Tom Bartnikas, M.D. Ph.D. is assistant professor in the Department of Pathology and Laboratory Medicine at Brown University where he studies the role of metals in human health and disease. He obtained a B.A. from Cornell University then an M.D. Ph.D. from Washington University in St. Louis (Ph.D. in Molecular Cell Biology with Dr. Jonathan Gitlin). He did his postdoctoral studies with Drs. Nancy Andrews and Mark Fleming at Boston Children's Hospital. His work is funded by the National Institutes of Health.
|Traeger L, Gallitz I, Sekhri R, Bäumer N, Kuhlmann T, Kemming C, Holtkamp M, Müller JC, Karst U, Canonne-Hergaux F, Muckenthaler MU, Bloch DB, Olschewski A, Bartnikas TB, Steinbicker AU. "ALK3 undergoes ligand-independent homodimerization and BMP-induced heterodimerization with ALK2." Free Radical Biology and Medicine, vol. 129, 2018, pp. 127-137.|
|Zhao, Luqing, Bartnikas, Thomas, Chu, Xiangpeng, Klein, Janet, Yun, Chris, Srinivasan, Shanthi, He, Peijian. "Hyperglycemia promotes microvillus membrane expression of DMT1 in intestinal epithelial cells in a PKCα-dependent manner." The FASEB Journal, 2018, pp. fj.201801855R.|
|Thomason RT, Pettiglio MA, Herrera C, Kao C, Gitlin JD, Bartnikas TB. "Characterization of trace metal content in the developing zebrafish embryo." PLoS ONE, vol. 12, no. 6, 2017, pp. e0179318.|
|Bartnikas TB. "Matriptase-2 links erythropoietin to iron." Blood, vol. 127, no. 19, 2016, pp. 2270-1.|
|Mercadante CJ, Herrera C, Pettiglio MA, Foster ML, Johnson LC, Dorman DC, Bartnikas TB. "The effect of high dose oral manganese exposure on copper, iron and zinc levels in rats." Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, vol. 29, no. 3, 2016, pp. 417-22.|
|Gutschow P, Schmidt PJ, Han H, Ostland V, Bartnikas TB, Pettiglio MA, Herrera C, Butler JS, Nemeth E, Ganz T, Fleming MD, Westerman M. "A competitive enzyme-linked immunosorbent assay specific for murine hepcidin-1: correlation with hepatic mRNA expression in established and novel models of dysregulated iron homeostasis." Haematologica, vol. 100, no. 2, 2015, pp. 167-77.|
|Foster ML, Bartnikas TB, Johnson LC, Herrera C, Pettiglio MA, Keene AM, Taylor MD, Dorman DC. "Pharmacokinetic Evaluation of the Equivalency of Gavage, Dietary, and Drinking Water Exposure to Manganese in F344 Rats." Toxicological Sciences, 2015.|
|Bu JT, Bartnikas TB. "The use of hypotransferrinemic mice in studies of iron biology." Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 2015.|
|Zhang Z, Guo X, Herrera C, Tao Y, Wu Q, Wu A, Wang H, Bartnikas TB, Wang F. "Bmp6 expression can be regulated independently of liver iron in mice." PLoS ONE, vol. 9, no. 1, 2014, pp. e84906.|
|Herrera C, Pettiglio MA, Bartnikas TB. "Investigating the role of transferrin in the distribution of iron, manganese, copper, and zinc." Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry, vol. 19, no. 6, 2014, pp. 869-77.|
|Bartnikas TB. "Liver not making hepcidin? Hemochromatosis!." Blood, vol. 123, no. 23, 2014, pp. 3535-6.|
|Bartnikas TB, Wildt SJ, Wineinger AE, Schmitz-Abe K, Markianos K, Cooper DM, Fleming MD. "A novel rat model of hereditary hemochromatosis due to a mutation in transferrin receptor 2." Comparative medicine, vol. 63, no. 2, 2013, pp. 143-55.|
|Bartnikas TB, Steinbicker AU, Campagna DR, Blevins S, Woodward LS, Herrera C, Bloch KD, Justice MJ, Fleming MD. "Identification and characterization of a novel murine allele of Tmprss6." Haematologica, vol. 98, no. 6, 2013, pp. 854-61.|
|Bartnikas TB, Fleming MD. "Hemojuvelin is essential for transferrin-dependent and transferrin-independent hepcidin expression in mice." Haematologica, vol. 97, no. 2, 2012, pp. 189-92.|
|Bartnikas TB. "Known and potential roles of transferrin in iron biology." Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, vol. 25, no. 4, 2012, pp. 677-86.|
