Pamela Bond Cassidy, Ph.D.
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Research Associate Professor
Melanoma is the most deadly of the skin cancers. My research is focused on melanoma chemoprevention. All of my current projects use agents that are designed to alleviate the mutagenic effects of UV-induced oxidative stress in order to prevent melanoma. The most mature of these projects is centered on an NCI-funded Phase II clinical trial of N-acetylcysteine for relief of UV-induced oxidative stress in human nevi (moles). In addition to testing this promising new agent in patients, we are working towards an understanding of the genetic basis of susceptibility to melanoma and response to chemopreventive agents. This effort is the foundation of our ultimate goal of offering patients a personalized program for melanoma prevention.
Another chemoprevention project arose from collaborative work with Drs. Sancy Leachman (Chair of Dermatology at OHSU) and Zalfa Abdel-Malek (world expert on melanocyte biology at the University of Cincinnati). Our group studies the melanocytes (pigment producing cells from which melanoma arises) and the effects on these cells of mutations in the melanocortin-1 receptor gene (MC1R, a.k.a the red hair gene). Our group conducted microarray expression studies of MC1R mutant melanocytes. The results suggested that a particular class of antioxidant represented by the natural product sulforaphane might compensate for loss of function of the mutant receptor, and thereby lower the risk for melanoma in patients with inherited mutations in MC1R. Preliminary in vitro and clinical studies are supportive of this model and Dr. Leachman and Dr. Cassidy are working to secure funding for testing sulforaphane for efficacy in a mouse model of UV-induced melanoma as one of the final steps in our efforts to advance the agent into a clinical trial in humans.
Quackenbush JF,** Cassidy PB,** Pfeffer LM, Boucher KM, Hawkes JE, Pfeffer SR, Kopelovich L, Leachman. (2014) Isolation of Circulating MicroRNAs from Microvesicles found in Human Plasma. Methods Mol Biol. 1102, 41-53. ** These authors contributed equally to the work
Domyan ET, Guernsey MW, Kronenberg Z, Krishnan S, Boissy RE, Vickrey A, Rodgers C, Cassidy P, Leachman SA, Fondon JW III, Yandell M, Shapiro MD. Epistatic and combinatorial effects of pigmentary gene mutations in the domestic pigeon. Current Biology 2014 Feb 17;24(4):459-64.
Cassidy PB,* Fain HD, Cassidy JP Jr., Tran S, Moos P, Boucher K, Gerads R, Florell S, Grossman D, Leachman SA (2013). Selenium for the prevention of cutaneous melanoma. Nutrients, 5(3), 725-749. * Corresponding author
Hawkes JE, Campbell J, Garvin D, Cannon-Albright L, Cassidy P, Leachman SA. (2013) Lack of GNAQ and GNA11 Germ-Line Mutations in Familial Melanoma Pedigrees with Uveal Melanoma or Blue Nevi. Front Oncol. 3(160), 1-5.
Hawkes JE, Cassidy PB, Manga P, Boissy RE, Goldgar D, Cannon-Albright L. Florell SR, Leachman SA (2013). Report of a Novel OCA2 Gene Mutation and an Investigation of OCA2 Variants on Melanoma Risk in a Familial Melanoma Pedigree.J. Dermatol. Sci., 69, 30-37.
Fan M, Pfeffer SR, Lynch HT, Cassidy P, Leachman S, Pfeffer LM, Kopelovich L. Altered transcriptome signature of phenotypically normal skin fibroblasts heterozygous for CDKN2A in familial melanoma: relevance to early intervention (2013). Oncotarget., 4, 128-41.
Harris K, Florell SR, Papenfuss J, Kohlmann W, Jahromi M, Schiffman JD, Quackenbush J, Cassidy P, Leachman S (2012). Melanoma Mimic: A Case of Multiple Pagetoid Spitz Nevi. Arch Dermatol. 148, 370-374.
Moos PJ, Olszewski K, Honeggar M, Cassidy P, Leachman S, Woessner D, Cutler NS, Veranth JM. (2011) Responses of human cells to ZnO nanoparticles: a gene transcription study. Metallomics, 3,1199-1211.
Jenkins NC, Liu T, Cassidy P, Leachman SA, Boucher KM, Goodson AG, Samdashwily G, Grossman D. (2011). The p16(INK4A) tumor suppressor regulates cellular oxidative stress. Oncogene, 30, 265-274.
Edes K, Cassidy PB, Shami PJ, Moos PJ. (2010) JS-K cytotoxicity is enhanced with knockdown of thioredoxin reductase 1. PLoS One, 5, e8786.
Kadekaro AL, Leachman S, Kavenagh RJ, Swope V, Cassidy P et al., (2010) Melanocortin 1 receptor genotype: an important determinant of the damage response of melanocytes to ultraviolet radiation. FASEB J. 24, 3850-3860.
Warters RL, Cassidy PB, Sunseri JA, Parsawar K, Zhuplatov SB, Kramer GF, Leachman SA (2010). The nuclear matrix shell proteome of human epidermis. J. Dermatol. Sci. 58, 113-122.
Goodson AG, Cotter MA, Cassidy PB, Wade M, Florell SR, Liu T, Boucher KM, Grossman D (2009). Use of oral N-acetylcysteine for protection of melanocytic nevi against UV-induced oxidative stress: towards a novel paradigm for melanoma chemoprevention. Clin Cancer Res. 15, 7434-7440.
