The importance of gut health to overall well-being is frequently underestimated. Like breathing, we often don’t appreciate the essential tasks that the gut carries out or understand how interconnected maintaining good gut health is in keeping our other systems balanced.
If food antigens and contaminated bacteria enter the bloodstream, they can pose serious threats to body organs, resulting in inflammation. When the gut is healthy, however, it creates a protective seal that safeguards the organs from exposure to food antigens and inflammation.
Prasun Guha, a School of Life Sciences assistant professor, joined 51ԹϺ in 2022 and established his lab to explore links between gut health and disease. When the protective seal of our gut lining becomes affected and causes inflammation, this condition is commonly referred to as leaky gut.
In more scientific terms, his research focuses on higher-order inositol signaling mechanisms and their crucial role in regulating intestinal permeability. His research is tracing a potential connection between leaky gut and the inositol polyphosphate multikinase (IPMK) gene as well as the effects of IPMK on cancer metastasis and drug therapies.
All of these future research endeavors are made possible thanks to a recent grant Guha received from the National Institutes of Health (NIH).
An Unexplored Avenue of Research
The higher-order inositol signaling pathway, leaky gut syndrome, and IPMK's role as a novel lipid kinase regulating metastasis represent an area of research that has, so far, been left unexplored by researchers. But, that sense of the unknown is exactly what Guha finds appealing.
“Having a lot of previous literature in a field often hinders my ideas for new hypotheses as I feel biased by that previous body of work,” says Guha. “When exploring uncharted research areas, I rely heavily on fundamental scientific principles. I carefully observe new phenomena and cultivate these observations to understand potential causes.
"This approach enables me to generate more robust hypotheses. The experimental validation of these hypotheses is immensely rewarding, evoking a feeling of discovering something entirely original from scratch.”
Guha’s main principle, a mantra provided to him by his previous mentor, Solomon Snyder, during his time working in Snyder’s lab at Johns Hopkins Medicine, was, “Where the science takes you, go there.”
“Looking at something new brings me more joy,” says Guha. “You’re literally following where the science takes you because it is new, and I’m not biased by the current literature. It’s an approach that works well for me.”
Tell us more about your research and what the Guha Lab at 51ԹϺ is working on.
My work focuses on higher-order inositol phosphate (HOIP) signaling, specifically looking at their role in regulating nuclear functions that influence the pathophysiology of inflammatory bowel disease (IBD), the gut-brain axis, and separate projects dealing with tumor metastasis.
Here at 51ԹϺ my research has shifted to concentrate on a specific, smaller part of this pathway in the IPMK (Inositol polyphosphate multikinase) gene. I am primarily looking at two things – leaky gut and how it could be influenced by IPMK, and also the effects of IPMK on cancer metastasis and what this might mean for current cutting-edge drug therapies. The latter is the work which will be further supported through funding from the SuRE program grant.
What does it mean to you to receive the National Institutes of Health SuRE program grant?
I am excited to receive this award from the NIH, especially since I am still relatively young in my career and have only been with 51ԹϺ for about two and a half years. It feels like great progress and recognition of the work I am doing in this newer area of study.
Our research on the IPMK gene has revealed its significant role in cell migration signaling, a process crucial in cancer metastasis — the primary challenge in cancer treatment. Through our studies, we've demonstrated that knocking out IPMK in cells impairs their migration ability.
Building on these findings, we plan to investigate the effects of IPMK deletion in animal models. If successful, this research could pave the way for developing novel therapeutics aimed at inhibiting metastasis and potentially discovering new cancer treatment strategies.
Can you explain the IPMK gene’s connection to leaky gut?
Leaky gut has been found to be a precursor for many autoimmune diseases, such as Crohn’s disease. IPMK is a risk gene for Crohn’s. Our research is trying to determine how IPMK may contribute to this disease and other autoimmune diseases.
We found that the intestinal loss of IPMK in the mouse model causes a leaky gut, a hallmark of Crohn’s disease. Our hypothesis is that a chronic leaky gut allows unwanted gut-derived microbial and antigenic particles to build up, resulting in a persistent immune reaction over time, rendering chronic inflammation. This may not only be restricted to the intestine; it can also create inflammation in various other organs like the brain, liver, etc., by circulating through the blood.
Over time, this research could help develop a way to test for leaky gut. Potentially, we may also be able to figure out inter-organ signaling and the root cause of various chronic inflammation-related diseases like Alzheimer's, rheumatoid arthritis, Crohn's disease, etc. Therapy to fix leaky gut could be a means to deal with these diseases, which truly have no cure.
You received your Ph.D. from the University of Calcutta in India, where you grew up. How did building your first lab from scratch during your Ph.D. help you as a researcher?
During my Ph.D. in India, I gained invaluable experience in establishing a tissue culture lab from scratch, which proved instrumental in setting up my own lab at 51ԹϺ. This process was comprehensive, extending beyond mere equipment acquisition. It involved hands-on tasks like painting and sealing windows to create a dust-free environment crucial for cell cultures.
The journey continued with identifying and purchasing the right instruments and culminated in the exhilarating moment of initiating cell cultures and witnessing the entire process come to life successfully. My friend and I even manually activated the air conditioning every Sunday to protect our incubators from summer heat.
This hands-on experience fostered a deep emotional connection and provided invaluable knowledge about lab operations. It's akin to building a home, creating a unique bond with the work. This experience has given me lasting confidence in my ability to troubleshoot problems and achieve results with limited resources — skills that continue to serve me well in my scientific career in the United States.
Opportunities for scientific research in the U.S. are exceptional and are supported by a very robust infrastructure. This made it an appropriate next step for me to continue pursuing independent thoughts and exploring innovative ideas.
What brought you to 51ԹϺ?
A philosophy I live by is to surround yourself with good human beings. When I met with the people at 51ԹϺ, from the dean of the college to the department chairs and potential colleagues, they were all good human beings. It felt like a supportive environment where I would be able to establish my lab and then allow it to shine based on the research.
