My lab research primarily focuses on elucidating the molecular mechanisms underlying environmental oxidant induced respiratory pathogenesis, including lung cancer. AP-1 acts as one of the environmental biosensors that participate in cellular switching of the genetic program in response to various toxic and mitogenic stimuli. However, the physiological relevance and specific contribution of individual AP-1 family members to lung biology and toxicant-induced respiratory pathogenesis remain enigmatic. We have recently shown that cigarette smoke and diesel exhaust particles as well as tumor porters strongly stimulate Fra1 expression in lung epithelial cells, suggesting that Fra-1 (Fosl1) modulates toxicant induced gene expression. Ectopic expression of Fra-1 enhances lung cancer cell motility and invasiveness and promotes tumor growth and metastasis in vivo. Several studies have shown that Fra-1 is over-expressed in a wide variety of cancer cells and silencing of Fra-1 blunts cancer cell motility and invasion. Fra-1 is known to regulate the expression of genes associated with tumor progression and invasiveness. Currently, we are elucidating both transcriptional and signal transduction pathways regulating the induction of Fra-1 by various toxicants, including cigarette smoke. Also, targeted gene knockout models are being utilized to better understand the functional role of Fra-1 and its dimeric partner c-Jun in acute lung injury, repair, and cellular transformation. These studies may lead to the development of novel treatment strategies against toxicant-induced respiratory pathogenesis.

In our secondary area of research, we are using molecular approaches to understand the mechanisms involved in oxidant (hyperoxia) and mechanical stress-induced lung injury. Oxygen supplementation, often leading to a hyperoxic exposure, is widely used to support critical ill patients with non-infectious and infectious acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), as well as emphysema. However, hyperoxia causes extensive pulmonary damage that is characterized by inflammation and endothelial and alveolar epithelial cell death, resulting in pulmonary edema and respiratory dysfunction. We have recently shown that NF-E2-related transcription factor 2 (Nrf2) regulates hyperoxia and mechanical stress induced ALI and this process is mainly occurs through GSH induced signaling. Our research is currently focused on elucidating upstream signaling mechanisms that control the activation of Nrf2 and its downstream effectors, as a means of gaining insight into the pathogenesis of ALI by oxidants. This endeavor may not only help us devise new strategies to minimize the potentially hazardous effects of hyperoxia but may also lead to new therapeutic strategies aimed at minimizing the excessive morbidity and mortality associated with ALI.

Environmental pollutants, acute lung injury, bronchial carcinogenesis, cigarette smoke, oxidants and antioxidants, hyperoxia, mechanical ventilation, cyclic stretch, gene regulation, transcription factors, AP-1, Nrf2, signal transduction.

1985-1989 National Merit Ph.D. Fellowship, University Grants Commission, India.

1994-1996 Young Investigator's Research Award American Lung Association of California

1998-2003 First Award, National Heart, Lung and Blood Institute, NIH.

2001-2002 Recently Recruited Young Investigator Award, The Johns Hopkins Center for Childhood Asthma in the Urban Environment

Reddy NM, Suryanaraya V, Yates MS, Kleeberger SR, Hassoun PM, Yamamoto M, Liby KT, Sporn MB, Kensler TW, Reddy SP (2009). The Triterpenoid CDDO-Imidazolide Confers Potent Protection Against Hyperoxic Acute Lung Injury in Mice. Am J Respir Crit Care Med. 2009 Aug 13. [Epub ahead of print] PMID: 19679692

Reddy NM, Suryanaraya V, Kalvakolanu D, Yamamoto M, Kensler TW, Hassoun PM, Kleeberger SR , Reddy SP (2009). Innate Immunity Against Bacterial Infection Following Hyperoxia Exposure Is Impaired in NRF2-Deficient Mice. J Immunol. 2009 Oct 1;183(7):4601-8. Epub 2009 Sep 4.

Reddy NM, Kleeberger SR, Bream J, Kensler TW, Yamamoto M, Reddy SP (2009). Deficiency in Nrf2-depednent antioxidant response impairs the resolution of hyperoxia induced lung injury and inflammation in mice. Journal of Immunology Jun 1;182(11):7264-71. PMID: 19454723

Liu M, Grigoryev DN, Crow MT, Haas M, Yamamoto M, Reddy SP and Rabb H (2009). Nrf2 transcription factor serves a protective role in both ischemic and nephrotoxic acute kidney. Kidney International May 13. [Epub ahead of print] PMID: 19436334

Bierman A, Yerrapureddy A, Reddy NM, Hassoun PM, Reddy SP. Epidermal Growth Factor receptor (EGFR) regulates mechanical ventilation-induced lung injury in mice. Translational Res. 2008 Dec;152(6):265-72. Epub 2008 Oct 31.

Reddy SP. The antioxidant response element and oxidative stress modifiers in airway diseases. Curr Mol Med. 2008 Aug;8(5):376-83.

Reddy NM, Kleeberger SR, Bream JH, Fallon PG, Kensler TW, Yamamoto M, Reddy SP. Genetic disruption of the Nrf2 compromises cell-cycle progression by impairing GSH-induced redox signaling. Oncogene. 2008 Oct 2;27(44):5821-32. Epub 2008 Jun 9.

Adiseshaiah P, Li J, Vaz M, Kalvakolanu DV, Reddy SP. ERK signaling regulates tumor promoter induced c-Jun recruitment at the Fra-1 promoter. Biochem Biophys Res Commun. 2008 Jun 27;371(2):304-8. Epub 2008 Apr 22.

