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Hridayesh Prakash

  Dr. Hridayesh Prakash, Ph. D 
  Ramanujan Fellow and
  Group Leader  
  Laboratory of Translational Medicine 
  School of Life Science , University of Hyderabad
  Prof. C.R.Rao Road, Gachibowli
  Hyderabad, 500046, India.

 E mail:  This e-mail address is being protected from spambots. You need JavaScript enabled to view it.

Education

M.Sc(Biosciences): University of Roorkee (IIT Roorkee)

PhD –Institute of Nuclear Medicine and Allied Science, DRDO, New Delhi (1999-2004) and Jamia Millia Islamia, New Delhi

Field of specialization: 

 Pulmonary Infection Biology, Macrophages Immunobiology, Host Apoptosis regulation, Signal Transduction, Tumour Immunology(lung and pancreatic cancer) and, Cell based Immunotherapy

Major research area: Infection and Cancer Interface

My major research focus is to unravel the molecular mechanism (s) by which Chlamydia and Mycobacterial pulmonary pathogens dysregulate both apoptotic and innate immune signalling for their escape from eradication by innate immune system during chronic and persistent infections using transgenic and knock out mouse model systems. My second major research focus is to unravel the impact of macrophage polarization during persistent infection induced cancer development in the host.

Position held

  • DST Ramanujan Fellow, University of Hyderabad, Hyderabad ( April, 2013-Present)
  • Post Doctoral Scientist: (June, 2011 ----March, 2013) , Department of Dermatology, University Medical Center, Heidelberg, Germany
  • Post Doctoral Scientist: (Oct, 2008----May,2011) Translational Immunology Group, National Center for Tumor Diseases, German Cancer Research Centre,  Heidelberg Germany
  • Postdoctoral fellow (August, 2007- September, 2008): Cell Biology and Biophysics Division, European Molecular Biology Laboratory, Heidelberg.
  • Postdoctoral fellow (May, 2005 - July, 2007): Department of Molecular Biology, Max-Planck Institute for infection Biology, Berlin, Germany

 Awards/Achievements

  • Ramanujan Fellowship, Department of Science and Technology, Govt of India (2013-Present)
  • Travel Grant from European Society for Dermatological Research Foundation
  • Reviewer of Austrian and Romanian Research Council
  • Young Scientist Award, International Conference on Radiation Damage and its Modification, DRDO, New Delhi, from 13th -15th November 2002
  • Laboratory Technology Group Award (DRDO), Delhi, India for development of Herbal Radioprotectors. 2001
  • A process for preparation of a Radioprotective herbal extract”. ERIP/IP/0001037/M/01 DOI: 28Feb, 2001 ( DRDO patent)
  • A process for preparation of Radio Protective herbal extracts (Based on Tinospora sp.). No- ERIP/IP/0101018/M/01, DOI: 30 Dec, 2001 (DRDO patent)

Memberships of Professional Societies

Life membership of The Indian Immunology Society
Life membership of The Biotechnology Society of India
Life membership of Indian Society of Radiation Biology
Life membership of German Immunology Society

 Editorship of journal

  1. Journal of Microbiology and Microbial Technology
  2. Frontiers in Immunology, Review Editor,
  3. Frontrier in Microbiology, Review Editor
  4. Sphingolipid and Respiratory Syndrome , Inflammation section, Topic editor
  5. Austin Surgical Oncology
  6. Tumor and Microenvironment

