“I would tell my younger self to not be so afraid to be wrong. I’m wrong way more times than I’m right because I’m working at the edge of knowledge. And that’s ok. That’s where discoveries are made.”

A deadly cancer that takes the lives of dogs and kids

Jason studies cancer progression at Duke Cancer Institute. He studies a special type of cancer called sarcomas. Sarcomas are cancers that arise in muscles, bone, and blood cells that line your blood vessels. Human sarcomas are quite rare, but when sarcomas affect humans they usually manifest in children patients. It is more common for sarcomas to affect dogs, so by identifying genes that stop sarcomas in dogs, Jason and his team may also be able to save the lives of kids.

We caught up with Jason to learn more about this specific type of cancer, his team’s approach to understand the disease, and how understanding sarcomas could lead to discoveries relevant to treating other forms of cancer.

Jason Somarelli: My name is Jason Somarelli and I am a researcher at the Duke Cancer Institute. I study cancer progression, in particular, in sarcomas.

Cindy Wu: Tell us more about what sarcomas are?

Sarcomas are cancer of the mesenchymal cells. This means cancers that arise in muscles, bone, and even the blood cells that line your blood vessels. Sarcomas are really pretty rare in humans and they affect children much more than adults. Even though these cancers are rare, they are highly aggressive, which means that once sarcomas are diagnosed, they are very hard to treat, and can spread quickly through the body. Even though these cancers are rare, they are highly aggressive, which means that once sarcomas are diagnosed, they are very hard to treat, and can spread quickly through the body.

Let’s take a step back. How did you first get involved in science?

I sort of always had that drive to question things. Maybe to my parents’ dismay, I was always poking and prodding everything. Taking it apart and trying to understand it. My family really helped support me in that. I was always asking questions and always trying to understand, not just things superficially, but things at a deeper, more mechanistic level. I don’t really know where that came from but I’ve just always had that drive. I think if your family encourages that behavior then you tend to stick to it.

How did your interest in just picking apart things and understanding how things work lead you to cancer research career?

Like everybody does in their lives I had some family members become ill with cancer. Those two things sort of came together. Research tasks and these life experiences made me really start to think about changing career.

In cancer research there are so many areas that you could focus on. Why did you decide to focus on sarcomas?

All of these things kind of wind around, and looking back you’re never sure how you got where you are. I was studying metastasis during my post doc and I continue to study metastasis because that’s really the big killer. Ninety percent of patients with solid tumors die from metastatic disease. I continued to study that, and it turns out that we were studying epithelial cancers, things of an epithelial origin, which are known as carcinomas. Carcinomas undergo this really interesting transition during metastasis and they become more mesenchymal-like. It is really strange but it’s really well documented that it happens. That’s the focus of my current work. During my post doc what we realized was that sarcomas might be a really interesting way to understand more broadly aggressive metastatic carcinomas because sarcomas start out mesenchymal. We can learn a lot about the epithelial cancers, the carcinomas that become mesenchymal. That was our idea. The I met a really dynamic and interesting, amazing guy. He is an MD surgeon who works on human patients, but he’s also a vet, which is a really unique mix. He has this really cool comparative oncology aspect that he brought to my work. The credit really goes to him for this idea of comparative oncology, studying one species to understand the disease in another and vice versa.

You are seeing sarcomas in kids and dogs. What is similar in kids and dogs that makes them susceptible to sarcomas?

I posted a lab note about this because I keep getting this question. I’m sorry to say I don’t really have a good answer. My speculation is not based on any evidence, I have to be clear, but my speculation is that there are a couple of things happening.

In children it’s known that there are some preexisting mutations that are at least associated with the likelihood for getting sarcoma. Maybe there is an underlying genetics component to it or inherited component to it. In dogs my suspicion is that there is at least some contribution from all of the inbreeding that we’ve done to select breeds with unique traits. The downside to all this inbreeding in dogs is that they end up with genetic predispositions to disease. Not only are dogs more prone to sarcomas, but certain breeds are more prone to other diseases as well. Those are my suspicions, that there is some underlying genetic component in both populations.

