People : Scientific : Faculty & Scientists

DR. GURUPRASAD R. MEDIGESHI, Ph.D. 

Associate Professor
+91-129-2876311  (+91-129-6525537)
gmedigeshi [at] thsti [dot] res [dot] in
Ph.D. from Georg-August University, Goettingen, Germany.
M.Sc. Biotechnology, University of Mysore, Karnataka, India.
B.Sc., Yuvaraja College, University Of Mysore, Karnataka, India.

 

 

 

 

 

 

 

 

Present Research Interest

Majority of childhood infections in India are viral in nature and most of these infections cannot be prevented by vaccines or treated by commercial drugs. Our group primarily focuses on the host-pathogen interactions in human viral infections with particular focus on flaviviruses (Ex: Dengue virus) and respiratory viruses (Ex: Respiratory Syncytial Virus). Our primary objective is to generate basic knowledge in virus-host interactions that can be harnessed for vaccine and drug development. Focus areas include:

  • Identifying cellular signaling pathways and protein trafficking components that play an essential role at various stages of viral life-cycle
  • Understanding the interactions between cellular permeability barriers and viral infections
  • Identifying host and viral factors that influence disease outcomes in patients
  • Using high-throughput screening and in vitro assays to identify novel scaffolds for antiviral development and also for repurposing drugs

Collaborations

  • National Institute of Immunology, New Delhi
  • National Brain Research Center, Manesar
  • International Center for Genetic Engineering and Biotechnology, New Delhi
  • Indian Institute of technology, New Delhi
  • All India Institute of Medical Sciences, New Delhi
  • India Institute of Science, Bangalore

1.         Bosch I, de Puig H, Hiley M, Carré-Camps M, Perdomo-Celis F, Narváez CF, Salgado DM, Senthoor D, O’Grady M, Phillips E, Durbin A, Fandos D, Miyazaki H, Yen C-W, Gélvez-Ramírez M, Warke RV, Ribeiro LS, Teixeira MM, Almeida RP, Muñóz-Medina JE, Ludert JE, Nogueira ML, Colombo TE, Terzian ACB, Bozza PT, Calheiros AS, Vieira YR, Barbosa-Lima G, Vizzoni A, Cerbino-Neto J, Bozza FA, Souza TML, Trugilho MRO, de Filippis AMB, de Sequeira PC, Marques ETA, Magalhaes T, Díaz FJ, Restrepo BN, Marín K, Mattar S, Olson D, Asturias EJ, Lucera M, Singla M, Medigeshi GR, de Bosch N, Tam J, Gómez-Márquez J, Clavet C, Villar L, Hamad-Schifferli K, Gehrke L. Rapid antigen tests for dengue virus serotypes and Zika virus in patient serum. Science Translational Medicine. 2017;9(409). doi: 10.1126/scitranslmed.aan1589.

2.         Kar M, Singla M, Chandele A, Kabra SK, Lodha R, Medigeshi GR. Dengue Virus Entry and Replication Does Not Lead to Productive Infection in Platelets. Open Forum Infectious Diseases. 2017;4(2):ofx051-ofx. doi: 10.1093/ofid/ofx051.

3.         Ojha A, Nandi D, Batra H, Singhal R, Annarapu GK, Bhattacharyya S, Seth T, Dar L, Medigeshi GR, Vrati S, Vikram NK, Guchhait P. Platelet activation determines the severity of thrombocytopenia in dengue infection. Scientific reports. 2017;7:41697. doi: 10.1038/srep41697. PubMed PMID: 28139770.

4.         Kumar P, Medigeshi GR, Mishra VS, Islam M, Randev S, Mukherjee A, Chaudhry R, Kapil A, Ram Jat K, Lodha R, Kabra SK. Etiology of Acute Respiratory Infections in Infants: A Prospective Birth Cohort Study. Pediatr Infect Dis J. 2017;36(1):25-30. doi: 10.1097/INF.0000000000001359. PubMed PMID: 27753796.

5.         Jain N, Oswal N, Chawla AS, Agrawal T, Biswas M, Vrati S, Rath S, George A, Bal V, Medigeshi GR. CD8 T cells protect adult naive mice from JEV-induced morbidity via lytic function. PLoS neglected tropical diseases. 2017;11(2):e0005329. doi: 10.1371/journal.pntd.0005329. PubMed PMID: 28151989.

