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.
Innate Immunity: Elucidation and Modulation for Cancer Therapy
PI: Michael A. Caligiuri, MD
Monoclonal antibody (mAb) therapy for cancer has improved clinical outcome for patients with both liquid and solid tumors, but is usually not curative. This program project grant is elucidating how tumors weaken the immune system, thereby preventing more effective mAb therapy for cancer. Several clinical trials will be undertaken to learn whether reversing this suppression will strengthen cancer mAb therapy.
Circumventing Barriers to Effective Oncolytic Virotherapy of Malignant Gliomas
PI: Michael A. Caligiuri, MD
Oncolytic virotherapy-based clinical trials of malignant gliomas have been well tolerated by humans, but more work is required to enhance the efficacy of the treatment. This program project is characterizing fundamental barriers and host responses that are deleterious to the efficacy of oncolytic herpesvirus therapy, and it will provide solutions that will increase this therapy’s effectiveness while maintaining its record of safety.
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 Analysis of the Breast Tumor Microenvironment
PI: Michael Ostrowski, PhD
This Program Project focuses on how the stroma of breast tumors promotes growth and spread of breast cancer, using human samples and mouse models. Our studies will significantly advance knowledge of tumor-stroma interactions and provide the tools to better stratify breast cancer patients for individualized treatment.
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.