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Principal Investigator: Dr. ABHIJIT DE

Contact details

Office Phone: +91-22 27405038

Laboratory Phone: +91-22 27405432 /5419

Fax: +91-22 27405038

 

Research Area

One Key Research Area: Preclinical Molecular Imaging

Special interests: Molecular imaging; Gene therapy; Drug screening; Cell based assays; Theranostic nanoparticles; Cell engineering; Viral and non-viral vector design

About us: Our mission is to expand molecular functional imaging toolbox to successfully translate various facets of cancer research to the cancer clinic; beside we foster teaching and training of young researchers in this area.

Brief information on the activities of the Laboratory :

Molecular imaging provides real time visualization and quantitative measurement abilities of cellular processes at the molecular or genetic level. Important developments in molecular sciences have significantly contributed to our understanding of the molecular mechanisms of disease like cancer. As our knowledge of cancer increases, so does the recognition that each tumor is an entity that requires individual characterization to determine its susceptibility to the most appropriate treatments. Here, functional imaging of cancer progression in experimental animal model is beneficial for translating basic research to the clinic.

The current focus of my lab is to take advantage of the miniaturized medical imaging equipments suitable for testing experimental concepts in small animal models, which can be directly translated into imaging-guided clinical applications to serve both cancer diagnosis and personalized therapy. We are working on therapeutic evaluation of gene targeted radiotherapy and nanotherapeutics for breast and oral cancers. We are also developing optical imaging based tools for live monitoring of various cellular protein functions such as protein-protein interactions, protein phosphorylation and protease activation etc.

Projects

Projects: 

Gene therapy imaging. My lab is aimed at understanding the basic biology of human sodium iodide symporter (hNIS) gene function in non-thyroidal cell / tissue environment like breast cancer (BC). We are actively exploring hNIS gene mediated targeted radioiodine therapy and diagnosis as an option in breast cancer patient and factors that can improve this gene therapy approach. Currently, this project is funded by ICMR, New Delhi and institutional intramural funds.

Project: 1 We have performed subtype specific IHC analysis of over 150 breast cancer patient tissue samples from Tata Memorial Hospital. Interestingly, of all the major subtype, hormone receptor positive cases represent 84% NIS positive cases. In the process we have also developed ImageJ based digital IHC image analysis tool for automated scoring.

Our results indicate that human NIS is naturally over-expressed in majority of BC, raising the possibility of using different radioactive isoforms e.g. I-131, I-125, and I-124 compatible with radioiodine therapy or SPECT or PET based diagnostic imaging respectively. We are currently exploiting experimental cell and mouse tumor models towards verifying these possibilities.

Project: 2 We are developing and testing novel experimental approaches in cell and preclinical mouse model by targeting transcriptional modulators of endogenous NIS. Screening of various pharmacological compounds is undergoing using NIS promoter driven reporter vector to identify genetic or epigenetic regulators which can potentially regulate NIS expression in breast cancer. In the process we expect to understand NIS regulation biology better in breast cancer cells.

Project: 3 To unravel the mystery of predominant cytoplasmic rather than membrane localization of NIS protein in BC tissues/cells, we have established engineered breast cancer cell lines with NIS protein predominantly localized either on the cell membrane or cytoplasm (Figure 2) and characterized their functional significance in terms of iodine uptake. Utilizing this unique cell model, we expect to understand the key glycosylation mechanism of NIS functional regulation in BC cells and find out devices that may enhance NIS protein localization on cell membrane impacting better radioiodide uptake needed for the therapeutic benefit.

Collaborators: Dr. Rajiv Kalraiya, Dr. B.V. Venugopalareddy and Dr. Neelam Shirsat from ACTREC; Dr. Sudeep Gupta, Dr. Vani Parmar, Dr. Ashwini Budrukkar, Dr. Venkatesh Rangarajan and Dr. Asawari Patil from Tata Memorial Hospital; Dr. Samit Chattopadhyay, NCCS Pune; Dr. Andreas Kjaer, University of Copenhagen, Denmark.

Research products: Lentiviral and non-viral stable gene integration vectors for human NIS expression; human NIS promoter-reporter vector; engineered breast cancer cell lines with correlated NIS and luciferase reporter over-expression; an automated digital IHC scoring method useful for cytoplasmic and nuclear staining analysis.

Research Funding: TMC-ACTREC intramural, ICMR

Data published - PLoS One. 2013. 8(1):e54055

NanoTherapeutics. Due to highly heterogeneous nature of diseases like cancer, rapid development of effective therapies using targeted drug combination is required while minimizing the effects to the normal tissues. To support this new approach in cancer medicine, development of targeted nanomaterials using small sized targeting moieties are critical to reduce the side effects caused by the generic drug targets. Here, we are running multiple collaborative projects with an aim to develop and conduct preclinical testing of various bio-compatible and bio-functionalized targeted nanoparticles with therapeutic (Figure 3) and diagnostic loads, using non-invasive in vivo imaging procedure. As product and procedural output, we have already demonstrated the use of long chain lipid based tamoxifen loaded nano-carriers (Tmx-NLCs) and are now working on lipid-polymer nano-particle formulation for delivering genetic medicine. We are also actively working on the Au-Lipo and Au-PLGA nanoparticles to take advantage and compare various treatment modalities that AuNP supports such as photo-thermal ablation, low dose X-ray radiation ablation etc.

