Despina Siolas, MD, PhD

GI Oncology Now

Despina Siolas, MD, PhD, is a medical oncologist at Weill Cornell Solid Tumor Oncology Practice and Assistant Professor at Weill Cornell Medical College. Since joining Weill Cornell Medicine, Dr. Siolas established the Siolas Laboratory where she leads research aimed at understanding how tumor genes interact with the immune system to shape cancer development, particularly in the most challenging gastrointestinal (GI) cancers, such as colorectal and pancreatic cancer. With her research, Dr. Siolas aims to develop new cancer treatment regimens and fill gaps in therapy. In addition to the impactful research being conducted in her laboratory, Dr. Siolas provides mentorship to multi-level trainees ranging from undergraduates to medical oncology fellows seeking a career in GI oncology research. 
In this exclusive interview, Dr. Siolas reflects on her career journey and the path she took to get to where she is now—from her mother being diagnosed with colon cancer to working with mentors who guided her along the way. She highlights key projects in the Siolas Laboratory and comments on recent advancements she finds promising for GI cancer treatment. Beyond her research, Dr. Siolas reflects on her role as a mentor and patient advocate.  
 —
What motivated or influenced you to pursue a career in gastrointestinal oncology? Did you have any mentors who had an impact on your career early on? 
Dr. Siolas: For me, getting into GI oncology was actually solidified when I was 16 years old and my mom was diagnosed with colon cancer. I was an only child, and I didn’t know what cancer was. I didn’t know what was going on. But I know that now. She was 48, and at the time, colonoscopies weren’t [done] until later, so she was never referred for a colonoscopy. Here I am, 16, I just got an internship at New York Academy of Science, so I had the opportunity to go to this fancy New York academy and do science research, and my mom was diagnosed with colon cancer.
She had to go for multiple surgical opinions. Ultimately, she had her tumor removed, and during her chemo, she distanced herself, in that she stayed with her parents. I got to do my internship, but I would visit her on weekends. But I knew at that point that I wanted to work on this, specifically GI oncology, because I had faced it as the loved one of a patient. I knew that this was something that I needed to really dedicate my training and my life to. But I would never have gotten here if I didn’t have mentors who really, not just inspired me, but pushed me.
I had this phenomenal mentor at Cold Spring Harbor Lab in Long Island. His name was Dr. Greg Hannon, and at the time, he really tried to challenge me. He gave me two projects. And I was like, “Oh, this is really difficult.” But we were doing so well with the one project and it just took off. And he really just ingrained in me, even though I was very young, a lot of his philosophy and approach. And not only that, but I’ll never forget, he put me on a patent. I came into his office and he said, “Most people don’t put their students on patents, but I want to do this, and I want you to do it for your future students.” So, really having the right mentors helped me focus but also taught me how to be a better person, a better professor, a better doctor. I think the people who mentor a young student or trainee are really important.
You are a professor at Weill Cornell Medical College and the founder of the Siolas Laboratory. What motivated you to start the Siolas Lab?
Dr. Siolas: If you were to just say, “Describe yourself,” I would say, “I’m a person who always liked to ask questions.” For example, when I was a little girl, one of my dad’s friends gave me this book on the scientific method. It was a cartoon book, and the girl looked like me. She was asking questions like, “What came first—the chicken or the egg? And how would we solve it?” And I remember looking at the book and being really excited. And when I got into high school, I was in a research program where I got to do little experiments. But then life came about and my mom got colon cancer, that really changed things.
I was also very torn because I wanted to do medicine and I liked it, but I also wanted to do research. I realized at the time there weren’t a lot of physician-scientists running around. I didn’t have exposure to them. But when I found out that you could be a physician AND a scientist, I thought this was the most amazing job in the world. That’s why I ended up pursuing [this role]. Once I became a professor, I got a little bit of funding from the government, and I was able to start my own lab.
Because I started it from scratch, I was able to go in whatever direction I wanted. And it is harder. It’s harder when someone doesn’t hand you something. It’s harder when you have to build it on your own. But you become more, or at least I’ve become, very proud and very passionate. And I know that the things that we’re answering are clinically relevant questions that will affect people because that’s how they were designed. They were designed by me working with patients and seeing certain things and then going back into the lab to solve problems.
