From a Postdoc’s Perspective: Dr. Brian Aguado
"I believe that biomaterials scientists will have to synergize with systems biologists to develop more effective therapies as a function of a patient's unique biology."
I'm Brian Aguado, and this is why I research.
Dr. Brian Aguado is currently an NIH and Burroughs Wellcome Fund postdoctoral fellow at the University of Colorado in the laboratory of Prof. Kristi Anseth. His current research is focused on developing precision biomaterials for applications in personalized medicine. Guided by his interest in biomaterials and their potential therapeutic applications, Dr. Aguado is developing innovative biomaterials to evaluate how diseases such as cancer metastasis and organ fibrosis can vary from patient to patient.
Could you elaborate on experiences that helped spark your interest in science?
My parents, first and foremost, created a fun and engaging environment during my childhood that naturally guided me to science, math, and engineering. My earliest memories were putting together a fun-looking multiplication table booklet with my dad and playing Legos with my mom. I also remember being obsessed with the Human Body Atlas we had at home, looking at illustrations about different organ systems with amazement. My parents also set up lots of activities at home from do-it-yourself science project books, where we made traditional volcanoes with baking soda and vinegar, which made science fun.
I also had influential experiences with my high school anatomy teacher, who always knew of my interests in engineering and medicine. He pointed me to a Scientific American article about Biomaterials and Tissue Engineering, where I learned about engineers creating tissues and organs using cells and materials as building blocks. After reading about those concepts, I immediately knew the kind of work and research I wanted to do in my life and haven't looked back since that moment.
Would you say that a specific mentor inspired you to become a scientist or had a significant influence in your path in science?
Collectively, I hit the jackpot with my research mentors. I have been fortunate to have multiple unconditionally supportive mentors throughout my career – I have close relationships with my mentors and they have influenced me in numerous ways. I credit my first undergraduate mentor, Sarah Heilshorn, for sparking my initial zeal for research and supporting me during my first independent research project. She encouraged me to attend graduate school and helped me navigate the graduate school application process. My PhD mentor, Lonnie Shea, encouraged me to step out of my comfort zone during graduate school and taught me the value of pursuing cross-disciplinary research. His passion for science, patience, guidance, and constructive criticism pushed me forward, and he promoted a lab environment where we all worked as a team – we dubbed ourselves Team Tumor. My current postdoctoral mentor, Kristi Anseth, has provided me with a blank slate in the laboratory to craft my own ideas for my future laboratory and encourages me to pursue my outreach efforts. My supportive mentors have given me a fantastic model to mentor future PhD students in my laboratory, and I hope to serve as a good role model for future scientists.
Give us your elevator pitch. Why your research is important to the ordinary citizen?
The “one size fits all” approach to medicine is becoming increasingly outdated, as disease progression and response to treatments can vary from patient to patient depending on sex, ancestry, and age. To meet the increasing demand for individualized precision medicine, new biological and drug products will need customized delivery systems to deliver therapies to patients. I have become very interested in the development of “precision biomaterials” – implantable material systems that can deliver personalized therapies to patients, or enable the more effective detection/treatment of disease via materials with the appropriate chemistries that can synergize with an individual patient’s biology. Through the design of innovative precision biomaterials, I hope to elucidate strategies on how to treat diseases that vary from patient to patient more effectively, including cancer metastasis or organ fibrosis.
What advice would you give to other postdocs on how to efficiently use resources in their institutions to identify and pursue funding opportunities?
Take ample time (2-3 months) to (i) identify a critical research question, (ii) orient yourself within your new institution, and (iii) start building connections with colleagues. First, coming up with a provocative research question during your postdoc position is challenging and takes time. Give yourself the time to immerse yourself in literature and consult with mentors to understand the research problem to the best of your ability. I also attended grant writing workshops hosted by my Office of Postdoctoral Affairs, which gave me important insights for crafting a strong research proposal. Second, I familiarized myself with the equipment available at my institution. The research you accomplish during your postdoc position will depend entirely on the equipment and resources that are available to you. Learn about different resources from core facility managers while you are crafting your research question – core managers will be able to write letters of support for your application. Last but certainly not least, make connections with friends and colleagues during happy hours and socials organized by your university postdoc association. Often, you will find a colleague in a similar field that has been awarded a fellowship, and will be willing to share their application so you can learn from successful examples when writing up your own proposal.
You are actively involved in science communication activities (e.g., writing research blogs, science-blogs for the general audience and initiatives aimed at promoting science interest in the young). What unforeseen benefits to your career development may be attributed to these activities?