Collaborators: Dr. Rohit Srivastava and Dr. Rinti Banerjee, IIT, Mumbai; Dr. Mangal Nagarsenker, Bombay College of Pharmacy; Dr. Vandana Patravale, Institute of Chemical Technology, Mumbai.

Research Funding: TMC-seed-in air, IITB healthcare initiative grants, DBT Nanobiotechnology

Data published – Nanoscale, 2014. 6 (2), 916-923 {Hyperlink to publication page}; Int. J Pharmaceut. 2013. 454(1):584-92 {Hyperlink to publication page}

Members

Laboratory Members:

Present members:

Dr. Soumya Basu, Ph.D from Jadavpur University, DBT Research Associate. Contact: This email address is being protected from spambots. You need JavaScript enabled to view it.

Ms. Sushmita Chatterjee, M.Sc. Microbiology, Graduate Student. Contact: This email address is being protected from spambots. You need JavaScript enabled to view it.

Ms. Madhura G. Kelkar, M.Sc. Biotechnology, Graduate Student. Contact: This email address is being protected from spambots. You need JavaScript enabled to view it.

Ms. Shalini Dimri, M.Sc. Biochemistry, Graduate Student. Contact: This email address is being protected from spambots. You need JavaScript enabled to view it.

Mr. Deepak Chavan, Technician E

Mrs. Renu S. Malhotra, Scientific Assistant B. Contact – This email address is being protected from spambots. You need JavaScript enabled to view it.

Mr. Amirali Bukhari completed Integrated Integrated M.Tech in Biotechnology, Pune in 2012; currently working as project JRF since 2013. Contact - This email address is being protected from spambots. You need JavaScript enabled to view it.

Mr. Rohit Arora completed Integrated Integrated M.Tech in Biotechnology, Pune in 2012; currently is working as project Research Assistant since 2013. Contact - This email address is being protected from spambots. You need JavaScript enabled to view it.

Mr. Pritish Tidke M.Sc. Biotechnology, working as project SRF since 2013. Contact - This email address is being protected from spambots. You need JavaScript enabled to view it.

Ms. Pooja Tajpara M.Sc. in Biotechnology working as project assistant since 2013. Contact - This email address is being protected from spambots. You need JavaScript enabled to view it.

Ms. Akanksha Bansal M.Sc. Biotechnology, Pune in 2012; currently is working as project SRF since 2013. Contact - This email address is being protected from spambots. You need JavaScript enabled to view it.

Ms. Tanha Rana has completed Integrated M.Sc. in Biotechnology from ARIBAS in 2013; she is currently volunteering in the lab. Contact - This email address is being protected from spambots. You need JavaScript enabled to view it.

Ms. Shruti Menon completing Integrated M.Sc. in Biotechnology from IBB, University of Pune. Contact - This email address is being protected from spambots. You need JavaScript enabled to view it.

Alumni

Mr. Swapnil Joshi, M.Sc. Biotechnology; he is working as R&D Executive, Biotron Ltd. since 2012.

Ms. Deepal H. Parikh, completed B.Tech in Biotechnology; joined Masters in Biotechnology Program, Chicago, USA in 2010.

Ms. Rucha V. Rane, completed B.Tech in Biotechnology; joined Masters Course in Biotechnology Program, Florida, USA in 2010.

Mr. Abhishek Babu, completed M.Sc. in Molecular Human Genetics from the Dept. of Molecular and Human Genetics, Banaras Hindu University, Varanasi in 2010; he is working in OMICS group.

Ms. Manasi Kulkarni, completed M.Sc. Biotechnology, Mumbai University in 2010; she has joined Ph.D program in National Institute of Immunohaematology.

Ms. Jennifer James, completed M.Sc. Biotechnology, VIT University in 2011.

Ms. Manjari Shah, completed M.Sc. Biotechnology, Mumbai University in 2011.

Mr. Frency Varghese, MS in Biomedical Engineering; he has joined Ph.D program at Syracuse University New York, USA in 2012.

Mr. Ishan Deshpande, completed Integrated M.Sc. in Biotechnology from IBB, University of Pune; he joined Ph.D program at Friedrich Miescher Institute, Switzerland in 2012.

Ms. Smita Jadhav, completed M.Sc. Biotechnology, St. Xaviers College, Mumbai in 2012.

Mr. Nirmal Thaker, completed B.Tech in Biotechnology from Dr. D.Y. Patil Biotechnology and Bioinformatics Institute, Pune in 2013; he has joined M.Tech in VIT.

