Dr. Chandramani Pathak

 

Dr. Chandramani Pathak
Assistant Professor
Cell Biology Laboratory
School of Biological Sciences and Biotechnology
Indian Institute of Advanced Research
Koba, Gandhinagar, Gujarat, India
Ph: +91-79-30514244
Fax: +91-79-30514110
Email : cmpathak@iiar.res.in


Research Interests:

1. Cellular signaling of apoptosis & inflammation: Cross talk and implication in cancer

Our research is focused on understanding the molecular mechanism and cross talk between apoptosis and inflammatory signaling in cancer. Apoptosis and inflammation are two closely related cellular processes which are important to maintain homeostasis, development, immune response and many other important processes in multi-cellular organisms. An impairment of the apoptotic machinery of the cells contributes to the development of cancer and helps to invade and metastasize. Several human diseases are directly or indirectly attributed to a dysregulation of apoptosis.  There are several reports highlight that evasion of apoptosis is considered to be one of the hallmarks of human cancers. On other hand, inflammation is a complex biological response to harmful stimuli, which immediately activate the immunological defense system and protect the tissue from damage. So that inflammation is essentially beneficial at earlier stage but, excess or prolonged inflammation can cause harm and may lead to promotion of several diseases including cancer, cardiovascular and neurological disorders. Prolong chronic inflammation is linked to various steps involved in tumorigenesis, including cellular transformation, promotion, survival, proliferation, invasion, angiogenesis, and metastasis. Inflammatory mediators and inhibition of apoptosis are major giver of cell survival in malignancy. Inflammatory processes often rely on the activation of protein kinases and due to alteration of cellular signaling which results activation of nuclear transcription factor NF-kB. Subsequent activation of NF-kB induces the transcription of genes for immune and inflammatory responses and inhibits apoptosis which leads to cell proliferation and survival. There are complex cellular signaling cascades are involved behind regulation cellular process in defined manner. Therefore, it is important to find out a new molecular target and explore the cellular mechanism which can control activation of inflammatory mediators and cell proliferation in cancer. We are trying to explore possible molecular mechanism and targeting to regulate critical regulators of cell death to induce apoptosis in cancer cells by modulating the apoptotic signaling which may help to develop potential target for both prevention and therapy. 

 

2. NANOPARTICLE BASED DRUG DELIVERY IN CANCER CELLS:

Cancer is one of the most serious fatal diseases in worldwide. Recent advances in cancer therapy a variety of approaches are being applied for the treatment of cancer but have various limitations and side effects including toxicity, poor drug metabolism, delivery, tissue distribution and non specific targeting. Conventional chemotherapy fails to target the cancerous cells selectively without interacting normal cells, resulted a serious side effects. Recent advances in Nanotechnology have paved the way for therapeutic potential using different strategies and pharmacological manipulation. We are focusing our research on nanoparticle based drug delivery and evaluating their molecular mechanism for cell death. In our laboratory we are using Dendrimers and other polymeric nanocarrier for drug delivery in cancer cells. These approaches may bring new hope for intervention of cancer therapy.


Research Group:

Kishu Ranjan (ICMR SRF)

Bhargav Vaghela (JRF)

Suhasini Dhumle (JRF)

Kavita Shirsath (JRF)

Vinita Mishra (Research Scholar)

Foram Vaidya (JRF)

 
Research Publications:

