Dr. Santiswarup Singha
Research Interest:
Summary of Research:Application of nano-engineering principles for rational designing of the immunomodulatory nano-therapeutic platform.
Nanotechnology-based therapeutics have immense potential for fighting against a broad spectrum of diseases, including cancer and infectious diseases. The field of nanotechnology allied chemistry provides the tools for designing a diversified array of nanoparticles based on their sizes, shapes, engineered surface, chemical composition, and, most importantly, the nano-specific property. Harvesting the potential of nanotechnology to induce sustainable anti-tumor immune response is one of the prime interests of our research. Currently, monoclonal antibodies such as anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4), programmed cell death protein 1(PD1), and/or PD1-ligand (PD1-L) therapy to block the immune checkpoint inhibitors is the promising and successful immunotherapy for cancer. In earlier research, we developed autoimmune disease-relevant peptide-major histocompatibility complex (p-MHC) coated nanoparticle to blunt autoimmune responses without compromising systemic immunity. This nanomedicine modulates the regulatory immune network by converting and expanding disease-specific T-regulatory type-1(T-reg) cells to prevent autoimmune diseases. Inspired by these scientific advancements, we are interested in developing the nanotherapeutic platform based on designing of artificial antigen-presenting cells (aAPCs) displaying and/or carrying optimized immune stimulatory molecules and empowering professional APCs by delivering stimulator of interferon genes (STING) agonist to present tumor-associated antigen (TAA). Additionally, using the nanotechnology platform, we will modulate the activity of the chaperone network of tumor cells to elicit tumor-specific effector T-cell response. We consider the multidisciplinary approach comprising of nanotechnology, biochemistry, and immunology to study the complex immunological responses for the rational designing of the nanotherapeutic platform.
Group Members:
Tarandeep Singh Bansal
Ph.D. Students : Khushboo Chaudhury, Arnab Kumar Sahoo, Antara Mondal, and Faisal Jamal.
Project Students : Arpita Das (JRF, DBT Project), Richa Pahuja (SRF, DBT Project), Aayush Raj Tyagi (JRF, SERB project).
Technical Support : Raghav Ram Yadav and Rajit Ram.
Tarandeep Singh Bansal
Ph.D. Students : Khushboo Chaudhury, Arnab Kumar Sahoo, Antara Mondal, and Faisal Jamal.
Project Students : Arpita Das (JRF, DBT Project), Richa Pahuja (SRF, DBT Project), Aayush Raj Tyagi (JRF, SERB project).
Technical Support : Raghav Ram Yadav and Rajit Ram.
Awards:
• Ramalingaswami Re-entry Fellowship 2020-2021 of the Department of Biotechnology (DBT), Govt. of India.
Funding:
Department of Biotechnology (DBT), Department of Science and Technology (SERB), and Ramalingaswami Fellowship (DBT).
Patents:
(1) Singha S, Dasgupta AK. Light Energy Induced Stability of Biomaterials.(Pub. No. US 2011/0250670 A1, Pub. Date: Oct, 13,2011) (PCT/IB2010/001373)
Publications:
- Yang, Y.; Ellestad, K. K.; Singha, S.; Uddin, M. M.; Clarke, R.; Mondal, D.; Garabatos, N.; Sole, P.; Fandos, C.; Serra, P.; Santamaria, P., Extremely short bioavailability and fast pharmacodynamic effects of pMHC-based nanomedicines. J Control Release. 2021,338, 557-570.
- Umeshappa, C. S.; Mbongue, J.; Singha, S.; Mohapatra, S.; Yamanouchi, J.; Lee, J. A.; Nanjundappa, R. H.; Shao, K.; Christen, U.; Yang, Y.; Ellestad, K. K.; Santamaria, P., Ubiquitous antigen-specific T regulatory type 1 cells variably suppress hepatic and extrahepatic autoimmunity. J Clin Invest. 2020, 130 (4), 1823-1829.
