Research Projects

Rationale The prevalence of chronic respiratory conditions like asthma, which are marked by reversible airflow restriction, chronic inflammation primarily caused by type 2 immune responses, is high in India. The functions of other immune cells, such as Th9 and regulatory T cells (Tregs), in asthma are still incompletely understood, though. New insights into the pathophysiology of asthma have brought attention to the role that signaling pathways and transcription factors play in immune control, which has led to the development of specific anti-inflammatory treatments. It is possible that the transcription factors HOXB4, MEIS1, and PBX1, which are known to regulate hematopoietic stem cells and immune cell development, have unidentified roles in allergic inflammation and asthma by affecting oxidative stress responses and immune cell differentiation. Scientific Objectives • To delve into how the transcription factors HOXB4, MEIS1, PBX1 (the last two belong to the three amino acid loop extension [TALE] group of proteins) regulate immunological responses related to asthma, including the regulation of Th9 cells and Tregs. • To illustrate how HOXB4 controls cytokine expression and immune cell differentiation in asthma by interacting with non-TALE proteins such SMADs, and FOXP3. • To identify the molecular pathways through which the HOXB4-MEIS1/PBX1 and HOXB4-non-TALE protein axes support the pathophysiology of asthma and allergic airway inflammation. Hypothesis / Model to be Tested The transcription factors HOXB4, MEIS1 and PBX1 individually and in combination control the differentiation and activity of immune cells linked to asthma, including Th9 and Treg cells, via interacting with TALE and non-TALE proteins. Airway hyperresponsiveness and allergic inflammation are influenced by oxidative stress responses and cytokine profiles, which are modulated by this control. Main Experiments • Use in vitro T cell differentiation assays to test the impact of HOXB4, PBX1 and MEIS1 overexpression or knockdown on Th9 and Treg cell development and function. • Perform protein interaction studies (Co-IP, ChIP-seq) to map HOXB4 interactions with TALE and non-TALE proteins. • Utilize murine asthma model (House dust mite induced airway inflammation) to study the in vivo effects of manipulating HOXB4, MEIS1 and/or PBX1 on airway inflammation, hyperresponsiveness, and lung pathology. Significance of the Proposal Asthma remains a major public health concern in India. While Th2 responses have been well-studied, the roles of other immune cells—particularly Th9 and Tregs—in the disease remain incompletely defined. By investigating how important transcription factors—HOXB4, MEIS1, and PBX1—regulate immunological pathways implicated in the pathophysiology of asthma, our proposal fills a crucial gap. These factors may have unidentified roles in regulating immune responses and cytokine production in allergic inflammation, despite their typical roles in hematopoietic stem cell biology. The proposed research provides new information on how Th9 and Treg cell function is influenced by the HOXB4-MEIS1/PBX1 axis and interactions between HOXB4 and non-TALE proteins such as SMADs, FOXP3. The proposal is thus significant not only for advancing our understanding of immune regulation in asthma but also for paving the way toward innovative, transcription factor–based interventions. Key novel aspects: • Examining how the HOXB4-MEIS1/PBX1 axis regulates the immune system during asthma, a relationship that has not been explored in relation to allergic airway inflammation previously. • The way that HOXB4 regulates the formation of Th9 and Treg cells, two important but little-studied immune subsets in asthma, by interacting with non-TALE proteins. • The possibility of finding new molecular processes that underlie transcription factor-mediated regulation of cytokine networks in asthma, which could lead to more targeted therapeutic interventions than those already on the market.