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

Rogers RA, Antonini JM, Brismar H, Lai J, Hesterberg TW, Oldmixon EH, Thevenaz P, Brain JD. In situ microscopic analysis of asbestos and synthetic vitreous fibers retained in hamster lungs following inhalation. Env Health Perspec, 1999; 107:367-375.

Brain JD, Molina RM, DeCamp MM, and Warner AE. Pulmonary intravascular macrophages: their contribution to the mononuclear phagocyte system in 13 species. Am J Physiol (Lung Cell Mol Physiol), 1999, 20:L146-L154.

Brain JD, Molina RM, DeCamp MM, Warner AE. Effects of a perfluorochemical emulsion on the fate of circulating Pseudomonas aeruginosa. Am J Physiol (Lung Cell Mol Physiol), 1999; 20:1037-1045.

Trujillo JR, Goletiani NV, Bosch I, Kendrick C, Rogers RA, Trujillo EB, Essex M, Brain JD. T-tropic sequence of the V3 loop is critical for HIV-1 infection of CXCR4-positive colonic HT-29 epithelial cells. JAIDS, 2000; 25:1-10.

Rao CY, Burge HA, Brain JD. The time course of responses to intratracheally instilled toxic Stachybotrys chartarum spores in rats. Mycopathologia, 2000; 149:27-34

Brain JD, Kavet R, McCormick DL, Poole C, Silverman LB, Smith TJ, Valberg PA, Van Etten RA, Weaver JC. Childhood leukemia: electric and magnetic fields (EMF) as possible risk factors. Environ Health Perspec, 2003; 111:962-70.

Bellows, CF and Brain JD. Role of fibronectin in pancreatitis-associated lung injury. Dig Dis Sci, 2003; 48:1445-1452.

Brain JD. Unlocking the opportunity of tight glycaemic control. Diabetes Obes Metab. 7 Suppl 1: S14-8, 2005.

Feng Y, Hsu YH, Terwedow H, Chen C, Xu X, Niu T, Zang T, Wu D, Tang G, Li Z, Hong X, Wang B, Brain JD, Cummings SR, Rosen C, Bouxsein ML, Xu X. Familial aggregation of bone mineral density and bone mineral content in a Chinese population. Osteoporos Int. 2005; 16: 1917-23.

Heilig E, Molina R, Donaghey T, Brain JD, Wessling-Resnick M. Pharmacokinetics of pulmonary manganese absorption: Evidence for increased susceptibility to manganese loading in iron deficient rats. Am J Physiol Lung Cell Mol Physiol. 2005; 288: L887-93.

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.

Hsu YH, Venners SA, Terwedow HA, Feng Y, Niu T, Li Z, Laird N, Brain JD, Cummings SR, Bouxsein ML, Rosen CJ, Xu X. Relation of body composition, fat mass, and serum lipids to osteporotic fractures and bone mineral density in Chinese men and women. Am J Clin Nutr. 2006; 83:146-54.

Hsu YH, Niu T, Terwedow HA, Xu X, Feng Y, Li Z, Brain JD, Rosen CJ, Laird N, Xu X. Variation in genes involved in the RANKL/RANK/OPG bone remodeling pathway are associated with bone mineral density at different skeletal sites in men. Hum Genet. 2006; 118:568-77.

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.

Barrero LH, Hsu YH, Terwedow H, Perry MJ, Dennerlein JT, Brain JD, Xu X. Prevalence and physical determinants of low back pain in a rural Chinese population. Spine. 2006; 31(23):2727-34.

Thompson K, Molina RM, Brain JD, Wessling-Resnick M. Belgrade rats display liver iron loading. J Nutr. 2006; 136(12):3010-4.

Brain JD. Rationale for the pulmonary delivery of insulin and other therapeutic proteins. Insulin IDEAS. 2006; 1(3):6-9.

Zalloua PA, Hsu YH, Terwedow H, Zang T, Wu D, Tang G, Li Z, Hong X, Azar ST, Wang B, Bouxsein ML, Brain JD, Cummings SR, Rosen CJ, Xu X. Impact of seafood and fruit consumption on bone mineral density. Maturitas. 2007; 56(1):1-11.

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.

Hsu YH, Xu X, Terwedow HA, Niu T, Hong X, Wu D, Wang L, Brain JD, Bouxsein ML, Cummings SR, Rosen CJ, Xu X. Large-scale genome-wide analysis for loci linked to BMD at different skeletal sites in extreme selected sibships. J Bone Miner Res. 2007; 22(2):184-94.

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.

• Parker B. Francis Fellowship Program - Parker B. Francis Fellowship Program in Pulmonary Research.
• NIEHS Center for Environmental Health
• Center for Children's Environmental Health and Disease Prevention Research