BHATTACHARYA, JAHAR M.D, PH.D. Professor of Physiology & Cellular Biophysics and Medicine Endothelial mechanisms of lung injury using cultured cells and the optically imaged lung. Email:jb39@columbia.edu

Current Research

We study the cell and molecular biology of lung inflammation by real-time fluorescence imaging and multiple other approaches. Severe, rapidly progressing lung inflammation causes the disease called Acute Lung Injury (ALI), a debilitating condition in which there is breakdown of fluid barriers separating blood from the inhaled air, causing fluid accumulation in the lung’s airspaces. The resulting respiratory failure requires respiratory support by mechanical ventilators in critical care units. It is estimated that about 250,000 people suffer from ALI in the US alone, with a mortality rate of 20-25%. Patients who survive the disease continue to have a high rate of morbidity for many years. Despite these statistics, there is really no "cure" for ALI in the sense that one cannot administer an agent that reverses the illness or blocks its progress. The available therapy continues to be supportive in that the patient's physiological deterioration is kept in check.

Prime causes of ALI are infection and sepsis. According to the WHO, lower respiratory tract infections are the fifth largest cause of death in high-income countries and the third largest cause worldwide. Other causes include gastric acid aspiration, lung barotrauma, pulmonary embolism and smoke inhalation. These conditions can be replicated in animal models, providing a means to understand basic disease mechanisms and to develop products that might be therapeutically effective in the clinical setting.

Our ongoing projects include research in immunity, fluid barriers, barrier-enhancing biologics (we have patented one biologic), surfactant secretion, water secretion, micromechanics, stem cells and macrophages. In the last three years, our publications have appeared in high-impact journals, including the Journal of Clinical Investigation, Nature Communications, Nature Medicine and Nature. Despite the competitive times for federally supported research funding, we expect our research to grow considerably in the near future.

Selected Publications

Westphalen K, Gusarova G, Islam MN, Subramanian M, Cohen TS, Prince AS, J Bhattacharya. Sessile alveolar macrophages modulate immunity through connexin 43-based epithelial communication. Nature. 2014 Feb 27; 506(7489):503-506. PMID:24463523

Huang SXL, Islam MN, O’Neil J, Hu Z, Yang Y-G, Chen Y-W, Mumau M, Green MD, Vunjak-Novakovic G, Bhattacharya J, Snoeck H-W. Efficient generation of lung and airway epithelial cells from human pluripotent stem cells. Nature Biotechnology. Nat Biotechnol. 2014 Jan; 32(1):84-91. PMID: 24291815

Islam MN, Gusarova GA, Monma E, Das SR, Bhattacharya J. F-actin scaffold stabilizes lamellar bodies during surfactant secretion. Am. J. Physiol. Lung Cell Mol. Physiol. 2014 Jan 1; 306(1): L50-57. PMID:24213916

Looney MR, J Bhattacharya. Live imaging of the lung. Annu. Rev. Physiol. 2014 Feb 10; 76:431-445. PMID: 24245941

Rogers RS, J Bhattacharya. When cells become organelle donors. Physiology (Bethesda). 2013 Nov; 28(6):414-422. PMID:24186936

Huertas, A., Das, S., Emin M., Rifkind JM, J. Bhattacharya and S. Bhattacharya. Erythrocytes induce proinflammatory endothelial activation in hypoxia. Am J Respir Cell Mol Biol. 2013; 48:78-86. PMID:23043086

Bhattacharya J, Matthay MA. Regulation and repair of the alveolar-capillary barrier in acute lung injury. Annu Rev Physiol. 2013; 75:593-615. PMID: 23398155

Quadri S, Sun L, Islam MN, Shapiro L, Bhattacharya J. Cadherin selectivity filter regulates endothelial sieving properties. Nat Commun. 2012;3:1099. PMID:23033075.

Emin, Memet T, Li Sun, A Huertas, S Das, J Bhattacharya, S Bhattacharya. Platelets induce endothelial tissue factor expression in a mouse model of acid-induced lung injury. Am. J. Physiol. Lung Cell Mol. Physiol. 2012 Jun 1;302(11):L1209-20. PMID:22505671.

Kristin Westphalen, Eiji Monma, Mohammad N. Islam & Jahar Bhattacharya. Acid contact in the rodent pulmonary alveolus causes proinflammatory signaling by membrane pore formation. Am. J. Physiol. Lung Cell Mol. Physiol. 2012. 303:L107-16. PMID:22561462.

Islam MN, S Das, MT Emin, M Wei, L Sun, K Westphalen, D Rowlands, S Quadri, S Bhattacharya, J Bhattacharya. Mitochondrial transfer from bone marrow-derived mesenchymal stromal cells to pulmonary alveoli protects against acute lung injury. Nat Med. 2012. 18:759-765. PMID:22504485.

Bhattacharya, J. 2012. Lung capillaries raise the hypoxia alarm. J Clin Invest. 2012 Nov 1;122(11):3845-7. PMID: 21191375.

