Research
Cutting Edge of Science
Genetic information is the basis of life and now we have the tools to precisely change this information to design a new life form, make us disease free and make permanent changes to become disease resistant. With the complete human genome sequencing information available, we are at a time where we have understood how this information codes the functions of life. Genome editing techniques like CRISPR-Cas have become widely available and recent successful clinical trials have encouraged the use of this technology across different domains of life. We are taking advantage of these recent developments in genetic engineering designing next generation therapies for a wide range of human diseases. Our major focus is to develop engineered immune and stem cells and delivery vectors which can directly make the changes in organisms. We have developed ex-vivo methods to engineer immune cells and stem cells for the treatment of various inflammatory and infectious diseases.
Leveraging on the success of recent COVID-19 vaccines, and direct in vivo delivery of the CRISPR-Cas system in humans, we are exploring the idea to treat genetic disease and cancer directly without any manipulation of the cells outside the body. Besides, our laboratory has developed a vast repertoire of chimeric antigen receptors for the development of next generation inducible and allogenic CAR-T and CAR-NK cells for the treatment of solid tumors, besides B cell malignancies.
Focused Precision
Key Research Areas
EDITING THE GENOME
Robust CRISPR-Cas methods for cellular therapy
We are using the CRISPR-Cas system to generate the next-generation inducible and armored CAR-T and CAR-NK cells.
We are also working on inducible bi-specific CARs and expanding to tri-specific CARs targeting various tumor antigens. Our laboratory has optimized the CRISPR-Cas system to generate patient specific and universal CAR-T and CAR-NK cells for solid tumors such as oral cancer and lung cancer.
We are exploring the prime editing approach for in vivo gene delivery and cell therapy.
ENGINEERING IMMUNE CELLS
Ex vivo CAR-T cells
- Autologous CAR-T cells
- Universal CAR NK cells
In vivo CAR-T cells
- CAR-T cells
- CAR-NK cells
We are working on targeting cancer cell receptors particularly B-cell malignancies, and effective killing of these cancerous cells by our genetically armored T cells.
Our laboratory has developed inducible bi-specific chimeric antigen receptors (CARs) and is also expanding to tri-specific CARs targeting various tumor antigens. We have also found come unique signaling domains which are specifically required for NK cells
The CAR-T and CAR-NK cells are initially being tested to target cancer cell receptors particularly B-cell malignancies, and effective killing of these cancerous cells by our genetically armored T cells.
MODULATING STEM CELLS
Metabolically engineered MSCs for the treatment of inflammatory and infectious diseases
Our laboratory has generated engineered MSCs for the treatment of lung diseases. We are currently expanding the clinical application of MSCs for the treatment of infectious diseases like SARS-CoV-2 and other inflammatory diseases.
DESIGNING GENETIC VECTORS
- CRISPR-Cas based gene therapy
- Adeno-associated viral (AAV) vector therapy for cell and gene therapy
- Targeted antibody based AAVs
- Lentiviral vectors for cell and gene therapy
We are working on various strategies to directly deliver the CRISPR-Cas into the cells in-vivo. In this direction, we are exploring the LNPs and AAV based vectors for the direct delivery for the CRISPR-Cas RNP into the cells.
Our laboratory has developed potent and safe lentiviral vectors for use in cell and gene-based therapy. These lentiviral vectors are 3rd generation replication deficient with modifications that substantially increased the titer of the transgene. These lentiviral vectors have been used to develop the engineered cells for therapeutic purpose.
We have also developed various serotypes of AAVs to which include AAV2, AAV6, AAV9 etc. These AAVs are currently being explored for in-vivo gene delivery. We have engineered AAVs to make them tissue and cell type specific by including target specific antibodies and cell specific promoters.
DIAGNOSING WITH CRISPR
Cas12 and Cas13-based Diagnostics for infectious diseases and cancer
We are working on various strategies to directly deliver the CRISPR-Cas into the cells in-vivo. In this direction, we are exploring the LNPs and AAV based vectors for the direct delivery for the CRISPR-Cas RNP into the cells.
Our laboratory has developed potent and safe lentiviral vectors for use in cell and gene-based therapy. These lentiviral vectors are 3rd generation replication deficient with modifications that substantially increased the titer of the transgene. These lentiviral vectors have been used to develop the engineered cells for therapeutic purpose.
We have also developed various serotypes of AAVs to which include AAV2, AAV6, AAV9 etc. These AAVs are currently being explored for in-vivo gene delivery. We have engineered AAVs to make them tissue and cell type specific by including target specific antibodies and cell specific promoters.