6.         Singla M, Kar M, Sethi T, Kabra SK, Lodha R, Chandele A, Medigeshi GR. Immune Response to Dengue Virus Infection in Pediatric Patients in New Delhi, India-Association of Viremia, Inflammatory Mediators and Monocytes with Disease Severity. PLoS neglected tropical diseases. 2016;10(3):e0004497. doi: 10.1371/journal.pntd.0004497. PubMed PMID: 26982706.

7.         Medigeshi GR, Kumar R, Dhamija E, Agrawal T, Kar M. N-Desmethylclozapine, Fluoxetine and Salmeterol inhibit post-entry stages of dengue virus life-cycle. Antimicrob Agents Chemother. 2016. doi: 10.1128/AAC.01367-16. PubMed PMID: 27572397; PMCID: PMC5075077.

8.         Kumar R, Agrawal T, Khan NA, Nakayama Y, Medigeshi GR. Identification and characterization of the role of c-terminal Src kinase in dengue virus replication. Scientific reports. 2016;6:30490. doi: 10.1038/srep30490. PubMed PMID: 27457684.

9.         Kakumani PK, Medigeshi GR, Kaur I, Malhotra P, Mukherjee SK, Bhatnagar RK. Role of human GRP75 in miRNA mediated regulation of dengue virus replication. Gene. 2016;586(1):7-11. doi: 10.1016/j.gene.2016.03.053. PubMed PMID: 27039024.

10.      Jenum S, Dhanasekaran S, Lodha R, Mukherjee A, Kumar Saini D, Singh S, Singh V, Medigeshi G, Haks MC, Ottenhoff TH, Doherty TM, Kabra SK, Ritz C, Grewal HM. Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum. Scientific reports. 2016;6:18520. doi: 10.1038/srep18520. PubMed PMID: 26725873; PMCID: 4698754.

11.      Chandele A, Sewatanon J, Gunisetty S, Singla M, Onlamoon N, Akondy RS, Kissick HT, Nayak K, Reddy ES, Kalam H, Kumar D, Verma A, Panda H, Wang S, Angkasekwinai N, Pattanapanyasat K, Chokephaibulkit K, Medigeshi GR, Lodha R, Kabra S, Ahmed R, Murali-Krishna K. Characterization of human CD8 T cell responses in dengue virus infected patients from India. Journal of virology. 2016. doi: 10.1128/JVI.01424-16. PubMed PMID: 27707928.

12.      Kakumani PK, Rajgokul KS, Ponia SS, Kaur I, Mahanty S, Medigeshi GR, Banerjea AC, Chopra AP, Malhotra P, Mukherjee SK, Bhatnagar RK. Dengue NS3, an RNAi suppressor, modulates the human miRNA pathways through its interacting partner. The Biochemical journal. 2015;471(1):89-99. doi: 10.1042/BJ20150445. PubMed PMID: 26221025.

13.      Kakumani PK, Ponia SS, S RK, Sood V, Chinnappan M, Banerjea AC, Medigeshi GR, Malhotra P, Mukherjee SK, Bhatnagar RK. Role of RNA interference (RNAi) in dengue virus replication and identification of NS4B as an RNAi suppressor. Journal of virology. 2013;87(16):8870-83. doi: 10.1128/JVI.02774-12. PubMed PMID: 23741001; PMCID: 3754049.

14.      Haridas V, Rajgokul KS, Sadanandan S, Agrawal T, Sharvani V, Gopalakrishna MV, Bijesh MB, Kumawat KL, Basu A, Medigeshi GR. Bispidine-amino acid conjugates act as a novel scaffold for the design of antivirals that block Japanese encephalitis virus replication. PLoS neglected tropical diseases. 2013;7(1):e2005. doi: 10.1371/journal.pntd.0002005. PubMed PMID: 23350007; PMCID: 3547849.

15.      Agrawal T, Sharvani V, Nair D, Medigeshi GR. Japanese encephalitis virus disrupts cell-cell junctions and affects the epithelial permeability barrier functions. PloS one. 2013;8(7):e69465. doi: 10.1371/journal.pone.0069465. PubMed PMID: 23894488; PMCID: 3722119.

16.      Agrawal T, Schu P, Medigeshi GR. Adaptor protein complexes-1 and 3 are involved at distinct stages of flavivirus life-cycle. Scientific reports. 2013;3:1813. doi: 10.1038/srep01813. PubMed PMID: 23657274; PMCID: 3648799.

