Program Official

Principal Investigator

Robert Stephen
Chapkin
Awardee Organization

Texas A&M Agrilife Research
United States

Fiscal Year
2022
Activity Code
R35
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Molecular basis for dietary chemoprevention

If the healthcare community hopes to head off the impending cancer storm, we need to get more serious about cancer prevention soon. Unfortunately, less than 1.5% of total biomedical research funding is targeted to early detection and prevention of chronic disease. With respect to all human malignancies, 35% are linked directly to diet and an additional 14-20% to obesity. Consistent with these data, cancer risk can be lowered by 36% when humans adhere to healthy dietary principles. Establishing a causal role for cancer dietary chemoprevention approaches that are free of safety problems intrinsic to drugs administered over long periods of time would have a major translational impact in cancer prevention and patient survivorship. Therefore, our overall goal is to better understand the molecular (nuclear and plasma membrane targeted) mechanisms linking intestinal epithelial cell responses to diet-derived natural botanical products, and endogenous (gut microbial) modifiers of colon cancer risk. Our extensive experience in the dietary chemoprevention field has afforded us with a unique mechanistic perspective in this regard. We propose to pursue two novel research themes. Project 1 will assess the combined agonist and antagonistic role of Arylhydrocarbon Receptor (AhR) ligands as determinants in colon stem cell homeostasis and malignant transformation. Our studies to date indicate that AhR ligands have profound short-term effects on stemness, and may be beneficial in terms of malignant transformation. Project 2 is designed to determine whether by altering cell membrane liquid ordered nanoscale assemblies, and therefore protein spatial localization and signaling, that select amphiphilic dietary agents will reduce oncogenic K-Ras signaling leading to reduced tumorigenesis. This strategy is consistent with recent reports from our lab and others that select amphiphilic agents, through direct modulation of the biophysical properties of the plasma membrane, alter oncogenic K- Ras nanoclustering and suppress signal transduction.

Publications

  • Kim E, Ivanov I, Hua J, Lampe JW, Hullar MA, Chapkin RS, Dougherty ER. The Model-Based Study of the Effectiveness of Reporting Lists of Small Feature Sets Using RNA-Seq Data. Cancer informatics. 2017 Jun 12;16:1176935117710530. doi: 10.1177/1176935117710530. eCollection 2017. PMID: 28659712
  • Kim E, Wright GA, Zoh RS, Patil BS, Jayaprakasha GK, Callaway ES, Ivanov I, Turner ND, Chapkin RS. Establishment of a multicomponent dietary bioactive human equivalent dose to delete damaged Lgr5+ stem cells using a mouse colon tumor initiation model. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP). 2019 Sep;28(5):383-389. PMID: 30234553
  • Hou TY, Davidson LA, Kim E, Fan YY, Fuentes NR, Triff K, Chapkin RS. Nutrient-Gene Interaction in Colon Cancer, from the Membrane to Cellular Physiology. Annual review of nutrition. 2016 Jul 17;36:543-70. PMID: 27431370
