Student working on a research project.

Issues In Metal Homeostasis

Our lab is interested in multiple issues relating to iron metabolism in animals and humans. From the practical viewpoint, iron is an important nutrient, but its ability to act in the ferrous and ferric state also makes it toxic. Thus iron deficiency is the most frequent disorder in the world and hereditary hemochromatosis (HH) is the most common Mendelian disorder in the USA. The research is related to differentiation on the fundamental level and to genetic and acquired diseases on the applied level. Recently new vistas have opened for the anemia of chronic diseases for example, leading to re-examination of how microbes and their hosts (us) fight for iron. We approach these issues by working on rodent models and focus now on the Belgrade rat plus a series of genetically engineered mice. The rat has a hypochromic, microcytic anemia inherited as an autosomal recessive. The defect is in an iron transporter called DMT1 (previously Nramp2 or DCT1) that is responsible for iron uptake by enterocytes and immature red blood cells and is also responsible for iron exiting endosomes in the transferrin cycle. The rats appear to have a severe iron deficiency. Although dietary iron and iron injection increase the number of RBCs, they do not restore the RBCs nor the rat itself to a normal phenotype. Past students have worked on the nature of the anemia, on the response to iron supplementation, on gastrointestinal iron uptake or on the serum levels of iron and iron binding capacity, on the levels of iron regulatory proteins (IRPs) in tissues. Recent discoveries show that DMT1 is ubiquitous and responsible for tranport of multiple other metals such as Mn and Ni. It occurs in the kidney, brain and lung at even higher levels than in the GI tract or in erythroid cells. It also has multiple isoforms and we have cloned them and developed cell lines that express high levels of particular isoforms. We have specific antibodies to the isoforms and assays for each of the mRNAs too. Future projects in this lab will continue to address whether DMT1 is dysregulated in HH, tackle how DMT1 functions in neurons, pneumocytes and other tissues, look at isoforms of DMT1 under circumstances where we suspect that they must have different functions from one another, and examine DMT1's relevance to iron metabolism and human disease. Because we recently cloned the gene and identified the mutation, a number of molecular and cellular approaches can now be used. As evidence indicates that metal ion homeostasis fails in Huntingtons Disease, Alzheimers Disease and Parkinson Disease, research on DMT1 has opened new vistas for these disorders too.

Research Project Information

Disciplines: Biochemistry
Student Skill-Set Needed: Should be ready to major in a Biological or Biomedical Science or have exceptional capabilities (like in honors program)
Compensation: Academic Credit, Volunteer, Work Study
Available: Fall, Spring, Summer
Website: http://medicine.buffalo.edu/content/medicine/faculty/profile.html?ubit=mgarrick

Contact

For further information on this opportunity, or to apply, contact:

Faculty Member: Michael Garrick
Department: Biochemistry
Office: 3A Cary Hall
Phone: 829-3926
Email: mgarrick@buffalo.edu