods. In Bioactive Food as Dietary Interventions for Liver and Gastrointestinal Disease, Ronald Watson, Victor Preedy (Ed), Elsevier Press, Oxford, UK, ISBN 9780123971548.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: 1. Nichenametla S, Weidauer LA, Wey HE, Beare TM, Specker BL, and Dey M* (2014) Resistant starch type 4-enriched diet lowered blood cholesterols and improved body composition in a double-blind controlled crossover intervention. Molecular Nutrition and Food Research: 58 (6):1365-1369.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Dey M* (2014) Dietary bioactives: the road ahead. Cereal Foods World, 59 (2): 60-62.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: 3. Wang D , Upadhyaya B , Liu Y , Knudsen D, and Dey M* (2014) Phenethyl isothiocyanate up regulates death receptors 4 and 5, and inhibits proliferation in human cancer stem-like cells. BMC Cancer: 14:591.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: 4. Ilic N, Dey M, Poulev A, Logendra S, Raskin I (2014) Anti-inflammatory activity of Grains of Paradise (Aframomum melegueta Schum) extract. Journal of Agriculture and Food Chemistry: Published online ahead of print-DOI: 10.1021/jf5026086.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2014 Citation: Dey M, Specker BL, Wey HE, Weidauer LA, and Nichenametla S (2014). Prebiotic intervention improved dyslipidemia and body composition. FASEB Journal. 28:624.29
  • Type: Conference Papers and Presentations Status: Published Year Published: 2014 Citation: Dey M, Liu Y (2014) Site-and promoter-specific epigenetic alterations by a common dietary compound, FASEB Journal. 28:271.5.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2014 Citation: Liu Y, Dey M (2014) Histone modifications in phenethyl isothiocyanate treated cancer cells may contribute to its chemopreventive effects. Journal of Alternative and Complement Medicine. 20(5):A5.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2013 Citation: Dey M, Li F, Wise ML, Liu Y, Wang D (2013) Aberrant beta-catenin signaling as a molecular target for bioactive phytochemicals. FASEB Journal. 27:637.2.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Liu Y, Chakravarty S and Dey M* (2013) Phenethylisothiocyanate alters site- and promoter-specific histone tail modifications in cancer cells. PLOS ONE 8(5): e64535.
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: Wang, D., Wise, M.L., Li, F. and Dey, M. 2012. Phytochemicals Attenuating Aberrant Activation of beta-catenin in Cancer Cells. PLOS ONE, PLoS ONE 7(12): e50508
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: Dey, M. 2012. Molecular Nutrition, Nutrigenomics and Health Promotion: A Long Road Ahead. J Food Nutritional Disorders, doi: 10.4172/2324-9323.1000e101.
  • Type: Journal Articles Status: Published Year Published: 2012 Citation: Dey, M. 2012. Molecular mechanism-based model to enhance outcomes of dietary intervention studies for disease prevention. J. Mol .Biochem. 1:150-154.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2011 Citation: Dey, M., Liu, Y., Reuhl, K., Raskin, I., and Kuhn, P. (2011) Alleviation of bowel inflammation by dietary phenethylisothiocyanate in a mouse ulcerative colitis model, FASEB Journal, 25: 599.6.
  • Type: Journal Articles Status: Published Year Published: 2010 Citation: Dey, M., Kuhn, P., Ribnicky, D., Premkumar, V., Reuhl, K. and Raskin, I. 2010. Phenethylisothiocyanate, attenuates bowel inflammation in mouse models. BMC Chemical Biology 10:4.
  • Type: Journal Articles Status: Published Year Published: 2010 Citation: Premkumar V, Dey M, Dorn R, and Raskin I. 2010. MyD88-Dependent and Independent pathways of Toll-Like Receptors are engaged in Biological Activity of Triptolide in ligand-stimulated macrophages. BMC Chemical Biology 10:3.
  • Type: Journal Articles Status: Published Year Published: 2010 Citation: Zeng F, Wang W, Wu Y, Dey M, Ye M, Avery MA, Khan IA, Guo DA. 2010. Two prenylated and C-methylated flavonoids from Tripterygium wilfordii. Planta Med.76:1596-1599.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2010 Citation: Dey M, Premkumar V, Raskin I. 2010. TLR-pathway is involved in the biological activity of triptolide, the active compound from a botanical clinically shown to alleviate RA symptoms. FASEB J. 24:lb509
  • Type: Other Status: Published Year Published: 2010 Citation: Ribnicky D, Dey M, Raskin I. 2010. Anti-inflammatory activity of Barbarea verna seed preparation. US 7,838,045B2.