  • Knight JM, Kim E, Ivanov I, Davidson LA, Goldsby JS, Hullar MA, Randolph TW, Kaz AM, Levy L, Lampe JW, Chapkin RS. Comprehensive site-specific whole genome profiling of stromal and epithelial colonic gene signatures in human sigmoid colon and rectal tissue. Physiological genomics. 2016 Sep 1;48(9):651-9. Epub 2016 Jul 8. PMID: 27401218
  • Triff K, McLean MW, Callaway E, Goldsby J, Ivanov I, Chapkin RS. Dietary fat and fiber interact to uniquely modify global histone post-translational epigenetic programming in a rat colon cancer progression model. International journal of cancer. 2018 Sep 15;143(6):1402-1415. Epub 2018 May 10. PMID: 29659013
  • Fan YY, Davidson LA, Chapkin RS. Murine Colonic Organoid Culture System and Downstream Assay Applications. Methods in molecular biology (Clifton, N.J.). 2019;1576:171-181. PMID: 27539462
  • Levental KR, Malmberg E, Symons JL, Fan YY, Chapkin RS, Ernst R, Levental I. Lipidomic and biophysical homeostasis of mammalian membranes counteracts dietary lipid perturbations to maintain cellular fitness. Nature communications. 2020 Mar 12;11(1):1339. PMID: 32165635
  • Safe S, Kothari J, Hailemariam A, Upadhyay S, Davidson LA, Chapkin RS. Health Benefits of Coffee Consumption for Cancer and Other Diseases and Mechanisms of Action. International journal of molecular sciences. 2023 Jan 31;24. (3). PMID: 36769029
  • Roitershtein A, Rastegar R, Chapkin RS, Ivanov I. Extinction scenarios in evolutionary processes: a multinomial Wright-Fisher approach. Journal of mathematical biology. 2023 Sep 26;87(4):63. PMID: 37751048
  • Han H, Davidson LA, Fan YY, Goldsby JS, Yoon G, Jin UH, Wright GA, Landrock KK, Weeks BR, Wright RC, Allred CD, Jayaraman A, Ivanov I, Roper J, Safe SH, Chapkin RS. Loss of aryl hydrocarbon receptor potentiates FoxM1 signaling to enhance self-renewal of colonic stem and progenitor cells. The EMBO journal. 2020 Oct 1;39(19):e104319. Epub 2020 Aug 10. PMID: 32915464
  • Kim E, Davidson LA, Zoh RS, Hensel ME, Salinas ML, Patil BS, Jayaprakasha GK, Callaway ES, Allred CD, Turner ND, Weeks BR, Chapkin RS. Rapidly cycling Lgr5+ stem cells are exquisitely sensitive to extrinsic dietary factors that modulate colon cancer risk. Cell death & disease. 2016 Nov 10;7(11):e2460. PMID: 27831561
  • Athinarayanan S, Fan YY, Wang X, Callaway E, Cai D, Chalasani N, Chapkin RS, Liu W. Fatty Acid Desaturase 1 Influences Hepatic Lipid Homeostasis by Modulating the PPARα-FGF21 Axis. Hepatology communications. 2020 Dec 25;5(3):461-477. doi: 10.1002/hep4.1629. eCollection 2021 Mar. PMID: 33681679
  • Kumar R, Herold JL, Schady D, Davis J, Kopetz S, Martinez-Moczygemba M, Murray BE, Han F, Li Y, Callaway E, Chapkin RS, Dashwood WM, Dashwood RH, Berry T, Mackenzie C, Xu Y. Streptococcus gallolyticus subsp. gallolyticus promotes colorectal tumor development. PLoS pathogens. 2017 Jul 13;13(7):e1006440. doi: 10.1371/journal.ppat.1006440. eCollection 2017 Jul. PMID: 28704539
  • Yang F, DeLuca JAA, Menon R, Garcia-Vilarato E, Callaway E, Landrock KK, Lee K, Safe SH, Chapkin RS, Allred CD, Jayaraman A. Effect of diet and intestinal AhR expression on fecal microbiome and metabolomic profiles. Microbial cell factories. 2020 Nov 30;19(1):219. PMID: 33256731
