Meet a Whitehead Postdoc: Anushka Dongre

Anushka Dongre is a postdoc in Whitehead Institute Member Robert (Bob) Weinberg’s lab investigating how cancers spread and how the body’s own immune system can be used to fight them. We sat down with Dongre to learn more about her and her experiences in and out of the lab.

What are you investigating?

In Bob's lab, we study metastasis, which is when a cancer that starts out localized in one tissue, like the breast, spreads to other parts of the body. More specifically, we study how cancer cells become metastatic through a process called the epithelial-to-mesenchymal transition (EMT). During this process, epithelial cells, which are one of the basic cell types in our bodies, including in the breast, change from cobblestone- to spindle-shaped and take on stem-cell like properties, after which they can leave the primary tumor to disseminate to other parts of the body. The spindle-shaped cells that arise after activating the EMT program, called mesenchymal cells, are very difficult to treat and are resistant to most chemotherapies and drugs.

What I'm interested in is understanding how these epithelial and mesenchymal cancer cells interact with the patient’s immune response—the body’s natural approach for protecting itself from threats. I look at breast cancer cells that either have or have not activated this EMT program, and ask how their EMT profile influences the immune response to the tumors made by these cells. This is important because the field of immunotherapy is currently centered around exploring strategies that can take the foot off the brakes of the body’s own immune system to fight cancer. But I don't think that engaging the immune response is sufficient, on its own, to eliminate tumors, because different types of cancer cells within the same tumor can have different interactions with the immune response. What I've found is that cells that have gone through the EMT tend to be resistant to immunotherapies—specifically a type called checkpoint blockade immunotherapy, which targets different molecules that can regulate the immune response. Breast cancer cells that remain epithelial are vulnerable to attack in response to checkpoint immunotherapy whereas cells that have gone through the EMT and become more mesenchymal are quite resistant to elimination by immunotherapy. My work now is focused on understanding why we see this profound difference in vulnerability and identifying ways to sensitize mesenchymal carcinomas to checkpoint blockade immunotherapy.

One big problem in the clinic at present is that we often can't predict how a person is going to respond to immunotherapy. The side effects of these treatments are very serious, potentially deadly, so we really need to understand how to screen patients better to determine in advance whether they are likely to benefit from a given type of immunotherapy. I hope to improve prediction of breast tumors’ responses to immunotherapy, using both indicators of epithelial or mesenchymal cancer cells as well as a set of other indicators called immune markers to provide insight into the state of the immune response to checkpoint therapy.

What has been your experience of working in the Weinberg lab?

It's great. I have benefited greatly from Bob’s style of mentorship, and his lab provides very valuable training towards becoming an independent investigator. We get a lot of freedom to explore our research interests. They have to be related to the overall interests of the lab, but we get the opportunity to explore our own research agendas. I really value that creative freedom, as not many postdocs get this kind of training and I think it's helped me grow as a scientist. We have weekly journal clubs, lab meetings and discussions, so we are well versed with the literature outside of our own immediate areas of interest. The Weinberg lab is also a very diverse lab. You meet people from different parts of the world. We do a lot of things together as a group; there's the annual lab beach day, the lab picnic in the summer, and a hike at Bob’s cabin in New Hampshire. It’s a well-integrated lab and a great collaborative environment.

What did you want to be as a kid?

I had no idea. I just knew that I wanted to do something where I could explore my curiosity and creativity. I was a very curious kid and I asked a lot of questions. I think that's why being in science research ended up being the best fit, because you need curiosity to ask the right kind of questions and you need creativity to find the best way to address them. We use those skills every day.

 How did you end up at Whitehead Institute?

I always liked biology in school. In India, where I'm originally from, there's a big expectation to go to medical school if you are good at biology, or engineering if you are good at math. I considered being an MD, but I didn't find that exciting; I wanted to do something where I could question why things work the way they do. I decided to get a BS instead of pursuing medicine, so I could really understand the fundamentals in biology. Then, while I was doing my master's, the head of my department sent me to a research institute called the Tata Institute of Fundamental Research (TIFR) to complete my thesis—since in India most schools don't have labs associated with the educational institute the way the United States (U.S.). does. So, the TIFR is this renowned research center, and after working there I really realized that this is exactly what I wanted to do. I saw and learned from other people who were very passionate about what they were doing and motivated by the thrill of discovery. I was interested in the work of a scientist from the U.S., Barbara Osborne, and so I decided to apply to grad school at UMass Amherst, where I trained with her. That's where I got to further explore my interest in immunology and understand T-cell signaling, and towards the end of my PhD I knew I wanted to apply immunology in the setting of disease. That's what made me apply to Bob’s lab, where I can explore the immunological aspects of cancer.

What’s the biggest disaster you’ve ever had in the lab?

 What comes to mind wasn’t really a disaster, but it was a very stressful situation. This was in grad school. I started doing a very big experiment early in the morning, and I was using this machine called a flow cytometer that was in the basement of the lab building. The rule of the department was that the last person using the flow cytometer has to turn it off; you cannot leave it on overnight. I finished my work and went home, and it had been a long day so I was very tired by the time I got home. Around eleven at night, I was going over what I needed to do for the next day, and suddenly I realized that I was the last person on the flow cytometer but I just couldn't remember if I had turned off the machine. I was a poor grad student, I did not have a car, and it was late, but I didn’t want an email being circulated saying I was the one who left it on, so I actually called a taxi and went back to the lab at midnight. I walked down to the basement, and the machine was, in fact, already off. Even now, when I use a machine and I'm the last user, I make a deliberate mental note that I turned it off, so I won’t have to worry later. 

What are your hobbies outside of work?

I have a two-and-a-half-year-old son, and I like to spend time with him and watch him grow. I like to hang out at the park with him these days. He is already a very curious person; it's sort of amusing how my husband and I can see personality traits that we have in him. He talks a lot for his age and asks a lot of questions. “Mama, what is this?” Or “What does this do?” His big interests right now are busses and excavators.

I also play the piano and I like to paint. I do water and acrylic, and I like to do paint by numbers pieces to relax. I use a rubric with numbers and instructions that tell you which color goes in which number, so it's a little bit of a guided approach. I find that to be a calming, stress releasing activity. I don’t get to indulge in those hobbies very often though. Pretty much all of my time outside of the lab is with my son.

Do you collect anything?

My refrigerator is covered with magnets that I collect from the different places that I visit. Two of my favorite trips memorialized on the fridge are to Athens, which was very beautiful, and Lugano. Lugano is a small town in Switzerland bordering the Italian side, and it's very different from other parts of Switzerland that are closer to the German or the French border. It's a very small, pretty town with great food. We didn't go to Italy, but we felt like we were there even though we were in Switzerland.

Where do you see yourself in ten years?

I want to be an independent investigator and have my own lab. I got my PhD in Immunology in Barbara’s lab, and I did cancer biology in Bob's lab, so I'm hoping to use both backgrounds to integrate these two ideas of the EMT and the immune response, and translate this to patients to improve our ability to predict their responses to checkpoint immunotherapy. I’d also like to keep mentoring students—I’ve been mentoring students since grad school. I’d like to take the lessons that I've learned from both Bob's and Barbara’s labs, their style of mentoring, and use that to help other students become better scientists.