Collins Laboratory

Background

Dr. Collins has broad training and expertise in physiology, molecular biology, genetics, and nutrition, and he has been involved in biomedical research for over 25 years. His formal post-baccalaureate educational training includes master’s studies in molecular biology, doctoral studies in molecular physiology at Vanderbilt University and post-doctoral work in transport physiology at the University of Arizona. Dr. Collins’ research previously focused on molecular aspects of intestinal sodium and phosphate absorption, but more recently, over the past 15 years or so, his research efforts have shifted to the investigation of iron metabolism and how this is influenced by copper, with a particular focus on mechanisms of intestinal transport of these essential nutrients. This is an important area of research, as body iron homeostasis, unlike most other nutrients, is controlled principally at the level of intestinal absorption since no active excretory systems exist in humans or other mammals. Studies over the past 10+ years have identified copper-dependent aspects of intestinal iron transport. Ongoing studies relate to iron supplementation and how this negatively impacts copper homeostasis (e.g. in pregnancy), and to development of therapeutic approaches to modulate intestinal iron absorption in various disease states (e.g., hereditary hemochromatosis and β-thalassemia). Model systems include wild-type and genetically engineered (knockout) laboratory mice and rats, as well as surgical human intestinal tissues. Commonly used experimental techniques include molecular biology methods such as qRT-PCR and western blotting, radiotracer iron and copper absorption studies (by oral, intragastric gavage), quantification of iron in blood and tissues (using various methods including ICP-MS), a variety of physiological techniques, and Ussing chamber analysis to determine mechanistic (and kinetic) aspects of nutrient absorption. The Collins laboratory is staffed predominantly by Nutritional Sciences doctoral students, several of whom have graduated over the past few years. Funding for his work has been competitively awarded by the National Institutes of Health (NIDDK, ODS) for the past 15+ years.  

Current Grant Support (role)

  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (PI)
  • Office of Dietary Supplements (ODS) (PI)
  • National Institute of General Medical Sciences (NIGMS) (Co-I)
  • United States Department of Agriculture (USDA) (Co-I)

Professional Affiliations

  • International Society for Trace Element Research in Humans (ISTERH) [2007]
  • East Coast Iron Club (2005; Chair, 2010-2013)
  • International BioIron Society (2004)
  • American Physiological Society (1999)
  • American Gastroenterological Association (1998) 

Advisory Group Service

Chair, Scientific Merit Review Board for Gastroenterology (VA-GAST), Department of Veterans Affairs, Veterans Health Administration; Dec. 2016-June 2018. 

Standing Member, Scientific Merit Review Board for Gastroenterology (VA-GAST), Department of Veterans Affairs, Veterans Health Administration; May 2013-June 2016.

 Standing Member, Clinical and Integrative Molecular Gastroenterology study section, National Institute for Diabetes and Digestive Kidney Diseases (NIDDK); July 2012-June 2018. 

Editorial Board Member

  • American Journal of Physiology: Gastrointestinal and Liver Physiology; June 2015-present
  • Journal of Biological Chemistry; July 2014-present
  • PLOS One; May 2013-present
  • Journal of Nutrition; May 2010-present

Editorships

J. F. Collins, Editor: Molecular, Genetic, and Nutritional Aspects of Major and Trace Minerals (Elsevier Inc.) Contains 44 chapters on the essential minerals. ISBN: 978-0-12-802168-2. (2017).

