The focus of my work is on understanding how dendritic cells, monocytes, and macrophages regulate immune responses, contribute to specific disease pathologies, and can be manipulated to stimulate or inhibit specific immune responses. We are also using our knowledge of immunology to develop diagnostics and therapeutics for a variety of human diseases.
The lab started with our discovery of the lymphoid chemokines, which regulate the migration of lymphocytes and dendritic cells to and within secondary lymphoid organs. We identified the chemokine (CCL21) that mediates the entry of naïve T cells and activated dendritic cells into lymph nodes and the chemokine (CXCL13) that mediates the entry of B cells into lymphoid follicles. Our focus then shifted to understanding how specific cell types, primarily dendritic cells, and cell migration events regulate immune responses. We identified murine plasmacytoid dendritic cells, the cell type that causes pulmonary immune pathology during influenza infection, the dendritic cell type that stimulates Th1 immune responses, and the cell type that induces neuronal injury in Alzheimer's disease. Our current work continues these basic studies while applying our findings to models of human disease.
Identification and characterization of inflammatory cell populations in models of human disease – We have developed advanced methods of flow cytometric analysis that allows us to quantify and fully characterize all inflammatory cell types in murine and human tissues. Using these methods, we are working to identify the cells that mediate a variety of immune pathologies. Examples include the identification of immune-stimulatory and immune-suppressive cell types in brain tumors, identification of the cells that induce vascular changes pulmonary hypertension, and characterization of the inflammatory response to a variety of infectious pathogens.
Tumor immune therapeutics – We have developed a novel cellular vaccine strategy for the treatment of cancer. This strategy is much simpler, more cost effective, more clinically feasible, and much more efficacious than classic dendritic cell vaccines. We are now testing this vaccine in various preclinical tumor models including melanoma and glioblastoma and will soon be advancing it to initial human clinical trials.
Treatment of Acute Lung Injury – We have identified the first small molecule pharmacologic agent that is effective in reducing respiratory dysfunction, vascular leak, tissue injury, and mortality during Acute Lung Injury. We are currently validating this agent in animal models of chemical-induced ALI and testing its efficacy in reducing ALI caused by other agents such as influenza and smoke inhalation. We hope to develop this agent as the first effective pharmacologic treatment for ALI in humans.
Development of recombinant antibodies as diagnostic reagents – Our lab has developed novel methods to generate recombinant single chain antibodies using phage display technology. We are currently using these methods to generate pathogen-specific antibodies for use in diagnostic tests for a variety of human bacterial, viral, and fungal infections. In collaboration with Duke Biomedical Engineering, we are testing the use of our antibodies in a novel diagnostic assay platform to develop point-of-care assays for the diagnosis of infections by agents such as Zika virus, Dengue virus, Salmonella typhi, and Aspergillus fumigatus.
Education and Training
- Fellowship in Cardiology, Cardiology, University of California, San Francisco, 0018
- Internship and Residency, Internal Medicine, Parkland Health & Hospital System, 0018
- M.D., UT Southwestern Medical School, 1983
- Duke University Program in Environmental Health
- Duke Resident Physician-Scientist Program- NIAID
- Biasing CXCR3 Signaling to Modulate the Inflammatory Response
- Duke Training Grant in Nephrology
- CCL3 as a Developmental Therapeutic to Enhance Brain Tumor Therapy
- Multidisciplinary Heart and Vascular Diseases
- TIE2 Activation for the Treatment of Chemical-Induced Acute Lung Injury
- Role of Dendritic Cell-mediated T Cell Activation in Salt-sensitive Hypertension
- Role of Resident Monocytes in the Pathogenesis of Pulmonary Arterial Hypertension
- Interdisciplinary Training Program in Lung Disease
- Targeting Extracellular Histones with Novel RNA Biodrugs for the Treatment of Acute Lung Injury