It seems like there’s a lot we still don’t know about sarcomas, which is one big reason why we need more scientists to work on this problem. What are some specific things that you would like to know about sarcomas?

It is really unknown what the cell of origin for sarcomas are. We also need to understand more mechanistic things about their aggressive nature that could lead to novel treatments we can’t forsee at this point.

Without those basic science questions answered a lot of novel treatments remain on the shelf. For example, it’d be great to understand which subsets of sarcomas metastasize. Are there ways that we can know that sarcomas will metastasize ahead ahead of time? Those would be called prognostic biomarkers. The other need is for better treatments and predictive biomarkers to identify subsets of patients who will respond to those treatments. So, those are really the main questions for me at this point.

Lets talk more about the specific project that your have on experiment that you’re raising $2,500.00 for. For those of The people that haven’t seen the project page yet, what will $2,500 help you accomplish?

What we originally set out to do was to study was a specific gene that’s related to this transition from epithelial to mesenchymal carcinoma. That gene seems to play a role in sarcoma. We set out to just study that gene and understand how it might contribute to more aggressive sarcoma by modulating stem-like properties of sarcoma cells.

The project is now expanding with the more recent collaboration of another really great scientist here at Duke, who is working on creating cell lines from canine sarcomas directly from canine patients. Directly after the tumors are removed from surgery he can create a cell line and he can actually create what’s called a patient derived xenograft. He can take a piece of the tumor out and implant it directly into a mouse to study howthe, progression of the cancer would happen. What we can do is instead of looking at a single gene, with these new tools, we can look at thousands of genes. We can screen drugs by the hundreds using these cell lines maybe even identify new treatments. The goal is to understand which genes contribute to more aggressive disease in both dogs and kids and also to identify drugs that might work in specific individuals. So, we’ve moved from one gene to potentially looking at thousands of genes and hundreds of drugs, each for single patients. This is the next paradigm in cancer research: personalized medicine. This new collaboration has the potential to help us get there with sarcomas.

What is your specific project working on? The one on Experiment.

We are looking at a single gene that we think contributes to sarcoma aggressiveness and stemness. We think that this gene enhances sarcoma aggression by making cells more stem-like. The goal of the immediate experiment is to really manipulate this gene, to knock it down and then look for differences in stemness and aggression of sarcoma cell lines. We can also now do this in the patient-derived xenografts from dogs.

Last two questions. First one. What advice you could give to a younger version of yourself what would it be?

I would tell my younger self to not be so afraid to be wrong. As a scientist, I’m wrong way more times than I’m right, but that’s because I’m working at the edge of knowledge. And that’s ok. That’s where the discoveries are made. My younger self was always really focused on being right. As a result, I didn’t challenge myself as much as I could have.

Second question, when you were a kid what did you want to be when you grew up?

Well, I really and truly always wanted to be a scientist. Full disclosure, scientist was the bronze medal. It was third behind rock star and professional soccer player. So I think I’ll take third place.

You can be a scientist and a rock star at the same time. I don’t know if any scientists are also professional soccer players, but it is possible.

I have to check on that. I didn’t have the skill set for that anyway.

Do you play soccer?

Yeah, I played in college.

Is there anything that you wanted to add that readers should know?

I do want to acknowledge that a lot of this work is not just me and not just my collaborators, who are already established in their careers, but it’s the work of really talented young scientists, undergrads, and post-bacs. These students are driving a lot of the work we’re doing. A much as the Experiment is a scientific pursuit it’s also a mentoring pursuit. It is something that I take really seriously and I think is really important. We try to always involve multiple, med students or undergrads or both in all of our projects if we can. So, it’s important to us that our science is not just a discovery pursuit, but a teaching and training pursuit as well.

Have additional questions about Jason’s cancer research? You can ask Jason questions directly. Jason has a week left to raise funds to start this project. You can support his project with a few dollars. In return you’ll receive updates in your inbox on his research progress and results.

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