Your research at the Siolas Laboratory focuses on cancer genetics and tumor immunology with the goal of developing new cancer treatment regimens for patients. Can you speak about some key projects you have been a part of and the implications they have for pancreatic and colorectal cancer treatment?
Dr. Siolas: The projects that I’m working on, I’m very proud of, mostly because they’re based on clinical observations, things that are occurring in patient care. I’ll give you two examples. One is if you look at patients with pancreatic cancer, 93% have a KRAS mutation. That’s a gene, an oncogene. But it turns out the type of KRAS mutation a person has affects their prognosis, meaning that [it] affects the amount of time they live. We saw this as a clinical observation that was coming out of studies, of let’s say, over the last 15 years. We said, “Well, why is that? Why is it that a particular KRAS mutation allows one person to live longer than another?”
We took that clinical observation, and we went back to the laboratory to try to figure out why. We do this with cells that have different KRAS mutations and mouse models—and also with human datasets as well—like sequencing/bioinformatics stuff. Why is this occurring? Then what we’re trying to do is ask, “Okay, these people are living longer. Why? Is there a particular treatment they should get that maybe is different than [what] the other patients [are getting]?” Because right now, unfortunately, all pancreatic cancer patients are given the same treatment regardless of what their KRAS mutation is. The vast majority all just get the same treatment. This is not just a one-size-fits-all disease.
The other project is also based on a clinical observation. In the clinic, we see that if a patient has colon cancer and liver metastasis, they don’t do as well when treated with immunotherapy as a patient who has colon cancer, but then either has no metastasis or has metastasis in a different organ like the lungs or lymph nodes. So, that means something about the liver, having a tumor in the liver, affects their immune system and makes them resistant to immunotherapy.
We want to find out why. Is this something that we can reverse? How are we going to do it? Again, we have to use multiple approaches. We use our mouse models to give us a little system that we can manipulate. We use patient datasets; we use patient samples. We take a clinical question, and then we attack it through different ways, different mechanisms to try to figure out why this is occurring in real life. How can we alter real life and stop this from happening?
As a mentor and leader in the Siolas Lab, what do you find the most rewarding when working with young people who are getting their start in GI oncology research? What advice do you have for other young professionals that want to become GI oncologists?
Dr. Siolas: Our laboratory is skewed towards young people. We have two undergraduates, a medical student, two technicians who finished their bachelor’s but are not in graduate school, and a postdoc. But what’s nice about that is they come in with excitement. They want to learn. What’s most rewarding is when I challenge them, and they rise to the challenge. I just say, “Listen, we’re all going to do a poster. Everyone is going to submit a poster for presentation.”
I’m like, “Okay, we’re going to have a lab meeting. We’re going to talk about what to put in a poster, what our previous posters look like. How should the figures look?” Then I have them peer review each other as well. I say, “Don’t submit this to me. You’re going to submit this to someone else first so you get the hang of it.” A lot of it is training, working one-on-one. Seeing them succeed and knowing I helped them along the way is incredibly fulfilling.
In terms of advice, though, research is a hard field. I would say [to] a young person—and I get lots of applicants from young people who want to do GI oncology research—, “Plan ahead.”
Don’t plan two months before the start of the summer. You need to really start looking at, thinking about things ahead of time and apply to everything. Apply to many programs because you never know which program is going to come through.
My parents went to an event, and they said, “Oh, this kid is looking for a lab. Can he join your lab? You have a lab. He can join your lab.” I’m like, “Yes, but we’re full. I know that you met this nice student, and that’s great and everything, but I don’t have the time. I don’t have the capacity.” So, I actually looked up programs for him, and I said, “I want you to apply to this program and advised him about the application.”
Guess what? He got into the program at Cornell for the summer, and he worked with someone else. I was just so happy that: A. he got a lab experience, which is what he wanted, [and] B. I was able to help him, even though I wasn’t able to work one on one with him because I [had] already dedicated myself to two other students.
I started putting up positive motivational quotes in the lab once a week. I have this printout of all these different quotes. Some are really good. There’s this one that’s says, “Part of making a mistake is admitting you’ve done something wrong and you need to change.” Another good quote talks about how the road bends, but you need to bend with it. A lot of advice for young professionals is to be resilient, use all your contacts, and keep looking for other ways of doing things, alternative means.
