Lung Biology Laboratory

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Jahar Bhattacharya, MD, DPhil,
Professor of Medicine, Physiology & Cellular Biophysics
Columbia University
Phone: 212-305-7310 (Office), 212-305-6724 (Lab)
Fax: 212-305-6701
Address: 630 W168th Street
Black Building 8-812
New York, NY10032



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.

Research Overview

Real-time confocal fluorescence imaging of alveolar epithelium and

Live views of alveoli and capillaries by confocal microscopy of a mouse lung. Images show the alveolar-capillary region of the lung. LEFT: Green dye shows vessels lying adjacent to an alveolus. RIGHT: High magnification shows epithelial cells (red) and an endothelial cell (green).

Alveolar acid instillation induces mitochondrial depolarization in capillary endothelium

Alveolar HCl causes transient H2O2-dependent mitochondrial depolarization in lung endothelium. Confocal images of live mouse lungs at baseline (left column) show calcein green (CG)-labeled alveolar (alv) epithelium (green), calcein red (CR)-labeled capillary (cap) endothelium (red) and potentiometric dye Tetramethylrhodamine ethyl ester (TMRE) labelling of lung endothelial mitochondria (pseudo-coloured blue). Alveolar HCL injection caused loss of alveolar CG in 10 mins but not of endothelial CR (middle column). However, reduced TMRE fluorescence indicates depolarization of endothelial mitochondria. Re-loading TMRE and CG 30 mins after HCL injection (rightmost column) indicate recovery of mitochondrial potential and resealing of the alveolar epithelial plasma membrane. Scale bars, 20 um: (Hough 2019).

Imaging bacterial dynamics on alveolar epithelium

S. aureus USA300 stabilize in lung alveoli by rapidly forming microaggregates in alveolar niches. Confocal image of live mouse lung alveoli (alv) shows microaggregates (arrowheads) of GFP-labeled S.aureus strain USA300 (green). The indicated alveolar septa (i-iii) demarcate an example of calcein-loaded epithelia (red) that converge to form a niche. CR, calcein red. Scale bar, 20 um. (Hook, 2018).

Live imaging of alveolar macrophages

Live confocal image of mouse lung shows sessile alveolar macrophages (arrows) lying adjacent to alveolar septa (red). The macrophages communicate with alveolar epithelium through connexin-43 containing gap junctions. The junctions communicate counter-inflammatory calcium signals from macrophages to the epithelium (Westphalen, 2014).

Imaging dynamic calcium responses of alveolar macrophages

LPS induces synchronized Ca2+ spikes in sessile alveolar macrophages (arrows, Westphalen 2014). 

Bone marrow stem cell-derived mitochondrial transfer to alveolar epithelial cells

Mitochondrial regulation of acute lung injury. One of our goals is to understand mitochondrial mechanisms underlying ALI. We reported that mitochondrial transfer from bone marrow-derived mesenchymal stem cells (BMSCs) to injured lung cells rescues ALI. Ongoing studies aim at molecular mechanisms underlying the mitochondrial protective effect.

Confocal image of alveoli in an endotoxin-treated lung shows alveoli containing airway-instilled bone marrow-derived stem cells (BMSCs). The colors depict alveolar septa (green), BMSC nuclei (blue) and BMSC mitochondria (red). The arrows point to regions at which BMSCs transferred mitochondria to epithelium (yellow) (Islam, 2012).

Micromechanics of fluid-filled alveoli

3-D alveolar geometry during lung inflation. The effect of lung volume on alveolar geometry impacts several aspects of lung function. Moreover, during lung expansion, the pattern of alveolar perimeter distension is an important determinant of lung functions as, for example, surfactant secretion. Using optical sectioning microscopy, this project aims to correlate inflation-induced changes in alveolar geometry with lung function.

Alveolar micromechanics. In a single-alveolus model of pulmonary edema, unexpected micromechanical effects ensue when air-filled and liquid-filled (green) alveoli are juxtaposed. The liquid-filled alveolus shrinks imposing mechanical stress on its air-filled neighbor. The mechanical stress reduces compliance of the air-filled alveolus, making it a target for over-expansion injury. (Perlman, 2011).

High tidal volume ventilation induces platelet protein deposition on lung endothelium

Activated platelets deposit proteins on the endothelial surface. Confocal images show freshly isolated single endothelial cells from lungs exposed to low- (LV) or High- (HV) volume ventilation. P-selectin and vWf were deposited on the endothelial surface after HV, not LV. Platelet depletion (PDB) in blood (WB) blocked the effect. Deposition of these proteins provides a platform for coagulation and further injury (Yiming, 2008).

