Skin cancer is the most common group of malignancies in humans.
Our research is focused on the mechanisms of skin cancer development and progression. For our studies, we utilize a combination of cell culture, in-vivo mouse models and human skin samples to explore four primary areas:
1) Genomic Analysis of Cutaneous Squamous Cell Carcinoma Progression
Cutaneous squamous cell carcinoma (cSCC) is the 2nd most common skin cancer. It has the best established clinical and histologic progression sequence of all skin cancers, most often arising in UV-irradiated skin, progressing to the preneoplastic actinic keratosis (AK), and then to invasive carcinoma (cSCC). We have undertaken a comprehensive integrated genomic approach to understand the molecular drivers of this progression sequence so as to identify molecular biomarkers that predict risk of progression and to identify pathways and genes. We are interested in addressing the following questions: (1) What are the major driver pathways of cSCC progression ?; (2) Which proteins or RNAs may be used as biomarkers of risk of progression and which may be used as targets for molecularly-driven chemoprevention ?
Click here for a video description of this project (Duncan Family Institute)
Recent papers: Nat Commun 2016, J Invest Dermatol 2016
2) Interactions of MAP Kinase Pathways in Targeted Therapy for Melanoma
Metastatic melanoma is an incurable cancer that often arises in the skin, but recent developments in targeted therapy and immune therapy offer important survival benefits. We have recently discovered a novel and unexpected interaction between targeted therapies for melanoma (vemurafenib / PLX4720) and stress-activated MAP kinase pathways. This has important clinical implications for combining these therapies with other modalities that induce apoptosis and may also explain in part some of the adverse reactions to these drugs, including the development of squamous cell carcinomas. We are interested in answering the following questions: (1) What are the mechanisms by which these drugs impact apoptosis and autophagy pathways ?; (2) How do the effects on these pathways affect response of tumor cells to therapy or explain adverse effects of these drugs ?
Recent papers: Oncotarget 2016, Elife 2013, Molecular Cancer Therapeutics 2013
3) Establishment of Skin as a Surrogate Biomarker in Targeted Therapies
Since the advent of imatinib, molecularly targeted therapy has revolutionized cancer treatment. There are now several rationally-designed antibody-based and small molecule inhibitors that have produced impressive clinical responses. Despite this, one fundamental problem is the inability to predict who will respond and who will not, a critical determinant of the ability to practice truly personalized medicine. How can the patients most likely to respond be identified and optimally treated with appropriate drugs ? How can mechanisms of acquired resistance be predicted ? Can off-target effects be predicted and managed proactively ?
This presents an opportunity to establish skin as a surrogate biomarker of drug efficacy in vivo. We have been actively involved in the development of a novel proprietary reagent that enables the solubilization of tissue with preservation of protein and nucleic acids. We have already validated its safety and functionality in mouse skin and will soon establish safety and efficacy of sample recovery and skin solubilization in humans. Our plan is to establish this technology as a means of profiling epidermal cells in vivo. We are interested in addressing the following questions: (1) Can gene expression and phospho-protein profiles of skin be used as biomarkers for targeted therapies or drugs with narrow therapeutic indices ?; (2) Can this non-invasive technology optimize drug dosing, safety, and monitoring ?
Recent papers: Drug Delivery and Translational Research 2012, 2013; European Journal of Pharmaceutical Sciences
4) The Immunology of Skin Cancer
The immune status of patients and model organisms dramatically impacts the development and progression of many cancers, in particular skin cancers such as squamous cell carcinoma (SCC). Organ transplant recipients are at extremely high risk for these cancers, which are not only more frequent, but more lethal in these immunosuppressed individuals. We are interested in answering the following questions: (1) How do immune cell subsets such as regulatory T-cells or cytotoxic T-cells contribute to tumor progression and tumor control ?; (2) How do tumors escape immune destruction or adapt to immune pressure ?
Recent papers: Exp Dermatol 2016, British Journal of Dermatology 2011
Copyright Kenneth Y. Tsai, 2011, Created with 1&1 WebsiteBuilder
H. Lee Moffitt Cancer Center & Research Institute
12902 Magnolia Dr, SRB-3
Tampa, FL 33612
Phone: (813) 745-4864