|Bartnikas TB, Fleming MD, Schmidt PJ. "Murine mutants in the study of systemic iron metabolism and its disorders: an update on recent advances." Biochimica et biophysica acta, vol. 1823, no. 9, 2012, pp. 1444-50.|
|Bartnikas TB, Parker CC, Cheng R, Campagna DR, Lim JE, Palmer AA, Fleming MD. "QTLs for murine red blood cell parameters in LG/J and SM/J F(2) and advanced intercross lines." Mammalian genome : official journal of the International Mammalian Genome Society, vol. 23, no. 5-6, 2012, pp. 356-66.|
|Steinbicker AU, Bartnikas TB, Lohmeyer LK, Leyton P, Mayeur C, Kao SM, Pappas AE, Peterson RT, Bloch DB, Yu PB, Fleming MD, Bloch KD. "Perturbation of hepcidin expression by BMP type I receptor deletion induces iron overload in mice." Blood, vol. 118, no. 15, 2011, pp. 4224-30.|
|Bartnikas TB, Andrews NC, Fleming MD. "Transferrin is a major determinant of hepcidin expression in hypotransferrinemic mice." Blood, vol. 117, no. 2, 2011, pp. 630-7.|
|Bartnikas TB, Fleming MD. "A tincture of hepcidin cures all: the potential for hepcidin therapeutics." Journal of Clinical Investigation, vol. 120, no. 12, 2010, pp. 4187-90.|
|Bartnikas TB, Campagna DR, Antiochos B, Mulhern H, Pondarré C, Fleming MD. "Characterization of mitochondrial ferritin-deficient mice." American Journal of Hematology, vol. 85, no. 12, 2010, pp. 958-60.|
|Rooijakkers SH, Rasmussen SL, McGillivray SM, Bartnikas TB, Mason AB, Friedlander AM, Nizet V. "Human transferrin confers serum resistance against Bacillus anthracis." Journal of Biological Chemistry, vol. 285, no. 36, 2010, pp. 27609-13.|
|Caruano-Yzermans AL, Bartnikas TB, Gitlin JD. "Mechanisms of the copper-dependent turnover of the copper chaperone for superoxide dismutase." Journal of Biological Chemistry, vol. 281, no. 19, 2006, pp. 13581-7.|
|Bartnikas TB, Gitlin JD. "Mechanisms of biosynthesis of mammalian copper/zinc superoxide dismutase." Journal of Biological Chemistry, vol. 278, no. 35, 2003, pp. 33602-8.|
|Bartnikas TB, Wang Y, Bobo T, Veselov A, Scholes CP, Shapleigh JP. "Characterization of a member of the NnrR regulon in Rhodobacter sphaeroides 2.4.3 encoding a haem-copper protein." Microbiology (Reading, England), vol. 148, no. Pt 3, 2002, pp. 825-33.|
|Subramaniam JR, Lyons WE, Liu J, Bartnikas TB, Rothstein J, Price DL, Cleveland DW, Gitlin JD, Wong PC. "Mutant SOD1 causes motor neuron disease independent of copper chaperone-mediated copper loading." Nature Neuroscience, vol. 5, no. 4, 2002, pp. 301-7.|
|Bartnikas TB, Gitlin JD. "How to make a metalloprotein." Nature structural biology, vol. 8, no. 9, 2001, pp. 733-4.|
|McLoughlin DM, Standen CL, Lau KF, Ackerley S, Bartnikas TP, Gitlin JD, Miller CC. "The neuronal adaptor protein X11alpha interacts with the copper chaperone for SOD1 and regulates SOD1 activity." Journal of Biological Chemistry, vol. 276, no. 12, 2001, pp. 9303-7.|
|Waggoner DJ, Drisaldi B, Bartnikas TB, Casareno RL, Prohaska JR, Gitlin JD, Harris DA. "Brain copper content and cuproenzyme activity do not vary with prion protein expression level." Journal of Biological Chemistry, vol. 275, no. 11, 2000, pp. 7455-8.|
|Bartnikas TB, Waggoner DJ, Casareno RL, Gaedigk R, White RA, Gitlin JD. "Chromosomal localization of CCS, the copper chaperone for Cu/Zn superoxide dismutase." Mammalian genome : official journal of the International Mammalian Genome Society, vol. 11, no. 5, 2000, pp. 409-11.|
|Wong PC, Waggoner D, Subramaniam JR, Tessarollo L, Bartnikas TB, Culotta VC, Price DL, Rothstein J, Gitlin JD. "Copper chaperone for superoxide dismutase is essential to activate mammalian Cu/Zn superoxide dismutase." Proceedings of the National Academy of Sciences, vol. 97, no. 6, 2000, pp. 2886-91.|
|Waggoner DJ, Bartnikas TB, Gitlin JD. "The role of copper in neurodegenerative disease." Neurobiology of disease, vol. 6, no. 4, 1999, pp. 221-30.|
