In the lower respiratory tract, alveolar macrophages (AMs) phagocytose inorganic particles and microorganisms, thus playing an important role in host defense. AMs have a complex array of intracellular machinery to respond and direct inflammatory and fibrotic processes. Through releasing peptide growth factors such as platelet-derived growth factor and insulin-like growth factor-I, they stimulate fibroblast proliferation and contribute to fibrosis. Through releasing interleukin-8 (IL-8), they attract neutrophils and lymphocytes by chemotaxis to participate in immune-effector functions. The macrophage processes antigen and presents it to naive T lymphocytes, activating them in immune or cytotoxic responses. AMs are a major source of cytokines IL-b, TNF-a, and IL-6, all of which participate in granulomatous lung inflammation. AMs can phagocytose apoptotic neutrophils and lymphocytes participating in programmed cell death.
We also analyze BAL cells, bronchial brush, and microdissected samples from lung resections to search for tumor suppressor gene mutations and gene expression changes that will help us identify workers exposed to asbestos and cigarette smoke making them at high risk for lung cancer.
In tuberculosis studies, we investigate IL-8, TNF-a, IL-1b, and IL-6 roles in the granulomatous response. Regarding the transcriptional regulation of these genes, we identified NF-IL6 enhancer site(s) that respond to Mycobacterium tuberculosis or cytokines stimulated by the mycobacterium. Interferon-g activates AM to enhance M. tuberculosis killing and IL-12 promotes the TH1 cytokine response; we evaluate how these cytokines alter the immune response in vivo by BAL. Also, we study the interaction of NF-IL6 with the natural resistance in the AM (Nramp) gene to dissect the genetic control of AM activation.
My research is on Environmental Lung Disease particularly fibrosis where we study alveolar macrophage growth factors. The William N Rom Environmental Lung Disease Laboratory in Bellevue Old Administration Building A778 does research on World Trade Center dust health effects as well as air pollution and occupational exposures.
We also have a research interest in the Early Detection of Lung Cancer as part of the NCI Early Detection Research Network for the past 15 years. The NYU Lung Cancer Biomarker Center enrolled over 1500 smokers > age 50 and > 20 pack-years in a CT scan and biomarker research program. Biomarker studies were often collaborative with other EDRN members and biotechnology companies. The projects were shared with Dr. Harvey Pass who provided lung cancer samples.
We have studied TB/AIDS at Bellevue and the University of Cape Town in South Africa. We have focused on TB patients studying their mechanisms of lung inflammation using bronchoalveolar lavage. A major study found that interferon-gamma aerosol dampened the lung inflammation and hastened the immune response in TB killing in patients recruited in South Africa.
My current research is on GLOBAL HEATING which has supplanted global warming and climate change as a term describing the global health effects of a hot planet. As part of the College of Global Public Health, research is on the health effects including air pollution, biomass cooking, heat waves, and public health effects from increased storms and droughts. Mortality is expected to increase 8-fold during the period 2050-2100 related to U.S. policies. Wind, solar and fourth generation nuclear are pathways to avert this mortality by lowering the increase in carbon dioxide.
Sol and Judith Bergstein Professor of Medicine, Department of Medicine
Professor, Department of Environmental Medicine
Fellowship, Harvard School of Public Health, Master's in Public Health
Fellowship, Mt Sinai, Occupational and Environmental Medicine
Fellowship, Mt. Sinai, Pulmonary Disease
Residency, University of California, Davis, Internal Medicine
MD from University of Minnesota
Carcinogenesis. 2017 Jan 3; ?-?
ERJ open research. 2016 Oct; 2(4):?-?
Lung cancer. 2016 Sep; 99:172-179
Neuromuscular disorders. 2016 Aug; 26(8):481-489
American journal of respiratory & critical care medicine. 2016 Jun 15; 193(12):1431-1433
Nature microbiology. 2016 Apr 04; 1:16031-16031
Journal of acquired immune deficiency syndromes. JAIDS. 2016 Apr 01; 71(4):420-427