Faculty Links

 

Recent Peer-Reviewed Papers (>90 total)

  1. Wang, X., Garrick, M.D., Collins, J.F. (2019) Animal Models of Normal and Disturbed Iron and Copper Homeostasis. Invited Critical Review. J. Nutr. In Press
  2. Wang, X., Zhang, M. Flores, S.R.L., Woloshun, R.R., Wang, Yang, C., L. Xiang, P., Xu, X., Garrick, M.D., Vidyasagar, S., Merlin, D., Collins, J.F. (2019) Oral Gavage of Ginger Nanoparticle-derived Lipid Vectors Loaded with Dmt1 siRNA Mitigates Iron Loading in Murine Hereditary Hemochromatosis. Mol. Ther. 27(3):493-506.
  3. Doguer, C., Ha, J-H., Collins, J.F. (2018) Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver. Comp. Physiol. 14;8(4):1433-1461, 2018.
  4. Wang, X., Flores, S.R.L., Ha, J-H., Doguer, C., Woloshun, R.R, Xiang, P., Grosche, A., Vidyasagar, S., Collins, J.F. (2018) Intestinal Divalent Metal-ion Transporter 1 (DMT1) is Essential for Optimal Assimilation of Dietary Copper in Male and Female Mice With Iron-Deficiency Anemia. J. Nutr. 148(8):1244-1252, 2018.
  5. Wang, T., Xiang, P., Ha, J-H., Wang, X., Doguer, C., Flores, S.R.L., Kang, Y.J., Collins, J.F. (2018) Copper supplementation reverses dietary iron overload-induced pathologies in mice. J. Nutr. Biochem. 59:56-63, 2018.
  6. Ha, J-H, Doguer, C., Flores, S.R.L., Wang, T., Collins, J.F. (2018) Progressive Increases in Dietary Iron are Associated with the Emergence of Pathologic Disturbances of Copper Homeostasis in Growing Rats. J. Nutr. 148(3): 373-378.
  7. Collins, J.F. (2018) Ferroxidases and Mammalian Iron Homeostasis: Novel Insight into a Physiological Phenomenon First Described More Than Half a Century Ago. Editorial Comment. Cell. Mol. Gastroenterol. Hepatol. 6(4):470-471.
  8. Doguer, C., Ha, J-H, Gulec, S., Vuple, C.D., Anderson, G.J., Collins, J.F. (2017) Intestinal Hephaestin Potentiates Iron Absorption In Weanling, Adult and Pregnant Mice Under Physiological Conditions. Blood Adv. 1:1335-1346.
  9. Ha, J-H., Doguer, C., Collins, J.F. (2017) Consumption of a High-Iron Diet Disrupts Homeostatic Regulation of Intestinal Copper Absorption in Adolescent Mice. Am. J. Physiol. GIL Physiol. 313: G353-G360.
  10. Zhang, M., Wang, X., Han, M.K., Collins, J.F., Merlin, D. (2017) Oral administration of ginger-derived nanolipids loaded with siRNA as a novel approach for efficient siRNA drug delivery to treat ulcerative colitis. Nanomedicine (Lond). 12(16): 1927-1943.
  11. Ha, J-H., Doguer, C., Wang, X., Flores, S.R., Collins, J.F. (2016) High-iron consumption impairs growth and causes copper-deficiency anemia in weanling Sprague-Dawley rats. PLoS One. 11(8):e0161033.
  12. Ha, J-H., Doguer, C. Collins, J.F. (2016) Knockdown of copper-transporting ATPase 1 (Atp7a) impairs iron flux in fully-differentiated rat (IEC-6) and human (Caco-2) intestinal epithelial cells. Metallomics. 8(9):963-972.
  13. Zhang, M., Collins, J.F., Merlin, D. (2016) Do ginger-derived nanoparticles represent an attractive treatment strategy for inflammatory bowel diseases? Nanomedicine (Lond). 11(23)3035-3037.
  14. Collins, J.F. (2015) Long noncoding RNAs and hepatocellular carcinoma. Editorial Comment. Gastroenterology. 148(2): 291-94.
  15. Gulec, S., Anderson, G.J., Collins, J.F. (2014) Mechanistic aspects of intestinal iron transport.  Am. J. Physiol. GIL Physiol. 307(4): G397-409.
