Thomas B. BartnikasAssistant Professor of Pathology and Laboratory Medicine
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 in part by the National Institutes of Health.
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.