Ana Luisa Luisa Kadekaro , PhD

Bachelor's Degree: University of Sao Paulo 1986 (Biological Sciences)

Master's Degree: University of Sao Paulo 1995 (Physiology)

Master's Degree: Uniformed Services University of the Health Sciences 1999 (Cell Biology)

Doctoral Degree: University of Sao Paulo 2000 (Physiology)

Doctoral Degree: University of Cincinnati School of Medicine Dermatology 2005 (Dermatology)

Sunlight is the most important environmental factor for melanoma development. Regardless of which spectrum of UVR is important in the genesis of melanoma, there is strong evidence in support of oxidative stress as the main cause of the malignant transformation of human melanocytes (MCs). A large percentage of individuals from Caucasian populations are carriers of disabling mutations on the melanocortin 1 receptor (MC1R) gene, the receptor of a-melanocyte stimulating hormone (a-MSH) and major regulator of the tanning responses of the skin. My research focuses in investigating the molecular pathways induced by UVR in human MCs, with emphasis on the antioxidant mechanisms that protect the cells against reactive oxygen species (ROS) and carcinogenesis. Our major contribution to the field of photobiology and skin carcinogenesis was to identify a new physiological role for a-MSH in the skin. We demonstratedthata-MSH elicits early responses in MCs that are independent of melanin synthesis (tanning) and protect against the damaging effects of UVR, by reducing oxidative stress and increasing the repair of damaged DNA.Our studies also revealed that this protection was absent in MCs derived from individuals with the clinical phenotype of red hair, fair and freckled skin and inability to tan. Our reports evidenced that MCs carrying variants of the MC1R sustained high levels of oxidative stress and DNA damage. The goal of my studies is to identify molecular targets to be tested in new strategies for prevention and development of melanoma. We anticipate that directly targeting key molecules of antioxidant pathways in MCs will be especially beneficial to individuals that are genetically susceptible to oxidative stress and melanoma.

Investigators:Zalfa Abdel-Malek, Ana Luisa Kadekaro 04-01-2008 -03-31-2013 NEIHS Signaling Pathways for UV-induced Melanogenic Response Role:Co-investigator $1,068,750 Active Type:Grant

Investigators:Ana Luisa Kadekaro 07-01-2010 -06-30-2011 Dermatology Foundation Research Award Increase in p53 Expression as a Stragety for Melanoma Prevention Role:Principal Investigator $20,000 Completed Type:Grant

Investigators:Ana Luisa Kadekaro 07-01-2010 -06-30-2012 NIEHS - R21 Defining a new role for a-MSH: antioxidante in UVB-irradiated melanocytes Role:Principal Investigator $431,750 Active Type:Grant

Investigators:Principal Investigator 04-06-2010 -08-02-2012 CEG-NGB, University of Cincinnati Role of melanocyte as a major contributor to skin homeostasis against oxidative stress Role:Principal Investigator $15,640 Active Type:Grant

Investigators:Ana Luisa Kadekaro 04-06-2010 -08-02-2012 CEG-NGB, University of Cincinnati Transfer of catalase from melanocytes to keratinocytes a novel mechanism of antioxidant protection in the skin Role:Principal Investigator $12,600 Active Type:Grant

Grant: #5206 Investigators:Kadekaro, Ana Luisa 07-01-2006 -06-30-2008 Ohio Cancer Research Associates Towards Understanding Melanoma Formation: Defining the Regulation of p53 and its Pathway Role:PI $49,998.00 Active Level:Private Non-Profit

Grant: #2003-UC-16-03-A0-S0-E0 Investigators:Kadekaro, Ana Luisa 11-01-2002 -10-31-2005 Johnson & Johnson Alpha-Melanocortin and Endothelin-1 Promote Humane Melanocyte Survival by Inhibiting Apoptosis in Response to Ultraviolet Radiation Role:PI $154,545.40 Closed Level:Industry

Grant: #004967-001 Investigators:Kadekaro, Ana Luisa 07-01-2007 -06-30-2008 Dermatology Foundation Post-Translational Modification of p53 Differentially Affects the UV Response of Human Melanocytes Role:PI $20,000.00 Closed Level:Private Non-Profit