  1. Kishu Ranjan and Chandrramani Pathak (2016) Expression of FADD and cFLIPL balances mitochondrial integrity and redox signaling to substantiate apoptotic cell death. Molecular and Cellular Biochemistry.
  2. Ranjan K, Pathak C (2016) FADD regulates NF-κB activation and promotes ubiquitination of cFLIPL to induce apoptosis. Scientific Reports. 2016 Mar 14;6:22787. doi: 10.1038/srep22787.
  3. Ranjan K and Pathak C. (2015) Expression of cFLIPL Determines the Basal Interaction of Bcl-2 with Beclin-1 and Regulates p53 Dependent Ubiquitination of Beclin-1 During Autophagic Stress. J Cell Biochem. Dec 18. doi: 10.1002/jcb.25474. [Epub ahead of print]
  4. Suhashini S. Dhumale, Bhargav N. Waghela and Chandramani Pathak (2015) Quercetin protects necrotic insult and promotes apoptosis by attenuating the expression of RAGE and its ligand HMGB1 in human breast adenocarcinoma cells. IUBMB Life, In press.
  5. Bhargav N. Waghela, Anupama Sharma and Chandramani Pathak (2015) Curcumin conjugated with PLGA potentiates sustainability, anti-proliferative activity and apoptotic cell death in human colon carcinoma cells. Plos One DOI: 10.1371/journal.pone.0117526.  
  6. Chandramani Pathak, Rajiv Ranjan Singh, Saurabh Yadav, Neha Kapoor, Varshiesh Raina, Sarika Gupta, Avadhesha Surolia (2014) Evaluation of Benzothiophene  carboxamides as analgesics and anti-inflammatory agents. IUBMB Life, 66 (3):201-211  
  7. Ranjan K, Sharma A, Surolia A, Pathak C. Regulation of HA14-1 mediated oxidative stress, toxic response, and autophagy by curcumin to enhance apoptotic activity in human embryonic kidney cells. Biofactors 2013 Apr 5. doi: 10.1002/biof.1098.
  8. Kishu Ranjan, Avadesha Surolia and Chandramani Pathak (2012)  Apoptotic potential of Fas-associated death domain on regulation of cell death regulatory protein cFLIP and death receptor mediated apoptosis in HEK 293T cells. Journal of Cell Communication and Signaling, 2012 August; 6(3): 155–168.
  9. Manjula Vinayak & Chandramani Pathak (2010) Queuosine modification of tRNA: Its divergent role in cellular machinery. Bioscience Reports, 30: 135-148.
  10. Chandramani Pathak, Yogesh K. Jaiswal and Manjula Vinayak (2008) Modified base queuine promotes cellular antioxidant defense system in cancer. Bioscience Reports, 28: 73-81.
  11. Chandramani Pathak, Yogesh K. Jaiswal and Manjula Vinayak (2008) Modulation in the activity of lactate dehydrogenase and the level of c-Myc and c-fos by modified base queuine on cancer. Cancer Biology & Therapy, 7: 85-91.
  12. Chandramani Pathak, Yogesh K. Jaiswal and Manjula Vinayak (2008) Queuine mediated inhibition in phosphorylation of tyrosine phosphoproteins in cancer. Molecular Biology Reports, 35: 369-374
  13. Chandramani Pathak, Yogesh K. Jaiswal and Manjula Vinayak (2007) Possible involvement of queuine in regulation of cell proliferation. BioFactors, 29: 159-173.
  14. Chandramani Pathak, Yogesh K. Jaiswal & Manjula Vinayak (2005) Hypomodification of transfer RNA in cancer with respect to queuosine. RNA Biology, 2: 143-148.      
  15. C. Pathak & Manjula Vinayak (2005) Modulation of lactate dehydrogenase Isozymes by modified base queuine. Molecular Biology Reports, 33: 191-196.

 

Patents:

  1. Surolia A., Pathak C., Kapoor N., Raina V., Gupta S. (2013) Benzothiophene Carboxamide compounds, composition and applications thereof. Application No.1646/DEL/2010 A; Date of filing of Application: 14/07/2010; Publication Date: 18/10/2013; The Patent Office Journal 42/2013. 

 

Book Chapter:

  1. Rakesh K Sharma and Chandramani Pathak (2014) A Novel Lamotrigine-Loaded Nanoparticles using PEO-PPO-PEO Tri-block Copolymers. Nanotechnology: Novel Perspectives and Prospects McGrew Hill USA; 898-906.

 

Papers Presented in Conferences and Symposia:

 