AUTOMATING DIAGNOSIS
- Diagnosis and prognosis of cancer
- Diagnosis of infectious diseases
- Mitochondrial shape classification for diagnosis
AI-powered diagnostic solutions provide a more accessible and affordable treatment to the patients. As the diagnosis of most of the cancer conditions is based on tissue biopsy pattern, the underlying tissue organization stores a lot of information to conclude about the exact issue in the tissue. Our main aim is to integrate the AI system with these medical image data which can detect the type and stage of cancer in a smarter, better, and faster way.
Recently, we have designed an AI-powered system that can help in the diagnosis of oral pre-malignant conditions like Oral sub-mucous fibrosis (OSMF) and oral leukoplakia, along with the stage-specific detection of oral squamous cell carcinoma (OSCC).
At the cellular level, the mitochondria is one of the prominent organelles whose structural and functional parameters behave differently under different disease conditions. Hence, we are focused on building an efficient and reliable AI system that can predict the fate of the cell only based upon the dynamics of one organelle, mitochondria.
Re-ENERGISING MITOCHONDRIA
- Intercellular mitochondrial transport (IMT)
- Mitophagy
- Mitochondrial DNA in health and disease
- Mitochondrial dysfunction in cancer
The highly dynamic nature of mitochondria makes them a vital component for most of the eukaryotic cells for proper functioning. Besides its essential role in energy production from molecular oxygen and nutrients, it also participates in several other cellular processes including calcium signaling, fatty acid metabolism, apoptosis and necroptosis. Since the beginning, our lab has explored various aspects of mitochondrial role in different disease conditions such as asthma, diabetes and oral submucous fibrosis (ongoing). In the present ongoing work of our lab, we are interested in investigating an unexplored area that includes mitochondrial calcium-mediated necroptosis in the pathogenesis of oral submucous fibrosis and oral cancer. We are also looking at the metabolic changes that progress pre-malignant conditions to oral cancer and the drug targets based on the cell and gene therapy.
COMPUTATIONAL BIOLOGY
- Mental Heallth- Depression and Anxiety
- Cardiovascular diseases
The use of RNA sequencing transcriptome analysis is a cutting-edge technology that is rapidly advancing our understanding of human disease.
Our lab is using RNA sequencing transcriptome analysis to study the genetic basis of mental health and cardiovascular disorders. We are particularly interested in screening blood biomarkers for these disorders, with the goal of developing a diagnostic system that can be used to identify people at risk or early in the course of the disease.
These projects are incredibly significant as they not only aim to enhance our understanding of the genetic underpinnings of these diseases but also pave the way for the development of more precise and personalized therapeutic strategies. By leveraging the power of bioinformatics, we are able to analyze vast amounts of genetic data, uncover novel insights into disease pathogenesis, and identify potential targets for therapeutic intervention.
Team Building
Collaborators
Growth is never by mere chance; it is the result of forces working together.
CSIR
Dr. Anurag Agrawal, CSIR-IGIB
Dr. Soumya Sinha Roy, CSIR-IGIB
Dr Ulaganathan Mabalirajan, CSIR-IICT
Dr. Sivaprakash Ramalingam, CSIR-IGIB
Jamia
Dr. Mohan C Joshi, MCARS, Jamia Millia Islamia
Dr. Jawed Iqbal, MCARS, Jamia Millia Islamia
Dr. Syed Mansoor Ali, Jamia Millia Islamia
Dr. Rahisuddin, Department of Chemistry, Jamia Millia Islamia
Dr. Deborah Sybil, Faculty of Dentistry, Jamia Millia Islamia
Dr. Sushma Suri, Department of Psychology, Jamia Millia Islamia
Dr. Meena Osmany, Department of Psychology, Jamia Millia Islamia
International
Dr. Isaac K Sundar, Kansas University, USA
Dr. Andres Buonanno, NIH, USA
Dr. Detlef Vullhorst, NIH, USA
Other Universities
Dr. Akhilanand Chaurasia
Dr. Anwesha Bhattacharya, Amity University, Noida
Dr. J Augustine, MAIDS
Clinical
Dr. Arpita Rai, RIMS, Jharkhand
Dr. Deepika Mishra, AIIMS
Dr. Gaurav Kharia, Apollo Hospital
NBRC
Dr. Pankaj Seth, NBRC, Manesar
Dr. Rituparna Chaudhuri, NBRC, Manesar
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