  • Yang Y, Li G, Zhong Y, Xu Q, Lin YT, Roman-Vicharra C, Chapkin RS, Cai JJ. scTenifoldXct: A semi-supervised method for predicting cell-cell interactions and mapping cellular communication graphs. Cell systems. 2023 Apr 19;14(4):302-311.e4. Epub 2023 Feb 13. PMID: 36787742
  • Petrov ME, Jiao N, Panchanathan SS, Reifsnider E, Coonrod DV, Liu L, Krajmalnik-Brown R, Gu H, Davidson LA, Chapkin RS, Whisner CM. Protocol of the Snuggle Bug/Acurrucadito Study: a longitudinal study investigating the influences of sleep-wake patterns and gut microbiome development in infancy on rapid weight gain, an early risk factor for obesity. BMC pediatrics. 2021 Aug 31;21(1):374. PMID: 34465311
  • Fuentes NR, Mlih M, Wang X, Webster G, Cortes-Acosta S, Salinas ML, Corbin IR, Karpac J, Chapkin RS. Membrane therapy using DHA suppresses epidermal growth factor receptor signaling by disrupting nanocluster formation. Journal of lipid research. 2021;62:100026. Epub 2021 Jan 27. PMID: 33515553
  • Jin UH, Park H, Li X, Davidson LA, Allred C, Patil B, Jayaprakasha G, Orr AA, Mao L, Chapkin RS, Jayaraman A, Tamamis P, Safe S. Structure-Dependent Modulation of Aryl Hydrocarbon Receptor-Mediated Activities by Flavonoids. Toxicological sciences : an official journal of the Society of Toxicology. 2018 Jul 1;164(1):205-217. PMID: 29584932
  • Madison CA, Hillbrick L, Kuempel J, Albrecht GL, Landrock KK, Safe S, Chapkin RS, Eitan S. Intestinal epithelium aryl hydrocarbon receptor is involved in stress sensitivity and maintaining depressive symptoms. Behavioural brain research. 2023 Feb 25;440:114256. Epub 2022 Dec 14. PMID: 36528169
  • Debler RA, Madison CA, Hillbrick L, Gallegos P, Safe S, Chapkin RS, Eitan S. Selective aryl hydrocarbon receptor modulators can act as antidepressants in obese female mice. Journal of affective disorders. 2023 Jul 15;333:409-419. Epub 2023 Apr 19. PMID: 37084978
  • Chapkin RS, Davidson LA, Park H, Jin UH, Fan YY, Cheng Y, Hensel ME, Landrock KK, Allred C, Menon R, Klemashevich C, Jayaraman A, Safe S. Role of the Aryl Hydrocarbon Receptor (AhR) in Mediating the Effects of Coffee in the Colon. Molecular nutrition & food research. 2021 Oct;65(20):e2100539. Epub 2021 Aug 31. PMID: 34406707
  • Erazo-Oliveras A, Muñoz-Vega M, Mlih M, Thiriveedi V, Salinas ML, Rivera-Rodríguez JM, Kim E, Wright RC, Wang X, Landrock KK, Goldsby JS, Mullens DA, Roper J, Karpac J, Chapkin RS. Mutant APC reshapes Wnt signaling plasma membrane nanodomains by altering cholesterol levels via oncogenic β-catenin. Nature communications. 2023 Jul 19;14(1):4342. PMID: 37468468
  • Wei Q, Lee JH, Wang H, Bongmba OYN, Wu CS, Pradhan G, Sun Z, Chew L, Bajaj M, Chan L, Chapkin RS, Chen MH, Sun Y. Adiponectin is required for maintaining normal body temperature in a cold environment. BMC physiology. 2017 Oct 23;17(1):8. PMID: 29058611
  • Chapkin RS, Navarro SL, Hullar MAJ, Lampe JW. Diet and Gut Microbes Act Coordinately to Enhance Programmed Cell Death and Reduce Colorectal Cancer Risk. Digestive diseases and sciences. 2020 Mar;65(3):840-851. PMID: 32006211