Progress 01/01/13 to 09/30/13

Outputs
Target Audience: Results of the project published in journals and presented orally in seminars can be used by the nutrition and food scientists and food/nutraceutical companies for development of new health foods. These findings can also be used by health educators to demonstrate health benefits of bioactive compounds present in Brassicaceae group of vegetables and by using resistant starch containing food products. The role of dietary active compounds in human health is one of the most important research areas of nutritional sciences. The findings on this subject have wide-ranging implications for consumers, health-care providers, and nutrition educators as well as the food industry. Research findings were covered in annual progress report of SD-AES as well asby healthy-living radio network of MO. PI was able to utilize the research data to present to highly motivated students in her class of NFS775 Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Training of graduate students: Yi Liu; joined PhD program in 2010, became doctoral candidate in 2013, expected graduation 2014, produced multiple manuscripts and abstracts in 2013 Bijaya Upadhyaya; joined PhD program 2012; expected graduation 2015; produced manuscript in 2013 Robert Juenemann; joined MS program in 2013; expected graduation in 2015; one manuscript planned How have the results been disseminated to communities of interest? 1. efficacy research data was shared with intervention population by menas of health reports 2. research results were reported to scientific journals as well as in the annual progress report of SD-AES that reaches stakeholders 3. research finding broadcasted in Healthy-living radio network of MO; dissemination to communities/public 4. multiple oral and poster presentations in national conferences What do you plan to do during the next reporting period to accomplish the goals? 1. accomplish remaining goals; most originals goals have already been accomplished 2. graduate Yi Liu with PhD 3. continue to publish 4. R01 grant to NIH and other applications

Impacts
What was accomplished under these goals? 1. In-depth study of cellular mechanisms for compounds that have known health benefits in animals and/or human. We identified and published epigenetic modulation of transcription factors by PEITC, a phytocompound from vegetables like brocolli. This compound was shown previously to be antiinflammatory by our research and anti-cancer from others research. 2. To evaluate the efficacy; we evaluated efficacy of resistant starch type 4 in human by conducting a clinical study. the reports are now accepted for publication

Publications

  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2014 Citation: VI. Dey M*, Liu Y (2014) Histone modifications in phenethyl isothiocyanate treated cancer cells may contribute to its chemopreventive effects. International Research Congress on Integrative Medicine and Health (basic research subcategory), May 13-16, Miami, Florida. Accepted and will be published in Journal of Alternative and Complementary Medicine.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Liu Y, Chakravarty S and Dey M* (2013) Phenethylisothiocyanate alters site- and promoter-specific histone tail modifications in cancer cells. PLOS ONE 8(5): e64535.
  • Type: Journal Articles Status: Accepted Year Published: 2014 Citation: II. Nichenametla S, Weidauer L, Wey H, Beare T, Specker B and Dey M* (2013) Resistant starch type 4-enriched diet lowered blood cholesterols and improved body composition in a double-blind controlled crossover intervention. Mol Nutr Food Res. In press.
  • Type: Journal Articles Status: Accepted Year Published: 2014 Citation: Dey M* (2013) Dietary Bioactives: the road ahead. Cereal Foods World. Accepted for publication
  • Type: Conference Papers and Presentations Status: Published Year Published: 2013 Citation: Dey M*, Li F, Wise ML, Liu Y, Wang D (2013) Aberrant beta-catenin signaling as a molecular target for bioactive phytochemicals. FASEB Journal. 2013;27:637.2