Publications

Under preparation 
  • IAP control macrophages polarization during bacterial infection and sterile inflammatory responses Varad Mazumdar, Aparna Mohanty, Lalita Sharma, Vinod Nadella, Ramesh Palaparthi, Madhavi B Mylavarapu, Kishor Parsa, Tanja Kuhlmann, Thomas Rudel, Hridayesh Prakash (*corresponding author, 1st paper as Ramanujan fellow)
Under revision 
  • The Phosphodiestrease-4 inhibitor apremilast inhibits Th1 programming but promote Th17 response induced by 6 –sulpho LacNac (slan) Dendritic cells Stephanie Oehrl*, Hridayesh Prakash*, Annette Ebling, Eckstein Priscila, Anja Kunze, Thomas Dobel, Marc Schmitz, Alexander Enk and Knut Schäkel, (Experimental Dermatology) (* shared first Authorship)
Published / accepted 
  • CD14/ TLR4 priming potentially recalibrates and exerts anti-tumor efficacy in tumor associated macrophages in a mouse model of pancreatic carcinoma. Hridayesh Prakash* , Vinod Nadella, Sandhya Singh, Hubertus Schmitz-Winnenthal* Nature Scientific Report ( Accpeted ) (*corresponding author) 
  • Macrophages directed approaches are paramount for effective cancer immunotherapies - Invited review Vinod Nadella, Sandhya Singh, Hridayesh Prakash* , Integrative Cancer Sciences and Therapeutics, (* corresponding Author)
  • Recent advances in biosensor technology for multifaceted applications-An overview- Review S. Vigneshvar, C.C. Sudhakumari, B. Senthilkumaran* and H. Prakash* F. Biotechnology and Bioengineering (* Shared Corresponding author)
  • Low doses gamma irradiation (LDR) potentially modifies immunosuppressive tumor microenvironment by retuning Tumor Associated Macrophages (TAM): lesson from insulinoma Hridayesh Prakash*, Felix Klug, Hubertus Schmitz-Winnenthal and Liudmila Umansky (Carcinogenesis- IF 5.6 ) (*corresponding author) 19th January
  • Low Dose irradiation programs macrophage differentiation to an iNOS+/M1 phenotype that orchestrate effective T cell immunotherapy Felix Klug*1 , Hridayesh Prakash*, Tobias Seibel*1 , Noemi Bender, Niels Halama, Christina Pfirschke, Ralf Holger Voss, Carmen Timke, Ludmila Umansky, Kay Klapproth, Knut Schäkel, Natalio Garbi, Dirk Jäger, Jürgen Weitz, Hubertus Schmitz-Winnenthal, Günter Hämmerling, Peter Huber5 , Philipp Beckhove. Cancer Cell 2013;24:589-602. (*Shared first authorship) Impact factor -27.5
  • Pulmonary gene silencing in transgenic EGFP mice using aerosolized chitosan/siRNA nanoparticles. Ebbe J.B. Nielsen, Jan M. Nielsen, Daniel Becker, Alexander Karlas, Hridayesh Prakash,  Sys Z. Glud, Jonathan Merrison, Flemming Besenbacher, Thomas F. Meyer, Jørgen KjemsKenneth A. Howard: Pharm Res. 2010 Dec;27(12):2520-7
  • Deficiency of XIAP leads to sensitization for C. pneumoniae pulmonary infection and dysregulation of innate immune response in mice. Hridayesh Prakash, Marco Albrecht, Daniel Becker, Tanja Kuhlmann, Thomas Rudel, Journal of Biological Chemistry vol. 285, NO 26, pp. 20291–20302, June 25, 2010.
  • Sphingosine Kinase-1 (Sphk-1) Regulates Mycobacterium smegmatis infection in Macrophages. Hridayesh Prakash*, Anja Lüth, Natalia Grinkina, Daniela Holzer, Raj Wadgaonkar, Alexis Perez Gonzalez, Elsa Anes, Burkhard Kleuser,  (*Corresponding author)PLoS ONE 5(5): e10657. doi:10.1371/journal.pone.0010657.
  • cIAP-1 controls innate immunity to C. pneumoniae pulmonary infection. Hridayesh Prakash, Martin Witzenrath, Becker Daniel, Lori Albert, S.Rousseau, Thomas F. Meyer, Thomas Rudel PLoS One 4(8): e6519. doi:10.1371/journal.pone.0006519.
  • Podophyllum hexandrum modulates gamma radiation induced immunosuppression In Balb/c mice: Implication in Radioprotection. H.C.Goel, H.Prakash, Arif Ali and Madhu bala. Molecular and Cellular Biochemistry, 295(1-2): 93-103, 2007
  • Oxygenation by cyclooxygenase-2 (cox-2) of 3 Hydroxyeicostetraenoic acid (3-HETE), a fungal mimetic of arachidonic acid, produce a cascade of novel bioactive 3-hydroxy-eicosanoids. Roberto Ciccoli, Shakti Sahi, Sandhya Singh, Hridayesh Prakash, Maria-Patapia   Zafiriou, Ganchimeg Ishdorj, Johan L.F. Kock, Santosh Nigam Biochem. J. 390, 737–747, 2005.
  • Anti-inflammatory effects of Podophyllum hexandrum (RP-1) against Lipopolysaccharides induced inflammation in mice. H.Prakash, Arif Ali, Madhu bala and Harish Chandra Goel Journal of Pharmacy and Pharmaceutical Sciences, 8(1): 107-114, 2005
  • Modification of gamma radiation induced responses of Macrophage and Splenocyte by Hippophae rhamnoides in mice. H.Prakash, Madhubala, Arif Ali and H.C. Goel, Journal of Pharmacy and Pharmacology, 57(8):1065-1072, 2005.
  • Protection of jejunal crypts by RH-3 (a preparation of Hippophae rhamnoides) against lethal whole body gamma irradiation; H. C .Goel. C.A. Salin and Prakash.H Phototherapy Res. 17(3): 222-226, 2003
 