17.      Medigeshi GR. Mosquito-borne flaviviruses: overview of viral life-cycle and host–virus interactions. Future Virology. 2011;6(9):1075-89. doi: 10.2217/fvl.11.85.

18.      Wertheimer AM, Uhrlaub JL, Hirsch A, Medigeshi G, Sprague J, Legasse A, Wilk J, Wiley CA, Didier P, Tesh RB, Murray KO, Axthelm MK, Wong SW, Nikolich-Zugich J. Immune response to the West Nile virus in aged non-human primates. PloS one. 2010;5(12):e15514. doi: 10.1371/journal.pone.0015514. PubMed PMID: 21151986; PMCID: 2996299.

19.      Medigeshi GR, Hirsch AJ, Brien JD, Uhrlaub JL, Mason PW, Wiley C, Nikolich-Zugich J, Nelson JA. West nile virus capsid degradation of claudin proteins disrupts epithelial barrier function. Journal of virology. 2009;83(12):6125-34. doi: 10.1128/JVI.02617-08. PubMed PMID: 19369347; PMCID: 2687390.

20.      Goodman AG, Fornek JL, Medigeshi GR, Perrone LA, Peng X, Dyer MD, Proll SC, Knoblaugh SE, Carter VS, Korth MJ, Nelson JA, Tumpey TM, Katze MG. P58(IPK): a novel "CIHD" member of the host innate defense response against pathogenic virus infection. PLoS pathogens. 2009;5(5):e1000438. doi: 10.1371/journal.ppat.1000438. PubMed PMID: 19461876; PMCID: 2677460.

21.      Medigeshi GR, Krikunova M, Radhakrishnan K, Wenzel D, Klingauf J, Schu P. AP-1 membrane-cytoplasm recycling regulated by mu1A-adaptin. Traffic. 2008;9(1):121-32. doi: 10.1111/j.1600-0854.2007.00672.x. PubMed PMID: 17988225.

22.      Medigeshi GR, Hirsch AJ, Streblow DN, Nikolich-Zugich J, Nelson JA. West Nile virus entry requires cholesterol-rich membrane microdomains and is independent of alphavbeta3 integrin. Journal of virology. 2008;82(11):5212-9. doi: 10.1128/JVI.00008-08. PubMed PMID: 18385233; PMCID: 2395215.

23.      Medigeshi GR, Lancaster AM, Hirsch AJ, Briese T, Lipkin WI, Defilippis V, Fruh K, Mason PW, Nikolich-Zugich J, Nelson JA. West Nile virus infection activates the unfolded protein response, leading to CHOP induction and apoptosis. Journal of virology. 2007;81(20):10849-60. doi: 10.1128/JVI.01151-07. PubMed PMID: 17686866; PMCID: 2045561.

24.      Scott GK, Fei H, Thomas L, Medigeshi GR, Thomas G. A PACS-1, GGA3 and CK2 complex regulates CI-MPR trafficking. The EMBO journal. 2006;25(19):4423-35. doi: 10.1038/sj.emboj.7601336. PubMed PMID: 16977309; PMCID: 1589982.

25.      Hirsch AJ, Medigeshi GR, Meyers HL, DeFilippis V, Fruh K, Briese T, Lipkin WI, Nelson JA. The Src family kinase c-Yes is required for maturation of West Nile virus particles. Journal of virology. 2005;79(18):11943-51. doi: 10.1128/JVI.79.18.11943-11951.2005. PubMed PMID: 16140770; PMCID: 1212629.

26.      Medigeshi GR, Schu P. Characterization of the in vitro retrograde transport of MPR46. Traffic. 2003;4(11):802-11. PubMed PMID: 14617361.

27.      Roy N, Guruprasad MR, Kondaiah P, Mann EA, Giannella RA, Visweswariah SS. Protein kinase C regulates transcription of the human guanylate cyclase C gene. European journal of biochemistry / FEBS. 2001;268(7):2160-71. PubMed PMID: 11277940.

28.      Meyer C, Eskelinen EL, Guruprasad MR, von Figura K, Schu P. Mu 1A deficiency induces a profound increase in MPR300/IGF-II receptor internalization rate. Journal of cell science. 2001;114(Pt 24):4469-76. PubMed PMID: 11792812.

