Ph.D: Microbiology,
Osmania University,
India

MSc Biochemistry:
Sri Venkateswara University,
India

• Excessive neutrophil’s influx, NETs and NPA exacerbate pulmonary damage in influenza.

  Highly pathogenic influenza virus infections are associated with acute lung injury (ALI), respiratory distress, and multi-organ failure. Both host- and virus-mediated factors contribute to ALI in severe influenza. My lab has been focussing on understanding the role innate immune cells in influenza pathogenesis. My research findings highlight that excessive neutrophils recruited during influenza, contribute to immunopathology and ALI, through neutrophil extracellular traps (NETs) induction,

   

  release of extracellular histones (ECH) and formation of neutrophil-platelet aggregates (NPAs). These inflammatory and thrombotic responses lead to pathologic manifestations of acute respiratory distress syndrome (ARDS) in severe influenza. Through neutrophil and/or macrophage depletion-strategy, we identified that neutrophils potentially cause alveolar-capillary disruption in the lung alveoli. Although NETs are characterized as anti-bacterial effect, influenza-induced NETs do not possess any bactericidal or fungicidal effects. Further, we found that neutrophils interact with platelets via neutrophil MAC-1- platelet-GPIbα binding in NPA formation. Further, accumulated NPA aggravates pulmonary capillary damage via induction of NETosis. Narasaraju et al, Am J Pathol 2011; Ashar et al, Am J Pathol 2018; Sivasami et al, Am J Resp Cell Mol Biol. 2019; Ashar et al Am J Pathol 2021).

  A novel combination therapy for influenza pneumonia in mice and piglets.

  Phenotypic characterization of neutrophils for their chemokine receptor (CR) repertoire during influenza identified high induction of CXCR2. Mechanistically, we have identified a novel functional role of CXCR2 signaling in NETopathic death in neutrophils isolated from influenza-infected animals. Based on temporal dynamics of neutrophil’s recruitment, activation and NETosis, we evaluated a combination treatment using a selective CXCR2 antagonist, SCH527123 plus antiviral agent, oseltamivir in highly lethal influenza challenged mice, and sub-lethal swine-influenza challenged piglets. Combination treatment showed high protection against lethal influenza challenged mice and alleviated lung pathology in swine influenza-challenged piglets. (US Provisional Patent No: 62/163,583, 2016). Rudd et al, Front.in Cell and Infect Microbiol, 2019; Ashar et al, Am J Pathol 2021.

  Macrophages aids in alveolar repair during influenza.

  Our studies have identified a novel function of macrophages in alveolar repair through production of hepatocyte growth factor (HGF). HGF, a pleotropic factor that induce alveolar epithelial proliferation in injured lungs. Further, administration of a recombinant human-HGF plus antiviral agent oseltamivir yielded significant protection in lethal-influenza infected mice. Narasaraju et al. Am J Resp Cell & Mol Biol, 2010; Narasaraju et al. Curr. Mol Med 2014.

  Influenza virus genomic analyses to evaluate adaptation of the virus in a new host species.

  To evaluate genetic changes that occur in the virus during adaptation in a novel host, we performed serial lung-to-lung passaging of a human influenza virus in a murine model. We have identified critical mutations in hemagglutinin, neuraminidase and non-structural proteins, which conferred high pathogenicity in mice. Transcriptomic analyses have shown neutrophil and macrophage predominant cytokine and inflammatory signaling cascades in mouse-adapted virus, which displayed high pathogenicity compared to non-adapted virus. Further, prior vaccination with attenuated Bordetella pertussis suppressed neutrophilic inflammation and pro-inflammatory responses and provide high protection thus suggest a potential involvement of exaggerated innate immune regulation in severe lung pathology in influenza. Narasaraju et al., Microbes Infect 2009; Ivan X et al Functional Integrative Genomics 2012; Li et al, J Virol 2010.

  Neutrophils and NETs in secondary bacterial superinfection following influenza.

