Thomas V. O'Halloran
Charles E. and Emma H. Morrison Professor
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.
Nano-Encapsulation of Arsenic Trioxide Enhances Efficacy against Murine Lymphoma Model while Minimizing Its Impact on Ovarian Reserve In Vitro and In Vivo. Ahn RW, Barrett SL, Raja MR, Jozefik JK, Spaho L, Chen H, Bally MB, Mazar AP, Avram MJ, Winter JN, Gordon LI, Shea LD, O'Halloran TV, and Woodruff TK. PLoS ONE. 2013 March 20;8(3):e58491.
Role of CTR4 in the Virulence of Cryptococcus neoformans. Waterman SR, Park Y-D, Raja M, Qiu J, Hammoud DA, O'Halloran TV, and Williamson PR. mBio. 2012 October 2;3(5):e00285-12.
Zinc Maintains Prophase I Arrest in Mouse Oocytes Through Regulation of the MOS-MAPK Pathway. Kong BY, Bernhardt ML, Kim AM, O'Halloran TV, and Woodruff TK. Biology of Reproduction. 2012 July 1;87(1):11,1-12.
Fluxes in “Free” and Total Zinc Are Essential for Progression of Intraerythrocytic Stages of Plasmodium falciparum. Marvin RG, Wolford JL, Kidd MJ, Murphy S, Ward J, Que EL, Mayer ML, Penner-Hahn JE, Haldar K, and O'Halloran TV. Chemistry & Biology. 2012 June 22;19(6):731-741.
A Zinc-Dependent Mechanism Regulates Meiotic Progression in Mammalian Oocytes. Bernhardt ML, Kong BY, Kim AM, O'Halloran TV, and Woodruff TK. Biology of Reproduction. 2012 April 1;86(4):114,1-10.
High-Throughput Screen for Identifying Small Molecules That Target Fungal Zinc Homeostasis. Simm C, Luan C-H, Weiss E, and O'Halloran T. PLoS ONE. 2011 September 29;6(9):e25136.
Design, Implementation, Simulation, and Visualization of a Highly Efficient RIM Microfluidic Mixer for Rapid Freeze-Quench of Biological Samples. Schmidt B, Mahmud G, Soh S, Kim SH, Page T, O'Halloran TV, Grzybowski BA, and Hoffman BM. Applied Magnetic Resonance. 2011 August;40(4):415-425.
Zinc Sparks Are Triggered by Fertilization and Facilitate Cell Cycle Resumption in Mammalian Eggs. Kim AM, Bernhardt ML, Kong BY, Ahn RW, Vogt S, Woodruff TK, and O'Halloran TV. ACS Chemical Biology. 2011 July 15;6(7):716-723.
Triggered Release of Pharmacophores from [Ni(HAsO3)]-Loaded Polymer-Caged Nanobin Enhances Pro-apoptotic Activity: A Combined Experimental and Theoretical Study. Lee S-M, Lee O-S, O'Halloran TV, Schatz GC, and Nguyen ST. ACS Nano. 2011 May 24;5(5):3961-3969.
Zinc Requirement During Meiosis I–Meiosis II Transition in Mouse Oocytes Is Independent of the MOS-MAPK Pathway. Bernhardt ML, Kim AM, O'Halloran TV, and Woodruff TK. Biology of Reproduction. 2011 March 1;84(3):526-536.
Modular Polymer-Caged Nanobins as a Theranostic Platform with Enhanced Magnetic Resonance Relaxivity and pH-Responsive Drug Release. Lee S-M, Song Y, Hong BJ, MacRenaris KW, Mastarone DJ, O'Halloran TV, Meade TJ, and Nguyen ST. Angewandte Chemie Int Ed. 2010 December 17;49(51):9960-9964.
View all publications by Thomas V. O'Halloran in the National Library of Medicine (PubMed). Current and former IBiS students in blue.