Education & Training
- B.Sc. with Honors Class I, Physiology & Pharmacology, University of Queensland, Brisbane, Australia, 1999
- PhD, Pharmacology, School of Biomedical Sciences, University of Queensland, Brisbane, Australia, 2004
Research Interest Summary
We are interested in understanding the molecular mechanisms that regulate tumor cell metastasis. Tumor progression depends on a multitude of signaling pathways, and we hope that our understanding of these will result in the discovery of novel markers and therapies for metastatic disease. Our lab is specifically interested in elucidating what roles reactive oxygen species, antioxidant enzymes and mitochondrial function play in metastatic progression of ovarian cancer. Some of our current projects include:
Role of antioxidant enzymes and redox signaling during ovarian cancer metastasis: Many tumor cells adapt their antioxidant expression pro>le to cope with exogenous and intrinsic changes in reactive oxygen species during tumor progression. Tumor cells are therefore able to survive and thrive under higher steady-state levels of reactive oxygen species. Moreover, cells can use these oxidants to their advantage by altering pro-metastatic cellular signaling cascades that are redox responsive. We focus on the mechanisms of regulation and function of antioxidant enzymes and try to understand how they manipulate the cellular redox environment to aid in ovarian cancer metastasis.
Regulation of Mitochondrial Form and Function during tumor progression: We aim to understand how mitochondrial function is regulated during tumor progression in ovarian cancer and to elucidate the molecular mechanisms behind our observed histological variances in mitochondrial (dys)function and metabolism. We are currently investigating the role of altered mitochondrial fission/fusion dynamics and mitophagy in this context and are assessing how different histological subtypes may benefit from metabolism-based therapeutics to target their divergent metabolic requirements.
Monavarian M, Elhaw A, Tang P, Javed Z, Shonibare Z, Scalise CB, Arend R, Jolly MK, Sewell- Loftin MK, Hempel N#, Mythreye K# (2022) Emerging perspectives on the growth factor metabolic relationship in the ovarian cancer ascites environment. Seminars in Cancer Biology. S1044-579X(22)00060-8. #Co-corresponding Authors.
Javed Z, Worley BL, Stump C, Shimko SS, Crawford LC, Mythreye K, Hempel N (2022) Optimization of Extracellular Flux Assay to Measure Respiration of Anchorage-independent Tumor Cell Spheroids. Bio-Protocol. 12(4):e4321.
Kim YS, Gupta Vallur P, Jones VM, Worley BL, Shimko S, Shin DH, Crawford LC, Chen CW, Aird KM, Abraham T, Shepherd TG, Warrick JI, Lee NY, Phaeton R, Mythreye K, Hempel N (2020). Context-dependent activation of SIRT3 is necessary for anchorage-independent survival and metastasis of ovarian cancer cells. Oncogene. 39(8):1619-1633. PMCID: PMC7036012.
Pathak T, Gueguinou M, Walter V, Delierneux C, Johnson MT, Zhang X, Xin P, Yoast RE, Emrich SM, Yochum GS, Sekler I, Koltun WA, Gill DL, Hempel N, Trebak M (2020) Dichotomous role of the human mitochondrial Na+/Ca2+/Li+exchanger NCLX in colorectal cancer growth and metastasis. Elife. 9:1-41, e59686. PMCID: PMC7529464.
Worley BL, Kim YS, Mardini J, Zaman R, Leon KE, Gupta Vallur P, Nduwumwami A, Warrick JI, Timmins PF, Kesterson JP, Phaëton R, Lee NY, Walter V, Endres L, Mythreye K, Aird KM, Hempel N (2019). GPX3 supports ovarian cancer progression by manipulating the extracellular redox environment. Redox Biology. pii: S2213-2317(18)30891-7. PMCID: PMC6859581.
Kim YS, Gupta Vallur P, Phaëton R, Mythreye K, Hempel N. (2017) Insights into the Dichotomous Regulation of Sod2 in Cancer. Antioxidants. 6(4). pii: E86. PMCID: PMC5745496. Review.
Hempel N#, Trebak M. (2017) Crosstalk between calcium and reactive oxygen species signaling in cancer. Cell Calcium. 63:70-96. PMCID: PMC5466514. Review. #Corresponding Author
Shin DH, Dier U, Melendez JA, Hempel N (2015) Hypoxia mediated transcriptional regulation of MMP-1 is dependent on the redox status of metastatic cancer cells. BBA Molecular Basis of Disease, 1852:2593-2602. PMCID: PMC4615546.
Hemachandra LP, Shin DH, Dier U, Iuliano JN, Engelberth SA, Uusitalo LM, Murphy SK, Hempel N (2015) Mitochondrial superoxide dismutase has a pro-tumorigenic role in ovarian clear cell carcinoma. Cancer Research. 75:4973-84. PMCID: PMC4651777.
Dier U, Shin DH, Hemachandra LP, Uusitalo LM, Hempel N (2014) Bioenergetic analysis of ovarian cancer cell lines: Profiling of histological subtypes and identification of a mitochondria-defective cell line. PLoS One, 9(5) e98479. PMCID: PMC4032324.