  • Dry Eye Assessment and Management Study Research Group, Asbell PA, Maguire MG, Pistilli M, Ying GS, Szczotka-Flynn LB, Hardten DR, Lin MC, Shtein RM, Hom MM, Quintana M, Zermeno A, Pendleton R, McCluskey D, Amador D, Corona I, Wechter V, Childs C, Do U, Lerma M, Li W, Young Z, Yuen T, Dubiner H, Ambrosia H, Bowser M, Chen P, Dubiner H, Fuller C, New K, Nguyen TV, Seville E, Strait D, Wang C, Williams S, Weber R, Sutphin J, Bishara M, Bryan A, Ertel A, Green K, Pantoja G, Small A, Williamson C, Greiner J, DiPronio E, Lindsay M, McPherson A, Oliver P, Wu R, Dana R, Abud T, Adams L, Arnofsky M, Candlish J, Chilakamarri P, Ciolino J, Crandall N, Di Zazzo A, Fernandes M, Jafri M, Johnson B, Kheirkhah A, Kiebdaj S, Mullins A, Nova M, Satitpitakul V, Shao C, Suri K, Tadla V, Ujwala S, Yin J, Yu M, Hood C, Hussain M, Manno E, Rozek L, Baker K, Belsaas A, Berg E, Blakstad A, DauSchmidt K, Fallenstein L, Fahmy AM, Fahmy MM, Georges G, Harter DE, Hauswirth SG, Johnson M, Meshalkin E, Pelzer R, Tisdale J, Wick JC, Tauber J, Hefter M, Silverstein S, Bentley C, Dominguez E, Kleinsasser K, Barry B, Kuklinski E, Amir A, Chen N, Oydanich M, Spahiu V, Vo A, Weinstein M, Vaz T, Hindman H, Aleese R, Czubinski A, Gagarinas G, McDowell P, O’Gara G, Steinmetz K, Bunya V, Bezzerides M, Caggiano D, Drossner S, Dupont J, Keiser M, Massaro M, Orlin S, O’Sullivan R, Christensen M, Adkins H, Brafford R, Ervin C, Grant R, Newman C, Shettle L, Shettle D, Cohen S, Rodman D, Caster T, Gupta P, Raghupathy S, Sayegh R, Shen J, Drutz N, Joyner L, Mathis M, Menghini M, Robinson C, Goldberg D, Jenkins L, Rodriguez B, Jones JP, Thompson N, Wolstan B, Jones M, Lemaster A, Ransom-Chaney J, Rudy W, Hamrah P, Commodore M, Iyore C, Lazarev L, Mullen L, Pondelis N, Satsuma C, Jain S, Cowen P, Hallak J, Mun C, Toh R, Singh I, Lightfield P, Lowery E, Ornelas S, Sanka RK, Saunders B, Mulqueeny SP, Pohlmeier M, Aune C, Gabriel H, Walker KM, Newsome J, Centers R, Farkouh M, Kim-Schulze S, Chapkin R, Greco G, Simopoulos A, Lashley I, Dentone P, Gadaria-Rathod N, Massingale M, Antonova N, Brightwell-Arnold M, Farrar J, Harkins S, Huang J, McWilliams K, Peskin E, Ryan S, Smolen H, Whearry C, Yu Y, Wei Y, Roy N, Epstein S, Rockwell K Jr, Moser A, Jones RO, Daniel E, Martin ER, Ostroff CP, Smith E, Kadakia PA, Redford M, McWilliams K, Wisniewski S, Brenna T, Christen WG Jr, Huang JF, McCarthy CS, Mayne ST, Palta M, Schein OD, Chuang J, Marchan M, Hao T, Heisler C, Hu C, Throop C, Moolchandani V. n-3 Fatty Acid Supplementation for the Treatment of Dry Eye Disease. The New England journal of medicine. 2018 May 3;378(18):1681-1690. Epub 2018 Apr 13. PMID: 29652551
  • Mullens DA, Ivanov I, Hullar MAJ, Randolph TW, Lampe JW, Chapkin RS. Personalized Nutrition Using Microbial Metabolite Phenotype to Stratify Participants and Non-Invasive Host Exfoliomics Reveal the Effects of Flaxseed Lignan Supplementation in a Placebo-Controlled Crossover Trial. Nutrients. 2022 Jun 8;14. (12). PMID: 35745107
  • Whitfield-Cargile CM, Cohen ND, He K, Ivanov I, Goldsby JS, Chamoun-Emanuelli A, Weeks BR, Davidson LA, Chapkin RS. The non-invasive exfoliated transcriptome (exfoliome) reflects the tissue-level transcriptome in a mouse model of NSAID enteropathy. Scientific reports. 2017 Oct 31;7(1):14687. PMID: 29089621
  • Navarro SL, Neuhouser ML, Cheng TD, Tinker LF, Shikany JM, Snetselaar L, Martinez JA, Kato I, Beresford SA, Chapkin RS, Lampe JW. The Interaction between Dietary Fiber and Fat and Risk of Colorectal Cancer in the Women's Health Initiative. Nutrients. 2016 Nov 30;8. (12). PMID: 27916893