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Other Studies 

  • Mechanism of surfactant secretion. Pulmonary surfactant maintains patency of alveoli, the sites of gas exchange in the lung. Vesicles containing surfactant in alveolar type 2 epithelial cells are held stationary by the actin cytoskeleton, while surfactant flows between the vesicles en route to the secretion locus in the plasma membrane (American Journal of Physiology: Lung, 2014).
  • Differential cadherin mobility determines endothelial barrier properties. Real-time confocal imaging of endothelial junctions shows mobile cadherins that assemble at focal points in a F-actin dependent manner to establish the protein selectivity filter that determines endothelial sieving properties (Nature Communications, 2012).
  • Red blood cells generate reactive species in lung hypoxia. Optically imaged lungs show that in hypoxia, erythrocytes flowing in lung microvessels generate peroxide that diffuses to the adjoining endothelium to induce proinflammatory activation (Blood, 2008; American Journal of Respiratory Cell & Molecular Biology, 2013)
  • Acid injury. Acid aspiration, modeled in mouse lung by micropuncturing alveoli and delivering concentrated acid directly in the alveolar space, caused pore formation in the alveolar epithelium, leading to generation of reactive oxygen species and inflammatory outcomes (American Journal of Physiology: Lung, 2012).Lung endothelial mitochondrial calcium determines shedding of the luminal TNF-α receptor. Real-time confocal microscopy reveals that lung endothelial mitochondrial calcium increase induces TNF-α receptor shedding. The findings indicate that endothelial mitochondria determine the severity of soluble TNF-α-induced microvascular inflammation (J. Clin. Invest:2011).
  • Mechano-induction of mitochondrial calcium. Vascular stretch induced by an increase in the vascular pressure causes calcium release from endosomal stores and increase of mitochondrial calcium. Mitochondrial peroxide diffuses to the cytosol to activate expression of proinflammatory receptors (J. Clin. Invest: 2003.)
  • Protein therapy in ALI. We have developed a patented method for introducing purified, barrier-enhancing proteins in lung endothelium and alveolar epithelium. By this strategy, loading lung endothelium with focal adhesion kinase (FAK) protected against endotoxin-induced ALI.
  • Real-time studies of alveolar actin. Sub-cortical actin can act as a fence to negatively regulate surface expression of pro-inflammatory receptors in alveoli. We developed methods for real-time actin determination in live alveoli. In this project, we aim to determine the physiological regulation of the alveolar F-actin fence and the extent to which enhancement of alveolar F-actin fence is protective in ALI.
  • Liquid secretion in alveolar wall. Our goal in this project is to understand mechanisms underlying formation of the alveolar wall liquid (AWL), which constitutes the alveolar aqueous phase. The AWL enables surfactant phospholipids and proteins to distribute along the alveolar wall. As such it is critical for gas exchange and defense functions of the lung. However, factors underlying AWL formation are largely unknown. 

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 Lab Members

Jahar Bhattacharya, MD, DPhil 
Professor of Medicine 
Professor of Physiology & Cellular Biophysics

