Computational Structural Biology Group

Lab Director

Welcome to the Computational Structural Biology Laboratory, Our laboratory is committed to addressing key biological questions through a combination of computational (in-silico) and experimental (in-vitro) approaches. Our core research focuses on the design and optimization of Chimeric Antigen Receptor (CAR) T cells targeting cancer-specific antigens, particularly for the treatment of B-cell malignancies.

In addition, we are actively engaged in anti-mitotic drug discovery, with a strong emphasis on microtubules and microtubule-associated proteins (MAPs) such as katanin. By integrating machine learning, structure-based drug design, and in-vitro validation, we aim to identify novel therapeutic candidates and contribute to precision medicine initiatives in oncology.


Research Area

1. Design and Optimization of Chimeric Antigen Receptor (CAR) T cell

Chimeric Antigen Receptor (CAR) T cell therapy is an adoptive immunotherapy with significant potential for improving cancer treatment. Recently, first indigenous CAR-T cell therapy for leukaemia treatment were approved. Our approach is to optimized the CAR-T cell therapy by optimizing the entire CAR regions which mainly includes the scFvs. We are currently working on design and development of optimized CAR T cell against the cancer specific B-Cell malignancies using the In-silico followed by In-vitro approach.

Reference
  • Purva Khodke, Dhananjay Hasurkar, Aakanksha Upadhyay, Aditi Shedge, Rhea Sippy and Bajarang Vasant Kumbhar*, B Cell Antigens: A Key to Optimizing CAR-T Cell Therapy. Accepted International Review of Immunology (IF:4.3), Q1
  • Purva Khodke and Bajarang Vasant Kumbhar*, Engineered CAR-T Cells: An Immunotherapeutic Approach for Cancer Treatment and Beyond. Advances in Protein Chemistry and Structural Biology: Immunology for Engineers. Vol. 140 (IF: 5.4) (Q1)
  • Alka Dwivedi, Atharva Karulkar, Sarbari Ghosh, Srisathya Srinivasan, Bajarang Vasant Kumbhar, Ankesh Kumar Jaiswal, Atish Kizhakeyil, Sweety Asija, Afrin Rafiq, Sushant Kumar, Albeena Nisar, Deepali Pandit, Minal Poojary, Hasmukh Jain, Shripad D. Banavali, Steven L. Highfill, David F. Stroncek, Nirali N. Shah, Terry J. Fry, Gaurav Narula, Rahul Purwar. “Robust anti-tumor activity and low cytokine production by novel humanized CD19 CART-cells”. American Association for Cancer Research, Molecular Cancer Therapeutics. 2021 May; 20(5):846-858. (IF: 6.009), ISSN No: 1535-7163.
CAR-T Cell Diagram
Anti-tubulin Structure
2. Discovery of Anti-tubulin Agents

Microtubules (MTs) play essential role in mitosis; therefore, it makes them important target for the treatment of various carcinomas. There are 8 α-tubulin and 10 β-tubulin isotypes are reported in eukaryotes. The expression of different β-tubulin isotypes gives a unique stage to development of drugs with expanded specificity for those isotypes communicated mainly in cancerous cells.

We are targeting the tubulin isotypes those are expressed in various carcinomas for to design a potential anti-cancer agent. We are employing In-silico methods such structure-based drug design, machine learning, molecular dynamics simulation followed by the In-vitro approach including the tubulin isolation, purification and tubulin-drug interaction study for the identify the potential inhibitors. We are also working on the identification of microtubule severing enzyme inhibitors.

Reference
  • Bajarang Vasant Kumbhar* and Vishwambhar Vishnu Bhandare. ‘Exploring the interaction of peloruside-A with drug resistant αβII and αβIII tubulin isotypes present in human ovarian carcinoma using molecular modeling approach.’ Journal of Biomolecular Structure and Dynamics, 2020, Apr 3; 1-13 (IF: 5.235), ISSN No: 1538-0254.

Announcement

  • Congratulation to Purva Khodke for publication in Biomolecules (IF:4.8)
  • Congratulation to Purva Khodke and all co-authors for publications in International Review of Immunology (IF:2.9)
  • Congratulations to Ms. Vibhuti Saxena for publication in Scientific Report (IF:3.9)
  • Congratulation to Vrinda Salvi for publication in Journal of Biomolecular Structure and Dynamics
  • Congratulation to Pruthanka for the award of Savitribai Jyotirao Phule Single girl child fellowship


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