Progress 01/01/12 to 12/31/12

Outputs
OUTPUTS: Activities and products: The current project provided an opportunity to hire a new graduate student (who received his MS from UNL, NE) and continued mentoring to the existing student, both of who were mentored to have an in depth understanding of the goals of the current project. A large human intervention study and an in vitro mechanistic has been undertaken to study "Dietary influences on inflammation at genetic and epigenetic levels". The project funding provided for a start-up laboratory in Nutrition Genomics. PI joined SDSU in Fall of 2009. In the past decade or so there has been a paradigm shift in nutritional science facilitated by nutrigenomics. Nutrigenomics, or nutritional genomics, is a multidisciplinary science that combines information from genetics, nutrition, physiology, pathology, molecular biology, bioinformatics, biocomputation, sociology, ethics, and other disciplines. We believe that understanding diet - nutrient interactions in different individuals will help explain and help alleviate health disparities - hence, the knowledge that has already been and will be generated from this research program will apply to national and international societal issues in personal and public health. Events in 2012 that helped disseminate research results to communities (students, scientists, scholars, practitioners, business, general public and policy makers since research data relates to public health) of interests: 1. 4 peer reviewed manuscripts 2. One book chapter 3. 2 abstracts presented at regional and national conferences 4. One invited talk at an international Congress for gastroenterology/urology 5. One newsletter article to French Consulate at Chicago, USA 6. Introduced and taught a new graduate course at SDSU NFS775, Nutrigenomics and Health that used lot of research information generated from this project. The course was designed to complement the Nutrigenomic research program at SDSU and each one of the research and teaching builds on each other, given the entire field is still in its infancy and very little is out there as overall. 7. Also an industry grant was acquired by utilizing the preliminary data generated from this AES hatch project Research Collaborations fostered by the current project are listed below: 1. Dr. Mitchell L. Wise, Research Chemist, USDA, Cereal Crops Research, 502 Walnut St., Madison, WI 53726 (joint publication came in 2012) 2. Prof. Kenneth Reuhl, PhD, Interim Director, Environmental and Occupational Health Science Institute, 170 Frelinghuysen Road, Piscataway, NJ 08854 (joint publication came in 2010) 3. Dr. Bonny L Specker, Director Ethel Austin Martin Program in Human Nutrition, South Dakota State University (joint publication expected in 2013) 4. Dr. Feng Li, Department of Biology and Microbiology at SDSU (joint publication came in 2012) 5. Dr. S. Chakaravarty, Department of Chemistry and Biochemistry at SDSU (joint conference proceeding/publication in 2012) 6. Dr. Hemchand Tummala, College of Pharmacy at SDSU (joint NIFA/USDA competitive seed grant submitted) PARTICIPANTS: Individuals: Moul Dey, P.I., department of Health and Nutritional Sciences, South Dakota State University was responsible for all major aspects of the project. She carried out together with graduate student s and postdocs, experiments and was responsible for evaluations and analyses of data and preparing reports and manuscripts for publications. Laboratory personnel consists of two post-doctoral associates who received their PhDs from US Universities and two highly qualified PhD students who had previously had masters (both) and DVM-equivalent (one of the two) degrees from US or a non-US University. A part-time trained technician is hired as per need basis to assist in the laboratory/animal research, editing jobs etc. All laboratory personnel are well trained in the procedures involved in research with cell lines, animals, humans and appropriate chemical and biological safety procedures as well as research ethics and other regulatory processes. Yi Liu, graduate research assistant in the department of Health and Nutritional Sciences at SDSU was responsible for maintenance of cell cultures and mice and also for carrying out biochemical techniques. Research Associate, Dr. Sailendra Nichenametla also contributed to the planning of the human dietary intervention study. Dr. Bonny L Specker is a renowned epidemiologist who is collaborating on this dietary intervention study. Dr. Donald Coffey at MGPI, Atchinson, KS has generously provided for the test diet ingredients through a industry-SDSU sponsored research partnership. TARGET AUDIENCES: Results of the project published in journals and presented orally in seminars can be used by the nutrition and food scientists and food/nutraceutical companies for development of new health foods. These findings can also be used by health educators to demonstrate health benefits of bioactive compounds present in Brassicaceae group of vegetables and by using resistant starch containing food products. The role of dietary active compounds in human health is one of the most important research areas of nutritional sciences. The findings on this subject have wide-ranging implications for consumers, health-care providers, and nutrition educators as well as the food industry. PI was able to utilize the research data to present to highly motivated students in her class of NEW NFS775 PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Findings, results, techniques generated from the project led to various scholarly outcomes and new collaborations across various setting. Also future research ideas were conceived based on the work carried out under this AES project that provided foundation for new federal grant applications. Following SEVEN grants applications were received are submitted or will be submitted by March 1, 2013. 1. BCAAP Exploratory grant (Moul Dey co-investigator) by SD-state 2010 center of excellence: Cancer Stem Cell, A Biochemical Model for Epigenetic Basis of Gene Regulation and Targeted Therapeutics 2011-2012, funding ended in 2012 2. Awarded 2/23/2012) MGP Ingredients Inc, (Principle Investigator); USD 83,949; Title: Dietary Intervention with Resistant Starch Type-4 in a Hutterite Population of Mid-Western USA 3 LoI accepted by NIFA in 2012; PI Droke E. Co-PI Moul Dey and others. Consumption of Flaxseed or Chia seed-Containing Baked Products Reduces Pro- Inflammatory Mediators and Improves Endothelial Function and Gut Microbiome in Overweight and Obese Humans 4. Seed grant submitted to NIFA on Feb 6, 2013; PI Hemchand Tummala, co-PI Moul Dey; title: Enhancing the oral bioavailability of curcumin by a novel nano-formulation 6. EPSCOR Supercenter Proposal due March 1, 2013. Moul Dey Co-PI. Title South Dakota Research and Innovation Center for Integrative Computational Biology to Drive the Next "Green Revolution" 7. NIH R01 application toward RFA-AT11001, Moul Dey PI, deadline March 1, 2013. Title : DIETARY BIOACTIVES IN HEALTH: EPIGENETIC REGULATION OF GUT-IMMUNE RESPONSE GENES