Book Publication:

Hippophae rhamnoides, an effective mitigator of gamma radiation induced immune-suppression in Seabuckthorn (Hippophae L).: Bala M, Prakash H. and Goel HC A multipurpose Wonder plant Vol3 (2008) p 272-283,   Data Publishing   House, New Delhi, India

Posters / oral presentations in national and international Conferences / Symposia

  1. Low dose Irradiation retunes Immunosuppressive tumor associated macrophages (TAM), And induces immune mediated rejection of established Tumors of Pancreas International congress of Immunology, ICI 2016, Melbourne, Australia (Oral presentation)
  2. iNOs+ macrophages represent Potential Alternate of Radiotherapy for Treatment of Neuroendocrine Tumors of Pancreas International Conference of Cancer Research: New Horizon National center for Cell Science (NCCS) Pune, Nov. 19th -21st, 2015 (Invited talk)
  3. "INOS+ Macrophages : Potential Alternate And Tool For Effective Tumor Therapy" Hridayesh Prakash, Philipp Beckhove International conference of radiation biology NASC Complex, Delhi, Nov 11th - 13th, 2014 (Invited talk)
  4. Adoptive transfer of iNOs+ macrophages or low dose irradiation offer an easy alternate of cumbersome high dose radiotherapy Hridayesh Prakash Young Investigator meeting, 2014 (Participated as Young investigator against selection and invitation) Feb 9th -13th , 2014, Ramoji Film city, Hyderabad
  5. Re-tuning of immunosuppressive Tumor Associated Macrophages (TAM) by low dose of gamma radiation (2Gy) in Insulinoma model system. H. Prakash, Tobias Seibel, Philipp Beckhove Lymphocyte activation and Gene Expression meeting B8 Keystone meeting, 27th Feb- 4th March, 2010, Colorado, USA (Poster presentation)
  6. Sphingosine Kinase-1(Sphk-1) is Important for Innate Immune Defense of Macrophages Against Mycobacteria H.Prakash, Anja Lüth, Burkhard Kleuser 2nd European Congress of Immunology, Berlin, Germany, September 13 -16th, 2009 (oral presentation)
  7. Novel Immunoregulatory role of inhibitor of apoptosis proteins (IAPs) against C. pneumoniae pulmonary infection. H. Prakash, M. Witzenrath, T. Rudel 2nd European Congress of Immunology, Berlin, Germany, September 13– 16th , 2009
  8. Global identification and therapeutic knock down of host cell factors essential for influenza replication A. Karlas, N. Machuy, H. Prakash, D. Becker, E. Nielsen, K. Howard, S. Hess, E. Müller, K.-P. Pleissner, T. Rudel, J. Kjems, T.F. Meyer NGFN Meeting, Innsbruck, Austria, 2008
  9. Application of RNA Interference against influenza A viruses: A. Karlas, N. Machuy, H. Prakash, D. Becker, E. Nielsen, K. Howard, S. Hess, E. Müller, K.-P. Pleissner, T. Rudel, J. Kjems, T.F. Meyer 6 th NGFN Meeting, German Cancer Research Centre, Heidelberg, 11th November, 2007
  10. Modification of gamma radiation induced Immunosuppression in mice by Podophyllum hexandrum ( young scientist award presentation) H. Prakash, H.C.Goel. International Conference on Radiation Damage and its Modification Institute of Nuclear Medicine and Allied Science, Delhi, 13th -15th Nov. 2002
  11. Effect of Hippophae rhamnoides herbal extract (RH-3) on Gamma Rays induced immunosuppression in mice” H. Prakash and H.C.Goel. 29th Annual Meeting of Indian Immunology Society and Symposium on Immunoparasitology Regional Medical Research Center, Bhuvneshwar from 27th - 30th Nov, 2002.
