Research | Guru's Lab

Guru's Lab is studying how drug-tolerant persister (DTP) cells survive; these are a tough group of tumor cells that lead to cancer coming back in 75% of patients. These cells evade therapeutic attack through non-genetic adaptations, entering a dormant but resilient state that can withstand conventional treatments. The lab combines molecular biology, functional genomics, and computational tools to study key survival pathways, stress responses, and genetic reprogramming that allow DTPs to persist. Their work is focused on decoding the cellular machinery that protects these cells and promotes recurrence.

To disrupt this cycle, the lab investigates signals that cause DTP reactivation, with a focus on stromal interactions, cytokine responses, and metabolic dependencies. They use patient-derived models to identify vulnerabilities and map survival landscapes using RNA-seq, CRISPR screens, and proteomics. They hope to eradicate residual disease and avoid therapeutic failure by developing small-molecule inhibitors and testing synergistic therapies. These strategies represent the forefront of relapse prevention and precision oncology.

Guru Lab also pioneers novel technologies, such as single-cell multi-omics, to study DTP heterogeneity, particularly in Indian patient cohorts. They use AI for drug repurposing and create 3D tumor models that closely resemble in vivo microenvironments. The lab focuses on identifying signs of cancer relapse through liquid biopsies and developing new treatments to be tested in clinical trials. Their personalized, biology-driven strategies provide new hope for long-term cancer remission.

Research Interests

1. Regulated Cell Death (RCD) Triad in Cancer Persistence:

Cancer persistence and relapse are driven by a subpopulation of drug-tolerant persister (DTP) cells that escape therapy through adaptive mechanisms in cell death pathways. Our research focuses on the Regulated Cell Death (RCD) pathways-to uncover how their dysregulation promotes tumor survival and to develop strategies that force DTP cells into fatal vulnerability.

2. Investigating onco-metabolism:

By identifying the unique metabolic needs of cancer cells, nutrient utilization & metabolic rewiring, our research seeks to uncover the role of glycolysis (Warburg effect), amino acid metabolism and fatty acid oxidation in tumor survival. Also, to uncover potential therapeutic targeting of ATP/NADPH production pathways for therapy.

4. To develop "transcription-focused" combination regimens:

To exploit CDKs as epigenetic switches to convert dormant tumors into therapy-responsive states:

Chemosensitization Mechanisms of CDK-driven transcriptional alterations restore pro-apoptotic pathways (e.g., BAX, NOXA) to enhance platinum/taxane efficacy.
CRISPR-CDK screens to uncover synthetic lethal interactions in resistant models.
Single-cell multi-omics (scRNA-seq + ATAC-seq) to track chromatin re-opening during treatment.

3. Decoding the Integrated Vesicular and Organellar Trafficking (IVOT) Pathways in Cancer:

Our research focuses on elucidating the dynamic interplay between autophagy, lysosomes, exosomes, and peroxisomes, collectively termed Integrated Vesicular and Organellar Trafficking (IVOT) Pathways and their pivotal roles in cancer progression, therapy resistance, tumor adaptation, survival, and tumor microenvironment (TME) remodeling. By decoding IVOT pathways, we aim to pioneer next-generation organelle-targeted therapies that overcome resistance and metastasis in aggressive cancers.

5. Inhibiting Resistance Mechanisms:

A significant portion of our work is dedicated to unraveling the mechanisms behind cancer drug resistance and tumor progression, aiming to enhance the efficacy of current treatments.

6. Translational Impact:

Bridging laboratory discoveries with clinical applications is a key objective. We strive to translate our findings into novel, effective treatment strategies that can be evaluated in clinical trials.