  • Kim SM, Neuendorff N, Chapkin RS, Earnest DJ. Role of Inflammatory Signaling in the Differential Effects of Saturated and Poly-unsaturated Fatty Acids on Peripheral Circadian Clocks. EBioMedicine. 2016 May;7:100-11. Epub 2016 Mar 31. PMID: 27322464
  • Safe S, Jin UH, Park H, Chapkin RS, Jayaraman A. Aryl Hydrocarbon Receptor (AHR) Ligands as Selective AHR Modulators (SAhRMs). International journal of molecular sciences. 2020 Sep 11;21. (18). PMID: 32932962
  • Han H, Davidson LA, Hensel M, Yoon G, Landrock K, Allred C, Jayaraman A, Ivanov I, Safe SH, Chapkin RS. Loss of Aryl Hydrocarbon Receptor Promotes Colon Tumorigenesis in ApcS580/+; KrasG12D/+ Mice. Molecular cancer research : MCR. 2021 May;19(5):771-783. Epub 2021 Jan 25. PMID: 33495399
  • Seidel DV, Azcárate-Peril MA, Chapkin RS, Turner ND. Shaping functional gut microbiota using dietary bioactives to reduce colon cancer risk. Seminars in cancer biology. 2017 Oct;46:191-204. Epub 2017 Jul 1. PMID: 28676459
  • Park H, Jin UH, Karki K, Jayaraman A, Allred C, Michelhaugh SK, Mittal S, Chapkin RS, Safe S. Dopamine is an aryl hydrocarbon receptor agonist. The Biochemical journal. 2020 Oct 16;477(19):3899-3910. PMID: 32905582
  • Zhao D, Farnell MB, Kogut MH, Genovese KJ, Chapkin RS, Davidson LA, Berghman LR, Farnell YZ. From crypts to enteroids: establishment and characterization of avian intestinal organoids. Poultry science. 2022 Mar;101(3):101642. Epub 2021 Dec 4. PMID: 35016046
  • Park H, Jin UH, Martin G, Chapkin RS, Davidson LA, Lee K, Jayaraman A, Safe S. Structure-activity relationships among mono- and dihydroxy flavones as aryl hydrocarbon receptor (AhR) agonists or antagonists in CACO2 cells. Chemico-biological interactions. 2022 Sep 25;365:110067. Epub 2022 Jul 31. PMID: 35917944
  • Han H, Safe S, Jayaraman A, Chapkin RS. Diet-Host-Microbiota Interactions Shape Aryl Hydrocarbon Receptor Ligand Production to Modulate Intestinal Homeostasis. Annual review of nutrition. 2021 Oct 11;41:455-478. PMID: 34633858
  • Fuentes NR, Salinas ML, Wang X, Fan YY, Chapkin RS. Assessment of Plasma Membrane Fatty Acid Composition and Fluidity Using Imaging Flow Cytometry. Methods in molecular biology (Clifton, N.J.). 2021;2262:251-258. PMID: 33977481
  • Fan YY, Callaway E, M Monk J, S Goldsby J, Yang P, Vincent L, S Chapkin R. A New Model to Study the Role of Arachidonic Acid in Colon Cancer Pathophysiology. Cancer prevention research (Philadelphia, Pa.). 2016 Sep;9(9):750-7. Epub 2016 Jun 23. PMID: 27339171
  • Ma X, Wang X, Xu L, Shi H, Yang H, Landrock KK, Sharma VK, Chapkin RS. Fate and distribution of orally-ingested CeO2-nanoparticles based on a mouse model: Implication for human health. Soil & Environmental Health. 2023 Jun;1. (2). Epub 2023 Apr 17. PMID: 37830053
  • Kim SM, Neuendorff N, Alaniz RC, Sun Y, Chapkin RS, Earnest DJ. Shift work cycle-induced alterations of circadian rhythms potentiate the effects of high-fat diet on inflammation and metabolism. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2018 Jun;32(6):3085-3095. Epub 2018 Feb 5. PMID: 29405095
  • Osorio D, Zhong Y, Li G, Xu Q, Yang Y, Tian Y, Chapkin RS, Huang JZ, Cai JJ. scTenifoldKnk: An efficient virtual knockout tool for gene function predictions via single-cell gene regulatory network perturbation. Patterns (New York, N.Y.). 2022 Feb 1;3(3):100434. doi: 10.1016/j.patter.2022.100434. eCollection 2022 Mar 11. PMID: 35510185