How can an oncologist be an advocate for their patient and why is it important? How do you approach patient advocacy in your own care?
Dr. Siolas: A lot of patient advocacy means you really have to work with the patient at the level they’re coming from and then also listen. It’s hard to listen. I’m listening to 20 patients in a day. I spent 53 minutes with a patient on Monday because she had persistent nausea. We went into “out-of-the-box” reasons. What else could we do for nausea? How are you taking your medicines? The reason we spent all that time is because that is what was really impairing her quality of life. That symptom is what made her miserable every day.
The other thing that I wanted to mention in terms of patient advocacy, besides listening to what the patient is actually saying, is getting help from others. A lot of times we’re so into doing the same thing over and over again. Part of being a patient advocate means you talk to your team. I had a tough-to-treat patient and a nurse suggested, “Why don’t we do palliative radiation?” [I said,] “Oh, yes, that’s a great idea.”
Or you [can] discuss the patient at tumor board. You don’t necessarily only have to discuss the patient at tumor board when you don’t know what to do. Sometimes I discuss a patient at tumor board because I’m thinking, is there anything I missed? Does anybody have any other ideas of something that I didn’t try or should think about? I’m there to help people, and in order for me to help people, I need to tap into diverse ideas and that’s some of those may come from other people—and I need to listen and think about what is important to this patient.
Looking at your career so far in research and GI oncology, can you describe one of the most rewarding moments you’ve experienced? Why does this stand out to you?
Dr. Siolas: There have been a couple of moments that stand out. I got a 5-year grant Mentored Clinical Scientist Training Award from the NIH (K08 )to train young investigators. Nobody thought I was going to get it because at the time, at the institute I worked at, nobody had received it before. To get it on the first shot was amazing. If I didn’t get it, my life would be significantly different. I was told, you’re not going to be able to do lab work. And then I got it. Everyone was so happy!
The second most rewarding moment was when I received my current position because it was during the COVID epidemic. No one was hiring. I called up places; they said, “We have a hiring freeze.” And I was like, okay, but I need to keep moving. To get a tenure track position during COVID was a pretty amazing thing. At the institute, my mentors, my non-mentors, random people I worked with, other people from other fields, were so incredibly happy to see me move on to a new spot, a new position. So, I have to say that was really a rewarding moment.
With a focus on pancreatic and colon cancer, what recent advancements do you find particularly promising in the approach to treatment? What are the biggest challenges in GI oncology in the next 5 to 10 years, and how do you envision the field overcoming them?
Dr. Siolas: What we need in colon cancer and pancreas cancer is new drugs. We need new out-of-the-box drugs, not the same drug that’s been tweaked a little. Because in some of these cancers, for example in colon cancer, we’re giving the same drug that we’ve given for 20 years.
I am very excited to see what’s going to happen. There are some new targeted therapies focusing on that KRAS mutation. People have spent their lives, 40 years, trying to drug the KRAS mutation for pancreas cancer. To be able to get a drug that targets it after studying it for 40 years is a big deal. Let’s pretend that drug does go through, it’s not going to work for everyone. We’re going to need to put it maybe with another drug to get better effects. It’s going to really open up the field.
[There are] two things that I’m concerned about. The first is we’re getting all our funding cut. I had my funding cut, and it was a grant that was approved. Five [grants] were awarded in the nation at that time, I was one of the five people. I was so proud. That’s going to stifle my productivity. It’s going to stifle our lab. That’s going to be a challenge: adapting to a new world where we’re basically strapped for cash and can’t do certain experiments or can’t hire certain expertise and so forth.
But then the other challenge is [that] everyone’s really getting excited about AI [artificial intelligence]. I’m also excited about AI, but AI will not be able to replace testing things live—whether it’s a mouse, a cell, a person—because it cannot predict with 100% accuracy what’s going to happen. Sometimes a lot of science is unexpected things. There have been several Nobel Prizes that were accidental unpredictable findings. We need to keep innovating, adapting, and investing in research—because that’s the only way we’re going to make real progress.
Disclosures
Dr. Siolas serves on a Colon Cancer Advisory panel for Bristol Myers Squibb and is a part of a Clinical Expert Panel for Natera, Inc.