Cotter MA, Thomas J, Cassidy P, Robinette K, Jenkins N, Florell SR, Leachman S, Samlowski WE, Grossman D (2007). N-Acetylcysteine Protects Melanocytes against Oxidative Stress/Damage and Delays Onset of Ultraviolet-Induced Melanoma in Mice. Clin Cancer Res. 3, 5952-5958.
Cassidy PB, Edes K, Nelson CC, Parsawar K, Fitzpatrick FA, Moos PJ (2006). Thioredoxin reductase partial inactivation is required for p53 inhibition by endogenous electophiles Carcinogenisis, 27, 2538-2549.
Samlowski WE, Leachman S, Wade M, Cassidy PB, Porter-Gill P, Busby L, Wheeler R, Fitzpatrick FA, Jones DA, Karpf A (2005). Evaluation of a 7-Day Continuous Intravenous Infusion of Decitabine: Inhibition of Promoter-Specific and Global Genomic DNA Methylation. J. Clin. Oncol. 23, 3897-3905.
Yu MK, Moos PJ, Cassidy PB, Wade M, Fitzpatrick FA (2004). Conditional Expression of 15-Lipoxygenase-1 Inhibits the Selenoenzyme Thioredoxin Reductase. J Biol Chem., 279, 28028-28035.
Short MD, Xie Y, Li L, Cassidy PB, Roberts JC (2003).Characteristics of Selenazolidine Prodrugs of Selenocysteine: Toxicity and Glutathione Peroxidase Induction in V79 Cells. J. Med. Chem., 46, 3308-3313.
Moos PJ, Edes K, Cassidy PB, Massuda E, Fitzpatrick FA (2003). Electrophilic Prostaglandins and Lipid Aldehydes Repress Redox-sensitive Transcription Factors p53 and Hypoxia-inducible Factor by Impairing the Selenoprotein Thioredoxin Reductase. J Biol Chem. 278, 745-750.
Cassidy PB, Moos PJ, Kelly RC, Fitzpatrick FA (2002). Cyclooxygenase-2 Induction by Paclitaxel, Docetaxel and Taxane Analogs in Human Monocytes and Murine Macrophages: Structure-Activity Relationships and Their Implications. Clin. Cancer Res. 8,846-855.
Wilmore BH, Cassidy PB, Warters RL, Roberts JC (2001). Thiazolidine Prodrugs as Protective Agents against -Radiation-Induced Toxicity and Mutagenesis in V79 cells. J. Med. Chem. 44,2661-2666.
Dominick PK, Cassidy PB, Roberts JC (2001). A New and Versatile Method for Determination of Thiolamines of Biological Importance. J. Chromatography B 761, 1-7.
Xie Y, Short MD, Cassidy PB, Roberts JC (2001). Selenazolidines as Novel Organoselenium Delivery Agents. Bioorgan. Med. Chem. Lett., 11, 2911-2913.
Roberts JC, Phaneuf HM, Dominick PD, Wilmore BH, Cassidy PB (1999). Biodistribution of [35S]-Cysteine and Cysteine Prodrugs: Impact on Chemoprotection Strategies. J. Labeled Comp. Radiopharm. 42, 485-490.
Cassidy PB, Poulter CD (1996). Transition-state Analogs as Inhibitors for Protein:Farnesyl Transferase. J. Am. Chem. Soc. 118, 8761-8762.
Steady-state Kinetic Studies of Protein:Farnesyl Transferase (1995). Dolence JM, Cassidy PB, Mathis JR, Poulter CD. Biochemistry, 34, 16687-16692.
Cassidy PB, Dolence JM, Poulter CD (1995). A Continuous Fluorescence Assay for Protein:Prenyl Transferases. Meth. Enzymol. 250 30-42.
Brown MJ, Milano PD,# Lever DC, Epstein WW, Poulter CD Prenylated Protein: A Convenient Synthesis of Farnesyl Cysteinyl Thioethers (1991). J. Am. Chem. Soc., 113 3176-3177.
#Surname from previous marriage
Prodrugs and Conjugates of Thiol- and Selenol-Containing Compounds and Methods of Use Thereof. Roberts JC, Wilmore BH, Cassidy PB, Dominick PK, Short MD. United States Patent 6,340,746, 2002.
Preparation of 2-Acyl-1,3-cycloalkanediones as Intermediates for Pesticides. Heather JB, Milano PD#. United States Patent 4,695,673, 1987.
Acylaminoaryloxy and Arylthiopyrimidines as Herbicides. Milano PD,# James DR. United States Patent 4,888,047, 1989.
#Surname from previous marriage
Cassidy PB, Moos PJ, Leachman SA. “Selenium and skin cancer”. Royal Chemical Society, London. Submitted.
Cassidy PB, Leachman SA, Grossman D (2013). “N-acetylcysteine for Reduction of Oxidative Stress/Damage and Melanoma" in Bioactive Dietary Factors and Plant Extracts in Preventative Dermatology. Watson, RR; Zibadi, S (Eds.) Springer, New York.
Cassidy PB, Grossman D, Leachman SA (2012). “Melanoma Prevention” in Emerging Therapeutics for Melanoma, Francesco M Marincola Paolo Ascierto John M Kirkwood, editors. Future Medicine Ltd Unitec House, 2 Albert Place, London N3 1QB, UK 9781780840321.