The following is the sixth entry in a Q&A series highlighting selected Clinical Proteomic Tumor Analysis Consortium (CPTAC) researchers and their work. Join us as we discuss bioinformatics, proteogenomics, and research ethics with Fernanda Martins Rodrigues, PhD, a post-doctoral research associate at the Washington University School of Medicine, St. Louis. Transcript is edited for clarity.
Please provide a brief overview of your academic professional journey to the present.
Fernanda Martins Rodrigues: I am originally from Brazil, Southern Brazil, a city called Pelotas--that's where I started my journey. While I was still an undergraduate student in Biotechnology at Federal University of Pelotas I was awarded a scholarship to come to the US to do research, specifically a transgenic pig model for cancer research. That opportunity opened doors for me to later on enter graduate school in the US. First I [completed] a master's degree in bioinformatics, with an emphasis on animal sciences. I worked on a project with beef cattle back then, which had nothing to do with cancer research or what I do now, but that experience exposed me for the first time to bioinformatics, computational biology, and the field of data analysis. After obtaining my masters’ degree, I then came to Washington University in Saint Louis for my PhD in Molecular Genetics and Genomics, where I got back into the field of cancer research and oncology. It was during my doctoral studies that joined Dr. Li Ding’s lab , with whom I still work today as a postodoctoral research associate. Most of my work today involves consortia projects such as CPTAC and focuses more on understudied populations, including individuals of African ancestry. That's really what drives me nowadays.
As someone who has studied other specialties before arriving where you are today, has cancer research always been your goal?
FMR: I went into cancer research because, like a lot of people in our field I have people important to my heart that went through the disease. I lost an aunt to colorectal cancer at a very young age. My dad had prostate cancer. My grandma had breast cancer. It's all over my family and it's something that has always driven me. I think being Brazilian, being Latina, and trying to help communities that have not been looked at in detail [means a lot to me]. Most of what we know [in medicine] is based on people of European ancestry, so trying to look at communities that have been neglected in the research world up until now is something that will always drive me.
Please describe a project that you are proud to have contributed to and why.
FMR: I can talk a little bit about two projects. One, of course, is the work I did for CPTAC while I was still a graduate student, where we looked into germline predisposition variants across ten cancer types, but in a way that we hadn’t done before. Previously, with TCGA, for example, our group investigated rare germline variants in cancer and how they modulate disease predisposition, looking at their impact on gene expression and some proteome information. With CPTAC, however, we introduced the concept of personalized proteogenomics, where we looked at the impact of common and rare germline variants into the proteome and post-translational modification sites in a way that we hadn’t been able to do before. Thanks to our colleagues at the Broad Institute, we were able to use germline variants to help us identify, for example, phosphorylation sites that are being disrupted by germline variants, “deleted”, or even “created” by the presence of these variants and how the disruption of these sites may impact protein function, structure, downstream pathways, and consequently disease development, progression, and so on. This was the first time I contributed to and managed a project part of such a big consortia. It was such an amazing learning experience to work with so many people from so many different institutions and backgrounds, and quite honestly, way more experienced than me. Getting that kind of expert feedback is so valuable for an early career scientist. I am very grateful for that opportunity and hopeful for this manuscript to be available for everyone to see very soon.
Another project that I am proud of to be a part of is the Participant Engagement – Cancer Genome Sequencing (PE-CGS) network, which I have been helping currently as a postdoc. This is a very translational project, where the goal is to analyze patients’ raw sequencing data, which includes whole exome sequencing, RNA-Sequencing, and other datasets, and build a clinical report that is then reported back to the patients with the help of clinicians and genetic counselors. The network is mainly focused on understanding cancer in populations that have been understudied. Here at the WashU center, for example, we are recruiting individuals of African ancestry with multiple myeloma, colorectal cancer, or cholangiocarcinoma. It's the first time that I'm working on something that has a direct effect on patient care, with the help of genetic counselors that work on site. It is very exciting to contribute to that, but also to know that this data is available to us researchers to discover more, research more on these underserved communities, and hopefully, come up with better prevention and treatment strategies for them. For example, another center part of the same project focuses on indigenous communities in New Mexico. It is very impactful work for communities that have been overlooked for so long. [The patients] are learning more about their genetic makeup and can make informed decisions with their doctors. This is something that is really impactful and it reminds you that you're working with real people suffering from a real disease.
Please elaborate more on the impact of working with researchers with different histories/backgrounds from different consortiums and within your institution.
FMR: When you're working on your project within your own lab, people can start thinking alike. When you work with people from different institutions that have different expertise, it helps you think outside of the box, you know, gets you out of your bubble a little bit. For example, [at WashU] we analyze a lot of proteomics data, but we don't generate it. We're not experts on that part of the process and we need people from, for example, the Broad Institute or other institutions to generate that data for us and guide us through the analysis… especially in precision medicine, you really need the work as a team to be as accurate and precise as possible. That is what makes CPTAC and other consortiums so valuable, because you have people from so many different backgrounds coming in and giving you feedback on your work.
What are barriers in your field or unmet needs that you feel might be addressed during your career or potentially by the next generation of scientists?
FMR: I think the field of genetics, genomics, and cancer research in general is slowly moving towards looking more deeply into [underserved] communities in a more personalized, specific manner. For example, I mentioned that we're recruiting individuals of African ancestry here at WashU for one of our projects, which is something that we haven’t done before.
There are studies here and there that focus on a specific African population or a specific indigenous population, but it's never been done in such a large scale.
[Moreover] we just don't have a reference genome that is diverse enough, right? It has been tried, like the recent release of the pangenome which is an awesome step towards that, but I feel there's still a lot of improvements to be made before it as good as the existing, mostly white, reference.
Another point is that When you we are talking about an underserved population or people that have been neglected historically for generations and generations, it is really hard to convince them [to participate]. We can’t just say “hey, give me your sample, we're going to do some research”—[members of underserved populations] are not necessarily going to trust you. There is systemic prejudice and discrimination that happens within the health system so, as we move forward, scientists need to understand this. There's a need for ethical training, how to best communicate with people from these communities in a way that they feel cared for and respected—how best to communicate [the importance of] your science. I think we're making progress, but we're not there yet and I hope that we get there sometime soon.
If a student came up to you and asked you, “how do I get to where you are right now?” what would you tell them?
FMR: I would tell them to explore as much as you can. If you have the drive to do a PhD, do a postdoc, work on research, become a professor… I don't have to tell you to work hard, right? You already have the drive. I think a lot of people, especially in science, get so into the technical details that we forget about what's happening around the world. I think what makes a good scientist is not only knowing how to do the science, but also knowing the impact of their study… [someone who] understands the environmental and social factors that could impact their analysis.
Your phenotype is a mixture of your genetic makeup and your environment, so you need to understand the environment. You need to understand why we are studying this particular population. So be aware of everything that is going on beyond just the science itself.
I also think that, when I say explore, [you should] explore everything that you can in terms of what's going on in other fields. I think other fields have a lot to teach each other, right? Technologies that are being used for one thing can be used for something else and knowledge can be shared. This exchange is what really sets some projects apart and generates new ideas.