Groundbreaking discoveries over many decades have confirmed and elaborated on the close connection between the immune system and a host of diseases of major importance to public health, including cancer, sepsis, rheumatoid arthritis, asthma, diabetes and celiac disease. Recent technological breakthroughs have allowed us to gain unprecedented insight into the regulatory networks that govern immune responses. Medical interventions that manipulate the immune system to target cancer, so-called cancer immunotherapies, have seen spectacular results in the treatment of certain tumors. And this is just the beginning. 

The Ghosh lab has a long-standing interest in understanding and elucidating the complexities of transcriptional regulation, with a particular focus on the innate and adaptive immune system. As pathological changes to the transcriptional programs of immune cells lie at the heart of many diseases, we aim to obtain a deep, mechanistic understanding of the pathways that establish, maintain and fine-tune the immunological transcriptome. Based on this knowledge, we hope to devise novel, innovative approaches to combat some of humanities most vexing afflictions. 

Current projects in the Ghosh lab include: 

1. We use biochemical, molecular and genetic techniques to study and understand the mechanisms that control the activation, activity and specificity of the transcription factor NF-κB, a central regulator of gene expression in all immune cells. We are aiming to elucidate how specific modulators of NF-κB influence gene expression by regulating particular NF-κB subunit combinations, that then allows expression of the appropriate genes in the appropriate cells at the appropriate time, a topic of particular relevance for autoimmune diseases such as sepsis. Furthermore, we are using cutting-edge genomic technologies, such as RNA-seq, ATAC-seq and ChIP-seq, to unravel the mechanisms by which inflammatory signals regulate the gene expression program of macrophages.

2. We are studying the importance of individual NF-κB subunits in the regulation of conventional, effector T cells and regulatory, suppressive T cells (Tregs). Our recent findings have established a central role of c-Rel in the suppression of anti-tumor activity; now, we are exploring approaches to specifically inhibit c-Rel as a novel strategy for enhancing current cancer immunotherapy regimens.

3. Long non-coding RNAs (lncRNAs) have recently emerged as important regulators of a plethora of physiological processes, including immune responses. We are using GWAS data to identify interesting lncRNA targets and study them in the context of inflammatory diseases, such as celiac disease and rheumatoid arthritis. We are also identifying and characterizing novel microRNA regulators of the inflammatory response.

4. Mitochondria serve as hubs that connect various signaling networks to inflammatory signaling. We are studying the role of ECSIT, a mitochondrial complex I chaperone, in the regulation of mitochondrial ROS production. We are also investigating a novel role of ECSIT in neurodegenerative diseases, including Parkinson's and Alzheimer's disease.

5. The microbiome has recently emerged as a crucial variable that affects diverse physiological processes. Dysregulation of the microbiome is associated with pathologies as diverse as metabolic disease, cancer, inflammatory bowel disease, and depression. We are interested in understanding how the function of certain Toll-like receptors (TLRs) is influenced by the microbiome in organs such as the gut and lungs, and how these TLRs in return shape the microbiome.