  12. Anti-inflammatory properties of P. hexandrum and H. rhamnoides plant extracts in peritoneal macrophages. H. Prakash and H.C.Goel 28thAnnual Meeting of the Indian Immunology Society and Symposium on Immune Effectors Mechanisms All India Institute of Medical Sciences, Delhi, 4th - 6 th Oct. 2001
  13. Modulation of macrophage functions by Podophyllum hexandrum herbal extracts: A mechanism of Radioprotection” H. Prakash, V. Pathania and H.C.Goel FIMSA-IIS course on Basic and Molecular Immunology Department of Histocompatibility and Immunogenetics, All India Institute of Medical Sciences, 5th - 9 th March 2001
  14. Ex-vivo modulation of radiation induced immune response of peritoneal macrophage and splenocyte by Podophyllum hexandrum.” H. Prakash, V. Pathania and H.C.Goel. 27th Annual Conference of the Indian Immunology Society (IIS) & Symposium on Immunology of Infectious Diseases” Central JALMA Institute for Leprosy, Agra, 10th -13th December 2000
 
Research Background::

 I feel myself deeply attached to the macrophages which are ubiquitous and integrated part of both innate and adaptive immunity. I have been exploring macrophages as my most favorite model since over decade in different context. Macrophages display a range of plasticity in their phonotype in different pathological conditions which appeals me a lot. Both peripheral and tissue macrophages together constitute the Reticulo-endothelium system which play major role in sensing pathogens and tumor antigens for their effective eradication.

My study at Max Planck Institute for infection Biology on Chlamydia pneumonia pulmonary infection demonstrated the significance of macrophages in controlling the infection. We used IAP KO (cIAP-1, XIAP) mice to unravel their significance on innate and adaptive immunity against C. pneumoniae. Our results demonstrated the sensitization of the IAP KO mice which we found due to severe defect in antibacterial defense in IAP KO macrophages and CD8+ effector T cells. This study demonstrated the novel immunoregulatory role of IAP proteins in macrophages. In the same line, my study at European Molecular Biology laboratory identified Sphingosine kinase-1 as novel antimycobacterial component of macrophages against Mycobacterium smegmatis infection which is an obligate intracellular pathogen of macrophages. SphK-1 is GPCR coupled and TNFR1 associated membrane protein which phosphorylates sphingosine to S1P. During mycobacterial infection, SphK-1 induces P2X7 and CD69 receptor and induces actin nucleation. This creates a proinflammatory environment in macrophages which is pre-requisite of macrophages for the effective killing of mycobacteria by inducing phagolysosomal maturation. Our study has demonstrated the sensitization of Sphk-1 depleted and increased resistance of Sphk-1 overexpressed macrophages for infection which was due to the alteration in inducible NO, expression of iNOs, pp38 and LAMP-2 proteins in Sphk-1 overexpressed (Sphk-1++) infected macrophages which conferred M-1 bright phenotype of Sphk-1++ macrophages.