  • Yang Y, Li G, Zhong Y, Xu Q, Chen BJ, Lin YT, Chapkin RS, Cai JJ. Gene knockout inference with variational graph autoencoder learning single-cell gene regulatory networks. Nucleic acids research. 2023 Jul 21;51(13):6578-6592. PMID: 37246643
  • Fuentes NR, Salinas ML, Kim E, Chapkin RS. Emerging role of chemoprotective agents in the dynamic shaping of plasma membrane organization. Biochimica et biophysica acta. Biomembranes. 2017 Sep;1859(9 Pt B):1668-1678. Epub 2017 Mar 22. PMID: 28342710
  • Fan YY, Fuentes NR, Hou TY, Barhoumi R, Li XC, Deutz NEP, Engelen MPKJ, McMurray DN, Chapkin RS. Remodelling of primary human CD4+ T cell plasma membrane order by n-3 PUFA. The British journal of nutrition. 2018 Jan;119(2):163-175. Epub 2017 Dec 18. PMID: 29249211
  • Galbán S, Al-Holou WN, Wang H, Welton AR, Heist K, Hu XK, Verhaak RG, Zhu Y, Espinoza C, Chenevert TL, Hoff BA, Galbán CJ, Ross BD. MRI-Guided Stereotactic Biopsy of Murine GBM for Spatiotemporal Molecular Genomic Assessment. Tomography (Ann Arbor, Mich.). 2017 Mar;3(1):9-15. PMID: 28553660
  • Park H, Jin UH, Orr AA, Echegaray SP, Davidson LA, Allred CD, Chapkin RS, Jayaraman A, Lee K, Tamamis P, Safe S. Isoflavones as Ah Receptor Agonists in Colon-Derived Cell Lines: Structure-Activity Relationships. Chemical research in toxicology. 2019 Nov 18;32(11):2353-2364. Epub 2019 Oct 29. PMID: 31621310
  • Han H, Davidson LA, Fan YY, Landrock KK, Jayaraman A, Safe SH, Chapkin RS. Loss of aryl hydrocarbon receptor suppresses the response of colonic epithelial cells to IL22 signaling by upregulating SOCS3. American journal of physiology. Gastrointestinal and liver physiology. 2022 Jan 1;322(1):G93-G106. Epub 2021 Nov 10. PMID: 34755534
  • Fuentes NR, Kim E, Fan YY, Chapkin RS. Omega-3 fatty acids, membrane remodeling and cancer prevention. Molecular aspects of medicine. 2018 Dec;64:79-91. Epub 2018 Apr 12. PMID: 29627343
  • Erazo-Oliveras A, Fuentes NR, Wright RC, Chapkin RS. Functional link between plasma membrane spatiotemporal dynamics, cancer biology, and dietary membrane-altering agents. Cancer metastasis reviews. 2018 Sep;37(2-3):519-544. PMID: 29860560
  • Torres-Adorno AM, Vitrac H, Qi Y, Tan L, Levental KR, Fan YY, Yang P, Chapkin RS, Eckhardt BL, Ueno NT. Eicosapentaenoic acid in combination with EPHA2 inhibition shows efficacy in preclinical models of triple-negative breast cancer by disrupting cellular cholesterol efflux. Oncogene. 2019 Mar;38(12):2135-2150. Epub 2018 Nov 20. PMID: 30459358
  • Safe S, Han H, Goldsby J, Mohankumar K, Chapkin RS. Aryl Hydrocarbon Receptor (AhR) Ligands as Selective AhR Modulators: Genomic Studies. Current opinion in toxicology. 2018 Oct-Dec;11-12:10-20. Epub 2018 Nov 22. PMID: 31453421
  • Fuentes NR, Mlih M, Barhoumi R, Fan YY, Hardin P, Steele TJ, Behmer S, Prior IA, Karpac J, Chapkin RS. Long-Chain n-3 Fatty Acids Attenuate Oncogenic KRas-Driven Proliferation by Altering Plasma Membrane Nanoscale Proteolipid Composition. Cancer research. 2018 Jul 15;78(14):3899-3912. Epub 2018 May 16. PMID: 29769200
