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Blood Cell Development and Function

 Siddharth Balachandran and David Wiest are the co-leaders of the blood cell development and function program at Fox Chase, which is dedicated to understanding the basic mechanisms of immune development and function to catalyze new opportunities for cancer treatment. Siddharth Balachandran and David Wiest are the co-leaders of the blood cell development and function program at Fox Chase, which is dedicated to understanding the basic mechanisms of immune development and function to catalyze new opportunities for cancer treatment.

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 is historically rooted in investigations of immune function during chronic diseases, including viral infections and cancers, and in hematopoietic and lymphoid development. During the last five years, these strengths have organized around three related themes:

1. Development

Define processes that control hematopoiesis and assess their relevance to the etiology or treatment of hematologic malignancies. A major programmatic strength is its high-caliber expertise in immune cell development, and in the assessment of how dysregulated hematopoietic processes spark transformation. The Program has an extensive track record and established expertise in the study of B cell, T cell, and myeloid cell development, which has revealed novel therapeutic vulnerabilities in B cell lymphomas, as well as of acute myeloid leukemia (AML). Efforts to understand the inflammatory etiology of particular hematologic malignancies link the development and inflammation themes.

2. Inflammation

Determine how inflammation promotes cancer progression and how innate immunity can be exploited for cancer therapy. This Program’s long-standing connection to chronic and oncogenic virus infections was foundational for current efforts aimed at defining how inflammatory and innate-immune processes both promote and prevent tumorigenesis. Studies on immunogenic cell death mechanisms have had a major impact in revealing a critical new approach for leveraging innate immune signals to render cold tumors sensitive to immunotherapeutic interventions. The exploration of innate immune agonists as potentiators of immunotherapeutic interventions links the inflammation and immune effectors themes.

3. Immune Effectors

Leverage insights into the control of immune cell function to optimize their efficacy as anti-cancer effectors. Program members explore how the action of immune cells can be controlled, with the aims of reversing unresponsiveness to immunotherapy and preventing immune exhaustion. Exciting insights into innate immune signaling are being leveraged pre-clinically as well as in clinical trials to enhance the efficacy of immune checkpoint blockade. These efforts have led to the potentially practice-changing discovery that interferon is capable of mitigating immunotherapy related adverse events. Immune-based treatments of hematologic malignancies links the effector and development themes.

New and established collaborations between BCDF Program members and those in other Programs (e.g., MT and CSE) accelerate the translation of basic science observations. Progress toward this goal is aided by new collaborations with colleagues who have joined the Program as a result of the Temple affiliation, and by recent success in obtaining support for translational projects. Pursuit of programmatic goals is critically dependent on CCSG-supported Shared Resources comprising state-of-the-art technologies, including multi-parametric flow cytometry, next-generation sequencing, and the generation of novel animal models using CRISPR/Cas9 genome editing, achieved through essential support from the Cell Sorting (CSF), Genomics (GF), Laboratory Animal (LAF), and Transgenic Mouse Facilities (TMF).

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