Vikas Duhan

Overcoming Immune Dysfunction in Viral Infections and Cancer

Background: Control of viral infections and cancer depends on a well-functioning immune system. Natural killer (NK) cells and cytotoxic T cells are the primary immune cells responsible for eliminating virus-infected and tumour cells. However, uncontrolled virus replication and cancer growth result in dysfunction of these immune cells and lead to disease progression. Aims: This project aims to discover new molecules that can reactivate or enhance dysfunctional immune cells and boost their ability to fight disease. Using genetically modified mouse models and gene knockout/overexpression approaches, we will investigate how specific molecules regulate immune cell function and control viral infection and tumour growth. Promising targets will be validated in human immune cells to translate findings toward clinical applications. Methods 1. Preclinical mouse models for viral infection and cancer: animal handling, adoptive cell immunotherapy, drug treatments 2. Engineering immunotherapies: developing CAR-T and CAR-NK cell products from human blood samples; assessing antitumour efficacy in vivo using mouse models and in vitro by activation and cytotoxicity assays using flow cytometry 3. Gene modification: CRISPR/Cas9-based knockout or lentivirus-based overexpression in human immune cells to assess antiviral and antitumour potential 4. Additional techniques: bacterial cloning (plasmid transformation, amplification, purification), mammalian cell transfection for lentivirus production, qPCR and RNA-seq for gene expression analysis, and western blotting for protein detection in immune signaling pathways. Impact: Identification of novel therapeutic targets could lead to the development of new immunotherapies for cancer and viral infection treatment.