Rowlands DJ, MN Islam, S Das, A Huertas, S Quadri, K Horiuchi, N. Inamdar, MT Emin, J Lindert, VS Ten, S Bhattacharya, J Bhattacharya. Activation of TNFR1 ectodomain shedding by mitochondrial Ca2+ determines the severity of inflammation in mouse lung microvessels. J. Clin. Invest. 2011. 121:1986-99. PMID: 21519143.

Perlman, CE, DJ Lederer and J. Bhattacharya. Micromechanics of alveolar edema. Am. J. Resp. Cell. Mol. Biol. 2011. 44:34-9. PMID: 20118224.

Bhattacharya, J. 2010. Seeing is believing. N&V Nature Meth. 8:57-58. PMID: 21191375.

Bhattacharya J, Perlman CE. Commentaries on Viewpoint: Standards for quantitative assessment of lung structure. Air space connectivity. J Appl Physiol. 2010. 109:935-6; PMID: 20848692.

Kiefmann, R., Rifkind, J.M., Nagababu, E., and Bhattacharya, J. 2008. RBC induce hypoxic lung inflammation. Blood. (In press)

Bhattacharya, J. 2008. Lung neovascularization: a tale of two circulations. Am J Physiol Lung Cell Mol Physiol. (Epub)

Quadri, S., and Bhattacharya, J. 2007. Resealing of endothelial junctions by focal adhesion kinase. Am. J. Physiol. Lung Cell. Mol. Physiol. 292:L334-42.

Lindert, J., Parthasarathi, K., and Bhattacharya, J. 2007. Chloride-dependent secretion of alveolar wall liquid determined by optical-sectioning microscopy. Am. J. Resp. Cell. Mol. Biol. 36:688-96.

Perlman, C.E., and Bhattacharya, J. 2007. Alveolar micromechanics determined by optical sectioning microscopy. J. Appl. Physiol. 103:1037-44.

Bertuglia, S., Ichimura, H., Fossati, G., Parthasarathi K., Leoni, F., Modena, D., Cremonesi, P., Bhattacharya, J., and Mascagni, P. 2007. ITF1697, a stable Lys-Pro–containing peptide, inhibits Weibel Palade body exocytosis induced by ischemia/reperfusion and pressure elevation. Mol Med. 13:615-24.

Kuebler, W.M., Parthasarathi, K., Lindert, J., and Bhattacharya, J. 2007. Real-time lung microscopy. J Appl Physiol. 102:1255-64.

Bhattacharya, J. 2007. Interpreting the lung microvascular filtration coefficient. Am J Physiol Lung Cell Mol Physiol. 79:357-66

Chatterjee, S., Baeter, S., and Bhattacharya, J. 2007. Endothelial and epithelial signaling in the lung. Am J Physiol Lung Cell Mol Physiol, 293: L517-19.

Ichimura, H., Parthasarathi, K., Issekutz, AC., and Bhattacharya, J. 2005. Pressure-induced leukocyte margination in lung postcapillary venules. Am J Physiol Lung Cell Mol Physiol. 289:L407-12.

Safdar, Z., Yiming, M., Grunig, G., and Bhattacharya, J. 2005. Inhibition of Acid-induced Lung Injury by Hyperosmolar Sucrose in Rats. Am J Respir Crit Care Med. 172:1002-7.

Paik D.C., Fu, C., Bhattacharya, J., and Tilson, M.D. 2004. Ongoing angiogenesis in blood vessels of the abdominal aortic aneurysm. Exp Mol Med. 36:524-33.

Boitano, S., Safdar, Z., Welsh, D.G., Bhattacharya, J., and Koval, M. 2004. Related Articles, Links Cell-cell interactions in regulating lung function. Am J Physiol Lung Cell Mol Physiol. 287:L455-9. Review.

Ichimura, H., Parthasarathi, K., Quadri, S., Issekutz A.C., and Bhattacharya, J. 2003. Mechano-oxidative coupling by mitochondria induces proinflammatory responses in lung capillaries. J. Clin. Invest. 111: 691-699.

Quadri, S., Bhattacharjee, M., Parthasarathi, K., Tanita, T., and Bhattacharya, J. 2003. Endothelial barrier strengthening by activation of focal adhesion kinase. J. Biol. Chem. 278:13342-9.

Safdar, Z., Wang, P., Ichimura, H., Issekutz, A.C., Quadri, S., and Bhattacharya. J. 2003. Hyperosmolarity enhances the lung capillary barrier. J. Clin. Invest. 112:1541-9.

Bhattacharya, S., Sen, N., Yiming, M., Patel, R., Parthasarathy, K., Quadri, S., Issekutz, A., and Bhattacharya, J. 2003. High tidal volume ventilation induces proinflammatory signaling in rat lung endothelium. Am J Respir Cell Mol Biol. 28:218-24.

Parthasarathi, K., Ichimura, H., Quadri, S., Issekutz, A., and Bhattacharya, J. 2002. Mitochondrial reactive oxygen species regulate spatial profile of proinflammatory responses in lung venular capillaries. J. Immunol. 169:7078-7086.

Recent Honors

The Irene and Arthur Fishberg Prize for significant contributions to internal medicine, Columbia University.

Major Grants

Pending NHLBI, RO1HL122730-A1 (PI). Scored in 1st percentile. Proposed Project start date: 09/01/2014 Mitochondrial role in acute lung injury