Faculty
Thomas V. O'Halloran, PhD
Professor
Chemistry/BMBCB
PhD, Columbia
Email: t-ohalloran@northwestern.edu
Phone: (847) 491-5060
Fax: (847) 491-7713
Room: Pancoe Rm 1121
Research Interests
Metalloregulatory proteins; molecular mechanisms of metal-responsive gene expression; protein-DNA interactions; oxygen activation by nonheme iron proteins; bioinorganic chemistry
We are exploring the cell and molecular biology of transition elements. One of our approaches is to isolate novel receptors and characterize their function, structure and chemical mechanism. In other strategies, we are interrogating the vesicular trafficking of these elements by developing vital fluorescent probes that are specific for metal ions such as Zn(II). Together, these types of experiments are delineating elemental aspects of microbial and mammalian biology.
Two new classes of metalloprotein have emerged from these studies. Metalloregulatory proteins such as MerR, Fur, Zur, PcoRS, and ZntR act as metal responsive genetic switches. Our goal in studies of these proteins is to understand the basis of metal ion recognition, establish the mechanisms by which metal binding alters gene expression and ultimately uses these insights to describe global aspects of metal metabolism.
Metallochaperones are diffusible metal ion receptors involved in intracellular metal trafficking. It has long been thought that metalloproteins are highly specific chelators that select available metal ions in the cytoplasm of the cell. Our recent studies indicate the opposite: the 'free' copper concentration is lower than one atom per cell; too low to allow a protein to acquire copper without assistance. Atxl, a prototypical metallochaperone, protects and guides Cu(I) to a specific target enzyme in the cytoplasm. In humans, Atxl delivers Cu(I) to proteins involved in fatal metal-based disorders such as Menkes' syndrome and Wilson disease. Characterization of CCS, copper chaperone for superoxide dismutase, is another challenge, but has payoffs in our understanding and treatment of severe neurodegenerative diseases such as, ALS.
Size control of arsenic trioxide nanocrystals grown in nanowells. You EA, Ahn RW, Lee MH, Raja MR, O'Halloran TV, Odom TW. J Am Chem Soc. 2009 Aug 12;131(31):10863-5.
Folate-mediated intracellular drug delivery increases the anticancer efficacy of nanoparticulate formulation of arsenic trioxide. Chen H, Ahn R, Van den Bossche J, Thompson DH, O'Halloran TV. Mol Cancer Ther. 2009 Jul;8(7):1955-63. Epub 2009 Jun 30.
Complete loss of post-translational modifications triggers fibrillar aggregation of SOD1 in the familial form of amyotrophic lateral sclerosis. Furukawa Y, Kaneko K, Yamanaka K, O'Halloran TV, Nukina N. J Biol Chem. 2008 Aug 29;283(35):24167-76. Epub 2008 Jun 13.
A place for thioether chemistry in cellular copper ion recognition and trafficking. Davis AV, O'Halloran TV. Nat Chem Biol. 2008 Mar;4(3):148-51.
Chen H, MacDonald RC, Li S, Krett NL, Rosen ST, O'Halloran TV. Lipid encapsulation of arsenic trioxide attenuates cytotoxicity and allows for controlled anticancer drug release. J Am Chem Soc. 2006 Oct 18;128(41):13348-9. No abstract available.
Furukawa Y, Fu R, Deng HX, Siddique T, O'Halloran TV. Disulfide cross-linked protein represents a significant fraction of ALS-associated Cu, Zn-superoxide dismutase aggregates in spinal cords of model mice. Proc Natl Acad Sci U S A. 2006 May 2;103(18):7148-53. Epub 2006 Apr 24.
View all publications by Thomas V. O'Halloran in the National Library of Medicine (PubMed). Past and current IBiS students in blue