As part of the Department of Genetics’ series of roundtable discussions, two faculty members are taking time out of their schedules to discuss their particular areas of research, their inspirations for the work that they do, and how they hope their research will impact the future. Our first discussion is between assistant professors Chen Huang, Ph.D., and Bo-Kuan Wu, Ph.D.
Can you discuss your areas of research within the department, how long you have been doing it, and what do you hope your research leads to?
Wu: I have been at UAB for nearly one year. Currently, I’m working on using mouse genetics as the model to focus on studying the liver. In analyzing hepatocyte proliferation, I have observed that the liver can become enlarged via cell proliferation, which is called hepatomegaly. Such phenomena can affect the size of organs and potentially form tumors. I’m currently using Hippo-YAP, which is a signaling pathway that is used to control cell proliferation. I want to study the mechanism of how Hippo-YAP’s signals cause cell proliferation (especially as it is linked to DNA methylation). I’m also aiming to understand how transcription factors and co-factors are involved in determining the target genes.
Huang: I joined UAB in September 2022 as an assistant professor, and my lab is a computational dry lab where we primarily focus on developing and applying cutting-edge computational approaches or algorithms to study tumors systematically. Tumors are very complex diseases and are incredibly heterogeneous across different patient populations. For example, you can have two patients with breast cancer, but the molecular etiologies can be very different. To dissect the underlying biology and identify effective therapeutic targets for individual patients, high-throughput omics techniques have been used to profile the tumor molecular landscape comprehensively over the past several decades. The current technical challenge is to optimize the use of large multi-omics data. Our lab is focused on developing novel computational tools to maximize the power of such omics data by collaborating with the local research community at UAB, as well as nationwide.
Can you talk about some of the collaborative efforts that have gone into your research and the challenges that you may have run across in your particular area of work?
Wu: I currently do not have collaborations with other labs, but I am looking forward to establishing new collaborations. The most challenging aspect of my research is understanding the mechanisms of the Hippo-YAP signaling pathway, as different combinations can drive the mechanisms. Within different organs or cells, there may be different downstream targets, and the challenge is identifying the particular cell or organ you want to study that is more representative of the overall mechanism.
How do you make the public aware of the efforts that you're making to improve human health? What does that process look like for providing awareness to the public in an easily understood way?
Huang: My research focuses on translating large omics data into biological and clinical insights. In recent years, our understanding of complex diseases has been driven by large-scale omics data. Over time, we have come to understand that the molecular mechanisms of complex diseases such as cancer are more complicated than we initially realized. The advancement of high throughput technologies such as next-generation sequencing and mass spectrometry-based proteomics allows us to perform molecular profiling at a more efficient rate. These advancements have created larger data profiles and provided a more comprehensive understanding of the research being conducted.
Wu: I believe that the most interesting part of my studies is analyzing the causes of mouse phenotypes and understanding how they can be used to study human health. My studies can show people the changes in liver size through Hippo-YAP pathway modulation. If a person is suffering from liver disease, my pathway allows people to see the actual change in liver size, making it very easy for people to visualize and understand the results of this study. As YAP activation is also observed in many liver diseases, understanding such regulatory machinery may provide a new therapeutic potential.
What was the inspiration for you to get into your selected field of study within genetics?
Huang: I am fascinated by how the biological system runs and how data science can improve our understanding of the complex biological system. I have been interested in both biology and mathematics ever since my undergraduate studies. Traditionally, people may have considered biology a purely experimental science and thought that data science or math was not important in biology. However, with the advent of new biological and biomedical fields such as electronic health data and multi-omics studies, the application of data science techniques has become essential.
Wu: For me, the reason is that I like to do experiments with a very simple question or hypothesis, and it allows you to determine whether your hypothesis is right or wrong. Based on your observations through your studies, it allows you to acquire more evidence as it relates to your hypothesis and results, to better understand the connection between them.
How do you hope that your research efforts here at UAB will not only provide a better understanding of human health but also contribute to improving it?
Huang: I hope that my research can help people utilize biomedical data in a better way and interpret data-driven results more reasonably. I hope my research can help clinicians better understand patient cohorts and provide biologists with a data-driven knowledge source to guide their mechanistic studies. In the long term, I hope that my data-driven studies can deliver findings that serve as diagnostic biomarkers and therapeutic targets, with the potential to be developed into clinical or pharmaceutical products.
Wu: I’m really interested in the process of organ size control, particularly in the liver. I believe that using different ways to activate hepatocyte proliferation and hepatomegaly will allow us to better understand the mechanism. Ultimately, I would like to use a therapeutic approach to control the size of organs that will assist a patient who is suffering from either liver disease or deficiency.