Core 1: Biospecimen and Data Management Core

Our Biospecimen and Data Management Core will be utilized by all the Research Projects in our Center. All three Research Projects aim to identify mechanisms by which tumor cells, metastatic to regional lymph nodes, interface with the host immune system to perturb systemic immunity to induce global immune tolerance. While we will methodically study this process in murine models (Project 1), analysis of human tumor and lymph node specimens is paramount for two primary reasons. The first reason is to ensure the translation of the murine discovery approach to human disease. The second reason is to facilitate the discovery of critical mediators of tumor-induced immunosuppression directly from the human samples, then follow with functional validation in our murine models. Hence it is critical that we establish the necessary infrastructure to procure viable human tumor specimens and autologous immune tumorinfiltrating immune cells. Importantly, matched sets of fresh primary tumor cells, metastatic tumor cells, tumor-infiltrating immune cells (from the primary tumor and the lymph nodes) and circulating immune cells will be collected to address the hypotheses and goals of the Research Projects. Furthermore, in this shared core, a database of clinical annotation (aka clinical metadata) for these matched samples will be created and maintained. This clinical metadata is critical for interpretation of our molecular and imaging data given tumor and patient heterogeneity and will likely provide important insight into how the data generated by the proposed projects may be used to guide treatment and predict outcome. Our proposed Biospecimen and Data Management Core that will focus on collecting tissue and collating all the molecular data on our two index cancer models: melanoma and head and neck squamous cell carcinoma (HNSCC).

John Sunwoo, MD, PhD

John Sunwoo M.D., Ph.D. is Professor of Otolaryngology (Head and Neck Surgery). Dr Sunwoo received his undergraduate degree from Brown University in Providence, Rhode Island and his medical degree from Washington University in St. Louis, Missouri. He completed his training in Otolaryngology – Head and Neck Surgery at Washington University. Dr. Sunwoo has been at Stanford University since 2008, and his clinical focus is on the surgical management of head and neck cancer, specifically focusing on melanoma and neoplasms of the thyroid and parathyroid glands. He is a member of the Pigmented Lesions and Melanoma Clinic and the Melanoma Working Group at Stanford. He is also the co-founder of the Stanford Thyroid and Parathyroid Tumor Board.

In addition to his clinical work, Dr. Sunwoo is the Director of Head and Neck Cancer Research at Stanford University and the principal investigator of an NIH-funded laboratory in the Stanford Cancer Institute. His research is focused on three primary areas: (1) the immune response to cancer, particularly a tumorigenic population of cells within malignancies called cancer stem cells; (2) the biology and developmental programs of a special lymphocyte population involved in innate immunity called natural killer (NK) cells; and (3) intra-tumor and inter-tumor heterogeneity in head and neck cancer. A major focus of the Sunwoo lab is the study of natural killer (NK) cells, a special lymphocyte population critically involved in the innate immune response to viral infections and malignancy. They are interested in understanding the regulation of NK cell development, homeostasis, and effector functions. One such regulator of these processes is the aryl hydrocarbon receptor (AhR), a cytoplasmic receptor that binds numerous endogenous and exogenous ligands. They recently showed that these small molecule ligands can modulate NK cell homeostasis and anti-tumor functions.

An overarching goal of the lab is to understand how the immune system interfaces with and protects against developing and metastasizing tumor cells, especially a rare population of tumor-initiating cells called cancer stem cells. In these studies, they utilize human and mouse models of head and neck squamous cell carcinoma (HNSCC) and melanoma. The lab is investigating novel mechanisms by which malignant cells can alert the immune system at the earliest stages of transformation. The lab also studies how regulators of genetic networks control the behavioral features of a subset of cells with stem cell–like properties. These cells are more resilient and have the ability to metastasize and are more resistant to chemotherapy and radiation therapy. A particularl interest is identifying mechanisms by which these tumor-initiating cells can selectively suppress the host immune response and understanding how to overcome these immunosuppressive properties.

Andrew Gentles, PhD

Andrew Gentles, Ph.D. is Assistant Professor of Medicine (Biomedical Informatics Research) Dr. Gentles has been part of the Stanford ICBP for the past 8 years serving as Scientific Program Manager for the past 5 years. He lead the CCSB Data Integration and Analytics Core, creating a focal point for sharing data and facilitating collaborations between the different groups in the previous CCSB center and he co-leads the Data Core for the new center. Dr. Gentles developed prognostic signatures based on genomic data for AML, specifically the influence of leukemic stem cells, lung cancer, and large cell lymphoma. His research interests are in systems biology of cancer, integration/analysis of proteomic and genomic data to computationally infer biological insights about molecular pathways, analysis of next-generation sequencing data.