Shukla Research Lab Tests Limits of Asbestos Disease Science
August 15, 2022
When I decided to launch my research career in the United States a little over 20 years ago, I had no idea I would end up where I am now: On the cutting edge of asbestos science.
In India, my husband and I were biochemists at heart. I worked in neurological sciences and wound healing projects with little cancer experience. In 1997, we decided to update ourselves with advanced technologies for the next step in our research and moved to the USA.
While in Vermont I began looking for laboratory work in wound healing, but fate had other plans. I joined a lab led by a renowned asbestos researcher with plenty of funding and a desire to teach. Now, two decades later, asbestos and mesothelioma have become my passion.
At the Shukla Research Lab at The University of Vermont’s Larner College of Medicine, my team is working to understand how asbestos causes harm and disease on a molecular level. This understanding will help develop new approaches for mesothelioma treatment and solve the fundamental problems of asbestos diseases.
Focused Research Leads to Better Understanding of Asbestos Disease
One of my first extramural grants came from the Mesothelioma Applied Research Foundation, also known as MARF. It accelerated our study of extracellular-regulated kinase five, or ERK5. In cellular biology, kinases are signaling proteins that regulate various functions of cells, including growth and proliferation.
In 2013, our research showed that deleting the ERK5 gene in mesothelioma tumor cells and implanting them in animal models significantly decreased tumor growth. Translating this research in humans requires an ERK5-inhibiting drug (a chemical inhibitor) with potential for mesothelioma treatment.
The next phase of this research involved preclinical trials with an available experimental ERK5 inhibitor (XMD8-92), which showed promise in mouse models. Detailed advanced studies could uncover a new class of anti-cancer drugs for mesothelioma.
Understanding the role of ERK5 and other signaling pathways is critical for discovering potential targets for future mesothelioma treatments.
Additional Funding Leads to More Research
Thanks to funding from the National Institutes of Health, our lab is also exploring the role of inflammasomes in asbestos-induced inflammation and mesothelioma. Inflammasomes are proteins that regulate the immune and inflammatory response to antigens, such as infections, foreign bodies and cancer.
One of our most exciting studies, funded by the Department of Defense, has been the investigation of exosomes and how they may lead to the development of mesothelioma. The research in this area could also provide a potential drug delivery mechanism and a source of biomarkers for early mesothelioma diagnosis.
Exosomes are like tiny bubbles that carry information and materials between cells. After considering how lung-inhaled asbestos might influence distant mesothelial cells in transforming them into cancer, we devised the idea for this project.
Our main findings from this research showed that asbestos fibers interact with lung epithelial cells and macrophages, resulting in exosome secretion with specific information (content). These exosomes then affect mesothelial cell transformation and tumor development.
We also provided experimental evidence that mesothelioma tumor cells secrete exosomes rich in miRNA-16, a tumor suppressor RNA whose loss can help tumor growth and survival.
Our research demonstrated that inhibition of exosome secretion from mesothelioma tumor cells or force-feeding tumor secreted exosomes on mesothelioma cells increases the miRNA-16 concentration in cells, tumor cell death and drug sensitivity. This project’s next step is replicating this finding under in vivo conditions using animal models.
More research is warranted to identify exosomal biomarkers of asbestos exposure that may lead to mesothelioma development. This will help in the early diagnosis of this deadly cancer and save more lives.
Future of Asbestos Research Relies on Funding
As exciting as these new developments in asbestos research are, there is still much more worth investigating before taking these findings to the clinic. These experimental therapies need more pre-clinical trials to test their viability and significant clinical testing for their safety and effectiveness. However, none of that is possible without sufficient funding.
Research runs on money and time. It takes years of work from a dedicated team to develop new drugs. It isn’t very reassuring to look at the current state of asbestos research and not have the resources to pursue every unique opportunity that could lead to a cure.
Unfortunately, there are also several misconceptions in the asbestos research community, such as the idea that asbestos diseases only impact underprivileged communities. To address this, my presentations always begin with real-life facts and data to convince people that asbestos is still very much there, and its exposure can impact anybody.
There is a need for funding for further research in the field of asbestos.
I’m grateful for my opportunities to explore therapeutic targets for asbestos disease and the chance to have a tangible impact on mesothelioma patients. Mentoring enthusiastic students in my lab to become the next generation of cancer researchers has also inspired me to keep fighting for more research backing.
Asbestos is still out there and will be for a long time. I implore people to believe in this work and support the research however they can by raising awareness or participating in clinical trials. With everyone’s support, we can build a better future for mesothelioma patients, one discovery at a time.
For mesothelioma patients, I request that they hang in there with hope; we are working for you with all our resources.
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