Rashmi Patel
Administrative Manager

Galina A. Gusarova, PhD
Associate Research Scientist

Li Li MD, PhD
Postdoctoral Research Fellow

Rebecca Hough, MD, PhD
Instructor in Pediatrics

Akihisa Mino, PhD
Associate Research Scientist

Sunita Bhattacharya, MD
Associate Professor of Pediatrics

Sadiqa K. Quadri, PhD
Associate Research Scientist

Naeem Islam, PhD
Associate Research Scientist

Jin, Guangchun MD, PhD
Associate Research Scientist

Bongani Liberty Mthunzi, PhD
Postdoctoral Research Scientist

Jun Li
Research Technician

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Recent Publications

  1. Gusarova GA, Das SR†, Islam MN, Westphalen K, Jin G, Shmarakov IO, Li L, Bhattacharya S, Bhattacharya J. Actin fence therapy with exogenous V12Rac1 protects against Acute Lung Injury. JCI Insight 2021 (in press).
  2. Hidalgo A, Garcia-Mouton C, Autilio C, Carravilla P, Orellana G, Islam MN, Bhattacharya J, Bhattacharya S, Cruz A, Pérez-Gil J. Pulmonary surfactant and drug delivery: Vehiculization, release and targeting of surfactant/tacrolimus formulations. J Control Release. 2020 Nov 24;329:205-222. doi: 10.1016/j.jconrel.2020.11.042. Online ahead of print.PMID: 33245954
  3. Proto JD, Doran AC, Gusarova G, Yurdagul A Jr, Sozen E, Subramanian M, Islam MN, Rymond CC, Du J, J, Kuriakose G, Bhattacharya J, Tabas I. Regulatory T Cells Promote Macrophage Efferocytosis during Inflammation Resolution. Immunity 2018 Oct 16;49(4):666677.e6.doi:10.1016/j.immuni.2018.07.015. Epub 2018 Oct 2.
  4. Chen YW, Huang SX, de Carvalho ALRT, Ho SH, Islam MN, Volpi S, Notarangelo LD, Ciancanelli M, Casanova JL, Bhattacharya J, Liang AF, Palermo LM, Porotto M, Moscona A, Snoeck HW. A three-dimensional model of human lung development and disease from pluripotent stem cells. Nat Cell Biol. 2017 May;19(5):542-549. doi: 10.1038/ncb3510. Epub 2017 Apr 24.PMID: 28436965
  5. Hough RF, Islam MN, Gusarova GA, Jin G, Das S and Bhattacharya J. Endothelial mitochondria determine rapid barrier failure in chemical lung injury. JCI Insight. 2019, February 7; 4 (3): e124329. [Epub ahead of print]. PMID:30728333
  6. Hough RF, Bhattacharya S, and Bhattacharya J. Crosstalk signaling between alveoli and capillaries. Pulm Circ. 2018; 8 (3): 1-7. PMID: 29869931
  7. Hook JL, Islam MN, Parker D, Prince AS, Bhattacharya S and Bhattacharya J. Disruption of staphylococcal aggregation protects against lethal lung injury. J Clin Invest. 2018; 128 (3): 1074-1086. PMID: 29431734.
  8. Bhattacharya J, Westphalen K. Macrophage-epithelial interactions in pulmonary alveoli. Semin Immunopathol. 2016 May 12. [Epub ahead of print]. PMID: 27170185
  9. Sinha, P., Islam MN, Bhattacharya S, and Bhattacharya J. Intercellular mitochondrial transfer: bioenergetic crosstalk between cells. Current Opinion in Genetics & Development. 2016; 38:97–101. PMID: 27235808
  10. Westphalen K, Gusarova GA, Islam MN, Subramanian M, Cohen TS, Prince AS, Bhattacharya J. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity. Nature. 2014:506 (7489):503-6. PMID:24463523
  11. Schumacker PT, Gillespie MN, Nakahira K, Choi AM, Crouser ED, Piantadosi CA, Bhattacharya J. Mitochondria in lung biology and pathology: more than just a powerhouse. Am J Physiol Lung Cell Mol Physiol. 2014. 306(11):L962-74. Review. PMID:24748601
  12. Huang SX, Islam MN, O'Neill J, Hu Z, Yang YG, Chen YW, Mumau M, Green MD, Vunjak-Novakovic G, Bhattacharya J, Snoeck HW. Efficient generation of lung and airway epithelial cells from human pluripotent stem cells. Nat Biotechnol. 2014. 32(1):84-91. PMID: 24291815.
  13. Islam MN, Gusarova, GA, Monma, E, Das SR, and Bhattacharya J. F-actin scaffold stabilizes lamellar bodies during surfactant secretion. Am J Physiol Lung Cell Mol Physiol 306: L50–L57, 2014. PMID:24213916
  14. Looney MR, Bhattacharya J. Live imaging of the lung. Annu Rev Physiol. 2014;76:431-45. 2013. Review. PMID: 24245941
  15. Matthay MA, Anversa P, Bhattacharya J, Burnett BK, Chapman HA, Hare JM, Hei DJ, Hoffman AM, Kourembanas S, McKenna DH, Ortiz LA, Ott HC, Tente W, Thébaud B, Trapnell BC, Weiss DJ, Yuan JX, Blaisdell CJ. Cell therapy for lung diseases. Report from an NIH-NHLBI workshop, Am J Respir Crit Care Med. 2013. 188(3)370-5. PMID: 23713908.
  16. Rogers RS, Bhattacharya J. When cells become organelle donors. Physiology (Bethesda). 2013 28(6):414-22. Review. PMID: 24186936.