  • Cheng Y, Jin UH, Davidson LA, Chapkin RS, Jayaraman A, Tamamis P, Orr A, Allred C, Denison MS, Soshilov A, Weaver E, Safe S. Editor's Highlight: Microbial-Derived 1,4-Dihydroxy-2-naphthoic Acid and Related Compounds as Aryl Hydrocarbon Receptor Agonists/Antagonists: Structure-Activity Relationships and Receptor Modeling. Toxicological sciences : an official journal of the Society of Toxicology. 2017 Feb;155(2):458-473. Epub 2016 Nov 11. PMID: 27837168
  • Erazo-Oliveras A, Muñoz-Vega M, Salinas ML, Wang X, Chapkin RS. Dysregulation of cellular membrane homeostasis as a crucial modulator of cancer risk. The FEBS journal. 2022 Oct 25. Epub 2022 Oct 25. PMID: 36282100
  • He K, Donovan SM, Ivanov IV, Goldsby JS, Davidson LA, Chapkin RS. Assessing the Multivariate Relationship between the Human Infant Intestinal Exfoliated Cell Transcriptome (Exfoliome) and Microbiome in Response to Diet. Microorganisms. 2020 Dec 18;8. (12). PMID: 33353204
  • Navarro SL, Levy L, Curtis KR, Elkon I, Kahsai OJ, Ammar HS, Randolph TW, Hong NN, Carnevale Neto F, Raftery D, Chapkin RS, Lampe JW, Hullar MAJ. Effect of a Flaxseed Lignan Intervention on Circulating Bile Acids in a Placebo-Controlled Randomized, Crossover Trial. Nutrients. 2020 Jun 19;12. (6). PMID: 32575611
  • Schoeller A, Karki K, Jayaraman A, Chapkin RS, Safe S. Short chain fatty acids exhibit selective estrogen receptor downregulator (SERD) activity in breast cancer. American journal of cancer research. 2022 Jul 15;12(7):3422-3436. eCollection 2022. PMID: 35968335
  • Madison CA, Kuempel J, Albrecht GL, Hillbrick L, Jayaraman A, Safe S, Chapkin RS, Eitan S. 3,3'-Diindolylmethane and 1,4-dihydroxy-2-naphthoic acid prevent chronic mild stress induced depressive-like behaviors in female mice. Journal of affective disorders. 2022 Jul 15;309:201-210. Epub 2022 Apr 21. PMID: 35461819
  • Yoon G, Davidson LA, Goldsby JS, Mullens DA, Ivanov I, Donovan SM, Chapkin RS. Exfoliated epithelial cell transcriptome reflects both small and large intestinal cell signatures in piglets. American journal of physiology. Gastrointestinal and liver physiology. 2021 Jul 1;321(1):G41-G51. Epub 2021 May 5. PMID: 33949197
  • Yang Y, Osorio D, Davidson LA, Han H, Mullens DA, Jayaraman A, Safe S, Ivanov I, Cai JJ, Chapkin RS. Single-cell RNA Sequencing Reveals How the Aryl Hydrocarbon Receptor Shapes Cellular Differentiation Potency in the Mouse Colon. Cancer prevention research (Philadelphia, Pa.). 2022 Jan;15(1):17-28. Epub 2021 Nov 22. PMID: 34815312
  • Garcia-Villatoro EL, DeLuca JAA, Callaway ES, Allred KF, Davidson LA, Hensel ME, Menon R, Ivanov I, Safe SH, Jayaraman A, Chapkin RS, Allred CD. Effects of high-fat diet and intestinal aryl hydrocarbon receptor deletion on colon carcinogenesis. American journal of physiology. Gastrointestinal and liver physiology. 2020 Mar 1;318(3):G451-G463. Epub 2020 Jan 6. PMID: 31905023
  • Mohankumar K, Wright G, Kumaravel S, Shrestha R, Zhang L, Abdelrahim M, Chapkin RS, Safe S. Bis-indole-derived NR4A1 antagonists inhibit colon tumor and splenic growth and T-cell exhaustion. Cancer immunology, immunotherapy : CII. 2023 Dec;72(12):3985-3999. Epub 2023 Oct 17. PMID: 37847301
  • Safe S, Jayaraman A, Chapkin RS. Ah receptor ligands and their impacts on gut resilience: structure-activity effects. Critical reviews in toxicology. 2020 Jul;50(6):463-473. Epub 2020 Jun 29. PMID: 32597352