  1. Chandramani Pathak and Kishu Ranjan (2015) Depletion of cFLIP expression enhances Apoptotic signaling by regulating inflammatory response in cancer. 34th Annual convection of Indian association of cancer research, 19-21 Feb. Jaipur.
  2. Vinita Mishra and Chandramani Pathak (2015) Structural analysis of Toll like receptor 4 (TLR4) as anti-inflammatory target: An in silco study. The Ramanbhai Foundation 7th International symposium “Advances in Nre drug discovery, Feb 2-4 2015, ZRC, Ahmedabad. P031; 63.
  3. Chandramani Pathak and Kishu Ranjan (2014) Pivotal Role of FADD in the regulation of anti-apoptotic regulators cFLIP and NF-kB to promote apoptosis.  XXXVIII All India Cell Biology Conference & International Symposium on Cellular Response to Drugs, Dec.10-12, 2014, CDRI, Lucknow.P039:64
  4. Kavita Shirsath, Bhargav Waghela, Anupama Sharma, Chandramani Pathak (2014) A Novel Drug Delivery System: PAMAM Dendrimer- Gallic Acid Conjugate Substantiates Enhanced Apoptotic Effect and Sustained Release in Cancer Cells. 5th International Conference on Stem Cells and Cancer (ICSCC-2014): Proliferation, Differentiation and Apoptosis. 8-10 Nov, JNU, New Delhi, India. p102-103.
  5. Foram Vaidya, Rakesh Sharma, Chandramani Pathak (2014) Anticancer Activity of Curcumin Encapsulated Pluronic Block Co-polymer. National Conference on Herbal Drug Research: Opportunities and Challenges. 5-7 November, B.V. Patel Education Trust and B.V. Patel PERD Centre, Ahmedabad, Gujarat, India. P-65 (Best Poster Award).
  6. Kishu Ranjan, Shubita Tripathi, Chandramani Patahk (2014) A Novel function of Fas associated death domain in non-inflammatory activation of IL1β and IL-18. International Conference on Host Pathogen Interactions, July 12-15, NIAB Hyderabad, P-102.
  7. Anupama Sharma, Bhargav N. Waghela and Chandramani Pathak (2014) Evaluation of in vitro cytotoxicity and apoptotic cell death by surface modified dendrimers in human lung carcinoma cells. International conference on Chemical Biology, CSIR-IICT, Hyderabad, P-99
  8. Kishu Ranjan, Rajesh Kumar Shah, Chandramani Pathak (2013) Involvement of FADD in ubiquitin mediated degradation of ant-apoptotic protein cFLIP. International symposium on conceptual advances in cellular homeostasis regulated by proteases and chaperons, Dec 3-6, 2013, ACTREC, Mumbai, PP-7:45
  9. Kishu Ranjan, Chandramani Patahk (2013) Selective Knockdown of cFLIP Augments Death Receptor-mediated Apoptosis in cancer cells. The XXXVII AICB Conference and symposium on Cell Dynamics and cell fate, 22-24 dec. 2013, NCBS, Banagalore, P001,AICB-56:63
  10. Chandramani Pathak and Kishu Ranjan (2013) Crosstalk of FADD and cFLIP in regulation of death receptor mediated apoptosis. International conference on recent trends in cancer prevention & therapy, 19-20 Nov 2013, Central University Gujarat, PL-10:26 (Invited lecture)
  11. Kishu Ranjan and Chandramani Pathak (2013) Knockdown of cFLIP enhances apoptosis cell death in cancer. International conference on recent trends in cancer prevention & therapy, 19-20 Nov 2013, Central University Gujarat, P-14:58 (Best poster award)
  12. Suhashini Dhumale and Chandramani Patahk (2013) Inhibition of expression of RAGE and its ligand HMGB-1 by Quercetin towards promotion of apoptosis in human breast adenocarcinoma cells. International conference on recent trends in cancer prevention & therapy, 19-20 Nov 2013, Central University Gujarat, P-15:59
  13. Bhargav N. Waghela, Anupama Sharma and Chandramani Pathak (2013) Curcumin conjugated with PLGA augments cellular uptake and apoptosis in human colon carcinoma cells. 4th International Conference on Stem Cells and Cancer (ICSCC-2013): Proliferation, Differentiation and Apoptosis, 19-22 October 2013, Mumbai. Abs No. P 99. (Best Poster award)
  14. Kishu Ranjan & Chandramani Pathak (2013) Knockdown of cFLIP enhanced FADD and TNFα induced apoptosis. 5th EMBO Meeting-2013 from 21-24th Sept 2013 at Amsterdam  Netherland.
