alveolar macrophage function , lung cancer, M tuberculosis, environmental health policy, asbestos-related diseases, Climate Change
My research focuses on lung diseases, including environmental lung disease, tuberculosis (TB), TB/HIV, early detection of lung cancer, and policy related to air pollution and climate change.
A particular area of interest is the role of alveolar macrophages (AMs) in environmental lung disease. In the lower respiratory tract, AMs phagocytose inorganic particles and microorganisms, playing an important role in host defense. AMs also respond to and direct inflammatory and fibrotic processes via a complex array of intracellular machinery.
By releasing peptide growth factors, such as platelet-derived growth factor and insulin-like growth factor 1, AMs stimulate fibroblast proliferation, which contributes to fibrosis. Through the release of interleukin 8 (IL-8), macrophages attract neutrophils and lymphocytes by chemotaxis to participate in immune-effector functions. Macrophages also process antigen and present it to naive T lymphocytes, activating them in immune or cytotoxic responses. AMs are a major source of the cytokines interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNFα), and interleukin 6 (IL-6)—all of which participate in granulomatous lung inflammation. In addition, AMs can phagocytose apoptotic neutrophils and lymphocytes participating in programmed cell death.
At the William N. Rom Environmental Lung Disease Laboratory at NYC Health + Hospitals/Bellevue we research the health effects of exposure to World Trade Center dust, air pollution, and occupational particulate matter. We analyze bronchoalveolar lavage (BAL) cells, bronchial brush biopsies, and microdissected samples from lung resections to find tumor suppressor gene mutations and gene expression changes. The goal is to identify workers who are exposed to asbestos and cigarette smoke and therefore at high risk for lung cancer.
In our TB studies, we investigate the roles of interleukins TNFα, IL-1β, and IL-6 in the granulomatous response. In studying the transcriptional regulation of the genes encoding these cytokines, we identified nuclear factor interleukin 6 (NF-IL6) enhancer sites that respond to either Mycobacterium tuberculosis or cytokines stimulated by the mycobacterium. Interferon gamma (INF-γ) activates AM to enhance M. tuberculosis killing, and IL-12 promotes the type 1 helper T (Th1) cell cytokine response. We use BAL to evaluate how these cytokines alter the immune response in vivo. We also study the interaction of NF-IL6 with the natural resistance–associated macrophage protein 1, or NRAMP1, gene in the AM to elucidate the genetic mechanisms of AM activation.
We have studied TB and HIV at NYC Health + Hospitals/Bellevue and at the University of Cape Town in South Africa. Using BAL, we have focused on the mechanisms of lung inflammation in TB. One major study in patients with TB in South Africa found that aerosolized INF-γ dampened lung inflammation and hastened the immune response in TB killing.
We also have a research interest in the early detection of lung cancer and have been part of the National Cancer Institute’s Early Detection Research Network (EDRN) for the past 15 years. As a part of the EDRN, the NYU Lung Cancer Biomarker Center has enrolled over 1,500 smokers over the age of 50 with a smoking history of more than 20 pack-years in a CT-scan and biomarker research program. We performed biomarker studies in collaboration with other EDRN members and biotechnology companies. These projects also involved the work of Harvey Pass, MD, who provided lung cancer samples.
My most recent research is on “global heating”—a term that has supplanted “global warming” and “climate change” in describing the global health effects of a hot planet. As part of the NYU College of Global Public Health, I investigate the public health effects of air pollution, biomass cooking, heat waves, increased storms, and droughts. Based on current U.S. policies, mortality is expected to increase eightfold during the period 2050–2100. Wind, solar, and fourth-generation nuclear energy are possible pathways for averting this rise in death rates by reducing carbon dioxide emissions.
Bellevue, Old Administration Building
New York, NY 10016
Cancer discovery. 2021 Feb ; 11(2):293-307
Respiratory research. 2020 Sep 02; 21(1):228
Cancer research. 2019 Jan 01; 79(1):263-273