Laasya Madana

Green Fellows project abstract:

Neurofibromatosis Type I (NFI) results from inactivating mutations in the NF1 gene that encodes the tumor suppressor, neurofibromin. Nonfunctional neurofibromin predisposes NFI patients to tumor development including those on peripheral nerve sheaths. Some of these overtime develop into malignant peripheral nerve sheath tumors (MPNST) which currently do not have a cure. Immune checkpoint blocking (ICB) programs a patient’s immune system to enhance tumor destruction and is an effective approach to target cancers. However, MPNSTs are cold tumors characterized by low T cell infiltration in the tumor microenvironment. Given the ability to increase T cell density in the tumor microenvironment, ICB could be a potential therapy for MPNST. Activation of the cGAS-STING-IFN pathway in the tumor cells could upregulate the production of cytokines and chemokines, leading to the recruitment of T cells within the tumor. Therefore, we hypothesize that treatment with STING agonists would turn MPNSTs into “hot” tumors making them susceptible to targeting with ICB. To test, we treated MPNST cell lines with STING agonist ADU-S100 for varying durations of time and determined levels of STING-IFN pathway activation.

 

​​What does research mean to you? 

Research is something that builds on itself so what we’re working on now is a collaborative effort of so many scientists from years before and years into the future. It’s like everyone’s baby that we all raise until it can be directly implemented into a diagnosis or a cure-and even then there’s always things to build on. 

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Tell us about your journey​!

As someone who is more familiar with the medical side of things, I’ve always heard about research but never really dabbled in it myself-especially basic science research. It seemed a little scary with all the crazy chemicals and convoluted procedures. But working in a translational lab beforehand, I got to ease into research slowly and chose to apply to Green Fellows the semester after to try something new and exciting.

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What was your favorite part about the program? 

The people of my lab. I love everyone in my lab with all my heart; they made my experience so unforgettable.

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What was the biggest thing you learned from the program?

Research is a lot of thinking. I came into this program thinking the protocol/procedure is all I’ll need to complete my tasks and I couldn’t be more wrong. Yes, the protocol is a very good guideline, but there’s a lot of trial and error too. When an experiment doesn’t yield a certain amount of usable data, you have to find where the issue is and make tweaks. That was a bit of a surprise because I thought you just follow some directions and viola, you have perfect data. But no, that is not the case. But that is what makes research fun, though.

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Advice for Future Green Fellows

It’s okay to make mistakes. Everything is a learning process. It took me a while to understand because I’m a perfectionist and I like everything to be flawless the first time I do it. But being in the lab full time with so many new words, techniques, and tools being thrown around, of course it will take some time to get used to and make sense of. So don’t beat yourself up for dropping a beaker or accidentally killing some cells in culture; you’ll be fine :).

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