  16. Gulec, S., Collins, J.F. (2014) Molecular mediators governing iron-copper interactions. Ann. Rev. Nutr. 34: 95-116.
  17. Gulec, S., Collins, J.F. (2014) Silencing the Menkes copper transporting ATPase (Atp7a) gene in rat intestinal epithelial cells increases iron flux via transcriptional induction of ferroportin 1 (Fpn1). J. Nutr. 144(2): 12-9.
  18. Gulec, S., and Collins, J.F.  (2014) Silencing of the Menkes copper-transporting ATPase (Atp7a) gene increases cyclin D1 protein expression and impairs proliferation of rat intestinal epithelial (IEC-6) cells. J. Trace. Elem. Med. Biol. 28(4): 459-64.
  19. Jiang, L., Garrick, M.D., Garrick, L.M. Zhao, L., Collins, J.F. (2013) Divalent metal transporter 1 (Dmt1) mediates copper transport in the duodenum of iron-deficient rats and when overexpressed in iron-deprived HEK-293 cells. J. Nutr. 143(12):1927-33.
  20. Xie, L., Collins, J.F. (2013) Transcription factors Sp1 and Hif2α mediate induction of the copper-transporting ATPase (Atp7a) gene in intestinal epithelial cells during hypoxia. J. Biol. Chem. 288(33):23943-52.
  21. Gulec, S., Collins, J.F. (2013) Investigation of iron metabolism in mice expressing a mutant Menkes copper transporting ATPase (Atp7a) protein with diminished activity (Brindled; MoBr/y).  PLOS One. 11;8(6):e66010.
  22. Xie, L., Collins, J.F. (2012) Copper stabilizes the Menkes copper-transporting ATPase (Atp7a) protein in rat intestinal epithelial cells. Am. J. Physiol. Cell Physiol., 304(3):C257-62
  23. Lu, Y., Kim, C., Collins J.F. (2012) Multiple Menkes copper ATPase (Atp7a) transcript and protein variants are induced by iron deficiency in rat duodenal enterocytes.  J. Trace Elem. Biol. Med. 26(2-3):109-14
  24. Ranganathan, P.N., Lu, Y., Fuqua, B.K., Collins, J.F. (2012) Discovery of a cytosolic/soluble ferroxidase in rodent enterocytes. Proc. Natl. Acad. Sci. USA. 109(9):3564-9.
  25. Ranganathan, P.N., Lu, Y., Fuqua, B.K., Collins, J.F. (2012) Immunoreactive Hephaestin and ferroxidase activity are present in the cytosolic fraction of rat enterocytes. Biometals. 25(4):687-95.
  26. Klevay, L., Collins, J.F. (2011) Copper. Adv. Nutr. 2(6):520-22.
  27. Jiang, L, Ranganathan, P.N., Lu, Y., Kim, C., Collins J.F. (2011) Exploration of the Copper Related Compensatory Response in the Belgrade Rat Model of Genetic Iron Deficiency. Am. J. Physiol. Gastrointest. Liver Physiol. 301(5):G877-86.
  28. Ranganathan, P.N., Lu, Y., Jiang, L., Kim, C. Collins, J.F. (2011) Serum ceruloplasmin protein expression and activity increases in iron-deficient rats and is further enhanced by higher dietary copper intake. Blood. 118(11):3146-53.
  29. Xie, L., Collins, J.F.  (2011) Transcriptional regulation of the Menkes copper ATPase (Atp7a) gene by hypoxia-inducible factor (HIF2α) in intestinal epithelial cells. Am. J. Physiol. Cell Physiol. 300(6):C1298-305.
  30. Hu, Zihua, Gulec, S., Collins, J.F. (2010) Cross-Species Comparison of Genome-Wide Gene Expression Profiles Reveals a Preferential Induction of Hypoxia Inducible Factor (HIF) Responsive Genes in Iron Deprived Intestinal Epithelial Cells. Am. J. Physiol. Cell Physiol. 299:930-938.
  31. 31.    Collins, J.F., Prohaska, J.R., Knutson, M.K. (2010) Metabolic Crossroads of Iron and Copper. Nutr. Rev. 68(3):133–147.

Collins Team - 2019