   

  Bacterial superinfections are most common among fatal influenza infections. We have developed a dual-infection (influenza infection, followed by Streptococcus pneumoniae superinfection) animal model. Our studies have shown that NETs generation is dependent on the pneumococcal capsule thickness and varies with the different serotype infections. The increase in thickness of the capsule results in enhanced tissue damage and lung pathology. Further characterization of neutrophils for their phenotypic signature in the inflammatory lung micro-environment during influenza and bacterial superinfection lead to identification of novel chemokine receptor repertoire in lung-recruited neutrophils, compared to circulating neutrophils. These findings are in preparation for manuscript submission. Anandi et al., Front Immunol. 2013; Anandi et al, Oncotarget. 2016; Rudd et al, (manuscript in preparation).

  NETs contribute to tissue injury in Francisella tularensis infection in mice, domestic cats and rabbits.

  Our studies identified induction of NETosis in lungs, and liver of mice infected with a live attenuated strain of Francisella (Ft-LVS), and also domestic cats and rabbits naturally infected with Francisella. Further, we found myeloperoxidase enzyme as a critical regulator of NETs induction in Francisella infection in a mouse-model. Sivasami et al, Frontiers in Immunology 2020.

  Excessive neutrophil’s recruitment mediates acute lung pathology in SARS-COV-2 infection.

  SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses. Emerging evidence implicates neutrophils and the disbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of inflammation, coagulopathy, organ damage, and immunothrombosis that characterize severe cases of COVID-19. we found an evidence that supports the role for NETs in COVID-19 manifestations of tissue injury and immunothrombosis. We also present various therapeutic strategies, which have been successful in the treatment of immunο-inflammatory disorders by targeting dysregulated NET formation as a potential approach that may benefit patients with severe COVID-19. (Narasaraju et al Front Pharmacol, 2021; Narasaraju J Infect Dis 2021; Ackermann et al Cell Death Diff 2021). Further we performed whole genomic sequence analysis of SRS-COV-2 circulating in Oklahoma during May to June 2020. Our data found several novel mutations appeared in several isolates tested.

  Studies on hyperoxia-mediated lung injury and repair:

  We have established hyperoxia-injury rat and mouse models which mimics bronchopulmonary dysplasia, the most common chronic respiratory disease that affects preterm infants due to ventilation therapy and oxygen toxicity. My studies have identified the role of insulin like growth factor (IGF) signaling in alveolar epithelial cell differentiation, essential lung tissue remodeling after injury. We also developed methods for isolation of alveolar type I and type II pneumocytes and also identification of novel markers. We also demonstrated RNA interference (RNAi)-mediated post-transcriptional gene silencing in alveolar epithelial cells using SPC driven small hairpin RNAs with potential implication in RNAi therapy.                            Narasaraju et al, Am J Physiol 2003; Jiwang et al, Lab Invest 2004; Narasaraju et al, J Cell Biochem 2005; Narasaraju et al, Am J Resp Cell Mol Biol, 2015; Gou et al, Nucleic Acids Res 2004.