My Ph.D work has shown the activation of the Mac-1+ macrophages by low doses of gamma radiation and their potential involvement in conferring radioprotection and reverting hemopoietic syndrome in mice model system. With the help of this we explored the fate of LDR (Low doses of Radiations) mediated activation of Mac-1+ macrophages as potential tool to enhance immunity against insulinoma and pancreatic carcinoma (PancO2) model system at DKFZ, Heidelberg. We could clearly see the complete or significant retuning of M2 phenotype to M1 by LDR in spontaneous Insulinoma and also in the patients of pancreatic carcinomas. Moreover our macrophages depletion / transfer experiments have explicitly demonstrated the potential involvement of M1/M2 macrophages in adoptive T cells transfer in the tumor bearing RT5 mice. Significant reduction in the subcutaneous PancO2 tumor growth in macrophages depleted mice explicitly demonstrated potential role of macrophages in the course of tumerogensis.

Sponsored Projects from various extramural funding bodies as Principle investigator

Title of Project Name of sponsoring agency Total amount Total Period of support with dates
1. Unravelling the potential role of Inhibitor of Apoptotic------- lung infection model system Department of Science and Technology (DST) 85.80 lacs 5 years 2013-2018 (ongoing)
2 Analyzing anti-mycobacterial role of Sphingolipids against pulmonary infection with pathogenic Mycobacteria Project ref no- BT/PR8282/MED/29/722/2013 Department of Biotechnology (DBT) 74.34 lacs 2014-2017 Medical Biotechnology program (ongoing)
3 Role of CD11b+/Gr-1-(iNOs+) macrophages and T cells in the management of lethal radiation induced hemopoietic syndrome and radioprotection Life science Research Board Defense Research and Development Organization 50 lacs 2015-2018 Radiation medicine ( ongoing)

Details of the Research Projects

  • Role of Inhibitor of apoptosis proteins in Chlamydia pneumoniae pulmonary infection :
    Ramanujan project, ongoing (2013-2018)

Funding body: DST

Apoptosis (programmed cell death) is a fundamental biological process and well known homeostatic regulator in the biological system. Perturbation of this by biological, physical or chemical factors manifests immune dysfunctions, lethal infections and carcinogenesis. Among biological factors, members of the family Chlamydiaceae are known to hijack host apoptosis pathways for their own survival in host. During their bi-phasic life cycle, these bacteria both inhibit and induce host apoptosis pathways therefore represent the candidate pathogens and model system for studying host apoptosis in response to infection. Among various members of this family, Chlamydia pneumoniae is a major and most versatile respiratory pathogen which is responsible for atypical pneumoniae and has been associated with Chronic Obstructive Pulmonary Disorders (COPD) and Chronic Heart Disease. During early phase of C. pneumoniae infection where elementary bodies (EBs) differentiates into reticulate bodies (RBs), these bacteria induce various anti-apoptotic pathways and confer resistance in the infected host cells for induction of apoptosis for their own survival. Induced expression and increased stability of cellular and X -linked anti- inhibitors of apoptosis proteins (IAP) have been the key underlying reason of increased resistance in the infected host against cell death. On the basis of this, we presumed that deletion of these proteins would interfere in the inhibiton of apoptosis caused by these bacteria and limit the infection because induction of apoptosis has been considered an efficient strategy for the resolution of infection.

