PROJECT SUMMARY Nearly 20% of the worldwide burden of cancer is due to pathogens, mostly viruses and some specific bacteria. The Pathogen Associated Malignancies (PAM) Program studies pathogen associated malignancies to better prevent, diagnose, and treat these cancers. Additionally, the program aims to understand the mechanisms by which the microbiome can influence the development of cancers. The program spans basic research, treatment, and public health, and currently has 43 members across three institutions. Program members and leadership have expertise in viral and bacterial pathogenesis, infectious diseases, oncology, and public health research. Basic research focuses on HPV and genetic instability, mechanisms of Merkel Cell polyomavirus oncogenicity, KSHV latency, Helicobacter pylori’s ability to synergize with oncogenic mutations, and the effects of Fusobacterium nucleatum on the tumor microenvironment. Clinical trials include immunotherapeutic approaches to cure Merkel Cell Carcinoma. The program also has human and animal studies exploring the connections between the gut microbiota and cancer outcomes, including graft-versus-host disease, immune reconstitution after hematopoietic cell transplantation, and response to immunotherapy for cancer. The PAM program currently has $12.3M in grant funding (direct costs) of which $4.2M is from NCI. Much of the research is funded by R01s to individual investigators. Large, collaborative grants with members in both PAM and other Consortium programs include a P01 on immunology and immune therapy for Merkel cell carcinoma, a P20 on cancer health disparities, and a U54 on HPV-related cancer prevention. PAM provides many venues to stimulate intra- and inter-programmatic interactions including the yearly retreat bringing together researchers working on the microbiome with those working on virally induced cancers. There are also weekly virology meetings, monthly microbiome meetings and a wide array of sponsored seminars. Pilot grants promote new collaborations between PAM members with other investigators. The program published a total of 330 papers in the current grant cycle, of which 19% were intraprogrammatic and 43% were interprogrammatic.