Adiseshaiah P, Vaz M, Machireddy N, Kalvakolanu DV, Reddy SP. A Fra-1-dependent, matrix metalloproteinase driven EGFR activation promotes human lung epithelial cell motility and invasion. J Cell Physiol. 2008 Feb 20; [Epub ahead of print]

Papaiahgari S, Yerrapureddy A, Reddy SR, Reddy NM, Dodd-O JM, Crow MT, Grigoryev DN, Barnes K, Tuder RM, Yamamoto M, Kensler TW, Biswal S, Mitzner W, Hassoun PM, Reddy SP. Genetic and pharmacologic evidence links oxidative stress to ventilator-induced lung injury in mice. Am J Respir Crit Care Med. 2007 Dec 15;176(12):1222-35.

Reddy NM, Kleeberger SR, Yamamoto M, Kensler TW, Scollick C, Biswal S, Reddy SP. Genetic dissection of the Nrf2-dependent redox signaling regulated transcriptional programs of cell proliferation and cytoprotection. Physiol Genomics. 2007 Dec 19;32(1):74-81. Epub 2007 Sep 25.

Adiseshaiah P, Lindner DJ, Kalvakolanu D, Reddy SP (2007) FRA-1 proto-oncogene induces lung epithelial cell invasion and anchorage-independent growth in vitro, but insufficient to promote tumor growth in vivo. Cancer Research 67: 6204-6211

Reddy SP, Hassoun PM and Brower R (2007) Redox imbalance and ventilator-induced lung injury. Antioxid Redox Signal. 9(11):2003-12. Review.

Marzec JM, Christie JD, Reddy SP, Jedlicka AE, Vuong H, Lanken PN, Aplenc R, Yamamoto T, Yamamoto M, Cho HY, Kleeberger SR (2007). Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury. FASEB J. 9:2237-46. PMID: 17384144

Papaiahgari S, Yerrapureddy A, Hassoun PM, Garcia JG, Birukov KG, Reddy SP. (2007) EGFR-Activated Signaling and Actin Remodeling Regulate Cyclic Stretch-induced Nrf2-ARE Activation. Am J Respir Cell Mol Biol. 36: 304-312. Sep 28; [Epub ahead of print]

Adiseshaiah P, Kalvakolanu, D, Reddy, SP (2006) A JNK-independent signaling pathway regulates TNFa-stimulated, c-Jun-driven FRA-1 protooncogene transcription in pulmonary epithelial cells. J. Immunology. 177:7193-202

Thimmulappa RK, Lee H, Rangasamy T, Reddy SP Kensler TW, Yamamoto Biswal S. (2006) Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis. J. Clinical Invest. 116: 984-995.

Zhang Q, Adiseshaiah, P., Kalvakolanu D and Reddy, SP (2006) A phosphatidylinositol 3-kinase regulated Akt independent signaling promotes cigarette smoke induced FRA-1 expression. J Biol Chem. 281(15):10174-10181

Mossman BT, Lounsbury KM, Reddy SP (2006) Oxidants and Signaling by Mitogen-Activated Protein Kinases (MAPK) in Lung Epithelium (Invited Review). Am J Respir Cell Mol Biol. 34:666-9.

Papaiahgari SR, Zhang Q, Kleeberger SR, Cho H-Y., and Reddy SP (2006) Hyperoxia stimulates an Nrf2-ARE transcriptional response via ROS-EGFR-PI3K-Akt/ERK MAP kinase signaling in pulmonary epithelial cells. Antioxidants Redox Signaling 8(1-2):43-52

Adiseshaiah, P., Peddakama S., Zhang Q, Kalvakolanu D and Reddy, SP (2005) Mitogen regulated induction of FRA-1 proto-oncogene is controlled by the transcription factors binding to both serum and TPA response elements. Oncogene 24(26):4193-205.

Zhang Q, Adiseshaiah P, and Reddy, SP (2005). Matrix metalloproteinase/epidermal growth factor receptor/mitogen-activated protein kinase signaling regulate fra-1 Induction by cigarette smoke in lung epithelial cells. Am J Respir Cell Mol Biol. 32: 72-81

Cho, H-Y., Reddy, SP, DeBiase, A., Yamamoto, M and Kleeberger SR (2005). Gene expression profiling of Nrf2-mediated protection against oxidative injury. Free Radicals in Biology and Medicine 38: 325-343

Papaiahgari SR, Kleeberger SR, Cho H-Y, Kalvakolanu DV, and Reddy, SP. (2004) NADPH oxidase and ERK signaling regulates hyperoxia-induced Nrf2-ARE transcriptional response in pulmonary epithelial cells. J Biol Chem. 279:42302-12.

Cho H-Y, Reddy SP, Yamamoto M, and Kleeberger SR (2004) The transcription factor NRF2 protects against pulmonary fibrosis. FASEB J. 18:1258-60

Adiseshaiah P, Papaiahgari SR, Vuong H, Kalvakolanu DV, and Reddy, SPM (2003) Multiple cis-elements mediate the transcriptional activation of human fra-1 by 12-O-tetradecanoylphorbol-13-acetate in bronchial epithelial cells. Journal of Biological Chemistry 278:47423-33

Reddy, SPM and Mossman B.T (2002) Role and regulation of activator protein-1 in toxicant-induced responses of the lung. AJP: Lung Cellular and Mol. Physiology 283: L1161-L1178. Invited Review.

Cho, H-Y., A.E. Jedlicka., Reddy, SPM, Kensler, T.W., Yamamoto, M., Zhang, L.-Y., and Kleeberger, S.R. (2002). Role of NRF2 in protection against hyperoxic lung injury in mice. American Journal of Respiratory and Cell and Molecular Biology 26: 175-182.