1. Teluguakula Narasaraju, Amita Krishnappa, Marko Radic, and Vincent TK Chow. Testing an Efficacy of Ensovibep Therapy for COVID-19: A Requirement for Additional Criteria. Annals of Internal Medicine. ‘Letter to the Editor’ published online on September 7, 2022. (Impact Factor: 51.6)
2. Ackermann M, Anders HJ, Bilyy R, Bowlin GL, Daniel C, De Lorenzo R, Egeblad M, Henneck T, Hidalgo A, Hoffmann M, Hohberger B, Kanthi Y, Kaplan MJ, Knight JS, Knopf J, Kolaczkowska E, Kubes P, Leppkes M, Mahajan A, Manfredi AA, Maueröder C, Maugeri N, Mitroulis I, Muñoz LE, Narasaraju T, Naschberger E, Neeli I, Ng LG, Radic MZ, Ritis K, Rovere-Querini P, Schapher M, Schauer C, Simon HU, Singh J, Skendros P, Stark K, Stürzl M, van der Vlag J, Vandenabeele P, Vitkov L, von Köckritz-Blickwede M, Yanginlar C, Yousefi S, Zarbock A, Schett G, Herrmann M. Patients with COVID-19: in the dark-NETs of neutrophils. Cell Death Differ. 2021 May 24:1-15. (Impact Factor: 15.82)
3. Elliott, W., Jr.; Guda, M.R.; Asuthkar, S.; Narasaraju T.; Prasad, D.V.R.; Tsung, A.J.; Velpula,
   K.K. PAD Inhibitors as a Potential Treatment for SARS-CoV-2 Immunothrombosis.
   Biomedicines 2021, 9, 1867. (Impact Factor: 4.7)
4. Ashar HK, Rudd JM, Sivasami P, Achanta M, Maram P, Chow VTK, Malayer J, Tim S, and Narasaraju T. Administration of a CXCR2 antagonist, SCH527123 together with oseltamivir suppresses NETosis and protects mice from lethal influenza and piglets from swine-influenza infection. American Journal of Pathology 2021: 191:669-685. (Impact Factor: 5.77)
   
   News in the Medical and Scientific Magazines About This Article Science Daily
   
   https://www.sciencedaily.com/releases/2021/03/210318170325.htm;
   
   Physicians Weekly
   
   https://www.physiciansweekly.com/administration-of-a-cxcr2-antagonist-sch527123-together- with-oseltamivir-suppresses-netosis-and-protects-mice-from-lethal-influenza-and-piglets-from- swine-influenza-infection/;
   
   M3India
   
   https://www.m3india.in/contents/clinical_news/154572/combination-therapy-may-provide- significant;
   
   Elsevier News
   
   https://els-jbs-prod- cdn.jbs.elsevierhealth.com/pb/assets/raw/Health%20Advance/journals/ajpa/AJP_Apr2021_PR_T eluguakula_FINAL2.pdf)
   
   
5. Narasaraju T. Neutrophils set extracellular traps to injure lungs in COVID-19. Editorial Commentary. Journal of Infectious Diseases. 2021; 223:1503-1505. (Impact Factor: 7.7)
6. Narayanan S, Ritchey JC, Patil G, Narasaraju T, More S, Malayer J, Saliki J, Kaul A, Agarwal PK, Ramachandran A. SARS-CoV-2 Genomes From Oklahoma, United States. Front Genet. 2021;11:612571. (Impact Factor: 4. 5)
7. Narasaraju T. Commentary on “Histopathologic Changes and SARS–CoV-2 Immunostaining in the Lung of a Patient With COVID-19”. Annals of Internal Medicine. ‘Letter to the Editor’ 2020; 173:323-324. (Impact Factor: 51.6)
8. Narasaraju T, Tang B, Martin H, Sylviane M, Chow VT and Radic M. Neutrophilia and NETopathy as Key Pathologic Drivers of Progressive Lung Impairment in Patients with COVID-19. Frontiers Pharmacology, 2020:11:870. (Impact Factor: 6.0)
9. Narasaraju T, More S, Radic M, Chow, V. T. (2020). A Pathologic Perspective of COVID-19: Parallels with Severe Influenza Virus Pneumonia. https://doi.org/10.31219/osf.io/xp65w
10. Sivasami P, Maram P, Ramachandran A, Rezabek G, Timothy AS, Chow TK, Malayer JR, and Narasaraju T. Production of neutrophil extracellular traps contributes to the pathogenesis of Francisella tularemia. Frontiers in Immunology. 2020;11:679. (Impact Factor: 8.7)
11. Sivasami P, Rudd JM, Ashar HK, Maram P, Thomas PG, Akhilesh R, Malayer J, Chow VTK, and Narasaraju T. Combination therapy targeting platelet activation and virus replication protects mice against lethal influenza pneumonia. American Journal of Respiratory Cell and Molecular Biology. 2019; 61: 689-701. (Impact Factor: 7.74)
12. Rudd JM, Ashar HK, Sivasami P, Tim S, Maram P, Ritchey J, Malayer J, Chow VTK, and Narasaraju T. Characterization of phenotypic changes in neutrophils during pneumococcal super-infection following influenza. Frontiers in Cellular and Infection Microbiology. 2019; 9:
    
