SUNY Downstate Health Sciences University
Department of Medicine
Patrick Geraghty, PhD
Research Assistant Professor
Tel: (718) 270-3141
Education and Training:
- Position held:
- Associate Research Scientist (Dept of Medicine) Mount Sinai Roosevelt Hospital, Mount
Sinai Health Systems, New York, 2014-2015
Associate Research Scientist (Dept of Medicine) St. Luke's Roosevelt Hospital, New York, 2011-2014
- Postdoctoral Research Fellow, Columbia University College of Physicians and Surgeons,
New York, 2007-2011
Postdoctoral Research Scientist, Royal College of Surgeons in Ireland, Dublin, Ireland, 2004-2007
- Graduate School:
- Microbiology PhD, National University of Ireland, Maynooth, Co. Kildare, Ireland, 2000-2004
Career / Research Interests:
The primary interest of my research is to investigate immune responses in healthy and diseased lungs. I am particularly interested in immune responses in two lung diseases, chronic obstructive pulmonary disease (COPD) and alpha-1 antitrypsin deficiency. The long-term goal of my research is to identify key players associated with lung damage and resolution of sustained inflammation. To achieve this, I have primarily focused on key proteins that counter inflammation and return the lung to normal homeostasis. We employ several approaches to lung diseases, including transgenic and knock-out mouse models, cigarette smoke animal exposure models, e-cigarette animal exposure model, pulmonary viral infection animal models, antibody delivery, pulmonary function testing in mice, primary mammalian cell culture systems, proteomics, flow cytometry and immunohistochemistry. We provide training to pulmonary fellows and introduce them to basic research techniques. The major active research topics within the lab are:
Resolution of lung inflammation by phosphatases.
Despite the role of phosphatases being extensively characterized in multiple organs and diseases, the role of phosphatases in the lung is limited; especially in cigarette smoke exposure and lung infection models. Viral infections are considered a major driving factor of COPD exacerbations and thus contribute disease morbidity and mortality. We primarily focus on one phosphatase, protein tyrosine phosphatase 1B (PTP1B), and have identified that PTP1B regulates several key responses linked to disease progression, such as apoptosis, T-cell differentiation, cytokine production and expression of antimicrobial peptides. However, PTP1B responses are desensitized in the lung by prolonged cigarette smoke exposure and leave the lung more susceptible to enhanced damage due to prolonged inflammation. Indeed, Ptp1b knockout mice are more susceptible to lung damage following cigarette smoke exposure or viral infection. Elevated expression of S100A9, a damage-associated molecular pattern molecule, was observed in the lungs of Ptp1b knockout mice during lung viral infection. We have also identified that S100A9 signaling significantly impacts lung damage. It is unclear how S100A9 signaling impacts on lung injury and whether targeting S100A9 represents a potential approach to minimizing lung damage in COPD patients. In collaboration with Dr. Robert Foronjy at SUNY Downstate, our group is assessing these questions in animal and cell culture models. The Flight Attendant Medical Research Institute (FAMRI) funds this project.
Phospholipid transfer protein (PLTP) counters lung inflammation.
Our laboratory has found that extracellular phospholipid transfer protein (PLTP) prevents lungs inflammation but PLTP undergoes proteolytic cleave in the lungs of COPD patients. This degradation of PLTP in the lung predisposes the lung to prolonged inflammation that could contribute to the disease progression. We recently also determined that the alpha-1 antitrypsin protein prevents PLTP cleavage by neutralizing the activity of serine proteases. Alpha-1 antitrypsin also prevents inflammation in the lung and individuals deficient for alpha-1 antitrypsin develop lung complications early in life. We are investigating whether PLTP could counter the inflammation observed in alpha-1 antitrypsin deficient individuals and if alpha-1 antitrypsin's anti-inflammatory ability is partially due to its capacity to protect PLTP integrity. The Alpha-1 Foundation funds this project. In collaboration with Dr. Robert Foronjy (SUNY Downstate), Dr Ed Eden (Mount Sinai) and Dr Michael Campos (University of Miami), our group is assessing these questions in animal models and patient samples.
