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Q&A with Daniel Bondeson

Tell us a bit about yourself. Where did you grow-up? Where did you go to school? 

I grew up in Central Wisconsin, in a small city called Stevens Point with my parents and two older brothers. My parents both taught at the University of Wisconsin - Stevens Point (UWSP) for most of their careers: My dad was a Professor in the Chemistry department who moved into administration and my mom taught in and managed the English as a Second Language program. So I grew up in a university family, with the rhythms of departmental picnics and the academic year engrained early.

For my undergraduate education, I stayed local and went to UWSP to study chemistry. My initial vision was to pursue medical training: I knew that I liked science and that I wanted to help people. However, during my first semester I connected with Professor Nate Bowling who was looking for students to join his organic chemistry research lab. In that meeting, he told me  “I have molecules in my fridge that have never existed before.” For me, that was mind-blowing. I was immediately hooked on research and wanted to be at the ‘cutting edge’ of innovation and discovery.

During my undergraduate career, I was a bit disinterested in biology. It felt too “big” and disconnected from the beauty and simplicity of molecules and their reactions. But during my final summer, I decided to pursue a research experience  at the Mayo Clinic, where I was in Professor Michael Romero’s physiology lab, studying how transporter proteins move solutes in and out of cells: specifically, we were investigating oxalate, the main component of most kidney stones. Our thought was that if we understood how these proteins worked, we could better understand, prevent, or even treat kidney stones. In the Romero lab, I found the missing piece for my career: connecting the movement of molecules with human disease. 

From the Midwest, I moved to Yale University to pursue my PhD in the Molecular Biochemistry and Biophysics department and joined Professor Craig Crews’ lab for my thesis work. Continuing the theme of integrating chemistry with biology, in his lab I helped develop drug-like molecules that can reprogram cellular quality control to degrade disease-relevant proteins. This approach has profound therapeutic applications, but I was always fascinated by how a simple small molecule can radically affect protein function, even engendering new functions. 

After my PhD, I felt that I had developed good ‘chemistry’ intuitions, but I needed a better biological intuition in order to pursue the right biomedical research questions that would really make a difference to our understanding of biology, and help patients suffering from disease. I joined Professor Todd Golub’s lab at the Broad Institute, where I was interested in efforts to use large-scale functional genomic approaches to systematically identify new ways of killing cancer. In collaboration with the Dependency Map team, we found that ovarian cancer has a unique relationship with inorganic phosphate. For some reason, these cancers dramatically increase their import of phosphate, which we can take advantage of by inhibiting their phosphate export: this causes a cancer-specific toxic accumulation of phosphate. For me, this project was the perfect integration of my training: studying and manipulating the movement and interaction of molecules in an important disease-relevant setting with the potential for helping patients clearly in view.

What will your new lab study both broad and specific?

The initial focus of the lab is continuing to study phosphate homeostasis in cancer. The studies I’ve recently published have opened far more doors for inquiry than they have closed, and I am fascinated by the mechanisms that cells use to modulate nutrient availability to match their demands. In addition, we will study how these processes are adapted by cancer to promote tumorigenesis, and how we can, in turn, modulate those processes to treat those cancers. For phosphate specifically, I have examples of cancers that appear to increase their phosphate demands (like ovarian cancer) and others that appear to decrease their phosphate demands. My hope is that these initial questions will help us develop experimental and conceptual frameworks that can then be applied to study other nutrients.

What technologies do you apply to your research?

As with most systems, it’s often easiest to learn about biology by figuring out all of the ways to break the system that you’re studying. Building off my PhD work, we think about using targeted protein degradation and other chemical biology tricks for perturbing and altering protein function. We also use a lot of functional genomic approaches to profile either the entire genome (CRISPR/Cas9), characterize redundancy within specific pathways (CRISPR/Cas12), or characterize all of the structural features of a given protein (CRISPR-base editing). We also like to get as much information as possible out of these experiments: not just whether a cancer cell is dying or not, but what pathways and cellular programs are being turned on and off (e.g. Perturb-Seq or CITE-seq). 

What types of projects interest you?

I think good projects lie at the intersection of several features. First, the research question needs to be important: either in revealing a fundamental area of biology that remains hidden to us, or in the potential to impact human health in some way. “Importance” might seem obvious, but it’s a hard concept to pin down. Second, we need to be able to contribute something new and unique to that question.  It wouldn’t be exciting if all we could do is re-discover what is already known. But with new technologies, mindsets, or approaches, what areas of biology are now accessible to our inquiry? And third, the project has to be a good fit for the people involved in it. Some of the most fun I’ve had in doing science is when the right people come up with the right idea and have the right skills and bandwidth to pursue it. When all of these things are met, the scientific process is still hard – grueling at times – but also a joyful exploration.

What attracted you to the Department of Systems Biology?

When you look at the research being conducted within the department, you don’t find a common set of experimental techniques, or a common disease or biological setting, but you find a shared mindset: Biology is based on simple principles, but when integrated together into what we observe as “Life,” things get beautifully complex. And to truly understand this complexity and beauty, the effort to move past simplistic models and towards a ‘systems-level’ understanding is well worth it.

I’m also really excited about the culture and people of the department. When I interviewed, I met a group of scientists – students, postdocs, and faculty – that were excited to learn about my research, ask questions, and offer suggestions.  The culture feels more like a family than a workplace, which makes research so much more enjoyable and as I’ve experienced, more productive.  

What are you looking forward to as you begin your own lab?

As I was thinking about my career and where I could best pursue my research goals, I realized that there are a lot of places where good science is happening in today’s world. The academy, government, large pharma, biotech.  But a unique feature of the academy, and especially biomedical research, is the special relationships that form within the lab: both between me and my mentees and between lab members. I am most excited about creating and leading a nurturing, creative, and passionate research environment. Every decision – from the type of fridges in the lab to who we hire – will be aimed at creating that type of environment.  

What do you like to do outside of work?

I currently live in Newton with my wife, Gentley. When I’m not at UMass Chan, you’ll almost always find us together on some sort of adventure. We love being active and exploring the outdoors. We recently spent a week camping in Acadia, biking along the carriage trails, and hiking some of the iron-rung routes. There’s something about being outside and embracing the unpredictably of weather and the natural rhythms of the sun, that reminds us of our humble place in this world. Closer to home, the natural rhythms of our lives also revolve around rich friendships. Whether sharing dinner with close friends or enjoying our church community, we frequently experience how deep relationships have a profound capacity to shape us into the kind of people we want to be.

These rhythms of connection and fun will also be important for my lab: on the short list are pursuing volunteer activities in Worcester, visiting local artist studios, and hopefully hiking Mount Wachusett together!