- Serra, P.; Garabatos, N.; Singha, S.; Fandos, C.; Garnica, J.; Sole, P.; Parras, D.; Yamanouchi, J.; Blanco, J.; Tort, M.; Ortega, M.; Yang, Y.; Ellestad, K. K.; Santamaria, P., Increased yields and biological potency of knob-into-hole-based soluble MHC class II molecules. Nat Commun2019,10 (1), 4917.
- Umeshappa, C. S.; Singha, S.; Blanco, J.; Shao, K.; Nanjundappa, R. H.; Yamanouchi, J.; Pares, A.; Serra, P.; Yang, Y.; Santamaria, P., Suppression of a broad spectrum of liver autoimmune pathologies by single peptide-MHC-based nanomedicines. Nat Commun2019,10 (1), 2150.
- Singha, S.*; Shao, K.*; Ellestad, K. K.; Yang, Y.; Santamaria, P., Nanoparticles for Immune Stimulation Against Infection, Cancer, and Autoimmunity. ACS Nano2018,12 (11), 10621-10635.
- Mukhopadhyay, A.; Basu, S.; Singha, S.; Patra, H. K., Inner-View of Nanomaterial Incited Protein Conformational Changes: Insights into Designable Interaction. Research (Wash D C)2018, 2018, 9712832.
- Singha, S.*; Shao, K.*; Yang, Y.; Clemente-Casares, X.; Sole, P.; Clemente, A.; Blanco, J.; Dai, Q.; Song, F.; Liu, S. W.; Yamanouchi, J.; Umeshappa, C. S.; Nanjundappa, R. H.; Detampel, P.; Amrein, M.; Fandos, C.; Tanguay, R.; Newbigging, S.; Serra, P.; Khadra, A.; Chan, W. C. W.; Santamaria, P., Peptide-MHC-based nanomedicines for autoimmunity function as T-cell receptor microclustering devices. Nat Nanotechnol2017,12 (7), 701-710. Highlighted in Science Translational Medicine and Nature Reviews Materials
- Clemente-Casares, X.; Blanco, J.*; Ambalavanan, P.*; Yamanouchi, J.*; Singha, S.*; Fandos, C.; Tsai, S.; Wang, J.; Garabatos, N.; Izquierdo, C.; Agrawal, S.; Keough, M. B.; Yong, V. W.; James, E.; Moore, A.; Yang, Y.; Stratmann, T.; Serra, P.; Santamaria, P., Expanding antigen-specific regulatory networks to treat autoimmunity. Nature2016, 530 (7591), 434-40. Highlighted in The New EnglandJournalof Medicine, Nature-Biotechnology and Nature Reviews Drug Discovery.
- Shao, K.*; Singha, S.*; Clemente-Casares, X.; Tsai, S.; Yang, Y.; Santamaria, P., Nanoparticle-based immunotherapy for cancer. ACS Nano2015,9 (1), 16-30.
- Ray, N.; Roy, S.; Singha, S.; Chandra, B.; Dasgupta, A. K.; Sarkar, A., Design of heat shock-resistant surfaces to prevent protein aggregation: Enhanced chaperone activity of immobilized alpha-Crystallin. Bioconjug Chem2014,25 (5), 888-95.
- Singha, S.; Dasgupta, A. K.; Datta, H., Gold nanoparticle induces masking of amines and some therapeutic implications. J Nanosci Nanotechnol2011,11 (9), 7744-52.
- Singha, S.; Datta, H.; Dasgupta, A. K., Size dependent chaperon properties of gold nanoparticles. J Nanosci Nanotechnol2010,10 (2), 826-32.
- Singha, S.; Bhattacharya, J.; Datta, H.; Dasgupta, A. K., Anti-glycation activity of gold nanoparticles. Nanomedicine NBM2009,5 (1), 21-9.
- Singha S.;Lahiri T.; Dasgupta AK.; Chakrabarti P., Structural Classification of Protein Using Surface Roughness Index.Online Journal of Bioinformatics 2006, 7 (2), 74-84
- Roy, S.; Singha, S.; Bhattacharya, J.; Ghoshmoulick, R.; Dasgupta, A. K., A size dependent folding contour for cytochrome C. Biophys Chem2006,119 (1), 14-22.
* Equal Contribution
