"Let's Learn About Lysosomes" - An Interview with Gouri Yogalingam, Ph.D. of BioMarin, Novato

By Shoshana Harlem (MSS Intern, Terra Linda High School)

Dr. Gouri Yogalingam is currently working to develop therapies for treatments of genetically-defined diseases at the Bio Marin Pharmaceutical in Novato. She has already developed enzyme replacement therapy for a rare genetic disease, called mucopolysaccharidosis type Vl. 

1. What made you interested in studying lysosomes?

Dr. Gouri Yogalingam

I was working on lysosomal storage diseases in my PhD and got to know two young boys affected with MPSVI and MPS II, who came to our clinic in Adelaide, South Australia. Their names were Mathew and Vaughan. Over the years they both deteriorated and eventually died. This really affected me, making me realize how important and somewhat overlooked the lysosomal system is in terms of contributing to normal cellular homeostasis, as well as disease pathogenesis when lysosomes stop working. After my PhD I moved to the USA and into other research areas outside of lysosomal storage diseases but I think without realizing it I have always been interested in how lysosomes contribute to not only lysosomal storage diseases but also more common diseases that we all know about, like cancer and heart disease.

2. How do lysosomes contribute to cancer progression and cardiovascular disease?

In cancer cells the anti-cancer drug known as imatinib stops Abl kinase signaling and down-regulates autophagy, a lysosomal-mediated process that cancer cells have been reported to hijack to grow faster. In cardiovascular disease, a delta protein kinase C peptide inhibitor drug helps to up-regulate mitophagy, a cardio-protective lysosomal-mediated process that helps to remove damaged mitochondria in cardiomyocytes following myocardial infarction.

3. What are some benefits of lysosomes? In other words, how are they good for a person?

Think of lysosomes as the recycling center of your cells. If your lysosomes stop working old, damaged proteins and organelles build up and promote cellular damage.

4. What advice would you have to people who want to study lysosomes?

I don’t think anyone would graduate from high school wanting to specifically work on the humble old lysosome! My advice is to always think beyond the lysosome. I have several interests outside of lysosomes. For me my interest in lysosomes was because of a very emotional experience, seeing young children affected with lysosomal storage diseases passing away. The truth is that many of these kids still die and some of these diseases cannot be effectively treated with our current technologies. So perhaps the young scientists out there should take up the cause and get into this field of human disease with a fresh outlook and novel approaches that us oldies have not thought of. Assuming that high school students know that lysosomes are truly what they want to study then I guess that they should go to college and learn about cell and organelle biology. They can always reach out to me, and I'll point them in the right direction if they want to work in a lysosomal lab!

5. What has been your favorite project involving lysosomes that you have worked on?

There are many. I recently worked on a project at BioMarin, where we evaluated enzyme replacement therapy for the neurodegenerative lysosomal storage disease GM1 gangliosidosis. That was fun. We learned a lot of new things about the disease. The work that I care about the most was about a boy who was affected with another lysosomal storage disease, MPS IIIB. He passed away in his 30s after suffering from progressive neurodegeneration. I learned all about this patients genetic mutations. We worked out how the inherited mutations in this patient resulted in his unusually protracted disease symptoms. There is also the story about a naturally occurring form of MPS VI in cats, which I'll talk about at the Marin Science Seminar. Just like humans, even cats can inherit these devastating lysosomal storage disease. We learned that an extremely mild form of MPS VI can disguise itself as a very mild form of skeletal dysplasia - in cute, fluffy cats!

Want to learn more about Gouri Yogalingam and lysosomes? Join us on Wednesday, November 6, 2019 at Terra Linda High School from 7:30 PM - 8:30 PM in Room 207!

http://marinscienceseminar.com/lets-learn-about-lysosomes-wth-dr-gouri-yogalingam-of-biomarin/?fbclid=IwAR2hG7W2XGVQO6WYU41HcipuQ3Hcf5X0MPlI88GV-h3WPndP8quN3O9zhSc

Learn more at https://www.biomarin.com/, https://www.linkedin.com/in/gouri-yogalingam-b0912821, http://www.marinscienceseminar.com/mssarchive/speakers/gyogalingam.html, and https://www.facebook.com/events/1882261778587280/