- Foronjy, R.F., Ochieng, P.O., Salathe, M.A., Dabo, A.J., Eden, E., Baumlin, N., Cummins, N., Barik, S., Campos, M., Thorp, E.B. and Geraghty, P. Protein tyrosine phosphatase 1B negatively regulates S100A9-mediated lung damage during respiratory syncytial virus exacerbations. Mucosal Immunol. (In press)
- Dabo, A.J., Cummins, N., Eden, E. and Geraghty, P. Matrix metalloproteinase 9 exerts antiviral activity against respiratory syncytial virus. PLoS One. (2015) Aug 18;10(8):e0135970. doi: 10.1371/journal.pone.0135970. eCollection 2015.
- Yoo, S., Takikawa, S., Geraghty, P., Argmann, C., Campbell, J., Lin, L., Huang, T., Tu, Z., Foronjy, R., Spira, A., Schadt, E.E., Powell, C.A., Zhu, J. Integrative analysis of DNA methylation and gene expression data identifies EPAS1 as a key regulator of COPD. PLoS Genet. (2015) Jan 8;11(1):e1004898. doi: 10.1371/journal.pgen.1004898. eCollection 2015 Jan.
- Foronjy, R.F., Taggart, C.C., Dabo, A.J., Weldon, S., Cummins, N. and Geraghty, P. Type I interferons induce lung protease responses following respiratory syncytial virus infection via RIG-I-like receptors. Mucosal Immunol. (2015) Jan;8(1):161-75. doi: 10.1038/mi.2014.54. Epub 2014 Jul 9.
- Geraghty, P., Eden, E., Pillai, M., Campos, M., McElvaney, N.G. and Foronjy, R.F. α-1 antitrypsin activates protein phosphatase 2A (PP2A) to counter lung inflammatory responses. Am J Respir Crit Care Med. (2014) Dec 1;190(11):1229-42. doi: 10.1164/rccm.201405-0872OC.
- Foronjy, R.F., Dabo, A.J., Cummins, N. and Geraghty, P. Leukemia inhibitory factor protects the lung during respiratory syncytial viral infection. BMC Immunology (2014) 2014 Oct 3;15(1):41.
- Brehm, A., Geraghty, P., Campos, M. Gaffney, A., Eden, E., Jiang, X.C., D'Armiento, J.M. and Foronjy, R.F. Cathepsin G degradation of phospholipid transfer protein (PLTP) augments pulmonary inflammation. FASEB J. 2014 Feb 28;9(2):e90567. doi: 10.1371/journal.pone.0090567.
- Foronjy, R.F., Taggart, C.C., Dabo, A.J., Weldon, S. and Geraghty, P. Respiratory syncytial virus infections enhance cigarette smoke induced COPD in mice. PLoS One. (2014) Feb 28;9(2):e90567. doi: 10.1371/journal.pone.0090567. eCollection 2014.
- Geraghty, P., Hardigan, A. and Foronjy, R.F. Cigarette smoke activates the proto-oncogene c-Src to promote airway inflammation and lung tissue destruction. Am. J. Respir. Cell Mol. Biol., (2014) 2014 Mar;50(3):559-70. doi: 10.1165/rcmb.2013-0258OC.
- Geraghty, P., Wyman, A.E., Garcia-Arcos, I., Dabo, A.J., Gadhvi, S. and Foronjy, R. STAT3 Modulates Cigarette Smoke-Induced Inflammation and Protease Expression. Front. Physiol. (2013) doi: 10.3389/fphys.2013.00267
- Reeves, E.P., Banville, N., Ryan, D.M., O'Reilly, N., Bergin, D.A., Pohl, K., Molloy, K., McElvaney, O.J., Alsaleh, K., Aljorfi, A., Kandalaft, O., O'Flynn, E., Geraghty, P., O'Neill, S.J. and McElvaney, N.G. Intracellular secretory leukoprotease inhibitor modulates inositol 1,4,5-triphosphate generation and exerts an anti-inflammatory effect on neutrophils of individuals with cystic fibrosis and chronic obstructive pulmonary disease. Biomed Res Int. (2013) doi: 10.1155/2013/560141.
- Geraghty, P. and Foronjy, R. Protein transfection of mouse lung. J Vis Exp. (2013) May 15;(75). doi: 10.3791/50080.
- Geraghty, P., Hardigan, A., Wallace, A.M., Mirochnitchenko, O., Thankachen, J., Arellanos, L., Thompson, V., D'Armiento, J.M. and Foronjy, R.F. The GPx1-PTP1B-PP2A axis: a key determinant of airway inflammation and alveolar destruction. Am J Respir Cell Mol Biol. (2013) Nov;49(5):721-30. doi: 10.1165/rcmb.2013-0026OC.
