Program Project Grants (PPGs) support broadly based, multidisciplinary, often long-term research projects that have a major objective or theme. PPGs generally involve a relatively large group and subprojects directed toward understanding various aspects or components of the central objective.

Innate Immune Therapy for B-Cell Malignancies
PI: John Byrd, MD

This work builds on the hypothesis that combination approaches that enhance innate immune function, reduce tumor-cell mediated immune suppression and induce apoptosis in primary CLL cells will significantly improve therapy. This project is directed toward treating CLL through immune therapy and without chemotherapy.

Myeloid-Derived Suppressor Cell Effects on Antibody Therapy
PI: William Carson, MD

This project is directed toward developing anti-myeloid-derived suppressor cellregimens that will improve the effectiveness of cancer immunotherapy.

Role of 11q23 Chromosome Abnormalities in the Causation of Acute Leukemia
PI: Carlo M. Croce, MD

Patients with ALL1-associated leukemias, particularly infants, which constitute the largest group at risk, have a dismal prognosis. The failure to improve prognosis with either chemotherapy or bone marrow transplantation calls for devising innovative new therapies. Those would likely be based on recognition of the molecules critical for pathogenesis. Much of this proposal aims to identify such molecules.

Genes in the Predisposition to Papillary Thyroid Carcinoma
PI: Albert de la Chapelle, MD, PhD

At first, identifying predisposing genes is likely to improve the understanding of pathways of disease causation. Given the low penetrance of many or most of the genes, it is possible that they will have only a limited impact on diagnostics and risk assessment, except in the case of familial papillary thyroid cancer. This project focuses on high-penetrance genes in families based on our prior results to dissect gene function and to evaluate further families using whole-genome sequencing.

Retrovirus Models of Cancer
PI: Patrick Green, PhD

About 15-25 million people worldwide are infected with HTLV-1. A small percentage of those cases develop adult T-cell leukemia, an aggressive cancer that has no effective treatment. The interactive nature of this PPG will provide rationale hypotheses to support translational studies to define therapeutic intervention against retrovirus-induced lymphoma and refine animal models to determine molecular determinants of retrovirus-induced cancer.

Discovery of Anticancer Agents of Diverse Natural Origin
PI: A. Douglas Kinghorn, PhD

The goal of this program project is to discover novel chemicals from selected tropical rainforest plants, as well as cyanobacteria and fungi, for development as cancer chemotherapeutic agents, particularly for tumors not cured by present treatment methods.

Genetic and Signaling Pathways in Epithelial Thyroid Cancer
PI: Matthew Ringel, MD

Key issues in the clinical care of thyroid cancer relate to defining the risk of developing the disease, identifying key pathways involve in tumor formation or predisposition, developing methods to improve existing treatments and defining pathways involved in disease progression to develop new therapies. This Program Project addresses these critical areas to improve the outcomes of patients with thyroid cancer.

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