Despina Siolas, MD, PhD, is a medical oncologist at Weill Cornell Solid Tumor Oncology Practice and Assistant Professor at Weill Cornell Medical College. Since joining Weill Cornell Medicine, Dr. Siolas established the Siolas Laboratory where she leads research aimed at understanding how tumor genes interact with the immune system to shape cancer development, particularly in the most challenging gastrointestinal (GI) cancers, such as colorectal and pancreatic cancer. With her research, Dr. Siolas aims to develop new cancer treatment regimens and fill gaps in therapy. In addition to the impactful research being conducted in her laboratory, Dr. Siolas provides mentorship to multi-level trainees ranging from undergraduates to medical oncology fellows seeking a career in GI oncology research. In this exclusive interview, Dr. Siolas reflects on her career journey and the path she took to get to where she is now—from her mother being diagnosed with colon cancer to working with mentors who guided her along the way. She highlights key projects in the Siolas Laboratory and comments on recent advancements she finds promising for GI cancer treatment. Beyond her research, Dr. Siolas reflects on her role as a mentor and patient advocate.   —What motivated or influenced you to pursue a career in gastrointestinal oncology? Did you have any mentors who had an impact on your career early on? Dr. Siolas: For me, getting into GI oncology was actually solidified when I was 16 years old and my mom was diagnosed with colon cancer. I was an only child, and I didn’t know what cancer was. I didn’t know what was going on. But I know that now. She was 48, and at the time, colonoscopies weren’t [done] until later, so she was never referred for a colonoscopy. Here I am, 16, I just got an internship at New York Academy of Science, so I had the opportunity to go to this fancy New York academy and do science research, and my mom was diagnosed with colon cancer.She had to go for multiple surgical opinions. Ultimately, she had her tumor removed, and during her chemo, she distanced herself, in that she stayed with her parents. I got to do my internship, but I would visit her on weekends. But I knew at that point that I wanted to work on this, specifically GI oncology, because I had faced it as the loved one of a patient. I knew that this was something that I needed to really dedicate my training and my life to. But I would never have gotten here if I didn’t have mentors who really, not just inspired me, but pushed me.I had this phenomenal mentor at Cold Spring Harbor Lab in Long Island. His name was Dr. Greg Hannon, and at the time, he really tried to challenge me. He gave me two projects. And I was like, “Oh, this is really difficult.” But we were doing so well with the one project and it just took off. And he really just ingrained in me, even though I was very young, a lot of his philosophy and approach. And not only that, but I’ll never forget, he put me on a patent. I came into his office and he said, “Most people don’t put their students on patents, but I want to do this, and I want you to do it for your future students.” So, really having the right mentors helped me focus but also taught me how to be a better person, a better professor, a better doctor. I think the people who mentor a young student or trainee are really important.You are a professor at Weill Cornell Medical College and the founder of the Siolas Laboratory. What motivated you to start the Siolas Lab?Dr. Siolas: If you were to just say, “Describe yourself,” I would say, “I’m a person who always liked to ask questions.” For example, when I was a little girl, one of my dad’s friends gave me this book on the scientific method. It was a cartoon book, and the girl looked like me. She was asking questions like, “What came first—the chicken or the egg? And how would we solve it?” And I remember looking at the book and being really excited. And when I got into high school, I was in a research program where I got to do little experiments. But then life came about and my mom got colon cancer, that really changed things.I was also very torn because I wanted to do medicine and I liked it, but I also wanted to do research. I realized at the time there weren’t a lot of physician-scientists running around. I didn’t have exposure to them. But when I found out that you could be a physician AND a scientist, I thought this was the most amazing job in the world. That’s why I ended up pursuing [this role]. Once I became a professor, I got a little bit of funding from the government, and I was able to start my own lab.Because I started it from scratch, I was able to go in whatever direction I wanted. And it is harder. It’s harder when someone doesn’t hand you something. It’s harder when you have to build it on your own. But you become more, or at least I’ve become, very proud and very passionate. And I know that the things that we’re answering are clinically relevant questions that will affect people because that’s how they were designed. They were designed by me working with patients and seeing certain things and then going back into the lab to solve problems.Your research at the Siolas Laboratory focuses on cancer genetics and tumor immunology with the goal of developing new cancer