|Bartnikas TB, Tosques IE, Laratta WP, Shi J, Shapleigh JP. "Characterization of the nitric oxide reductase-encoding region in Rhodobacter sphaeroides 2.4.3." Journal of bacteriology, vol. 179, no. 11, 1997, pp. 3534-40.|
The Bartnikas lab explores the fundamental molecular, biochemical, genetic and physiologic basis of metal homeostasis in the human body. Using multiple in vivo and in vitro experimental approaches, our laboratory investigates the mechanisms by which metals are acquired by the body, distributed to various tissues and recycled or eliminated and how perturbations in these mechanisms can lead to human disease.
Metals are essential for many biological processes but are toxic when present in excess. To ensure adequate but not excessive metal levels in the body, metal absorption, distribution and excretion are tightly regulated. Metal deficiency and/or excess can result from specific genetic mutations, dietary imbalances or environmental exposures. Using both mouse and cell culture models and drawing upon collaborations with structural biologists and investigators studying patient cohorts and other model organisms, our laboratory investigates the molecular, biochemical, genetic and physiologic mechanisms underlying the regulation of metal absorption, distribution and excretion. We are currently investigating the toxicity of two physiological metals, iron and manganese, in inherited and acquired diseases.
One of our current projects focuses on mammalian iron excretion. This project employs hypotransferrinemic (hpx) mice, a model of inherited transferrin deficiency. Transferrin is an abundant, serum iron-binding protein. As transferrin is essential for iron delivery to the bone marrow for erythropoiesis, hpx mice develop severe anemia. These mice also develop a paradoxical severe iron overload due to deposition of non-transferrin bound iron in several tissues including the liver, heart, pancreas and brain. Hpx mice develop iron overload because transferrin is essential for expression of hepcidin, a liver-derived hormone that inhibits dietary iron absorption, and the resulting hepcidin deficiency in hpx mice leads to excessive dietary iron absorption. Our recent studies indicate that treatment of hpx mice with exogenous transferrin significantly reduces tissue and body iron levels. This suggests that iron excretion can be induced, which goes against the often-cited view in the iron biology field that body iron levels are determined by iron absorption, not excretion. This data also has implications for development of novel therapies for hereditary hemochromatosis, thalassemia major and transfusion-induced iron toxicity.
2006-08 Serum regulators of hepcidin expression
Cooley's Anemia Foundation
The major goal of the study was to identify serum molecules that modulate hepcidin mRNA levels in hepatocytes and to test candidate hepcidin regulatory proteins in vitro.
2009-15 Regulation of iron homeostasis by iron and transferrin
NIDDK K99/R00 DK084122
The major goals of the study were to determine the effect of metal-free, diferric and total transferrin levels on hepcidin levels in vivo, to determine if perturbations in cellular manganese homeostasis alter cellular iron homeostasis and to identify novel factors required for cellular manganese and iron homeostasis.
2016-21 Molecular basis of mammalian manganese homeostasiS
The major goals of the study were to determine if the characteristics observed in mice with deficiency in the manganese transport protein Slc30a10 are consequences of manganese excess or represent manganese-independent functions of Slc30a10, to establish the relative contribution of hepatic and neuronal Slc30a10 function to overall manganese homeostasis, and to interrogate the role of hypoxia signaling in pathophysiology of Slc30a10 deficiency.
International BioIron Society
American Society of Hematology
American Association for the Advancement of Science
Society of Toxicology
|BIOL 2860 - Molecular Mechanisms of Disease|