Cecil K. and Philip Drinker Professor of Environmental Physiology
Dr. Brain’s research emphasizes responses to inhaled gases, particulates, and microbes. His studies extend from the deposition of inhaled particles in the respiratory tract to their clearance by respiratory defense mechanisms. Of particular interest is the role of lung macrophages; this resident cell keeps lung surfaces clean and sterile. Moreover, the lung macrophage is also a critical regulator of inflammatory and immune responses. The context of these studies on macrophages is the prevention and pathogenesis of environmental lung disease as well as respiratory infection.
His research has utilized magnetic particles in macrophages throughout the body as a non-invasive tool for measuring cell motility and the response of macrophages to various mediators and toxins. Other experiments deal with the use of lung lavage to obtain and characterize macrophages. A rodent bioassay utilizing lung lavage has been developed; the assay has been used to estimate the relative toxicity of new and complex mixtures such as molds, urban dusts, welding fume, new materials being used in the workplace, as well as drugs and excipients administered by inhalation, including nanomaterials.
Respiratory infection is emphasized and includes mechanistic studies of the lung’s defenses against Pseudomonas aeruginosa, an important pulmonary pathogen for patients with cystic fibrosis. Related studies deal with opportunistic lung infections in AIDS such as Pneumocystis carinii.
Another area of study is drug delivery to and through the lungs. The amount and anatomic distribution of an inhaled radioactively-tagged asthma mediator antagonist and an elastase inhibitor have been measured. Other experiments focus on the fact of recombinant proteins such as macrophage colony stimulating factors, neutral endopeptidase, surfactant apoproteins, antibodies, interleukins, and hormones delivered to and through the lungs.
S.D., 1966, Harvard University
S.M., 1963, Harvard University
S.M., 1962, Harvard University
Brain JD, Heilig E, Donaghey TC, Knutson MD, Wessling-Resnick M, Molina RM. Effects of iron status on transpulmonary transport and tissue distrubiton of Mn and Fe. Am J Respir Cell Mol Bio. 2006; 34: 330-7.
Thompson K, Molina R, Donaghey T, Brain JD, Wessling-Resnick M. The influence of high iron diet on rat lung manganese absorption. Toxicol Appl Pharmacol. 2006; 210: 17-23.
Lichtenstein JHR, Molina RM, Donaghey TC, Brain JD. Strain differences influence murine pulmonary responses to Stachybotrys chartarum. Am J Respir Cell Mol Biol. 2006; 35:415-23.
Heilig E, Molina R, Ivanov A, Brain JD, Wessling-Resnick M. Manganese and iron transport across pulmonary epithelium. Am J Physiol Lung Cell Mol Physiol. 2006; 290(6):L1247-59.
Thompson K, Molina RM, Brain JD, Wessling-Resnick M. Belgrade rats display liver iron loading. J Nutr. 2006; 136(12):3010-4.
Thompson K, Molina R, Donaghey T, Schwob JE, Brain JD, Wessling-Resnick M. Olfactory uptake of manganese requires DMT1 and is enhanced by anemia. FASEB J. 2007; 21(1):223-30.
Trujillo JR, Rogers R, Molina RM, Dangond F, McLane MF, Essex M, Brain JD. Non-infectious entry of HIV-1 into peripheral and brain macrophages mediated by the mannose receptor. PNAS. 2007; 104(12):5097-5102.
Molina RM and Brain JD. In vivo comparison of cat alveolar and pulmonary intravascular macrophages: phagocytosis, particle clearanc,e and cytoplasmic motility. Exp Lung Res. 2007; 33(2):53-70.
Brain JD. Inhalation, deposition and fate of insulin and other therapeutic proteins. Diabetes Technology & Therapeutics. 2007; 9 Suppl 1:S4-S15
Thompson K, Molina RM, DOnaghey T, Brain JD, Wessling-Resnick M. Iron absorption by Belgrade rat pups during lactation. AJP: GI and Liver Physiology. 2007; 293(3):G640-4.
Brain JD, Curran MA, Donaghey T, Molina R. Responses of the lungs to nanomaterials depend on exposure, clearance, and material characteristics. Nanotoxicology. 2009; 3(1-4):173-9.
Demokritou P, Büchel R, Molina RM, Deloid GM, Brain JD, Pratsinis SE. Development and characterization of a Versatile Engineered Nanomaterial Generation System (VENGES) suitable for toxicological studies. Inhal Toxicol. 2010 Dec;22 Suppl 2:107-16.
Krishnan R, Klumpers DD, Park CY, Rajendran K, Trepat X, van Bezu J, van Hinsbergh VW, Carman CV, Brain JD, Fredberg JJ, Butler JP, van Nieuw Amerorgen GP. Substrate stiffening promotes endothelial monolayer disruption through enhanced physical forces. Am J Physiol Cell Physiol. 300: C146-154.
Bellows CF, Molina RM, Brain JD. Diminished organelle motion in murine Kupffer cells during the erythrocytic stage of malaria. J R Soc Interface. 2011 May 6;8(58):711-9.
Lichtenstein JHR, Molina RM, Donaghey TC, Amuzie C, Pestka JJ, Coull BA, Brain JD. Pulmonary responses to Stachybotrys chartarum and its toxins: Mouse strain affects clearance and macrophage cytotoxicity. Toxicol Sci. 2010 Jul;116(1):113-21.
Kim J, Molina R, Donaghey T, Buckett P, Brain J, Wessling-Resnick M. Influence of DMT1 and iron status on inflammatory responses in the lung. Am J Physiol Lung Cell Mol Physiol. 2011; 300(4): p. L659-L665.
Thompson K, Molina R, Donaghey T, Schwob J, Brain JD. Manganese uptake and distribution in the brain after methyl bromide-induced lesions in the olfactory epithelia. Toxicol Sci. 2011 Mar;120(1):163-72.