- D'Armiento, J., Goldklang, M., Hardigan, A.A., Geraghty, P., Roth, M., Connett, J., Wise, R., Sciurba, F., Scharf, S., Thankachen, J., Islam, M., Ghio, A. and Foronjy, R. Increased Matrix Metalloproteinase (MMPs) Levels Do Not Predict Disease Severity or Progression in Emphysema. PLoS One. (2013) 8(2):e56352. doi: 10.1371/journal.pone.0056352. Epub (2013) Feb 18.
- Mehra, D., Geraghty, P., Hardigan, A.A., Foronjy, R. A comparison of the inflammatory and proteolytic effects of dung biomass and cigarette smoke exposure in the lung. PLoS One. (2012) 7(12):e52889. doi: 10.1371/journal.pone.0052889. Epub (2012) Dec 20.
- Wallace, A.M., Hardigan, A., Geraghty, P., Salim, S., Gaffney, A., Thankachen, J., Arellanos, L., D Armiento, J.M. and Robert F. Foronjy. Protein phosphatase 2A (PP2A) regulates innate immune and proteolytic responses to cigarette smoke exposure in the lung. Toxicol Sci. (2012) 126(2): 589-99.
- Geraghty, P., Dabo, A.J. and D'Armiento, J. TLR4 Protein Contributes to Cigarette Smoke-induced Matrix Metalloproteinase-1 (MMP-1) Expression in Chronic Obstructive Pulmonary Disease. J Biol Chem. (2011) 286 (34): 30211-8.
- Geraghty, P., Wallace, A. and D'Armiento, J. Induction of the unfolded protein response by cigarette smoke is primarily an activating transcription factor 4-C/EBP homologous protein mediated process. Int J Chron Obstruct Pulmon Dis. (2011);6:309-19.
- Bergin, D.A., Greene, C.M., Sterchi, E.E., Kenna, C., Geraghty, P., Taggart, C.C, O'Neill, S.J., McElvaney, N.G. Activation of EGFR by a novel metalloprotease pathway. J Biol Chem. (2008) 283(46): 31736-44.
- Geraghty, P., Rogan, M.P., Greene, C.M., Brantly, M., O'Neill, S.J., Taggart, C.C., McElvaney, N.G. Alpha-1-antitrypsin aerosolised augmentation abrogates neutrophil elastase-induced expression of cathepsin B and matrix metalloprotease 2 in vivo and in vitro. Thorax (2008) 63 (7) 621-6.
- Geraghty, P., Greene, C.M., O'Mahony, M., O'Neill, S.J., Taggart, C.C., McElvaney, N.G. Secretory leucocyte protease inhibitor inhibits interferon-gamma-induced cathepsin S expression. J Biol Chem. (2007) 282 (46) 33389-95.
- Geraghty, P., Rogan, M.P., Catherine M. Greene, Boxio, R.M.M., Poiriert, T., O'Mahony, M., Belaaouaj, A., O'Neill, S.J., Taggart, C.C. and McElvaney, N.G. Neutrophil elastase upregulates Cathepsin B and Metalloprotease-2 expression. J Immunol. (2007) 178 (9) 5871-86.
- Rogan, M.P., Geraghty, P., Greene, C.M., O'Neill, S.J., Taggart, C.C. and McElvaney, N.G. Antimicrobial proteins and polypeptides in pulmonary innate defence. Respir Res. (2006) 17: 17-29.
- Geraghty, P. and Kavanagh, K. Disruption of mitochondrial function in Candida albicans leads to reduced cellular ergosterol levels and elevated growth in the presence of amphotericin B. Arch Microbiol (2003) 179: 295-300.
- Geraghty, P. and Kavanagh, K. Erythromycin, an inhibitor of mitoribosomal protein biosynthesis, alters the amphotericin B susceptibility of Candida albicans. J Phar Pharmacology (2003) 55: 179-184
- Book Chapter:
Geraghty, P. and Kavanagh, K. (2006) Extraction and Detection of DNA and RNA from Yeast. Chapter 8 (pp159-179) in Medical Mycology: Cellular and Molecular Techniques. Publishers: Wiley & Co. Ltd. Chichester, UK (ISBN: 0-470-01923-9 hardback) Edit: K. Kavanagh (Published: October 2006).