    108. (Impact Factor: 4.3)
    
    
13. Ashar HK, Nathan M, Rudd JM, Tim S, Achanta M, Maram P, Sivasami P, Thomas P, Akhilesh R, Ritchey J, Malayer J, Rachakatla R, Chow VTK, Esmon TC and Narasaraju T. Role of extracellular histones in influenza virus pathogenesis. American Journal of Pathology 2018; 188: 135-148. (Impact Factor: 5.77)
14. Moorthy AN, Tan KB, Wang S, Narasaraju T, Chow VT. Effect of High-Fat Diet on theFormation of Pulmonary Neutrophil Extracellular Traps during Influenza Pneumonia in BALB/cMice.Frontiers in Immunology 2016; 7: 289. (Impact Factor: 8.7)
15. Anandi NM, Prashant R, Jiao H, Shi W, Kong BT, Liang Q, Hiroshi W, Yongliang Z, Narasaraju T and Vincent Chow TK. Capsules of virulent pneumococcal serotypes enhance formation of neutrophil extracellular traps during in vivo pathogenesis of pneumonia. Oncotarget. 2016; 7: 19327-40. (Impact Factor: 3.33)
16. Rudd JM, Ashar HK, Chow VTK, Narasaraju T. Lethal Synergism between Influenza and Streptococcus Pneumonia. J Infect Pulm Dis. 2016; 2(2): doi http://dx.doi.org/10.16966/2470- 3176.114.
17. Audrey-Ann L, Narasaraju T, Tan KB, Wang S, Phoon MC, Vincent T.K. Chow. Caspase-1- deficient mice are more susceptible to influenza pneumonitis. European Journal of Inflammation. 2014; 12: 117-130. (Impact Factor: 0.466)
18. Narasaraju T, Shukla D, More S, Huang C, Zhang L, Xiao X, Liu L. Role of miR-150 and glycoprotein non- metastatic melanoma protein B in hyperoxia- induced neonatal lung injury. American Journal of Respiratory Cell and Molecular Biology. 2015; 52: 253-61. (Impact Factor: 7.74)
19. Narasaraju T, Edwin YY, H.H. Ng, Audrey A, Phoon MC, Vincent TK Chow. Therapeutic effect of combining hepatocyte growth factor and oseltamivir in amelioration of influenza pneumonitis. Current Molecular Medicine. 2014; 14: 1-13. (Impact Factor: 2.26)
20. Anandi NM, Narasaraju T Prashant R, perumalsamy R, Tan KB, Wang S, Bevin E, Vincent T.K. Chow. In vivo and in vitro studies on the roles of neutrophil extracellular traps during secondary pneumococcal pneumonia after primary pulmonary influenza infection. Frontiers in Immunology. 2013; 4: 56. (Impact Factor: 8.7)
21. Ng HH, Narasaraju T, Sim MK and Vincent TK Chow. Doxycyline treatment attenuates acute lung injury in mice infected with highly virulent influenza H3N2 virus: involvement of matrix metalloproteases. Experimental and Molecular Pathology. 2012; 92:287-95. (Impact Factor: 4.4)
22. Ivan FX, Rajapakse JC, Welsch RE, Rozen SE, Narasaraju T, Xiong GM, Chow VT. Differential pulmonary transcriptomic profiles in murine lungs infected with low and highly virulent influenza H3N2 viruses reveal dysregulation of TREM1 signaling, cytokines and chemokines. Functional & Integrative Genomics. 2012; 12:105-17. (Impact Factor: 3.36)
23. Bhaskaran M, Dong Xi, Yang W, H3.1)uang C, Narasaraju T, Weiqun Shu, Chunling Zhao, Xiao X, More S, Breshears M, and Liu L. Identification of microRNAs changed in the neonatal lungs in response to hyperoxia exposure. Physiological Genomics. 2012; 44: 970-80. (Impact Factor: 3.1)