Ms. Akshi Jasani, Completed integrated M.Sc. in Biotechnology from ARIBAS; she has joined Ph.D program at University of California, Santa Cruz USA in 2013.

Opportunities: Write to us for current openings in the lab.

Publications

Select Publications:

1. Abhijit De, Rohit Arora and Akshi Jasani. 2014. Engineering aspects of Bioluminescence Resonance Energy Transfer Systems. In: Engineering in Translational Medicine. Springer, London. Chapter 10: Pp. 257-300. (DOI: http://dx.doi.org/ 10.1007/978-1-4471-4372-7_10).

2. Abhijit De, Akshi Jasani, Rohit Arora and Sanjiv Sam Gambhir. 2013. Evolution of BRET biosensors from live cell to tissue-scale in vivo imaging. Frontiers in Endocrinology. Volume 4, Article 131: 1-6.

3. Madhura Kelkar and Abhijit De. 2012. Bioluminescence based in vivo screening technologies. Current Opinion in Pharmacology. 12 (5):592-600.

4. Sarah Shigdar, Alister C Ward, Abhijit De, Chaoyong James Yang, Mingqian Wei and Wei Duan. 2011. Clinical applications of aptamers and nucleic acid therapeutics in haematological malignancies. British Journal of Haematology. 155 (1):3-13.

5. Abhijit De. 2011. New era of bioluminescence resonance energy transfer technology. Current Pharmaceutical Biotechnology. 12 (4):558-568.

6. Tarik Massoud, R. Paulmurugan, Pritha Ray, Abhijit De, Carmel Chan, Hua Fan-Minogue and S.S. Gambhir 2010. Molecular Imaging of Protein-protein interactions. Chapter 47 In: Molecular Imaging: Principles and Practice. Editors: Weissleder R. et al. People’s Medical Publishing House, USA. pp. 781-807.

7. Abhijit De, Shahriar Shah Yaghoubi and Sanjiv Sam Gambhir. 2008. Applications of Lentiviral Vectors in Non-invasive Molecular Imaging. In: Gene therapy Protocols Vol.1. Methods in Molecular Biology. Editor: Joseph LeDoux. 3rd edition. Humana Press; 433:177-202.

8. Tarik F Massoud, Ramasamy Paulmurugan, Abhijit De, Pritha Ray and Sanjiv S Gambhir. 2007. Reporter gene imaging of protein–protein interactions in living subjects. Current Opinion in Biotechnology, 18:1–7.

9. R. Paulmurugan, P Ray, A. De, C.T. Chan and S.S. Gambhir 2005. Imaging protein-protein interactions in living subjects. Trends in Analytical Chemistry. 24(5): 446-458.

10. R. Paulmurugan, P Ray, A. De, C.T. Chan and S.S. Gambhir 2005. Imaging protein-protein interactions in living animals. In: Protein-Protein Interactions. A Molecular Cloning Manual from Cold Spring Harbor Laboratory Press. PP. 695-713.

11. Abhijit De and S.S. Gambhir 2004. PET as a Tool in Multimodality Imaging of Gene Expression and Therapy. Chapter 18 In: Positron Emission Tomography: Basic Sciences. Editors: Dale L. Bailey et al. Springer-Verlag London. pp. 343-367.

12. Abhijit De and S.S. Gambhir 2002. PET in Imaging Gene Expression and Therapy. Chapter 50 In: Positron Emission Tomography: Basic Sciences and Clinical Practices. Editors: Peter Valk et al. Springer-Verlag Inc. pp. 845-868

Links: Download IHC Profiler program free from http://sourceforge.net/projects/ihcprofiler/

Awards / Honors:

1997 Travel Award, Council of Scientific and Industrial Research (CSIR), New Delhi

2006 Young Investigator Travel Scholarship from Academy of Molecular Imaging, USA

2005 Young Investigator Travel Scholarship from Academy of Molecular Imaging, USA

2011 Idea grant award “Seed in Air” from TMC, Mumbai

2012 Healthcare initiative collaborative award, IIT Bombay

2012 Guest Editor, Theranostics, USA

Affiliations:

Associate Editor, American J Nuclear Medicine and Molecular Imaging, USA

Reviewer – PlosOne, Biophysical J., FASEB J, Molecular Cancer, European Journal of Pharmaceutical Sciences, J Biosciences, J Cancer Research and Therapeutics, Molecular Imaging and Biology, Translational Cancer Research etc.

Funding Reviewer – UK NC3Rs, BRNS, DBT Bioengineering, DBT Cancer Biology Technical Advisory Committee - BIRAC

Member: Life member -All India Cell Biology Society (AICB)

Member: Life member -Indian Association of Cancer Research (IACR)

Any other:

2005 US patent: Bioluminescence resonance energy transfer (BRET) systems and methods of use thereof.

Contact Us

Advanced Centre for Treatment, Research and Education in Cancer

Kharghar, Navi Mumbai - 410 210, india

Phone:+91-22-2740 5000

Fax: +91-22-2740 5085

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