treatment regimens for patients. Can you speak about some key projects you have been a part of and the implications they have for pancreatic and colorectal cancer treatment?Dr. Siolas: The projects that I’m working on, I’m very proud of, mostly because they’re based on clinical observations, things that are occurring in patient care. I’ll give you two examples. One is if you look at patients with pancreatic cancer, 93% have a KRAS mutation. That’s a gene, an oncogene. But it turns out the type of KRAS mutation a person has affects their prognosis, meaning that [it] affects the amount of time they live. We saw this as a clinical observation that was coming out of studies, of let’s say, over the last 15 years. We said, “Well, why is that? Why is it that a particular KRAS mutation allows one person to live longer than another?”We took that clinical observation, and we went back to the laboratory to try to figure out why. We do this with cells that have different KRAS mutations and mouse models—and also with human datasets as well—like sequencing/bioinformatics stuff. Why is this occurring? Then what we’re trying to do is ask, “Okay, these people are living longer. Why? Is there a particular treatment they should get that maybe is different than [what] the other patients [are getting]?” Because right now, unfortunately, all pancreatic cancer patients are given the same treatment regardless of what their KRAS mutation is. The vast majority all just get the same treatment. This is not just a one-size-fits-all disease.The other project is also based on a clinical observation. In the clinic, we see that if a patient has colon cancer and liver metastasis, they don’t do as well when treated with immunotherapy as a patient who has colon cancer, but then either has no metastasis or has metastasis in a different organ like the lungs or lymph nodes. So, that means something about the liver, having a tumor in the liver, affects their immune system and makes them resistant to immunotherapy.We want to find out why. Is this something that we can reverse? How are we going to do it? Again, we have to use multiple approaches. We use our mouse models to give us a little system that we can manipulate. We use patient datasets; we use patient samples. We take a clinical question, and then we attack it through different ways, different mechanisms to try to figure out why this is occurring in real life. How can we alter real life and stop this from happening?As a mentor and leader in the Siolas Lab, what do you find the most rewarding when working with young people who are getting their start in GI oncology research? What advice do you have for other young professionals that want to become GI oncologists?Dr. Siolas: Our laboratory is skewed towards young people. We have two undergraduates, a medical student, two technicians who finished their bachelor’s but are not in graduate school, and a postdoc. But what’s nice about that is they come in with excitement. They want to learn. What’s most rewarding is when I challenge them, and they rise to the challenge. I just say, “Listen, we’re all going to do a poster. Everyone is going to submit a poster for presentation.”I’m like, “Okay, we’re going to have a lab meeting. We’re going to talk about what to put in a poster, what our previous posters look like. How should the figures look?” Then I have them peer review each other as well. I say, “Don’t submit this to me. You’re going to submit this to someone else first so you get the hang of it.” A lot of it is training, working one-on-one. Seeing them succeed and knowing I helped them along the way is incredibly fulfilling.In terms of advice, though, research is a hard field. I would say [to] a young person—and I get lots of applicants from young people who want to do GI oncology research—, “Plan ahead.”Don’t plan two months before the start of the summer. You need to really start looking at, thinking about things ahead of time and apply to everything. Apply to many programs because you never know which program is going to come through.My parents went to an event, and they said, “Oh, this kid is looking for a lab. Can he join your lab? You have a lab. He can join your lab.” I’m like, “Yes, but we’re full. I know that you met this nice student, and that’s great and everything, but I don’t have the time. I don’t have the capacity.” So, I actually looked up programs for him, and I said, “I want you to apply to this program and advised him about the application.”Guess what? He got into the program at Cornell for the summer, and he worked with someone else. I was just so happy that: A. he got a lab experience, which is what he wanted, [and] B. I was able to help him, even though I wasn’t able to work one on one with him because I [had] already dedicated myself to two other students.I started putting up positive motivational quotes in the lab once a week. I have this printout of all these different quotes. Some are really good. There’s this one that’s says, “Part of making a mistake is admitting you’ve done something wrong and you need to change.” Another good quote talks about how the road bends, but you need to bend with it. A lot of advice for young professionals is to be resilient, use all your contacts, and keep looking for other ways