Grant: #SRS 5381 Investigators:Kadekaro, Ana Luisa 01-01-2008 -12-21-2008 American Skin Association The Role of Alpha-MSH in Melanocyte Neoplasia Role:PI $15,000.00 Active Level:Private Non-Profit

Grant: #R01 ES009110 Investigators:Abdelmalek, Zalfa; Boissy, Raymond; Kadekaro, Ana Luisa; McGraw, Dennis 04-01-2008 -03-31-2014 National Institute of Environmental Health Sciences Signaling Pathways for UV-Induced Melanogenic Response Role:Collaborator $1,629,641.00 Active Level:Federal

Grant: #R01 ES017561 Investigators:Abdelmalek, Zalfa; Kadekaro, Ana Luisa; Supp, Dorothy 07-20-2009 -04-30-2014 National Institute of Environmental Health Sciences Impact of MC 1R Functional Variants on the DNA Damage Response of Human Melanocytes Role:Collaborator $1,795,727.00 Active Level:Federal

Grant: #SRS 006872 Investigators:Kadekaro, Ana Luisa 07-01-2010 -06-30-2011 Dermatology Foundation Increase in p53 Expression as a Strategy for Melanoma Prevention Role:PI $20,000.00 Active Level:Private Non-Profit

Grant: #R21 ES016900 Investigators:Kadekaro, Ana Luisa; Shertzer, Howard; Tam, Neville Ngai Chung 07-07-2010 -06-30-2013 National Institute of Environmental Health Sciences Defining a New Role for Alpha-MSH: Antioxidant in UVB-Irradiated Melanocytes Role:PI $429,788.00 Active Level:Federal

Grant: #W81XWH-14-1-0348 / CA130409 Investigators:Abdelmalek, Zalfa; Kadekaro, Ana Luisa 09-30-2014 -09-29-2016 Department of the Army Medical Research Acquisition Activity Differential impact of p16 mutations with or without co-expression of MC1R mutation on the UV response of melanocytes, and hence on the risk for melanoma. Role:Collaborator $464,034.00 Awarded Level:Federal

Grant: #W81XWH-16-0-0489 (CA150055) Investigators:Abdelmalek, Zalfa; Kadekaro, Ana Luisa; Merino, Edward; Zhang, Yuhang 09-01-2016 -08-31-2018 Department of the Army Medical Research Acquisition Activity Exploring a New Paradigm in Melanoma Prevention Role:PI $631,883.00 Awarded Level:Federal

Grant: #R15 CA228014 Investigators:Abdelmalek, Zalfa; Kadekaro, Ana Luisa; Zhang, Yuhang 04-01-2018 -03-31-2021 National Cancer Institute Breaking down the matrix in the melanoma microenvironment: Mechanism and therapeutic evaluation Role:Collaborator $480,750.00 Awarded Level:Federal

Grant: #R15ES029675 Investigators:Kadekaro, Ana Luisa; Merino, Edward 09-12-2019 -08-31-2022 National Institute of Environmental Health Sciences Limiting UV-induced genome instability with self-cycling antioxidant reagents Role:Collaborator $461,056.00 Awarded Level:Federal

Grant: #W81XWH-16-1-0489 (CA150055) Investigators:Abdelmalek, Zalfa; Kadekaro, Ana; Merino, Edward; Zhang, Yuhang 09-01-2016 -08-31-2019 Department of the Army Medical Research Acquisition Activity Exploring a New Paradigm in Melanoma Prevention Role:PI $631,883.00 Closed Level:Federal

Grant: #R21CA183440 Investigators:Abdelmalek, Zalfa; Kadekaro, Ana 03-13-2014 -02-28-2017 National Cancer Institute How p16 and MC1R mutations synergistically exacerbate melanoma risk. Role:Collaborator $389,061.00 Closed Level:Federal

