Yale SPORE in Skin Cancer Directors: Ruth Halaban, PhD Mario Sznol, MD Robert Tigelaar, MD Funded by: National Institutes of Health The Roslyn and Jeremy Meyer funds Yale Dermatology Department

Milstein Meyer Center for Melanoma Research Jeremy Meyer and Roslyn Milstein Meyer “Couple with a Cause” Gift of $2 Million/year renewable for additional 4 years

The SPORE Program Translation Research in Skin Cancer Melanomas Basal Cell Carcinoma Adequacy of the plan and/or track record to evaluate the translational research productivity of existing projects and cores, discontinue activities of low productivity, initiate new activities in response to important translational research opportunities, establish collaborations, and utilize the advice of internal and external advisers.

The SPORE Program Three cores that support SPORE activities Four translational projects Developmental Research Projects Career Development Projects

Translational Research Team SPORE Expansion 7 Roslyn Milstein Meyer Susan Cambria Robin Bessin Robert Heffernan 6 5 Number of Investigators Patient advocates 1 2 3 4 Paid investigators 4 3 2 1 Y e a r 1 Y e a r 2 ( S u b m i s s i o n )

Translational Research Team 1 Dermatology 2 YCCC/Oncology 3 Pathology 4 Surgery 5 Genetics 6 Immunobiology 7 Epidemiology 8 Chemical & Biomedical Engineering 9 Therapeutic Radiology 10 Laboratory Medicine and Genetics Molecular, Cellular, and Developmental Biology Cell Biology, New York University, NY

“The Melanoma Landscape” Comprehensive understanding of: Critical changes that drive melanomas Immunobiology of melanomas The causes for drug resistance New targets for therapy, single and combination Markers for prognosis and therapy

SPORE Biospecimen Bank Normal skin and cells Tumors Tumor cells Blood from healthy individuals Blood from patients Specimen Tracking and Annotation caTissue

Specimens’ Collection in the Tissue Bank 700 600 500 Total Number of Specimens 400 300 200 100 Submission Year 1 Year 2 Current Year 2 1/2

Serological Profiling of Melanoma Patients Marker A Marker B Concentration (ng/ml) Weeks of Treatment

Global “Omics” Test Genetic and epigenetic variations Mutations Gene expression Kinases and signal transducers MicroRNA Mike Snyder Director of the Yale Center for Genomics and Proteomics Joanne Weidhaas Assistant Professor Therapeutic radiology

Global Epigenetic Differences Between Normal and Malignant Cells Melanoma Loss Gain

Differences in Gene Expression Between Normal and Malignant Cells Melanoma Normal Gain Loss

Interactions Between the SPORE and Clinicians Help in testing for mutations in tumors for targeted therapy For example: selection of patients to therapy with PLX4032 (Plexxikon Inc.) and Imatinib (Gleevec, Novartis Pharmaceuticals), activated BRAF and KIT inhibitors, respectively.

Educational Activities Invited speakers Research in Progress meetings Workshop for all SPOREs in Skin Cancer Outreach with patient advocates

Best-Case Scenario Tumor excised Draw blood Results Comprehensive analyses: Mutations Activated targets Drug response Identify best therapy Which therapy? Results 2 4 6 8 1 DRUG A+B A B None Surviving cells Yes, this is the best for you