Blood Cell Development and Function
The Blood Cell Development and Function (BCDF) program at FCCC focuses on how perturbation of the processes controlling the specification of normal cell fate leads to blood cancers, how inflammation within a solid tumor may accelerate tumor promotion or growth, and how unique interactions between immune effectors and their targets can be exploited to improve cancer immunotherapy. We believe that understanding basic mechanisms of immune development and function will catalyze new opportunities for cancer treatment.
The BCDF program has three themes:
Development. Define processes that control hematopoiesis and assess their relevance to the etiology of hematologic malignancies. We assess how genetic mutations skew normal blood cell development to result in lymphomas and leukemias. Specific areas of interest within this theme include identifying critical checkpoints and molecular effectors regulating blood cell development, and then assessing the relevance of these gene products to the etiology or treatment of cancer. Our extensive B cell, T cell and myeloid development research improves our understanding of T and B cell lymphomas, as well as acute myeloid leukemia.
Inflammation. Determine how the inflammatory response prevents or controls infections, and apply that knowledge to cancer etiology and treatment. Our connection to tumor-causing viruses and chronic infections provides the foundation for current efforts to define how certain pathogens (or the chronic immune responses they induce) promote tumorigenesis, and how the complex interplay of tissue-resident cells, immune cells, and cytokines can collectively contribute to inflammation and progression of solid tumors. Work in this area focuses on cell-specific responses to soluble immune mediators, signaling pathways that may protect cells from death following apoptotic stimuli, and the contributions of immune cells to the development of solid tumors.
Immune Effectors. Optimize therapeutic checkpoint inhibitor efficacy by identifying non-responders prior to treatment, and determine how to increase the number of patients who could benefit from such approaches. Immune therapies are emerging as one of the most promising new avenues of treatment modalities, yet their beneficial effects remain restricted to a minority of patients. In this developing theme, basic and clinical researchers explore how to reverse immunological tolerance toward solid tumors by defining the expression of checkpoint molecules, such as PD-1 and PDL-1. Exciting work in renal cell cancer patients shows a direct correlation between immunological quiescence and tumor stage, providing a foundation on which to build clinical trials aimed at reinvigorating immunological recognition. This work is now being expanded to other solid tumor types, and may lead to the identification of novel biomarkers that predict responsiveness to immune therapies, and to the development of strategies that extend the beneficial effects of immune therapies to the majority of cancer patients.
Our growing group includes 20 primary and several collaborating members who work with the Molecular Therapeutics and Cancer Epigenetics Programs to accelerate translation of our basic science observations. In addition to animal models, we use cutting-edge technologies to advance these themes, including multi-parametric flow cytometry, laser capture microdissection, next-generation sequencing, adoptive cell transfers, genome editing using Zn finger nucleases and CRISPR/Cas9-mediated gene targeting, and copy number analysis, accomplished with the support of the cell culture, biological imaging, genomics, cell sorting, histopathology and transgenic mouse facilities.