Preliminary work done

To demonstrate the significance of IAP proteins, we employed cIAP-1 and XIAP knock-out (KO) mice and the effect of deletion of proteins was analyzed on infection. Contrary to our prediction, both cIAP-1 and XIAP KO mice were for were heavily sensitized for C. pneumoniae pulmonary infection which was accompanied with dysregulated innate immune responses of pulmonary, peritoneal macrophages and CD8+ T cells (Prakash et al, 2009 PloS ONE, Prakash et al, 2010, JBC). These result therefore indicated for the first time that IAP proteins are indispensible for both innate and adaptive immunity during the course of infection. Our results also explicitly disapproved existing hypothesis that induction of apoptosis in infected host does not always augment host immunity and favor effective resolution of infection but rather predisposes the affected organism sensitive for infection.

Major question to be addressed:

During persistent infection, Chlamydia pneumonia, in addition to conferring resistance in infected cell for induction of apoptosis, also upregulate nf-KB, Ras/MAPK and PI-3K pathways in host which are the hallmark of the cancer cell and required for malignant transformation of cells. Thus in this regard infected cell resembles like tumor cells which also resist apoptosis. Active association of Chlamydia with development of various type of lung / cervical cancers indeed provides completing evidence of neoplastic transformation of infected cells in situ. This is supposed to be multilevel and multifactorial.

Work in progress

Our additional data, in line of above demonstrated M1dim and M2 polarization of cIAP1 and XIAP KO infected lung and pulmonary macrophages (unpublished data) during advance time point of Chlamydia pneumoniae pulmonary infection which potentially demonstrated for the first time that IAP proteins, other than regulating apoptosis are also important for the fine tuning of macrophages immune response during the course of infection. Unexpected M2 polarization of infected IAP KO macrophages also suggested their susceptibility for infection induced lung cancer (e.g. adenocarcinoma) development also. With this major research focus, Dr. Prakash and his team from Dept of Biochemistry at University of Hyderabad would employ Immunological and Molecular approaches, using pharmacological potential of small chemical toolbox, for the maintenance of M1/M2 balance and minimizing the risk of having cancer by Chlamydia persistent infection. In the frame of this, Prakash and his team will screen and explore the potential of small chemical entities for-

  • SMAC mimetic compounds to enhance both apoptosis in the dead and infected cell lying in infected single IAP KO mice and their clearance through lymphatic for assisting the IAP KO mice for resolution of the infection from their lungs.
  • Inhibitors of Sphingolipids, Th2/Th17 signalling / immune responses for minimizing M2 polarization of IAP KO macrophages for reducing the risk of having cancer in persistent infection model.

Collaboration, Max Planck Institute for Infection Biology, Berlin-Prof. Thomas Meyer
University of Wurzburg, Germany- Prof. Thomas Rudel

  • Analyzing anti-mycobacterial role of Sphingolipids against pulmonary infection with pathogenic Mycobacteria
    (2015-2018) :
    DBT funded project (74.35 lacs)

Sphingolipids are crucial bioactive molecules and involved in several fundamental and patho-physiological processes. A novel therapeutic potential of sphingolipids has been documented for the treatment of asthma, cystic fibrosis, respiratory tract infection and acute lung injuries.
Sphingosine kinases (Sphk) are the crucial and central proteins which are indispensible for Sphingolipids metabolism. Sphk phosphorylates sphingosine to S1P and executes both extra and intracellular signalling. Two subtypes of SphKs have been identified to date, namely SphK-1 and SphK-2. Among these, SphK-1 is a well-known regulator of intracellular calcium homeostasis, cellular differentiation, innate immunity, apoptosis and cancer while the role of SphK-2 remains unclear. Sphingosine kinase-1 is known to mediate Mycobacterium smegmatis induced inflammatory responses in macrophages but its role in controlling infection has not been reported to date. Our preliminary and novel study (Prakash et al, 2010) for the first time demonstrated that Sphk-1 not only mediates Mycobacterial infection induced innate immune response but also afford optimum defense against M. smegmatis infection. On the basis of our study, we feel that Sphk-1 protein may be efficient against pathogenic mycobacteria as well. Therefore we are unraveling the antimycobacterial role of Sphk-1 against Mycobacterium tuberculosis infection and also to investigating whether gain of Sphk-1 function on innate immune cells would be effective in controlling the pathogenic mycobacteria.