24. Narasaraju T, Edwin Y, Perumal S, Ng HH, Poh WP, Audrey-Ann L, Phoon Meng C, van Rooijen N and Chow VT. Excessive Neutrophils and Neutrophil Extracellular Traps Contribute to Acute Lung Injury of Influenza Pneumonitis. American Journal of Pathology. 2011; 179: 199-210. (Impact Factor: 5.77)
25. Li R, Lim A, Phoon MC, Narasaraju T, Jowin K.W. Ng, Wee Peng, Poh, Meng Kwoon Sim, Vincent T. Chow and Sylvie Alonso. Attenuated Bordetella pertussis protects against highly pathogenic Influenza A Viruses by dampening the Cytokine Storm. Journal of Virology, 2010; 84: 7105-13. (Impact Factor: 5.1)
26. Narasaraju T, H.H. Ng, Phoon MC and Vincent TK Chow. MCP-1 Antibody Treatment Enhances Damage and Impedes Repair of the Alveolar Epithelium in Influenza. American Journal of Respiratory Cell and Molecular Biology. 2010; 42: 732-43. (Impact Factor: 7.74)
27. Wei Peng P, Narasaraju T, Phoon MC, Macary P, Wong SH, Lu J, Koh DR and Vincent TK Chow. Characterization of cytotoxic T-lymphocyte epitopes and immune response to SARS coronavirus spike DNA vaccine expressing the RGD integrin-binding motif. Journal of Medical Virology, 2009; 81: 1131-9. (Impact Factor: 20.6)
28. Narasaraju T, Sim MK, Ng HH, Phoon MC, Shanker N, Lal SK, Chow VT. Adaptation of human influenza H3N2 virus in a mouse pneumonitis model: insights into viral virulence, tissue tropism and host pathogenesis. Microbes and Infection. 2009;11: 2-11. (Impact Factor: 9.57)
29. Chen J, Chen Z, Chintagari NR, Bhaskaran M, Jin N, Narasaraju T and Liu L. Alveolar Type I Cells Protect Rat Lung Epithelium from Oxidative Injury. Journal of Physiology. 2006; 572: 625-38. *Comment on this paper Journal of Physiol.2006;572:609-10. (Impact Factor: 5.18)
30. Chintagari NR, Jin N, Wang P, Narasaraju T, Chen J and Liu L. Effect of Cholesterol Depletion on Exocytosis of Alveolar Type II Cells. American Journal of Respiratory Cell and Molecular Biology. 2006; 34: 677-87. (Impact Factor: 7.74)
31. Narasaraju T, Nili Jin, Zhongming Chen and Liu L. Role of Insulin like growth factor system during the repair after hyperoxia mediated lung injury. Journal of Cellular Biochemistry. 2005, 97: 984-98. (Impact Factor: 3.44)
32. Jin N, Narasaraju T, Kuttiputi N, Chen J, Liu L. Differential expression of GABAA receptor pi subunit in cultured rat alveolar epithelial cells. Cell and Tissue Research. 2005; 321: 173-83. (Impact Factor: 3.0).
33. Maiti S, Dutta SM, Baker SM, Zhang J, Narasaraju T, Liu L, and Chen G. In vivo and in vitro oxidative regulation of rat sulfotransferase IV (AST IV). Journal of Biochemical and Molecular Toxicology. 2005 19: 109-18. (Impact Factor: 3.6)
34. Gou D*, Narasaraju T*, Chintagari N, Jin N, Wang P, Liu L. Gene silencing in alveolar type II cells using cell-specific promoter in vitro and in vivo. Nucleic Acids Research 2004; 32: e134. (*first author). (Impact Factor: 16.97)