  • Han H, Jayaraman A, Safe S, Chapkin RS. Targeting the aryl hydrocarbon receptor in stem cells to improve the use of food as medicine. Current stem cell reports. 2020 Dec;6(4):109-118. Epub 2021 Jan 5. PMID: 34395177
  • Lampe JW, Kim E, Levy L, Davidson LA, Goldsby JS, Miles FL, Navarro SL, Randolph TW, Zhao N, Ivanov I, Kaz AM, Damman C, Hockenbery DM, Hullar MAJ, Chapkin RS. Colonic mucosal and exfoliome transcriptomic profiling and fecal microbiome response to a flaxseed lignan extract intervention in humans. The American journal of clinical nutrition. 2019 Aug 1;110(2):377-390. PMID: 31175806
  • Zhou F, He K, Li Q, Chapkin RS, Ni Y. Bayesian biclustering for microbial metagenomic sequencing data via multinomial matrix factorization. Biostatistics (Oxford, England). 2022 Jul 18;23(3):891-909. PMID: 33634824
  • Jin UH, Cheng Y, Park H, Davidson LA, Callaway ES, Chapkin RS, Jayaraman A, Asante A, Allred C, Weaver EA, Safe S. Short Chain Fatty Acids Enhance Aryl Hydrocarbon (Ah) Responsiveness in Mouse Colonocytes and Caco-2 Human Colon Cancer Cells. Scientific reports. 2017 Aug 31;7(1):10163. PMID: 28860561
  • Zhou F, He K, Cai JJ, Davidson LA, Chapkin RS, Ni Y. A Unified Bayesian Framework for Bi-overlapping-Clustering Multi-omics Data via Sparse Matrix Factorization. Statistics in biosciences. 2023 Dec;15(3):669-691. Epub 2022 Jul 8. PMID: 38179127
  • DeClercq VC, Goldsby JS, McMurray DN, Chapkin RS. Distinct Adipose Depots from Mice Differentially Respond to a High-Fat, High-Salt Diet. The Journal of nutrition. 2016 Jun;146(6):1189-96. Epub 2016 May 4. PMID: 27146921
  • Fan YY, Vaz FM, Chapkin RS. Dietary fat and fiber interactively modulate apoptosis and mitochondrial bioenergetic profiles in mouse colon in a site-specific manner. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP). 2017 Jul;26(4):301-308. PMID: 27167153
  • Chapkin RS. Robert Chapkin on Relationships Between the Gut Microbiome, Diet, and Colorectal Cancer. Oncology (Williston Park, N.Y.). 2018 May 15;32(5):248-9. PMID: 29847856
  • Armstrong CM, Allred KF, Weeks BR, Chapkin RS, Allred CD. Estradiol Has Differential Effects on Acute Colonic Inflammation in the Presence and Absence of Estrogen Receptor β Expression. Digestive diseases and sciences. 2017 Aug;62(8):1977-1984. Epub 2017 Jun 1. PMID: 28573506
  • Salinas ML, Fuentes NR, Choate R, Wright RC, McMurray DN, Chapkin RS. AdipoRon Attenuates Wnt Signaling by Reducing Cholesterol-Dependent Plasma Membrane Rigidity. Biophysical journal. 2020 Feb 25;118(4):885-897. Epub 2019 Sep 16. PMID: 31630812
  • Whitfield-Cargile CM, Cohen ND, Chapkin RS, Weeks BR, Davidson LA, Goldsby JS, Hunt CL, Steinmeyer SH, Menon R, Suchodolski JS, Jayaraman A, Alaniz RC. The microbiota-derived metabolite indole decreases mucosal inflammation and injury in a murine model of NSAID enteropathy. Gut microbes. 2016 May 3;7(3):246-61. Epub 2016 Mar 23. PMID: 27007819
  • Knight JM, Ivanov I, Triff K, Chapkin RS, Dougherty ER. Detecting Multivariate Gene Interactions in RNA-Seq Data Using Optimal Bayesian Classification. IEEE/ACM transactions on computational biology and bioinformatics. 2018 Mar-Apr;15(2):484-493. Epub 2015 Oct 1. PMID: 26441451
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