Clara N Curiel
Director, Cutaneous Oncology Program
Professor, BIO5 Institute
Professor, Medicine - (Tenure Track)
Primary Department
Department Affiliations
(520) 626-0307
Research Interest
Clara Curiel-Lewandroski, PhD, is the director of the Pigmented Lesion Clinic and Multidisciplinary Cutaneous Oncology Program, both part of the University of Arizona Cancer Center Skin Cancer Institute. She completed two research fellowships, the first in the Department of Dermatology at Harvard Medical School, and the second at the Ludwig Boltzman Institute and Immunobiology of the Skin at Miinster University in Germany. Dr. Curiel is certified by the American Board of Dermatology.Dr. Curiel-Lewandroski’s research focus is on melanoma chemoprevention, early detection of melanoma, cutaneous T cell lymphomas and skin cancer. She studied the extended use of non-steroidal anti-inflammatory drugs, particularly aspirin, and their ability to possibly decrease the risk of cutaneous medanoma (CM) development. CM is responsible for more than 77 percent of skin cancer deaths.

Publications

Curiel-Lewandrowski, C., Kim, C. C., Swetter, S. M., Chen, S. C., Halpern, A. C., Kirkwood, J. M., Leachman, S. A., Marghoob, A. A., Ming, M. E., Grichnik, J. M., & , M. P. (2012). Survival is not the only valuable end point in melanoma screening. The Journal of investigative dermatology, 132(5), 1332-7.
Curiel, R., Perez-Gonzalez, J. F., Brito, N., Zerpa, R., & Curiel, C. N. (1989). Positive inotropic effect mediated by alpha-1 adrenoceptor in intact human subjects. J Cardiovasc Pharmacol, 61(4), 603-615.
Arzberger, E., Curiel-Lewandrowski, C., Blum, A., Chubisov, D., Oakley, A., Rademaker, M., Soyer, H., & Hofmann-Wellenhof, R. (2016). Teledermoscopy in High-risk Melanoma Patients: A Comparative Study of Face-to-face and Teledermatology Visits. Acta dermato-venereologica.

Teledermoscopy is considered a reliable tool for the evaluation of pigmented skin lesions. We compared the management decision in face-to-face visits vs. teledermatology in a high-risk melanoma cohort using total-body photography, macroscopic and dermoscopic images of single lesions. Patients were assessed both face-to face and by 4 remote teledermatologists. Lesions identified as suspicious for skin cancer by face-to-face evaluation underwent surgical excision. The teledermatologists recommended "self-monitoring", "short-term monitoring", or "excision". A 4-year monitoring was completed in a cohort of participating subjects. The general agreement, calculated by prevalence and bias-adjusted κ (PABAK), showed almost perfect agreement (PABAK 0.9-0.982). A total of 23 lesions were excised; all teledermatologists identified the 9 melanomas. The greatest discrepancy was detected in "short-term monitoring". During 4-year monitoring one melanoma was excised that had been considered benign. In conclusion, melanoma identification by experts in pigmented lesions appears to be equivalent between face-to-face and teledermatological consultation.

Janda, J., Burkett, N. B., Blohm-Mangone, K., Huang, V., Curiel-Lewandrowski, C., Alberts, D. S., Petricoin, E. F., Calvert, V. S., Einspahr, J., Dong, Z., Bode, A. M., Wondrak, G. T., & Dickinson, S. E. (2016). Resatorvid-based Pharmacological Antagonism of Cutaneous TLR4 Blocks UV-induced NF-κB and AP-1 Signaling in Keratinocytes and Mouse Skin. Photochemistry and photobiology, 92(6), 816-825.

Cutaneous exposure to solar ultraviolet (UV) radiation is a major causative factor in skin carcinogenesis, and improved molecular strategies for efficacious chemoprevention of nonmelanoma skin cancer (NMSC) are urgently needed. Toll-like receptor 4 (TLR4) signaling has been shown to drive skin inflammation, photoimmunosuppression, and chemical carcinogenesis. Here we have examined the feasibility of genetic and pharmacological antagonism targeting cutaneous TLR4 for the suppression of UV-induced NF-κB and AP-1 signaling in keratinocytes and mouse skin. Using immunohistochemical and proteomic microarray analysis of human skin, we demonstrate for the first time that a significant increase in expression of TLR4 occurs in keratinocytes during the progression from normal skin to actinic keratosis, also detectible during further progression to squamous cell carcinoma. Next, we demonstrate that siRNA-based genetic TLR4 inhibition blocks UV-induced stress signaling in cultured keratinocytes. Importantly, we observed that resatorvid (TAK-242), a molecularly targeted clinical TLR4 antagonist, blocks UV-induced NF-κB and MAP kinase/AP-1 activity and cytokine expression (Il-6, Il-8, and Il-10) in cultured keratinocytes and in topically treated murine skin. Taken together, our data reveal that pharmacological TLR4 antagonism can suppress UV-induced cutaneous signaling, and future experiments will explore the potential of TLR4-directed strategies for prevention of NMSC.

Gao, G., Zhang, T., Wang, Q., Reddy, K., Chen, H., Yao, K., Wang, K., Roh, E., Zykova, T., Ma, W., Ryu, J., Curiel-Lewandrowski, C., Alberts, D., Dickinson, S. E., Bode, A. M., Xing, Y., & Dong, Z. (2017). ADA-07 Suppresses Solar Ultraviolet-Induced Skin Carcinogenesis by Directly Inhibiting TOPK. Molecular cancer therapeutics, 16(9), 1843-1854.

Cumulative exposure to solar ultraviolet (SUV) irradiation is regarded as the major etiologic factor in the development of skin cancer. The activation of the MAPK cascades occurs rapidly and is vital in the regulation of SUV-induced cellular responses. The T-LAK cell-originated protein kinase (TOPK), an upstream activator of MAPKs, is heavily involved in inflammation, DNA damage, and tumor development. However, the chemopreventive and therapeutic effects of specific TOPK inhibitors in SUV-induced skin cancer have not yet been elucidated. In the current study, ADA-07, a novel TOPK inhibitor, was synthesized and characterized. Pull-down assay results, ATP competition, and in vitro kinase assay data revealed that ADA-07 interacted with TOPK at the ATP-binding pocket and inhibited its kinase activity. Western blot analysis showed that ADA-07 suppressed SUV-induced phosphorylation of ERK1/2, p38, and JNKs and subsequently inhibited AP-1 activity. Importantly, topical treatment with ADA-07 dramatically attenuated tumor incidence, multiplicity, and volume in SKH-1 hairless mice exposed to chronic SUV. Our findings suggest that ADA-07 is a promising chemopreventive or potential therapeutic agent against SUV-induced skin carcinogenesis that acts by specifically targeting TOPK. Mol Cancer Ther; 16(9); 1843-54. ©2017 AACR.