of doing things, alternative means.How can an oncologist be an advocate for their patient and why is it important? How do you approach patient advocacy in your own care?Dr. Siolas: A lot of patient advocacy means you really have to work with the patient at the level they’re coming from and then also listen. It’s hard to listen. I’m listening to 20 patients in a day. I spent 53 minutes with a patient on Monday because she had persistent nausea. We went into “out-of-the-box” reasons. What else could we do for nausea? How are you taking your medicines? The reason we spent all that time is because that is what was really impairing her quality of life. That symptom is what made her miserable every day.The other thing that I wanted to mention in terms of patient advocacy, besides listening to what the patient is actually saying, is getting help from others. A lot of times we’re so into doing the same thing over and over again. Part of being a patient advocate means you talk to your team. I had a tough-to-treat patient and a nurse suggested, “Why don’t we do palliative radiation?” [I said,] “Oh, yes, that’s a great idea.”Or you [can] discuss the patient at tumor board. You don’t necessarily only have to discuss the patient at tumor board when you don’t know what to do. Sometimes I discuss a patient at tumor board because I’m thinking, is there anything I missed? Does anybody have any other ideas of something that I didn’t try or should think about? I’m there to help people, and in order for me to help people, I need to tap into diverse ideas and that’s some of those may come from other people—and I need to listen and think about what is important to this patient.Looking at your career so far in research and GI oncology, can you describe one of the most rewarding moments you’ve experienced? Why does this stand out to you?Dr. Siolas: There have been a couple of moments that stand out. I got a 5-year grant Mentored Clinical Scientist Training Award from the NIH (K08 )to train young investigators. Nobody thought I was going to get it because at the time, at the institute I worked at, nobody had received it before. To get it on the first shot was amazing. If I didn’t get it, my life would be significantly different. I was told, you’re not going to be able to do lab work. And then I got it. Everyone was so happy!The second most rewarding moment was when I received my current position because it was during the COVID epidemic. No one was hiring. I called up places; they said, “We have a hiring freeze.” And I was like, okay, but I need to keep moving. To get a tenure track position during COVID was a pretty amazing thing. At the institute, my mentors, my non-mentors, random people I worked with, other people from other fields, were so incredibly happy to see me move on to a new spot, a new position. So, I have to say that was really a rewarding moment.With a focus on pancreatic and colon cancer, what recent advancements do you find particularly promising in the approach to treatment? What are the biggest challenges in GI oncology in the next 5 to 10 years, and how do you envision the field overcoming them?Dr. Siolas: What we need in colon cancer and pancreas cancer is new drugs. We need new out-of-the-box drugs, not the same drug that’s been tweaked a little. Because in some of these cancers, for example in colon cancer, we’re giving the same drug that we’ve given for 20 years.I am very excited to see what’s going to happen. There are some new targeted therapies focusing on that KRAS mutation. People have spent their lives, 40 years, trying to drug the KRAS mutation for pancreas cancer. To be able to get a drug that targets it after studying it for 40 years is a big deal. Let’s pretend that drug does go through, it’s not going to work for everyone. We’re going to need to put it maybe with another drug to get better effects. It’s going to really open up the field.[There are] two things that I’m concerned about. The first is we’re getting all our funding cut. I had my funding cut, and it was a grant that was approved. Five [grants] were awarded in the nation at that time, I was one of the five people. I was so proud. That’s going to stifle my productivity. It’s going to stifle our lab. That’s going to be a challenge: adapting to a new world where we’re basically strapped for cash and can’t do certain experiments or can’t hire certain expertise and so forth.But then the other challenge is [that] everyone’s really getting excited about AI [artificial intelligence]. I’m also excited about AI, but AI will not be able to replace testing things live—whether it’s a mouse, a cell, a person—because it cannot predict with 100% accuracy what’s going to happen. Sometimes a lot of science is unexpected things. There have been several Nobel Prizes that were accidental unpredictable findings. We need to keep innovating, adapting, and investing in research—because that’s the only way we’re going to make real progress.DisclosuresDr. Siolas serves on a Colon Cancer Advisory panel for Bristol Myers Squibb and is a part of a Clinical Expert Panel for Natera, Inc.

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Dr. Despina Siolas reflects on her career as a GI oncologist, her role as a mentor to young people in the field, and more. 