  17. Islam MN, Das SR, Emin MT, Wei M, L Sun, Westphalen K, Rowlands D, Quadri S, Bhattacharya S, Bhattacharya J. 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
  18. Quadri S, Sun L, Islam MN, Shapiro L, Bhattacharya J. Cadherin selectivity filter regulates endothelial sieving properties. Nat Commun. 2012;3:1099. PMID:23033075
  19. 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 Jan;48(1):78-86. PMID:23043086
  20. 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
  21. 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
  22. Rowlands, D.J., Das S., Huertas A., Islam M.N., Quadri S.K., Horiuchi K., Inamdar N., Emin M., Lindert J., Bhattacharya S. and Bhattacharya J. Mitochondrial Ca2+ oscillations determine severity of inflammation by activating TNFR1 ectodomain shedding in mouse lung microvessels. J Clin Invest. 2011 May 2;121(5):1986-99. PMID: 21519143.
  23. Bhattacharya J. Seeing is believing. Nat Methods. 2011 Jan;8(1):57-8. PMID: 21191375.
  24. Perlman C.E., Lederer D.J., Bhattacharya J. The micromechanics of alveolar edema. Am J Resp Cell Mol Biol.2011. 44:34-9. PMID: 20118224.
  25. Otsu K., S. Das, Houser S.D., Quadri S.K., Bhattacharya S., Bhattacharya J. Concentration-dependent inhibition of angiogenesis by mesenchymal stem cells. Blood. Apr 30 2009;113(18):4197-4205. PMID: 19036701. Editorial Comment: M. Matthay. “Mesenchymally stemming angiogenesis.”
  26. Kiefmann R., Islam M.N., Lindert J., Parthasarathi K., Bhattacharya J. Paracrine purinergic signaling determines lung endothelial nitric oxide production. Am J Physiol Lung Cell Mol Physiol. Jun 2009; 296(6):L901-910. PMID: 19304909.
  27. Quadri S.K. and Bhattacharya J. Resealing of endothelial junctions by focal adhesion kinase. Am J Physiol Lung Cell Mol Physiol. Jan 2007;292(1):L334-342. PMID: 17012369.
  28. Perlman C.E and Bhattacharya J. Alveolar expansion imaged by optical sectioning microscopy. J Appl Physiol. Sep 2007;103(3):1037-1044. PMID: 17585045.
  29. Lindert J., Perlman C.E., Parthasarathi K., Bhattacharya J. Chloride-dependent secretion of alveolar wall liquid determined by optical-sectioning microscopy. Am J Respir Cell Mol Biol. Jun 2007;36(6):688-696. PMID: 17290033.
  30. Kuebler W.M., Parthasarathi K., Lindert J., Bhattacharya J. Real-time lung microscopy. J Appl Physiol. Mar 2007;102(3):1255-1264. PMID: 17095639.
  31. Parthasarathi K., Ichimura H., Monma E., Lindert J., Quadri S.K. Issekutz A., Bhattacharya J. Connexin 43 mediates spread of Ca2+-dependent proinflammatory responses in lung capillaries. J Clin Invest. Aug 2006;116(8):2193-2200. PMID: 16878174.
  32. Ichimura H., Parthasarathi K., Lindert J., Bhattacharya J. Lung surfactant secretion by interalveolar Ca2+ signaling. Am J Physiol Lung Cell Mol Physiol. Oct 2006;291(4):L596-601. PMID: 16698857.

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Dr. Bhattacharya is the director of an NIH-funded training program. The goal of this program is to train a new generation of postdoctoral MD and PhD scientists to become future leaders in the basic and translational investigation of major lung diseases. The emphasis is on lung biology with incorporation of molecular biology, genetics, epigenetics and molecular imaging. The spectrum of lung disease includes asthma, COPD, lung cancer, cystic fibrosis, sleep, acute lung injury, pediatric pulmonary disease, and immunologic pulmonary disease. The training program provides world-class mentorship in the sciences, training in competitive grant writing, and is committed to an educational environment designed to provide trainees with the necessary skills to become successful independent investigators.

The mentors are specialists in basic and translational lung research, as well as specialists from non-lung areas whose expertise bears on lung disease who have in total, trained 72 postdoctoral trainees in the last 10 years. Of these trainees, 39 hold advanced academic positions. For details of this training program, please contact Rashmi Patel (

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Contact Us

Mailing Address:
BB 8-812
630 W 168th St
New York, NY 10032

Laboratory Locations:
650 W 168th St
Black Building 8-812
Physicians & Surgeons 9-460
Physicians & Surgeons 8-425
Campus Map

Phone: 212-305-7310
Fax: 212-305-6701

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