Publications

  • Liu, Y., Chakravarty, S. and Dey, M. 2013. Phenethylisothiocyanate alters site- and promoter-specific histone tail modifications in cancer cells. PLOS ONE in revision.
  • Wang, D., Wise, M.L., Li, F. and Dey, M. 2012. Phytochemicals Attenuating Aberrant Activation of beta-catenin in Cancer Cells. PLOS ONE, PLoS ONE 7(12): e50508.
  • Dey, M. and Thomas, M. 2012. Gastroprotective effects of bioactive foods. In Bioactive Food as Dietary Interventions for Liver and Gastrointestinal Disease, Ronald R. Watson and Victor R. Preedy (Eds), Elsevier Press, Oxford, UK. ISBN 9780123971548.
  • Dey, M. 2012. Molecular mechanism-based model to enhance outcomes of dietary intervention studies for disease prevention. J. Mol .Biochem. 1:150-154.
  • Dey, M. 2012. Molecular Nutrition, Nutrigenomics and Health Promotion: A Long Road Ahead. J Food Nutritional Disorders, doi: 10.4172/2324-9323.1000e101.
  • Dey, M. Attenuation of bowel inflammation by a common dietary compound in mouse, World Congress on Gastroenterology & Urology, March 12-14, 2012, Omaha, NE.
  • Wang, D., Chakravarty, S. and Dey, M. 2012. Dietary extracts and cervical cancer stem cell proliferation. PQCD symposium, June 13-15, Deadwood, SD.
  • Dey, M., Li, F., Wise, M.L., Liu ,Y. and Wang, D. 2013. Aberrant beta-catenin signaling as a molecular target for bioactive phytochemicals. Abstract accepted for presentation in Experimental Biology meeting April, 2013, Boston, MA.


Progress 01/01/11 to 12/31/11

Outputs
OUTPUTS: Activities and products: The current project provided an opportunity to hire a graduate student who was mentored to have an in depth understanding of the goals of the current project. A large human intervention study has been undertaken to study "Dietary influences on inflammation at genetic and epigenetic levels". The project funding provided for a start-up laboratory in Nutrition Genomics. PI joined SDSU in Fall of 2009 and was given a newly constructed laboratory space without any equipment in it. PI transformed this empty laboratory space into a functional and productive Nutrigenomics laboratory using start-up funds. Graduate students and researchers were hired and scientific collaborations were established within and outside of SDSU. In the past decade or so there has been a paradigm shift in nutritional science facilitated by nutrigenomics. Nutrigenomics, or nutritional genomics, is a multidisciplinary science. We believe that understanding diet - nutrient interactions in different individuals will help explain and help alleviate health disparities - hence, the knowledge that will be generated in the coming years from this research program will apply to national and international societal issues in personal and public health. Events: The PI attended following meetings and conferences in context of the project. 1. Nutrition: A Wholistic Approach seminar series: March 15-17, 2011, SD 2. Effect of an antiinflammatory phyto-compound on Phosphoenol pyruvate carboxykinase gene expression, a key enzyme for glucose metabolism. Invited talk, Avera Health Science Symposium, Sept 16, 2011, Sioux Falls, SD Research Collaborations fostered by the current project are listed below: 1. Dr. Mitchell L. Wise, Research Chemist, USDA, Cereal Crops Research, Madison, WI 53726 2. Dr. Kungsoo Woo, Senior Scientist, Nestle R&D, Solon, OH 44139 3. Prof. Kenneth Reuhl, PhD, Interim Director, Environmental and Occupational Health Science Institute, Piscataway, NJ 08854 4. Dr. Bonny L Specker, Director Ethel Austin Martin Program in Human Nutrition, South Dakota State University 5. Dr. Donald Coffey, MGP Ingredients, Atchinson, KS PARTICIPANTS: Moul Dey, Ph.D, Principle Investigator Yi, Liu, M.S, Graduate student whose training under supervision of Moul Dey was facilitated by this project Chaitanya Doddivenaka, M.S., researcher whose training under supervision of Moul Dey was facilitated by this project Dr. Sailendra Nichenametla, postdoctoral scientist whose training under supervision of Moul Dey was facilitated by this project Dr. Dan Wang, postdoctoral scientist whose training under supervision of Moul Dey was facilitated by this project MGP Ingredients, Atchison, KS, industrial collaborator on the project Dr. Bonny L. Specker, collaborator on the project TARGET AUDIENCES: Results of the project published in journals and presented orally in seminars can be used by the nutrition and food scientists and food/nutraceutical companies for development of new health foods. These findings can also be used by health educators to demonstrate health benefits of bioactive compounds present in Brassicaceae group of vegetables and by using resistant starch containing food products. The role of dietary active compounds in human health is one of the most important research areas of nutritional sciences. The findings on this subject have wide-ranging implications for consumers, health-care providers, and nutrition educators as well as the food industry. PROJECT MODIFICATIONS: The original proposal aimed at in vitro experiments and animal models to address the scientific questions. While the scientific questions and goals remained unchanged, we added human dietary intervention to the methodologies, which were not originally proposed. This is to better address the original objectives.

