A major focus for Dr. Nghiem’s group is Merkel cell carcinoma, a polyomavirus-driven skin cancer that is three times more likely to be lethal than malignant melanoma. Survival following diagnosis of this cancer is strongly linked to cellular immune function, with intratumoral CD8⁺ T cell infiltration into the tumor providing remarkable protection from subsequent recurrence/death, even among patients who present with advanced disease. The observation that antibodies to the Merkel polyomavirus oncoprotein fluctuate with disease burden is the basis for a blood test (available as of 2014) for detecting early disease recurrence. The identification and reversal of the immune evasion mechanisms of this cancer are the focus of several clinical trials led by members of an international collaborative group founded by Dr. Nghiem (www.merkelcell.org/MMIG.html). The Seattle team follows more than 1,000 patients with this cancer for outcomes and clinical trials. A second major focus is on the role of the ATR protein kinase in the replication checkpoint, a critical aspect of the response to UV DNA damage (www.pnlab.org). ATR is the relevant target of caffeine’s ability to selectively eliminate UV-damaged, p53-mutant, precancerous cells from skin. Large epidemiologic studies have shown that caffeine intake is associated with significant decreases in non-melanoma skin cancer incidence (decaf has no effect). Current studies focus on the mechanism by which ATR differentially senses the two main “pyrimidine dimer” UV DNA lesions (CPDs and 6-4PPs) and how ATR inhibition may affect error-prone lesion bypass to decrease the burden of DNA mutations in skin.