35. Zhongming Chen, Chen J, Narasaraju TA and Liu L. Identification of novel markers for alveolar epithelial cells. Biochemical and Biophysical Research Communications 2004; 319: 774-80. (Impact Factor: 3.57)
36. Jiwang C, chen Z, Narasaraju T and Lin Liu. Isolation of highly pure alveolar epithelial type 1 and type 2 cells from rat lungs. Lab Investigation. 2004, 84: 727-35. (Impact Factor: 4.87)
37. Abonyo BO, Gou D, Wang P, Narasaraju T, Wang Z, Liu L. Syntaxin 2 and SNAP-23 Are Required for Regulated Surfactant Secretion. Biochemistry. 2004; 43: 3499-506. (Impact Factor: 3.16)
38. Singh, T. K., Abonyo, B., Narasaraju, T and Liu, L. Reorganization of cytoskeleton during surfactant secretion in lung type II cells: a role of annexin II, Cell Signal. 2004; 16: 63-70. (Impact Factor: 4.31)
39. Narasaraju T, li Jin Reddy RN, Zhongming Chen and Liu L. Protein nitration during hyperoxia mediated lung injury: a possible role of myeloperoxidase. American Journal of Physiology, Lung Cell Molecular Physiology 2003; 285: L1037-45. (Impact Factor: 4.41)
40. Abonyo, B.O, Wang PC, Narasaraju T, William H Rowan III, David H. McMillan, Un-Jin Zimmerman and Liu, L. Characterization of a-SNAP in alveolar type II cells: implications in lung surfactant secretion. American Journal of Respiratory Cell and Molecular Biology. 2003; 29, 273-282. (Impact Factor: 7.4)
41. Anand. T, Narasaraju T, Vishnu. C, Venkateswar Rao. L, Sharma. G. Development of Dot- ELISA for the detection of human rotavirus and comparison with RNA-PAGE. Letters in Applied Microbiology. 2001; 32: 176-180. (Impact Factor: 3.00)
42. Anand T, Narasaraju T, Venkateshwarrao L, Sharma G. Symptomatic Rotavirus infection subgroups, serotypes and electropherotypes in Hyderabad, India. Indian Journal of Medical Research. 2000; 112: 1-4. (Impact Factor: 5.2)
43. Asymptomatic Human Rotavirus Serotype 3 Among Infants at Hyderabad, India.T Anand, TA Narasaraju, R Hemalatha, LV Rao, G Sharma. Indian Journal of Medical Microbiology, 18 (1), 37-39. (Impact Factor: 0.98)
44. Narasaraju T, Vijayalakshmi A, Anand T, Venkateshwarrao L, Sharma G. Protective role of quercetin during influenza induced oxidative stress. Asia Pacific Journal of Clinical Nutrition 2000; 9: 314-317. (Impact Factor: 1.66)
45.  

Academic Honors & Fellowships:

• Best Presentation Award, at International Conference on FLU; Chicago, USA, 2015.
• Best Presentation Award, at 2nd Oklahoma Center for Respiratory and Infectious Diseases (OCRID) retreat; Oklahoma, USA, April 2015.
• Scholarship Award at 9th Asia Pacific Congress for Medical Virology; Adelaide, Australia, 2012.
• Best Presentation Award, Poster at Singapore-MIT Alliance Annual Symposium; Singapore. 2010
• Best Presentation Award, Poster at 8th Asia Pacific Congress for Medical Virology; Hong Kong, 2009.
• DBT-Postdoctoral fellowship, India 2001.
• University Grants Commission (UGC) Senior Research Fellow, India 1997.
• University Grants Commission (UGC) Junior Research Fellow, India 1995.