Mukesh Varshney

Nuclear Receptors and Their Interplay in Health and Disease

My research focuses on the roles of nuclear receptors, particularly liver X receptors (LXRs) and estrogen receptor beta (ERβ), in neurodegeneration, inflammation, and cancer. These receptors, individually and synergistically, regulate essential biological processes such as cholesterol metabolism, immune responses, and cellular differentiation. Investigating their crosstalk provides critical insights into disease mechanisms and potential therapeutic targets.

LXRs, as oxysterol-activated nuclear receptors, are central to maintaining cholesterol homeostasis and modulating immune function, both of which are implicated in high-burden diseases such as Alzheimer’s and cancer. Dysregulated LXR pathways contribute to neuroinflammation, myelin abnormalities, and tumor progression. Simultaneously, ERβ plays a pivotal role in neural development and neuroprotection, interacting with LXR signaling to regulate cellular processes in neurodegenerative and inflammatory diseases.

Our research seeks to unravel how LXRs and ERβ coordinate neuronal survival, immune modulation (particularly macrophage responses), and tumor biology within the tumor microenvironment (TME). By employing advanced techniques, including knockout models, 3D organoid systems, and omics approaches, we investigate the molecular pathways driving these conditions. Our findings underscore the protective effects of LXRs and ERβ in reducing oxidative stress, inflammation, and their impacts on the tumor microenvironment.

In parallel, we develop innovative human-relevant, animal-free in vitro models such as organ-on-chip systems, leveraging stem cell and organoid technologies to study receptor interactions under physiologically relevant conditions. These platforms also enable us to explore lipid metabolism in cancer and neurodegenerative and reproductive disorders while evaluating potential therapeutic interventions.

Our ultimate goal is to integrate nuclear receptor biology with stem cell and regenerative medicine to identify and develop novel treatment strategies. By fostering collaborations across clinical and translational research fields, we aim to transform our discoveries into impactful solutions for neurodegenerative diseases, inflammatory disorders, and cancer.

• Nuclear Receptor Biology: Exploring the roles of liver X receptors (LXRs) and estrogen receptor beta (ERβ) in regulating cholesterol metabolism, immune responses, and cellular differentiation, with a focus on their interplay in neurodegeneration, inflammation, and cancer.
• Neurodegenerative Diseases: Investigating molecular pathways that contribute to neuronal survival, oxidative damage, and immune modulation in conditions such as Alzheimer’s and Parkinson’s diseases, with an emphasis on nuclear receptor signaling.
• Cancer Biology: Studying the impact of nuclear receptor pathways on tumor microenvironments, lipid metabolism, and inflammation to uncover novel therapeutic strategies for cancer treatment.
• Stem Cell and Organoid Technologies: Developing advanced human-relevant in vitro models, including 3D organoids and organ-on-chip systems, to study disease mechanisms and test therapeutic interventions in neurodegenerative and oncological contexts.
• Regenerative Medicine: Leveraging stem cell biology and nuclear receptor signaling to drive advancements in tissue engineering and personalized therapies for chronic diseases.