I have benefited greatly from my dedicated efforts in science communication, both professionally and personally. Professionally, I have been invited to give lectures and workshops on science communication as a direct result from my synergistic activities. On a personal level, I trained myself to distill my scientific message to anyone, including my family. Through effective science communication, I have been able to communicate the importance of my efforts and make myself and my science more personable and engaging.
Project Bridge Colorado aims at “connecting science and community”. What are some of your key goals as a representative of this organization?
Among several of our goals, Project Bridge Colorado seeks to forge key connections with our state legislators to help promote evidence-based policy, which I believe makes our organization especially unique. I have had valuable conversations with legislators from both sides of the aisle to learn more about how scientists can get involved in drafting policies and bills. I believe this form of activism to be especially productive, because as scientists, we can use our research skills to disseminate our findings in a way that can positively impact the lives of citizens in our communities.
You have recently developed systems-biology based strategies to identify critical mechanisms that promote metastasis progression. Do you think that this type of approach could eventually help develop tools for a more personalized management of metastatic cancers?
Absolutely – I believe that biomaterials scientists will have to synergize with systems biologists to develop more effective therapies as a function of a patient’s unique biology. High-throughput evaluation of multiple variables necessitates a systems-based approach for analyzing data, and the design of an implantable biomaterial that can help treat a patient’s symptoms depends on how the data are analyzed and interpreted.
In the recent AACR Conference (2018), your poster focused on how synthetic scaffolds used as pre-metastatic niches reduce tumor burden in animal models of breast cancer. Could you highlight some of the mechanisms underlying this effect?
We have designed implantable materials that can recapitulate critical aspects of the pre-metastatic niche, such as the recruitment of myeloid derived suppressor cells (MDSCs) to the implant that precedes the arrival of disseminating tumor cells. Interestingly, using an orthotopic murine model of metastatic breast cancer, we have shown the implant reduces the overall burden of MDSCs and disseminating tumor cells. We posit the implant serves as a “sink” to trap the MDSCs and tumor cells, and also systemically modulate immune cells at the primary tumor to create an invasion-suppressive phenotype.
Select Publications by Dr. Brian Aguado:
Aguado BA, Dudek RM, Bushnell GG, Decker JT, Azarin SM, Nanavati D, Schipma MJ, Rao SS, Oakes RS, Zhang Y, Jeruss JS, Shea LD. Biomaterial scaffolds as pre-metastatic niche mimics systemically alter the primary tumor and tumor microenvironment. Advanced Healthcare Materials. 2018; 7(10), e1700903. PMID: 29521008.
Aguado BA, Grim JC, Rosales AM, Watson-Capps JJ, Anseth KS. Engineering precision biomaterials for personalized medicine. Science Translational Medicine. 2018; 10(424), pii: eaam8645. PMID:29343626.
Pena B, Bosi S, Aguado BA, Borin D, Martinelli V, Jeong M, Taylor MRG, Long CS, Shandas R, Sbaizero O, Prato M, Anseth KS, Park D, Mestroni L. Injectable carbon nanotube-functionalized reverse thermal gel promotes cardiomyocyte survival and maturation. ACS Applied Materials and Interfaces. 2017; 9(37), 31645-31656. PMID: 28895403.
Aguado BA, Bushnell GG, Rao SS, Jeruss JS, Shea LD. Engineering the pre-metastatic niche. Nature Biomedical Engineering. 2017; 1, 0077. PMID: 28989814.
Rao SS, Azarin SM, Spicer G, Bushnell GG, Aguado BA, Stoehr JR, Jiang EJ, Backman V, Shea LD, and Jeruss JS. Enhanced survival with implantable scaffolds that capture metastatic breast cancer cells in vivo. Cancer Research. 2016; 76(18), 5209-5218. PMID: 27635043.
Aguado BA, Caffe JR, Rao SS, Bushnell GG, Azarin SM, and Shea LD. Extracellular matrix mediators of metastatic cell colonization identified using scaffold mimics of the pre-metastatic niche. Acta Biomaterialia. 2016; 33, 13-24. PMID: 26844426.
Dubash AD, Kam CY, Aguado BA, Patel D, Delmar M, Shea LD, Green KJ. Plakophilin-2 loss promotes TGF-β1/p38 MAPK-dependent fibrotic gene expression in cardiomyocytes. Journal of Cell Biology. 2016; 15, 212(4), 425-438. PMID: 26858265.