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Primary Phone: (520) 6269017
Arizona Cancer Center 3979 & 3977C
Primary Phone: (520) 6269017
Ph.D., Technical University Berlin, Germany
- College Of Pharmacy
Redox drug discovery targeting human skin cancer.
Environmental Health Research & Expertise:
Dr. Wondrak's research aims at redox drug discovery targeting skin cancer and solar photodamage: "My laboratory explores molecular mechanisms of skin photodamage and photocarcinogenesis with a focus on chemical processes including photooxidative and carbonyl stress. Identification of critical molecular targets that mediate UVA-induced skin alterations and contribute to the pathogenesis of nonmelanoma and melanoma skin cancer facilitates the development of novel experimental therapeutics for skin photoprotection and anti-melanoma intervention. (I) Our recent research suggests that redox dysregulation originating from metabolic alterations and dependence on mitogenic and survival signaling through reactive oxygen species represents a specific vulnerability of melanoma cells that can be selectively targeted by apoptogenic redox chemotherapeutics. We are therefore aiming at drug discovery and target identification of small molecule prooxidant modulators including genotype-directed quinones and synthetically-lethal endoperoxides displaying anti-melanoma activity in vitro and in vivo. (II) For skin cancer photo-chemoprevention and solar photoprotection we are aiming at the design of pharmacological activators of the innate skin photo-adaptive response (SPA) that antagonizes cutaneous damage from environmental UV exposure. Non-cytotoxic small molecule SPA-inducers, acting through Nrf2-activation and heat shock response upregulation, represent a novel class of topical agents targeting skin photo-oxidative stress."
- Thiostrepton is an inducer of oxidative and proteotoxic stress that impairs viability of human melanoma cells but not primary melanocytes.
- Autophagic-lysosomal dysregulation downstream of cathepsin B inactivation in human skin fibroblasts exposed to UVA.
- The redox antimalarial dihydroartemisinin targets human metastatic melanoma cells but not primary melanocytes with induction of NOXA-dependent apoptosis.
- Zinc pyrithione impairs zinc homeostasis and upregulates stress response gene expression in reconstructed human epidermis.
- DCPIP (2,6-dichlorophenolindophenol) as a genotype-directed redox chemotherapeutic targeting NQO1*2 breast carcinoma.
- Proteomic identification of cathepsin B and nucleophosmin as novel UVA-targets in human skin fibroblasts.
- The malondialdehyde-derived fluorophore DHP-lysine is a potent sensitizer of UVA-induced photooxidative stress in human skin cells.
- Resveratrol prevents epigenetic silencing of BRCA-1 by the aromatic hydrocarbon receptor in human breast cancer cells.
- The topical antimicrobial zinc pyrithione is a heat shock response inducer that causes DNA damage and PARP-dependent energy crisis in human skin cells.
- Antimelanoma activity of the redox dye DCPIP (2,6-dichlorophenolindophenol) is antagonized by NQO1.
- The experimental chemotherapeutic N6-furfuryladenosine (kinetin-riboside) induces rapid ATP depletion, genotoxic stress, and CDKN1A(p21) upregulation in human cancer cell lines.
- The cinnamon-derived Michael acceptor cinnamic aldehyde impairs melanoma cell proliferation, invasiveness, and tumor growth.
- Cinnamoyl-based Nrf2-activators targeting human skin cell photo-oxidative stress.
- Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2.
- NQO1-activated phenothiazinium redox cyclers for the targeted bioreductive induction of cancer cell apoptosis.
- Antimelanoma activity of apoptogenic carbonyl scavengers.
- Endogenous UVA-photosensitizers: mediators of skin photodamage and novel targets for skin photoprotection.
- Identification of quenchers of photoexcited States as novel agents for skin photoprotection.
- 3-hydroxypyridine chromophores are endogenous sensitizers of photooxidative stress in human skin cells. Previous years
- Photosensitization of DNA damage by glycated proteins.
- Vitamin b6: beyond coenzyme functions.
- D: -Penicillamine targets metastatic melanoma cells with induction of the unfolded protein response (UPR) and Noxa (PMAIP1)-dependent mitochondrial apoptosis.
- Photosensitized growth inhibition of cultured human skin cells: mechanism and suppression of oxidative stress from solar irradiation of glycated proteins.
- Proteins of the extracellular matrix are sensitizers of photo-oxidative stress in human skin cells.
- Therapeutic potential of Nrf2 activators in streptozotocin-induced diabetic nephropathy.
- DNA damage by carbonyl stress in human skin cells.
- HMGB1-directed drug discovery targeting cutaneous inflammatory dysregulation.
- Identification of alpha-dicarbonyl scavengers for cellular protection against carbonyl stress.
- Reactivity-based drug discovery using vitamin B(6)-derived pharmacophores.
- Redox-directed cancer therapeutics: molecular mechanisms and opportunities.
- Let the sun shine in: mechanisms and potential for therapeutics in skin photodamage.
- GLO1 overexpression in human malignant melanoma.
- Experimental therapeutics: targeting the redox Achilles heel of cancer.