BS Calvin College Grand Rapids, Mich. Chemistry
MS University of Washington Seattle, Wash. Organic Chemistry
PhD University of California-San Diego La Jolla, Calif. Biochemistry
My laboratory is interested in the molecular and cellular mechanisms of intracellular signal transduction. We are particularly interested in the signaling mechanism(s) that enable human cells to sense and respond to oxidative stress.
Our laboratory has identified an E3 ubiquitin ligase complex that is regulated by oxidative stress. The major substrate of this ubiquitin ligase complex is the Nrf2 transcription factor, which is brought into the ubiquitin ligase complex by the Keap1 protein. Keap1 contains redox-sensitive cysteine residues that, when modified by reactive electrophilic compounds, including reactive oxygen species (ROS), alter the ability of Keap1 to target Nrf2 for ubiquitin-dependent degradation. This leads to increased stabilization of Nrf2 and to activation of a transcriptional program that enables cells to neutralize reactive molecules and maintain cellular redox homeostasis. We have identified several new partners for Keap1, including a protein termed PGAM5 that anchors the Keap1-Nrf2 complex to the outer mitochondrial membrane. PGAM5 also regulates the morphological appearance of mitochondria. We propose that PGAM5 is a critical link between generation of ROS by mitochondria and Nrf2-dependent anti-oxidant genes. We are currently characterizing a gene knockout mouse model for PGAM5.
Roeseler DA, Sachdev S, Buckley DM, Joshi T, Wu DK, Xu D, Hannink M, Waters ST. Elongation factor 1 alpha1 and genes associated with Usher syndromes are downstream targets of GBX2. PLoS One. 2012;7(11):e47366. doi: 10.1371/journal.pone.0047366. Epub 2012 Nov 8.
Bhattacharyya K, Goldschmidt BS, Hannink M, Alexander S, Jurkevic A, Viator JA. Gold nanoparticle-mediated detection of circulating cancer cells. Clin Lab Med. 2012 Mar;32(1):89-101. doi: 10.1016/j.cll.2012.01.001. No abstract available.
Roberts D, Pedmale UV, Morrow J, Sachdev S, Lechner E, Tang X, Zheng N, Hannink M, Genschik P, Liscum E. Modulation of phototropic responsiveness in Arabidopsis through ubiquitination of phototropin 1 by the CUL3-Ring E3 ubiquitin ligase CRL3(NPH3). Plant Cell. 2011 Oct;23(10):3627-40. doi: 10.1105/tpc.111.087999. Epub 2011 Oct 11.
Lee S, Park Y, Zuidema MY, Hannink M, Zhang C. Effects of interventions on oxidative stress and inflammation of cardiovascular diseases. World J Cardiol. 2011 Jan 26;3(1):18-24. doi: 10.4330/wjc.v3.i1.18.
Powell MD, Manandhar G, Spate L, Sutovsky M, Zimmerman S, Sachdev SC, Hannink M, Prather RS, Sutovsky P. Discovery of putative oocyte quality markers by comparative ExacTag proteomics. Proteomics Clin Appl. 2010 Mar;4(3):337-51. doi: 10.1002/prca.200900024. Epub 2010 Jan 4.