Peer Reviewed Publications

Kadekaro, Ana Luisa; Leachman, Sancy; Kavanagh, Renny J; Swope, Viki; Cassidy, Pamela; Supp, Dorothy; Sartor, Maureen; Schwemberger, Sandy; Babcock, George; Wakamatsu, Kazumasa; Ito, Shosuke; Koshoffer, Amy; Boissy, Raymond E; Manga, Prashiela; Sturm, Richard A; Abdel-Malek, Zalfa A (2010. ) Melanocortin 1 receptor genotype: an important determinant of the damage response of melanocytes to ultraviolet radiation.The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, , 24 (10 ) ,3850-60 More Information

Abdel-Malek, Zalfa A; Kadekaro, Ana Luisa; Swope, Viki B (2010. ) Stepping up melanocytes to the challenge of UV exposure.Pigment cell & melanoma research, , 23 (2 ) ,171-86 More Information

Song, Xiuzu; Mosby, Nicole; Yang, Jennifer; Xu, Aie; Abdel-Malek, Zalfa; Kadekaro, Ana Luisa (2009. ) alpha-MSH activates immediate defense responses to UV-induced oxidative stress in human melanocytes.Pigment cell & melanoma research, , 22 (6 ) ,809-18 More Information

Abdel-Malek, Zalfa A; Ruwe, Andrew; Kavanagh-Starner, Renny; Kadekaro, Ana Luisa; Swope, Viki; Haskell-Luevano, Carrie; Koikov, Leonid; Knittel, James J (2009. ) alpha-MSH tripeptide analogs activate the melanocortin 1 receptor and reduce UV-induced DNA damage in human melanocytes.Pigment cell & melanoma research, , 22 (5 ) ,635-44 More Information

Abdel-Malek, Zalfa A; Knittel, James; Kadekaro, Ana Luisa; Swope, Viki B; Starner, Renny The melanocortin 1 receptor and the UV response of human melanocytes--a shift in paradigm.Photochemistry and photobiology, , 84 (2 ) ,501-8 More Information

Kadekaro, Ana Luisa; Abdel-Malek, Zalfa A (2007. ) Walking in the footsteps of giants: melanocortins and human pigmentation, a historical perspective.Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society, , 20 (3 ) ,150-2 More Information

Kadekaro, Ana Luisa; Wakamatsu, Kazumasa; Ito, Shosuke; Abdel-Malek, Zalfa A (2006. ) Cutaneous photoprotection and melanoma susceptibility: reaching beyond melanin content to the frontiers of DNA repair. Frontiers in bioscience : a journal and virtual library, , 11 ,2157-73

Hauser, Jennifer E; Kadekaro, Ana Luisa; Kavanagh, Renny J; Wakamatsu, Kazumasa; Terzieva, Silva; Schwemberger, Sandy; Babcock, George; Rao, M B; Ito, Shosuke; Abdel-Malek, Zalfa A (2006. ) Melanin content and MC1R function independently affect UVR-induced DNA damage in cultured human melanocytes.Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society, , 19 (4 ) ,303-14 More Information

Abdel-Malek, Zalfa A; Kadekaro, Ana Luisa; Kavanagh, Renny J; Todorovic, Aleksandar; Koikov, Leonid N; McNulty, Joseph C; Jackson, Pilgrim J; Millhauser, Glenn L; Schwemberger, Sandy; Babcock, George; Haskell-Luevano, Carrie; Knittel, James J (2006. ) Melanoma prevention strategy based on using tetrapeptide alpha-MSH analogs that protect human melanocytes from UV-induced DNA damage and cytotoxicity.The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, , 20 (9 ) ,1561-3 More Information

Kadekaro, Ana Luisa; Kavanagh, Renny; Kanto, Hiromi; Terzieva, Silva; Hauser, Jennifer; Kobayashi, Nobuhiko; Schwemberger, Sandy; Cornelius, James; Babcock, George; Shertzer, Howard G; Scott, Glynis; Abdel-Malek, Zalfa A (2005. ) alpha-Melanocortin and endothelin-1 activate antiapoptotic pathways and reduce DNA damage in human melanocytes.Cancer research, , 65 (10 ) ,4292-9 More Information

Rouzaud, Francois; Kadekaro, Ana Luisa; Abdel-Malek, Zalfa A; Hearing, Vincent J (2005. ) MC1R and the response of melanocytes to ultraviolet radiation.Mutation research, , 571 (1-2 ) ,133-52 More Information

