This time we present our chat with Gustav Smith, a clinician, group leader and former director at WCMTM in Gothenburg with an interest in translational research focusing on heart diseases. We asked about his work, how he manage to combine all the different roles he has and the successes and challenges within his field.
| You have been WCMM Clinical Researcher in Lund since 2016, but the last years you have also been the director of WCMTM in Gothenburg. How did that happen?
-Some time after becoming a WCMM Lund alumni I accepted a position as professor of cardiology in Gothenburg. I was hopeful that I would be able to bridge the two excellent cardiology research and clinical communities in Lund and Gothenburg. Later, when the previous WCMTM director in Gothenburg retired from the position, I was requested to take on the directorship, due to my background within the program I think.
| Being both a clinician, a researcher and a director, how have you manage to combine your different roles?
-Indeed, while it has been great fun to be able to combine such diverse roles it has also been demanding. I have had to make tough decisions on priorities. It would not have been possible without the excellent and understanding teams both in my research group in Lund-Gothenburg and at the WCMTM.
| How would you describe your research?
-My research has focused on omics tools, particularly genomics and transcriptomics but also proteomics and metabolomics, as unbiased tools to systematically dissect etiopathological mechanisms underlying the major heart diseases. While our work over the years to a large extent have confirmed the role of many established disease pathways, we have also identified both new pathways and molecules in traditional pathways which may prove to be more effective targets. As an example, inflammatory mechanisms in the heart muscle have long been known to contribute to heart failure, but drugs that broadly reduce immune functions such as glucocorticoids are problematic in this patient group and drugs targeting traditional systemic cytokines such as TNF alpha have been unsuccessful in clinical trials.
Our recent work on genetics of heart failure outcomes has pointed to a group of paracrine cytokines including TSLP which may be more effective and feasible targets. Another example is our unexpected finding ten years ago in genetic studies that lipoprotein (a) causes calcific aortic valve stenosis which has resulted in now ongoing phase III trials of lipoprotein (b) lowering treatments to prevent and treat this common condition which currently lacks medical treatment.
| How did you get into your field?
-My interest was initially in the methods rather than the specific disease area. As a medical student I became excited about the sequencing of the first human genome, and how it offered opportunities for systematic and unbiased dissection of human disease biology. I had the fantastic opportunity to take a pause from my medical studies and work as visiting student at MIT, in the team where much of the work on the human genome sequencing was conducted, with several of the first genome-wide association studies (GWAS) of human traits. Coming back to Sweden, I continued genetic studies in PhD work focused on application to heart disease, which I perceived as the major public health issue, in the large population cohorts from Malmö.
Another factor that attracted me to the cardiovascular field were the many great role models and genuinely nice persons that I encountered in this field during medical school and clinical rotations.
| What is the biggest challenge in your field?
-A major challenge which we have struggled with over the years has been to translate findings of genome-wide association studies (GWAS) loci to specific genes and insights in disease biology. However, with the development of gene editing methods and different methods for comprehensive RNA analysis we now have many tools in place and are making substantial progress.
| What are you most proud of?
-There were initially many opponents to the concept that common disease could be caused by genetic variants of individually small effect, but we can now say for certain that hundreds to thousands of common genetic variants collectively explain most of the heritability for common diseases, and that it takes exceptionally large cohorts to robustly identify such variants. For the major heart diseases, we have identified >750 loci, in international collaborative meta-analyses including millions of genotyped subjects, which we now dig into with functional genomic studies.
| Would you consider your research translational?
-I consider my research highly translational in the sense that it moves back and forth between the clinic and the lab. I draw many of my research questions and ideas from my clinical work with cardiomyopathy and heart failure patients and collect heart samples from the clinic both in Lund and Gothenburg. We bring these questions and samples into the lab, where we combine molecular and bioinformatic tools, and then try to bring new insights back to the clinic for patient benefits through prospective studies and clinical trials.
| Do you collaborate with other WCMM Fellows/researchers in Lund or other centres?
-Yes, I collaborate with several fellows in both Lund and Gothenburg. For example, I am currently actively in planning of a clinical trial to improve heart failure outcomes with Martin Magnusson in Malmö and conduct studies of heart tissue genomics in collaboration with Joan Camuñas-Soler and Abhishek Niroula in Gothenburg.