  15. Bhargav N. Waghela, Anupama Sharma, Suhashini Dhumale and Chandramani Pathak (2013) Anti-proliferative and apoptotic potential of Curcumin-PLGA conjugates in human colon carcinoma cells. Internatl. Conference on Emerging Trends in Chemical Sciences, Central Univ. Gujarat, March 14-15, 2013, PP15:102
  16. Chandramani Pathak, Kishu Ranjan and Anupama Sharma (2013) Regulation of HA14-1 mediated oxidative stress, toxic response and autophagy by curcumin to augment apoptotic activity in human embryonic kidney cells. National Conference on Emerging Trends and Challenges in Basic and Translational Research in Biochemistry. February 4-5, BHU, Varanasi SL-5, P-10 (Invited talk)
  17. Kishu Ranjan and Chandramani Patahk (2013) The interaction of FADD and cFLIP proteins on regulation of death receptor mediated apoptosis in cancer cells. International conference on molecular forms and functions Jan 8-13, 2013,IISc Bangalore. SN 113, P162.
  18. Chandramani Pathak and Anupama Sharma (2012) Effect of surface modified PAMAM dendrimers on apoptotic cell death in human lung carcinoma cells. 82nd NASI annual session and National symposium on Nano-science and Nanotechnology for mankind. Nov 29-Dec.1 2012. BHU, Varanasi. Abs No 18 P-11.
  19. Anupama Sharma, Kishu Ranjan, Ravikumar N. Patel and Chandramani Pathak (2012) Evaluation of cancer cell death with surface modified PAMAM dendrimer. XXXVI All India Cell Biology conference & International symposium on Stress adaptive response & Genomic Integrity. October 17-19, BARC, Mumbai. Abs No.  PHSM 23 P-171
  20. Kishu Ranjan & Chandramani Pathak (2012) Curcuma (curcumin) scavenges HA14-1 mediated ROS generation in cancer cells. International Symposium on Recent Advances in Cancer Research Therapeutics to Chemoprevention, February 08-09, 2012, Central University of Gujarat, Gandhinagar. Abs No. P22:57
  21. Kishu Ranjan & Chandramani Pathak (2011) Understanding the role of FADD in regulation of death receptor mediated apoptosis. XXXV All India Cell Biology conference and symposium, December, 16-18, NISER Bhuvaneshwar. Abs No P:S7
  22. Manjula Vinayak, Chandramani Pathak & Y.K. Jaiswal (2007) Regulation of cell proliferation by modified base queuine. 30th All India Cell Biology Conference & Symposium on molecules to compartments: cross talks and networks, Feb. 2-4, D.U., New Delhi, Abs No. D2-SV-IL15, p-24.
  23. Chandramani Pathak, Y.K. Jaiswal and Manjula Vinayak (2006) Modified base queuine promotes cellular enzymatic antioxidant defense system in cancer. 75th Annual meeting SBC India, Dec. 8-11, J.N.U., New Delhi, Abs No. P. I-17, p-23.
  24. Chandramani Pathak, Y.K. Jaiswal & Manjula Vinayak (2005) Regulation of queuosine modification of tRNA by transfer RNA guanine transglycosylase in cancer. 74th Annual meeting SBC India, Nov. 7-10, CDRI Lucknow, Abs No. P-146, p-102.
  25. Nibha Verma, C. Pathak and Manjula Vinayak (2004) Apoptotic action of aqueous extract of Terminalia arjuna in Dalton’s Lymphoma Ascitic mice, XXVII All India Cell Biology Conference & International Symposium (India), Jan. 7-10, P.U., Pune, Abst. No. P 9, p82.
  26. Chandramani Pathak and Manjula Vinayak (2004) Hypomodification of Queosine transfer RNA in tumorous mice, XXVII All India Cell Biology Conference & International Symposium (India), Jan 7-10, P.U., Pune, Abst. No. PA 45, p-57.
  27. Chandramani Pathak, Yogesh K. Jaiswal & Manjula Vinayak (2004) Determination of queuosine modification in tRNA by a modifying enzyme transfer RNA guanine transglycosylase, XXVIII All India Cell Biology Conference & Symposium on Genome Biology, Dec. 1-3, NCHGSR, P.U., Chandigarh, Abst. No. P 82, p-122.
  28. Nibha Verma, Chandramani Pathak and Manjula Vinayak (2004) Changes in the level of Lactate dehydrogenase & anti oxidant enzymes during tumor growth in mice, XXVIII All India Cell Biology Conference & Symposium on Genome Biology, Dec. 1-3, NCHGSR, P.U., Chandigarh, Abst. No. P 86, p-126.
  29. Chandramani Pathak and Manjula Vinayak (2002) Modulation of Metabolism and Expression of membrane associated tyrosine phosphoproteins by modified base queuine, XXVI All India Cell Biology Conference and Symposium (India), Dec 12-14, ACTREC, Mumbai, Abst. No.AP-8, p-70.