Education
| BSc | Biochemistry/Genetics | University of Melbourne | Melbourne, Australia |
| PhD | Genetics | University of Melbourne | Melbourne, Australia |
Research Area
Regulation of metal nutrition and impacts on common human diseases.
Research Description
The micronutrient copper (Cu) is essential for several key enzymatic processes involved in energy generation, protection against reactive oxygen species, formation of blood vessels, immune function, and healthy functioning of the central nervous system. This nutrient is able to exist in two oxidation states Cu1+ and Cu2+, and participate in the generation of reactive oxygen species. A delicate balance of copper homeostasis must be maintained to provide sufficient levels of this nutrient, while preventing toxic build up.
Copper and Cancer
Recent evidence suggests that copper plays a key role in tumor growth because this metal is essential for blood vessel formation (angiogenesis). Drugs that bind copper may inhibit tumor growth by preventing angiogenesis.
Copper and Alzheimer’s Disease
Copper has been shown to interact with the toxic beta-amyloid peptide, and is present in high concentrations in amyloid plaques within in the brains of Alzheimer’s disease patients. Whether this copper is function in a protective or detrimental capacity is unknown.
Current Projects
Our lab is interested in characterizing the copper homeostasis pathways in animal and cell culture models of microbial infection, tumor growth and Alzheimer’s disease, and how this essential nutrient contributes to these pathologies.
Notable Honors and service
- Organizer FASEB Conference on Trace Element Micronutrients, 2006
- Organizing Committee, 5th International Meeting on Copper Homeostasis and its Disorders, 2006
- Scientific Advisory Committee, Gordon Research Conference on Cell Biology of Metals, 2005
- 4th International Meeting on Copper Homeostasis and its Disorders, 2004
Selected Publications
Tao C, Wang Y, Zhao Y, Pan J, Fan Y, Liang X, Cao C, Zhao J, Petris MJ, Li K, Wang Y. (2019). Adipocyte-specific disruption of ATPase copper transporting α in mice accelerates lipoatrophy. Diabetologia. 2019 Aug 8. doi: 10.1007/s00125-019-4966-2. Epub ahead of print. [PubMed]
Shanbhag V, Jasmer-McDonald K, Zhu S, Martin AL, Gudekar N, Khan A, Ladomersky E, Singh K, Weisman GA, Petris MJ. (2019). ATP7A delivers copper to the lysyl oxidase family of enzymes and promotes tumorigenesis and metastasis. Proc Natl Acad Sci U S A. 116(14):6836-6841. doi: 10.1073/pnas.1817473116. [PubMed]
Chun H, Korolnek T, Lee CJ, Coyne HJ 3rd, Winge DR, Kim BE, Petris MJ. (2019). An extracellular histidine-containing motif in the zinc transporter ZIP4 plays a role in zinc sensing and zinc-induced endocytosis in mammalian cells. J Biol Chem. 294(8):2815-2826. doi: 10.1074/jbc.RA118.005203. [PubMed]
Woods LT, Camden JM, Khalafalla MG, Petris MJ, Erb L, Ambrus JL Jr, Weisman GA. (2018). P2Y(2) R deletion ameliorates sialadenitis in IL-14α-transgenic mice. Oral Dis. 24(5):761-771. doi: 10.1111/odi.12823. [PubMed]
Baker ZN, Jett K, Boulet A, Hossain A, Cobine PA, Kim BE, El Zawily AM, Lee L, Tibbits GF, Petris MJ, Leary SC. (2017). The mitochondrial metallochaperone SCO1 maintains CTR1 at the plasma membrane to preserve copper homeostasis in the murine heart. Hum Mol Genet. 26(23):4617-4628. doi: 10.1093/hmg/ddx344. [PubMed]