Impacts
The primary and long-term goal of my research is to understand nutrient-gene interactions and the cellular mechanisms of action of dietary components contributing to their health-promoting and/or-degrading properties. As part of the subproject A to investigate mechanism of biological activity of PEITC, we looked further into the mechanism by which the compound might be working against bowel inflammation. We observed that PEITC down regulates many of the genes that are known to be up regulated in human patients with colitis and that some of these gene repressions are mediated by epigenetic modifications. This is a novel observation and we are in the process of preparing a manuscript to submit for peer review. In order to carry out this investigation, new methods were optimized in our laboratory: 1. epigenetic methods 2. primary cell culture methods

Publications

  • Dey, M., Liu, Y., Reuhl, K., Raskin, I., and Kuhn, P. (2011) Alleviation of bowel inflammation by dietary phenethylisothiocyanate in a mouse ulcerative colitis model, FASEB Journal, 25: 599.6.
  • Thomas, M., and Dey, M. (2011) Gastroprotective effects of bioactive foods. In Bioactive Foods in Chronic Disease States: Bioactive Foods and chronic disease states: Liver and gastrointestinal diseases, Ronald Watson, Bethany Stevens (Ed), Elsevier Press, Oxford, UK (accepted for publication)


Progress 01/01/10 to 12/31/10

Outputs
OUTPUTS: Activities and products: The current project provided an opportunity to hire a graduate student who was mentored to have an in depth understanding of the goals of the current project. A large animal experiment has been undertaken to study "Dietary influences on inflammation at genetic and epigenetic levels". The project funding provided for a start-up laboratory in Nutrition Genomics. PI joined SDSU in Fall of 2009 and was given a newly constructed laboratory space without any equipment in it. PI transformed this empty laboratory space into a functional Nutrigenomics laboratory using start-up funds. PI also recruited researchers and launched a Nutrigenomics-Molecular Nutrition research program, the first of its kind at SDSU and possibly in the entire state of South Dakota. During 2010, PI purchased small and large equipments worth more than USD 200,000, using AES and other funds. Graduate students and researchers were hired and scientific collaborations were established within and outside of SDSU. In the past decade or so there has been a paradigm shift in nutritional science facilitated by nutrigenomics. Nutrigenomics, or nutritional genomics, is a multidisciplinary science that combines information from genetics, nutrition, physiology, pathology, molecular biology, bioinformatics, biocomputation, sociology, ethics, and other disciplines. We believe that understanding diet - nutrient interactions in different individuals will help explain and help alleviate health disparities - hence, the knowledge that will be generated in the coming years from this research program will apply to national and international societal issues in personal and public health. On Friday, September 24, 2010 a Nutrigenomic Lab open house was held to showcase the new facility and the research program and to appreciate the funding from SD Agricultural Experiment station for the original space renovation and laboratory modeling/construction. Active research began prior to the open house during the summer of 2010. Events: The PI attended following meetings and conferences in relevance to the project. 1. Nutrition: A Wholistic Approach seminar series: March 15-17, 2010, SD 2. American Association of Cereal Chemists International & Grains for Health Foundation Research Preview meeting; September 16-17, 2010, MN 3. Experimental Biology, April 24-28,2010, Anaheim, CA Research Collaborations fostered by the current project are listed below: 1.Dr. Mitchell L. Wise, Research Chemist, USDA, Cereal Crops Research, 502 Walnut St., Madison, WI 53726 2.Dr. Kungsoo Woo, Senior Scientist, Nestle R&D, 5750 Harper Road, Solon, OH 44139 3.Prof. Kenneth Reuhl, PhD, Interim Director, Environmental and Occupational Health Science Institute, 170 Frelinghuysen Road, Piscataway, NJ 08854 PARTICIPANTS: Individuals: Moul Dey, P.I., department of Health and Nutritional