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; the cell type that induces neuronal injury in Alzheimer's disease, and the macrophage type that stimulates pulmonary hypertension. Our current work continues these basic studies while applying our findings to models of human disease.
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 determining the mechanisms by which this vaccine induces such potent immune responses and advancing it to initial human clinical trials.
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 deploying our antibodies in a novel diagnostic assay platform to develop point-of-care assays for the diagnosis of a variety of emerging pathogens. Our recently developed point-of-care assay for Ebola virus displays a sensitivity superior to PCR at a fraction of the per assay cost.
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
- Synergestic microglial activation and tumor cell killing for improved GBM response
- A Fully Integrated Point-of-Care Test for Ebola
- Systemic Inflammation in Microphysiological Models of Muscle and Vascular Disease
- Generation of antibodies specific for optimal non-HRP2 malaria diagnostic antigens
- CCL3 as a Developmental Therapeutic to Enhance Brain Tumor Therapy
- BATF3+ Dendritic Cells for the Treatment of Malignant Gliomas
- Role of Dendritic Cell-mediated T Cell Activation in Salt-sensitive Hypertension
- Role of Resident Monocytes in the Pathogenesis of Pulmonary Arterial Hypertension