Khalafalla MG, Woods LT, Camden JM, Khan AA, Limesand KH, Petris MJ, Erb L, Weisman GA. (2017). P2X7 receptor antagonism prevents IL-1β release from salivary epithelial cells and reduces inflammation in a mouse model of autoimmune exocrinopathy. J Biol Chem. 292(40):16626-16637. doi: 10.1074/jbc.M117.790741. [PubMed]
Ladomersky E, Khan A, Shanbhag V, Cavet JS, Chan J, Weisman GA, Petris MJ. (2017). Host and Pathogen Copper-Transporting P-Type ATPases Function Antagonistically during Salmonella Infection. Infect Immun. 85(9). doi: 10.1128/IAI.00351-17. Print 2017 Sep. [PubMed]
Zhu S, Shanbhag V, Hodgkinson VL, Petris MJ. (2016). Multiple di-leucines in the ATP7A copper transporter are required for retrograde trafficking to the trans-Golgi network. Metallomics. 8(9):993-1001. doi: 10.1039/c6mt00093b. [PubMed]
Fieten H, Gill Y, Martin AJ, Concilli M, Dirksen K, van Steenbeek FG, Spee B, van den Ingh TS, Martens EC, Festa P, Chesi G, van de Sluis B, Houwen RH, Watson AL, Aulchenko YS, Hodgkinson VL, Zhu S, Petris MJ, Polishchuk RS, Leegwater PA, Rothuizen J. (2016). The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders. Dis Model Mech. 9(1):25-38. doi: 10.1242/dmm.020263. [PubMed]
Hodgkinson VL, Zhu S, Wang Y, Ladomersky E, Nickelson K, Weisman GA, Lee J, Gitlin JD, Petris MJ. (2015). Autonomous requirements of the Menkes disease protein in the nervous system. Am J Physiol Cell Physiol. 309(10):C660-8. doi: 10.1152/ajpcell.00130.2015. [PubMed]
Woods LT, Camden JM, El-Sayed FG, Khalafalla MG, Petris MJ, Erb L, Weisman GA. (2015). Increased Expression of TGF-β Signaling Components in a Mouse Model of Fibrosis Induced by Submandibular Gland Duct Ligation. PLoS One. 10(5):e0123641. doi: 10.1371/journal.pone.0123641. eCollection 2015. [PubMed]
Hlynialuk CJ, Ling B, Baker ZN, Cobine PA, Yu LD, Boulet A, Wai T, Hossain A, El Zawily AM, McFie PJ, Stone SJ, Diaz F, Moraes CT, Viswanathan D, Petris MJ, Leary SC. (2015). The Mitochondrial Metallochaperone SCO1 Is Required to Sustain Expression of the High-Affinity Copper Transporter CTR1 and Preserve Copper Homeostasis. Cell Rep. 10(6):933-943. doi: 10.1016/j.celrep.2015.01.019. [PubMed]
Ladomersky E, Petris MJ. (2015). Copper tolerance and virulence in bacteria. Metallomics. 7(6):957-64. doi: 10.1039/c4mt00327f. Review. [PubMed]
Hodgkinson VL, Dale JM, Garcia ML, Weisman GA, Lee J, Gitlin JD, Petris MJ. (2015). X-linked spinal muscular atrophy in mice caused by autonomous loss of ATP7A in the motor neuron. J Pathol. 236(2):241-50. doi: 10.1002/path.4511. [PubMed]
Zlatic S, Comstra HS, Gokhale A, Petris MJ, Faundez V. (2015). Molecular basis of neurodegeneration and neurodevelopmental defects in Menkes disease. Neurobiol Dis. 81:154-61. doi: 10.1016/j.nbd.2014.12.024. Review. [PubMed]
Matsui MS, Petris MJ, Niki Y, Karaman-Jurukovska N, Muizzuddin N, Ichihashi M, Yarosh DB. (2015). Omeprazole, a gastric proton pump inhibitor, inhibits melanogenesis by blocking ATP7A trafficking. J Invest Dermatol. 135(3):834-841. doi: 10.1038/jid.2014.461. [PubMed]
Current Funding
NIH/NIDDK R01 DK116859 01/01/2019 – 11/30/2022
“Copper and iron in nutritional immunity”
Total costs: $1,658,317
Role: PI
NIH/NCI R01 CA190265 12/01/2014 – 11/30/2019
“Copper metabolism as a unique vulnerability in cancer”
Total direct costs: $1,287,170
Role: PI
NIH/NIDCR R01DE0223342 12/12/2013 – 11/30/2019
“Restoring salivary gland function by reducing nucleotide-induced inflammation”
Total direct costs: $2,910,018
Role: Co-Investigator (PI: Gary A. Weisman, Biochemistry)