Collaboration: JALMA Agra, and NITR, Chennai

  • Role of CD11b+/Gr-1-(iNOs+) macrophages and T cells in the management of lethal radiation induced hemopoietic syndrome and radioprotection (2015-2018)
    LSRB, DRDO funded project (50.0 lacs)

One of the most important events after the radiation exposure is immunosuppression, opportunistic infections, systemic inflammation which ultimately culminates to death. For recovery from radiation damage, enhancement of immunocompetence is paramount requirement. Pre-irradiation administration of Podophyllum hexandrum and Hippophae rhamnoides rendered 82% and 80% radioprotection respectively in lethally irradiated (10Gy) mice. Our further studies explicitly demonstrated that Podophyllum hexandrum and Hippophae rhamnoides countered radiation induced immunosuppression (Salin et al, 2003, Prakash et al, 2005, Prakash et al, 2006; Goel et al, 2007) and stimulated macrophages and T cells. Therefore our major goal is to characterize macrophages / leukocyte binding principles (TLR agonist) from these extract and to unravel their mechanism of action (molecular and immunological) on macrophages and T cells. In the frame of this we are also exploring the potential role of activated or pre-condioned macrophages and / or T cells alone or in combination in both prophylactic and therapeutic radioprotection using adoptive cell transfer strategies.

Collaboration: INMAS, DRDO, New Delhi

WORKING HYPOTHESIS
MACROPHAGES REPRESENT A POTENTIAL TARGET FOR THE TRANSLATIONAL MEDICINE

I have been exploring macrophages as my research model for more than a decade in various discease models like hemopoietic syndrome, C. pneumoniae and mycobacterial pulmonary infection, ALRTI and pancreatic cancers. Macrophages are unique, ubiquitous and integrated part of both innate and adaptive immunity as well as components of tissue homeostatic apparatus. Both peripheral and tissue macrophages together constitute the Reticulo-endothelium system which play major role in sensing pathogens and tumor antigens for their effective eradication. Out of several immune cells, the macrophages display a range of plasticity in their phonotype in different pathological conditions which qualify them as one of potential target cells of body for the management of various human diseases clinically. Due to their plastic nature, these cells are literally involved in most of immunological and physiological process

Future Vision:

Macrophages polarization is decisive chronic bacterial infection induced carcinogenesis.

Our recent publications have shown M1dim phenotype of cIAP-1 KO and M2 polarization of XIAP KO (unpublished data) infected lung and alveolar macrophages during advance time point of Chlamydia pneumoniae pulmonary infection. This provides evidence for the first time that dysregulation of apoptosis pathways during the course of infection leads to alternative activation of M1 macrophage to their M2 phenotype. This seems to be the potential link to the sensitization for infection and may be for cancer development also. Therefore my vision lies mainly in the management of M1/M2 imbalance to minimize the risk of having cancer by chronic and persistent lung infection with intracellular pathogens like Chlamydia or Mycobacteria. This may be achieved by targeting major signaling pathways which drive M2 phenotype and are involved in cancer development e.g. Sphingolipids, Th2/Th17 responses.

In the frame of above, our second major goal is to scan molecular events which are important for the initialization of polarization of M1 phenotype of macrophages to M2 during cancer development and to explore how selective activation of M1 macrophages could improve existing anti-tumor immune therapies in both mouse and human model of tumor with special emphasis on pancreatic, colorectal, lung cancers and various gastric inflammatory discease like IBD which are responsible for global mortality.

 




Hridayesh Prakash