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Fetal Nicotine Exposure Alters Bone Marrow Stem Cell Functio

Institution: LA Biomedical Research Institute at Harbor-UCLA Medical Center
Investigator(s): Virender Rehan, M.D.
Award Cycle: 2018 (Cycle 27) Grant #: 27IP-0050 Award: $563,438
Subject Area: Pulmonary Disease
Award Type: High Impact Pilot Award
Abstracts

Initial Award Abstract

Tobacco smoke inflicts tremendous damage to the health and well-being of Americans; in fact, it accounts for one in every 5 deaths and almost 1,300 deaths every day. Importantly, the harm does not end with the smoker: an estimated 88 million Americans who do not smoke, including more than half of young children, are exposed to secondhand smoke.  The most obvious and blatant case of passive exposure to smoke where an innocent by-stander is affected is exposure of a fetus to maternal smoke during pregnancy. Despite being known for decades that this exposure is tremendously harmful to the developing fetus, unfortunately, >10% of U.S. women smoke during pregnancy, resulting in at least 400,000 smoke-exposed infants/year. Moreover, under the pretext of selling less harmful products, such as the Modified Risk Tobacco Products and E-cigarettes (E-cigs), as safer alternatives to traditional cigarettes, this problem is worse than it has ever been. However, very little research has been done on the safety or harm of these products, particularly on the developing fetus.

Though the mechanism underlying the increased proclivity to chronic lung disease (CLD) is not completely understood, with the TRDRP’s support, work from our laboratory has provided seminal contributions to the field, opening up the possibility of designing effective preventive and therapeutic molecular interventions. One of the key discoveries revealed that infant’s lung has crucial lipid-containing cells that on exposure to nicotine transform to muscle like cells, which are the hallmark of a damaged lung. Once this change has occurred, a normal functioning cell, which is essential for good lung function, is converted to a cell that has the potential to cause serious lung damage, resulting in impaired oxygenation to the body in the short term, and CLD in the long-term. We have explored complex molecular pathways that determine the fate of these crucial cells, i.e., what makes them to behave as “Good and Beneficial” cells and what makes them “Bad and Harmful” cells. We now propose that following exposure to nicotine whether via traditional cigarettes or via E-cigs during pregnancy, the “Bad and Harmful” cells are produced, not only locally in the lung, but also in the bone marrow of the exposed individual. This proposal aims to confirm this phenomenon, further advance understanding of the molecular mechanisms involved in the harm caused by nicotine exposed bone marrow stem cells, and discover ways to prevent the harmful effects of these cells. It is highly likely that the work proposed here will provide novel and effective techniques to make the nicotine exposed “Bad and Harmful” cells behave as “Good and Beneficial” cells; provide novel diagnostic and therapeutic tools to tackle not only the lung damage, but also the damage to many other organs following smoke/E-cig exposure during pregnancy; and provide further scientific evidence in framing nicotine exposure guidelines by the Food and Drug Administration and other regulatory agencies.