Sciences, South Dakota State University was responsible for all major aspects of the project. She carried out together with graduate students Milton Thomas and Yi Liu, experiments and was responsible for evaluations and analyses of data and preparing reports and manuscripts for publications. Milton Thomas and Yi Liu, graduate research assistants in the department of Health and Nutritional Sciences at SDSU were responsible for maintenance of cell cultures and mice and also for carrying out biochemical techniques. Collaborator, Dr. Kungsoo Woo, Adjunct assistant professor in the department of Health and Nutritional Sciences, South Dakota State University kindly agreed to collaborate on this project and provide P.I. with chemically analyzed resistant starch for her mouse experiment. TARGET AUDIENCES: Results of the project published in journals and presented orally in seminars can be used by the nutrition and food scientists and food/nutraceutical companies for development of new health foods. These findings can also be used by health educators to demonstrate health benefits of bioactive compounds present in Brassicaceae group of vegetables and by using resistant starch containing food products. PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
The primary and long-term goal of this research is to understand nutrient-gene interactions and the cellular mechanisms of action of dietary components contributing to their health-promoting and/or-degrading properties. As part of the subproject A to investigate role of PEITC with STAT signaling pathway, we looked into the mechanism by which the compound might be working against bowel inflammation. We confirmed our preliminary hypothesis that PEITC down regulates many of the genes that are known to be up regulated in human patients with colitis including a novel transcription factor (Signal Transducer and Activator of Transcription 1, STAT1) and this was published in the past year. As our next step we would like to investigate if an epigenetic mechanism may be involved in down-regulation of STAT1 by PEITC. As part of the second subproject under this proposal that aims at understanding effects of complex diet in epigenetic changes, an animal model study is designed including 2*2*2 factorial with obesity, diet, and induction of cancer. Resistant starch (RS) is not digested in small intestine but is fermented in colon by the microbes. Previous research has shown that RS could reduce calorie intake, lower weight gain, and prevent high-fat diet induced obesity. Obese individuals have greater risk of cancer development. Resistant starch can reduce the development of colon cancer in rat models. However, there is no study that evaluates the effect of resistant starch in obese models with colon cancer and if any epigenetic factor may be involved. The 13 week long experiment is currently underway. This mouse model will be a key tool for studies on diet, chronic diseases and epigenetics and the scientific information from this project will add valuable insight to the future directions in this new field of research. For subproject A, two out of three aims have been initiated/accomplished. For subproject B five out of twenty objectives have been initiated/accomplished in the past year, which was year1. Goals are described in the timeline Table in the original proposal.

Publications

  • 1. Dey, M., Kuhn, P., Ribnicky, D., Premkumar, V., Reuhl, K. and Raskin, I. 2010. Phenethylisothiocyanate, attenuates bowel inflammation in mouse models. BMC Chemical Biology 10:4.
  • 2. Premkumar V, Dey M, Dorn R, and Raskin I. 2010. MyD88-Dependent and Independent pathways of Toll-Like Receptors are engaged in Biological Activity of Triptolide in ligand-stimulated macrophages. BMC Chemical Biology 10:3.
  • 3. Zeng F, Wang W, Wu Y, Dey M, Ye M, Avery MA, Khan IA, Guo DA. 2010. Two prenylated and C-methylated flavonoids from Tripterygium wilfordii. Planta Med.76:1596-1599.
  • 4. Ribnicky D, Dey M, Raskin I. 2010. Anti-inflammatory activity of Barbarea verna seed preparation. US 7,838,045B2.
  • 5. Dey M, Premkumar V, Raskin I. 2010. TLR-pathway is involved in the biological activity of triptolide, the active compound from a botanical clinically shown to alleviate RA symptoms. FASEB J. 24:lb509.