Research Award Spotlight: Gerardo Balderas, CCS–Pfizer Transthyretin Amyloid Cardiomyopathy (ATTR-CM) Research Trainee Award Recipient

Gerardo is a Ph.D. student at the University of Calgary, Calgary, Alberta (Hotchkiss Brain Institute and LIBIN Cardiovascular Institute). He is supervised by Dr. Scott Ryan. He has completed a bachelor’s degree in biological science and a master’s degree in chemistry and biochemistry from the University of Lethbridge, Lethbridge, Alberta. Here, he trained as a protein biochemist, where he conducted biochemical and biophysical studies of a single-domain antibody that can target an HBV G-quadruplex. During his training, he was able to mentor four undergraduate students and lead their research projects accordingly. His master’s work earned him a publication in the Journal of Medical Virology. Currently, he focuses on the study of Transthyretin protein in relation to amyloidosis cardiomyopathy. He aims to understand the key events that lead to protein unfolding and protein deposition in the cardiac extracellular matrix. His work so far has earned him the opportunity to receive the Harley N Hotchkiss Doctoral Scholarship in Neuroscience for Ph.D. students.

Read below to hear from Gerardo on his award-winning research project, Phenoconversion of TTR Monomers to Fibrils in Blood and Cardiac Tissue:

Q1: What attracted you to this area of research?

A: There are two aspects that attracted me to this area of research. The first aspect revolves around our current ability to diagnose patients and how relatively common this cardiomyopathy is. One of our main hurdles in providing effective care to patients is our shortcomings in early diagnosis; thus, patients are often diagnosed in late stages, where the effectiveness of our therapeutic approaches is compromised. Thereby, focusing on the early environment of the disease may be critical to develop new tools for early detection. Interestingly, under normal conditions, TTR protein carries out its function throughout various tissues throughout the body. Consequently, the second aspect that attracts me to this project is the desire to find out what triggers this protein to misfold and what causes it to seemingly deposit in a tissue-specific manner rather than evolve into systemic pathology. These questions are key to understanding early pathology and may hold the key to developing more effective diagnostic tools.

Q2: What stage are you at in your research?

A: I am currently entering the second year of my PhD program at the University of Calgary. In terms of the research, we are currently at the stage of using biophysical tools to characterize TTR and understand its fibrillazation kinetics and nucleation events, as well as modelling the disease using iPSC-derived cardiomyocytes and recombinant proteins.

Q3: Can you walk us through what your project entails?

A: Overall, there are three main stages in this project. One focuses on the characterization of recombinant and patient-derived TTR species. This will allow us to understand what variables may trigger TTR disassembly and nucleation. The next stage will focus on ATTR-CM modelling in iPSC-derived cardiomyocyte cultures. This will allow us to gain insight into the interaction of TTR toxic species with the cardiac extracellular matrix, thus addressing the tissue-specific nature of the disease. Lastly, I plan to adopt our findings and novel amyloid detection techniques to design early detection diagnostics. Thus, we hope to not only expand our knowledge in the current knowledge gap that exists in ATTR-CM research but also provide a tool to improve patient care.

Q4: What knowledge gap will this fill?

A: This research will shed light on the early events of ATTR-CM. Understanding the biochemistry and structural integrity of TTR will be key to understanding nucleation of the fibrillization process and the reasons behind TTR’s tissue-specific deposition. Furthermore, we will explore an alternative diagnostic approach that will exploit our findings and focus on early detection.

Q5: What does this fellowship award mean to you, personally?

A: Throughout the world, we can see varying examples of the difficulties upcoming researchers face during their formative years. These challenges are often discouraging and prevent people from adopting science as a potential career option. I have also faced some challenges in my career so far. However, securing this award not only allows me to feel more secure in pursuing a scientific career, but it also highlights the commitment of institutions like CCS and Pfizer to science and trainees. At the personal level, I am passionate about advocating for scientific literacy and for scientific communication to the public; thus, this award also allows me to demonstrate to people outside of research the potential opportunities that exist within the field. 

In addition, having the financial support allows me to consider more cutting-edge techniques and complex experiments, which opens the doors to more innovative ideas. The funding will also support my travels to conferences where I can present my work to experts in the field and gain feedback that can affect the complexity of my research.  These opportunities will also support my career goals in research and industry by facilitating connections with companies and colleagues who can use my expertise in the topic. Lastly, this award also sets me apart from other PhD students due to the prestige it holds, its peer review process, and its association with the Canadian Cardiovascular Society and Pfizer.

Q6: Tell us about your research team.

A: My research team is located at the University of Calgary, and I work under the supervision of Dr. Scott Ryan. Dr. Ryan has expertise in biochemistry, cell biology, and stem cell research and was trained at the University of Ottawa (PhD), Ottawa Hospital Research Institute (PDF), and Stanford-Burnham Prebys Research Institute. Furthermore, we work in collaboration with Dr. Nowell M. Fine (MD/PhD) and Dr. Tammy Ryan (MD/PhD), cardiologists at the Libin Cardiovascular Institute. Dr. Fine has expertise in clinical research, and Dr. Tammy Ryan will be in charge of sample acquisition from patients. Lastly, the technicians and students at the Ryan Lab are highly multidisciplinary and possess a wide range of expertise that includes biophysics, stem cell biology, neuroscience and biochemistry.