Education
| BS | Chemistry | Calvin College | Grand Rapids, Mich. |
| MS | Organic Chemistry | University of Washington | Seattle, Wash. |
| PhD | Biochemistry | University of California-San Diego | La Jolla, Calif. |
Research Area
BTB-Kelch substrate adaptor family in development, oncogenesis and neurodegeneration.
Research Description
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.
Notable Honors and Service
- Associate Director for Fellowships and Education, Life Sciences Center
- PI NIGMS-funded T32 training grant in Molecular Cell Biology
- PI NIGMS-funded Initiative for Maximizing Student Diversity (IMSD)
Selected Publications
Puray-Chavez MN, Farghali MH, Yapo V, Huber AD, Liu D, Ndongwe TP, Casey MC, Laughlin TG, Hannink M, Tedbury PR, Sarafianos SG. (2019). Effects of Moloney Leukemia Virus 10 Protein on Hepatitis B Virus Infection and Viral Replication. Viruses. 11(7). doi: 10.3390/v11070651. [PubMed]
Alexander S, Hannink M. (2019). Exploring the molecular genetic foundations of cancer biology and how biomedical advances are made in an advanced undergraduate course. Biochem Mol Biol Educ. 47(4):408-416. doi: 10.1002/bmb.21247. [PubMed]
Tipton P, Su T, Hannink M. (2018). Assembly of PGAM5 into Multimeric Complexes Provides a Mechanism for Allosteric Regulation of Phosphatase Activity. Methods Enzymol. 607:353-372. doi: 10.1016/bs.mie.2018.05.017. [PubMed]
Sun GY, Simonyi A, Fritsche KL, Chuang DY, Hannink M, Gu Z, Greenlief CM, Yao JK, Lee JC, Beversdorf DQ. (2018). Docosahexaenoic acid (DHA): An essential nutrient and a nutraceutical for brain health and diseases. Prostaglandins Leukot Essent Fatty Acids. 136:3-13. doi: 10.1016/j.plefa.2017.03.006. Review. [PubMed]
Sun GY, Li R, Cui J, Hannink M, Gu Z, Fritsche KL, Lubahn DB, Simonyi A. (2016). Withania somnifera and Its Withanolides Attenuate Oxidative and Inflammatory Responses and Up-Regulate Antioxidant Responses in BV-2 Microglial Cells. Neuromolecular Med. 18(3):241-52. doi: 10.1007/s12017-016-8411-0. [PubMed]
Ajit D, Simonyi A, Li R, Chen Z, Hannink M, Fritsche KL, Mossine VV, Smith RE, Dobbs TK, Luo R, Folk WR, Gu Z, Lubahn DB, Weisman GA, Sun GY. (2016). Phytochemicals and botanical extracts regulate NF-κB and Nrf2/ARE reporter activities in DI TNC1 astrocytes. Neurochem Int. 97:49-56. doi: 10.1016/j.neuint.2016.05.004. [PubMed]
Sun GY, Chen Z, Jasmer KJ, Chuang DY, Gu Z, Hannink M, Simonyi A. (2015). Quercetin Attenuates Inflammatory Responses in BV-2 Microglial Cells: Role of MAPKs on the Nrf2 Pathway and Induction of Heme Oxygenase-1. PLoS One. 10(10):e0141509. doi: 10.1371/journal.pone.0141509. eCollection 2015. [PubMed]
Wilkins JM, McConnell C, Tipton PA, Hannink M. (2014). A conserved motif mediates both multimer formation and allosteric activation of phosphoglycerate mutase 5. J Biol Chem. 289(36):25137-48. doi: 10.1074/jbc.M114.565549. [PubMed]