The Hempel Group has interests in the following areas:

1. Role and regulation of antioxidant enzymes and redox signaling in cancer.

Although antioxidant enzymes were initially considered to be tumor suppressors in the context of cancer initiation, it is now well established that oxidant production is elevated within tumor cells and the tumor microenvironment during tumor progression and metastasis. Cancer cells thus must adapt by upregulating their antioxidant defenses to survive metastatic progression. As a consequence of altered metabolism and changes in antioxidant enzyme function oxidant fluxes not only drive lethal oxidative stress, but also contribute to redox signaling. We are exploring how redox signaling is altered in tumor cells and how antioxidant enzymes contribute to the regulation of redox signaling by focusing on functional changes elicited by cysteine thiol oxidation. Additionally, we are interested in the crosstalk between mitochondrial calcium homeostasis and redox signaling pathways in cancer.

GPX3 supports ovarian cancer tumor progression in vivo and promotes expression of GDF15. Chang C, Cheng YY, Kamlapurkar S, White S, Tang PW, Elhaw AT, Javed Z, Aird KM, Mythreye K, Phaëton R, Hempel N. Gynecol Oncol. 2024 Feb 10;185:8-16. PMID: 38342006.
HuR-dependent SOD2 protein synthesis is an early adaptation of ovarian cancer cells in response to anchorage independence. Kim YS, Tang PW, Welles JE, Pan W, Javed Z, Elhaw AT, Mythreye K, Kimball SR, Hempel N. Redox Biology. 2022. 53:102329
GPx3 supports ovarian cancer progression by manipulating the extracellular redox environment. Worley BL, Kim YS, Mardini J, Zaman R, Leon KE, Vallur PG, Nduwumwami A, Warrick JI, Timmins PF, Kesterson JP, Phaëton R, Lee NY, Walter V, Endres L, Mythreye K, Aird KM, Hempel N. Redox Biol. 2019 Jul;25:101051. PMID: 30509602
Context-dependent activation of SIRT3 is necessary for anchorage-independent survival and metastasis of ovarian cancer cells. 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. Oncogene. 2020 Feb;39(8):1619-1633. PMID: 31723239
Dichotomous role of the human mitochondrial Na⁺/Ca2⁺/Li⁺ exchanger NCLX in colorectal cancer growth and metastasis. 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. Elife. 2020 Sep 11;9:e59686. PMID: 32914752

2. Mitochondrial dynamics and function in tumor progression.

The regulation of mitochondrial dynamics is integral to mitochondrial function. Tumor cells often display aberrant mitochondrial fission/fusion, which can lead to changes in tumor metabolism. Our research has identified that ovarian cancer cells express distinct alternative splice variants of the mitochondrial fission protein Drp1/DNM1L with unique functions, demonstrating that these variants differentially regulate mitochondrial dynamics in tumor cells. We are exploring how this contributes to changes in tumor metabolism, tumor heterogeneity, and cell plasticity during metastatic progression.

Drp1 splice variants regulate ovarian cancer mitochondrial dynamics and tumor progression. Javed Z, Shin DH, Pan W, White SR, Elhaw AT, Kim YS, Kamlapurkar S, Cheng YY, Benson JC, Abdelnaby AE, Phaëton R, Wang HG, Yang S, Sullivan MLG, St Croix CM, Watkins SC, Mullett SJ, Gelhaus SL, Lee N, Coffman LG, Aird KM, Trebak M, Mythreye K, Walter V, Hempel N. EMBO Rep. 2024 Oct;25(10):4281-4310. doi: 10.1038/s44319-024-00232-4. Epub 2024 Aug 27. PMID: 39191946; PMCID: PMC11467262. 

3. Ovarian cancer cell survival adaptations during metastasis.

Ovarian cancer metastasis occurs primarily through transcoelomic dissemination, where tumor cells must evade detachment-induced cell death (anoikis) to enable metastasis throughout the peritoneal cavity as individual cells and multicellular aggregates. We are exploring novel mechanisms by which cells adapt to enable survival in anchorage independence:

Reciprocal SOX2 regulation by SMAD1-SMAD3 is critical for anoikis resistance and metastasis in cancer. Shonibare Z, Monavarian M, O’Connell K, Altomare D, Shelton A, Mehta S, Jaskula-Sztul R, Phaeton R, Starr MD, Whitaker R, Berchuck A, Nixon AB, Arend RC, Lee NY, Miller CR, Hempel N, Mythreye K. Cell Rep. 2022 Jul 26;40(4):111066. PMID: 35905726.
RHOV is a Detachment-Responsive Rho GTPase Necessary for Ovarian Cancer Peritoneal Metastasis. Elhaw AT, Tang PW, Cheng YY, Kamlapurkar S, Javed Z, Al-Saad S, White SR, Abdelnaby AE, Khan H, Choi AS, Cole AR, Kim YS, Atiya HI, Trebak M, Zervantonakis I, Buckanovich RJ, Aird KM, Coffman LG, Mythreye K, Hempel N. bioRxiv [Preprint]. 2025 Aug 13:2025.08.12.669944. doi: 10.1101/2025.08.12.669944. PMID: 40832333; PMCID: PMC12363840.