Joseph Brain

Cecil K. and Philip Drinker Professor of Environmental Physiology

Department of Environmental Health

Joseph Brain
Cecil K. and Philip Drinker Professor of Environmental Physiology

Department of Environmental Health

665 Huntington Avenue
Building I Room 1308A
Boston, Massachusetts 02115
Phone: 617.432.1272
brain@hsph.harvard.edu

Research

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, including inhaled insulin.

Education

S.D., 1966, Harvard T.H. Chan School of Public Health
S.M., 1963, Harvard Paulson School of Engineering and Applied Sciences
S.M., 1962, Harvard Paulson School of Engineering and Applied Sciences

B.A., 1961, Taylor University

Selected Publications

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.

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, 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.

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.

Molina RM, Phattanarudee S, Kim J, Thompson K, Wessling-Resnick M, Maher TJ, Brain JD. Ingestion of Mn and Pb by rats during and after pregnancy alters behavior in offspring. NeuroToxicology. 2011; 32(4):413-22.

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.

Mendivil CO, Teeter JG, Finch GL, Schwartz PF, Riese RJ, Kawabata T, Brain JD. Trough insulin levels in bronchoalveolar lavage following inhaled human insulin (Exubera®) in patients with diabetes mellitus. Diabetes Technol Ther. 2012; 14(1):50-8.

Molina R, Schaider L, Donaghey T, Shine J, Brain JD. Mineralogy affects geoavailability, bioaccessibility and bioavailability of zinc. Environ Pollut. 2013; 182:217-24.

Pirela S, Molina R, Watson C, Cohen J, Bello, Demokritou P, Brain JD. Effects of copy center particles on the lungs: A toxicological characterization using a Balb/c mice model. Inhalation Toxicology. 2013; 25(9):498-508.

Molina RM, Konduru NV, Jimenez RJ, Wohlleben W, Brain JD. Bioavailability, distribution and clearance of tracheally instilled, gavaged or injected cerium dioxide nanoparticles and ionic cerium. Environ Sci: Nano. 2014; 1:561-73.

Brain JD, Kreyling WG, and Godleski JJ. Inhalation Toxicology. In: Hayes’ Principles and Methods of Toxicology. Sixth Edition. Edited By: A. Wallace Hayes and Claire L. Kruger. CRC Press: Boca Raton. 2014. Pages 1385-1444.

Mendivil CO, Koziel H, Brain JD. Metabolic hormones, apolipoproteins, adipokines, and cytokines in the alveolar lining fluid of healthy adults: compartmentalization and physiological correlates. PLoS One. 2015 Apr 7;10(4):e0123344 (15 pages).

Rosenblum-Lichtenstein JH, Hsu Y-H, Gavin IM, Donaghey TC, Molina RM, Thompson KJ, Chi C-L, Gillis BS, Brain JD. Environmental mold and mycotoxin exposures elicit specific cytokine and chemokine responses. PLoS One. 2015 May 26;10(5):e0126926. (22 pages)

Watson CY, Damiani F, Ram-Moham S, Rodrigues S, de Moura Queiroz P, Donaghey TC, Rosenblum Lichtenstein JH, Brain JD, Krishnan R, Molina RM. Screening for chemical toxicity using cryopreserved precision cut lung slices. Toxicological Sciences. 2016;150(1):225-33.

Rosenblum Lichtenstein JH, Molina RM, Donaghey TC, Hsu YH, Mathews JA, Kasahara DI, Park JA, Bordini A, Godleski JJ, Gillis BS, Brain JD. Repeated mouse lung exposures to Stachybotrys chartarum shift immune response from type 1 to type 2. Am J Respir Cell Mol Biol. 2016 May 5. [Epub ahead of print]