29.       Vijayachandra K, Guruprasad M, Bhandari R, Manjunath UH, Somesh BP, Srinivasan N, Suguna K, Visweswariah SS. Biochemical characterization of the intracellular domain of the human guanylyl cyclase C receptor provides evidence for a catalytically active homotrimer. Biochemistry. 2000;39(51):16075-83. PubMed PMID: 11123935.

  • Charles Grose, L. M., Guruprasad R. Medigeshi, Gregory K. Scott, and Gary Thomas. (2006) Endocytosis of Varicella Zoster Virus Glycoproteins: Virion Envelopment and Egress, Horizon Scientific Press
  • Ph.D. fellowship from Boehringer Ingelheim Foundation, Germany.
  • Wellcome-DBT Intermediate Fellowship - 2014.

 

Rinki Kumar

M.Sc in Molecular and Human Genetics from Jiwaji University, Gwalior, India. (2009-2011)
Ph.D. student: 2012- till date
r.kumar@thsti.res.in

I am working on a project to identify host interacting proteins of the dengue virus capsid. Capsid is a structural protein, having a major role in virus assembly in addition to other functions that are not yet well understood. We have identified capsid interacting proteins using mass spectrometry approach and are characterizing the interactions to understand their biological significance. I have also been involved in identification of tyrosine kinases in dengue infection and antivirals acting against dengue virus.

Science has been a fascination since school time and delving into the mysteries of virology has been a recent interest of my PhD. Other than science, I love to listen to music, dance and read novels. Adventurous sports and travelling are an all- time favorite too.

Meetings and Conferences: Oral Presentation - "Identification of DDX3X as a Dengue Virus Capsid Interacting Protein and Characterizing Its Role in Virus Replication and Assembly" at the American Society for Virology, 35th Annual Meeting, June 18-22, 2016, Virginia Tech, Blacksburg, Virginia, USA.


Meenakshi Kar

B.Tech in Biotechnology from Deenbandhu Chhotu Ram University of Science and Technology, Murthal, Sonepat, Haryana
Ph.D. student: 2013- till date
meenakshi@thsti.res.in

I am studying endothelial functions in dengue infection and working to identify the mechanism of plasma leakage. The pathogenesis of severe dengue infection involving vascular leakage is not well characterized. Further understanding of mechanisms that affect platelet function and its potential role in vascular leakage in dengue infection will help in clinical management of the disease.

Apart from research I like to play table tennis and reading books and painting.


Naseem Ahmed Khan

B.Sc in Biotechnology from Kishinchand Chellaram College, Mumbai
M.Sc in Molecular Biology and Biotechnology, Tezpur University, Assam
Ph.D. Student – 2014- till date
naseemkhan@thsti.res.in

I’m fascinated by the simplicity and yet the complex nature of viruses and thus enjoy exploring this field. I’m currently studying zinc homeostasis in respiratory syncytial virus (RSV) infection to understand how virus utilizes cellular zinc to its advantage. Output of this study can contribute greatly to translational research.

Apart from science my interest lies in playing basketball, badminton, cricket and exotic cooking. I like to socialize with people to learn about different cultures and traditions. There is no fun in life without adventure thus to add thrill I occasionally go for adventurous tours.


Jitendra Shinde

MSc (Virology) - National Institute of Virology, University of Pune
Junior Research Fellow, THSTI – 2016 – till date
jitendra@thsti.res.in

I am a Virologist, and my quest for exploring this field stems from the need for it in the current situation, where most of the prevalent diseases are caused by viruses leading to outbreaks and epidemics. There is a need for understanding how the viruses evade the human immune system for their own advantage, and this can lead us to control them by vaccines or therapeutics.


I am working on a project which involves the study of transporters which regulates and responsible for maintaining cellular zinc in different viral infections conditions in vitro. In addition, I am also characterizing the dengue virus isolates from Indian patients. This information can be useful to develop vaccines and strategies for generation of prophylactic measures to control severe viral diseases.

Other than my interest in research I am also interested in extracurricular activities such as singing, cricket and other adventure sports.



Aleksha Panwar

PhD Student – 2016
M.Sc in Microbiology (2015) - CCS University, Meerut in 2015.
Following post-graduation I worked as a volunteer in a NGO. After that, I decided to extend my education.
aleksha@thsti.res.in

My current project focuses on understanding the role of innate immunity and host factors in dengue pathogenesis. Outside of my academic interests, I enjoy listening to music, playing badminton, travelling and reading novels.