Kadekaro, Ana Luisa; Andrade, Luciana N S; Floeter-Winter, Lucile M; Rollag, Mark D; Virador, Victoria; Vieira, Wilfred; Castrucci, Ana Maria de L (2004. ) MT-1 melatonin receptor expression increases the antiproliferative effect of melatonin on S-91 murine melanoma cells. Journal of pineal research, , 36 (3 ) ,204-11

Kadekaro, Ana Luisa; Kavanagh, Renny J; Wakamatsu, Kazumasa; Ito, Shosuke; Pipitone, Michelle A; Abdel-Malek, Zalfa A (2003. ) Cutaneous photobiology. The melanocyte vs. the sun: who will win the final round? .Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society, , 16 (5 ) ,434-47

Kadekaro, Ana Luisa; Kanto, Hiromi; Kavanagh, Renny; Abdel-Malek, Zalfa A (2003. ) Significance of the melanocortin 1 receptor in regulating human melanocyte pigmentation, proliferation, and survival. Annals of the New York Academy of Sciences, , 994 ,359-65

Scott, M Cathy; Wakamatsu, Kazumasa; Ito, Shosuke; Kadekaro, Ana Luisa; Kobayashi, Nobuhiko; Groden, Joanna; Kavanagh, Renny; Takakuwa, Takako; Virador, Victoria; Hearing, Vincent J; Abdel-Malek, Zalfa A (2002. ) Human melanocortin 1 receptor variants, receptor function and melanocyte response to UV radiation. Journal of cell science, , 115 (Pt 11 ) ,2349-55

Kadekaro, Ana Luisa; Chen, Juping; Yang, Jennifer; Chen, Shuna; Jameson, Joshua; Swope, Viki B; Cheng, Tan; Kadakia, Madhavi; Abdel-Malek, Zalfa (2012. ) Alpha-melanocyte-stimulating hormone suppresses oxidative stress through a p53-mediated signaling pathway in human melanocytes.Molecular cancer research : MCR, , 10 (6 ) ,778-86 More Information

Zhou, Linli; Yang, Kun; Dunaway, Spencer; Abdel-Malek, Zalfa; Andl, Thomas; Kadekaro, Ana Luisa; Zhang, Yuhang (2018. ) Suppression of MAPK signaling in BRAF-activated PTEN-deficient melanoma by blocking ?-catenin signaling in cancer-associated fibroblasts.Pigment cell & melanoma research, , 31 (2 ) ,297-307 More Information

AbdulSalam, Safnas F; Gurjar, Purujit N; Zhu, Haizhou; Liu, Jing; Johnson, Emma S; Kadekaro, Ana Luisa; Landero-Figueroa, Julio; Merino, Edward J (2017. ) Self-Cyclizing Antioxidants to Prevent DNA Damage Caused by Hydroxyl Radical.Chembiochem : a European journal of chemical biology, , 18 (20 ) ,2007-2011 More Information

Andl, Thomas; Zhou, Linli; Yang, Kun; Kadekaro, Ana Luisa; Zhang, Yuhang (2017. ) YAP and WWTR1: New targets for skin cancer treatment.Cancer letters, , 396 ,30-41 More Information

Zhou, Linli; Yang, Kun; Wickett, R Randall; Kadekaro, Ana Luisa; Zhang, Yuhang (2016. ) Targeted deactivation of cancer-associated fibroblasts by ?-catenin ablation suppresses melanoma growth.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, , 37 (10 ) ,14235-14248 More Information

2004 Young Investigator Award in the post-doctoral category PanAmerican Society for Pigment Cell Research Status:Recipient Level:International Type:Recognition

2006 Young Investigator Award in the junior faculty category PanAmerican Society for Pigment Cell Research Status:Recipient Level:International Type:Recognition

Research - Medical Science Building Room 7506
231 Albert Sabin Way
Cincinnati  Ohio, 45267-0592
Phone: 513-558-6659
Fax: 513-558-0198
kadekaal@uc.edu

Academic - Medical Science Building
Cincinnati  Ohio, 45267
Phone: 513-558-6242
analuisa.kadekaro@uc.edu