As part of the Department of Genetics' roundtable discussion series, two faculty members will share insights into their research, the inspirations behind their work, and the potential impact of their findings on the future. The discussion features assistant professors Zhangli Su, Ph.D., and Jia Xu, Ph.D. 
Can you share your research focus within the department? Specifically, how long have you been pursuing this work, and what do you hope your research will ultimately achieve?
Su: Our lab focuses on RNA modifications and their role in gene regulation and human disease. RNA modifications are prevalent on diverse RNA substrates, we are only at the beginning to understand the dynamic nature and their molecular mechanisms. I’m really excited to observe and be part of the rapid development of RNA modifications research.
Xu: Our research focuses on dissecting genetic and epigenetic regulation of signaling pathways in cancer development and progression, mainly centering on the PI3K/AKT/PTEN signaling pathway. One of the projects in our lab is integrative bioinformatics analysis and functional characterization of genetic or epigenetics transformation in the process of breast cancer development and metastasis and prostate cancer neuroendocrine differentiation. We also implement and integrate a comprehensive battery of high-throughput technologies, including genomics sequencing, transcriptome profiling, and proteomics analysis, to understand how alternative mRNA translation initiation reshapes the proteome and affects cancer development. We have a long research tracking record on PI3K/AKT/PTEN pathway in breast cancer and prostate cancer, and we hope our research will ultimately advance the understanding of breast cancer and prostate cancer development and how cancer cells respond to treatment.
What role does collaboration play in your work? Could you discuss some of the partnerships or team efforts involved in your research, along with any challenges you’ve encountered in your specific area of study?
Su: My work has involved several collaborations in the past and we are excited to engage with new collaborations here at UAB. I’m particularly excited about our participation in the Neuro-oncology program, which has fostered several new collaborations.
Xu: Collaboration plays a very important role in our work. Nowadays, only multi-disciplinary and interdisciplinary research can make breakthroughs in human health and society development. We recently discovered an interesting scientific question about discovering alternative protein translation induced by ER stress in Glioblastoma (GBM). We partnered with Dr. Yanfeng Zhang to utilize Ribo-Seq and RNA-seq data to dissect the mechanism of how ER stress induces the translation initiation for a specific tumor suppressor gene in GBM. This is our first time performing such a new experiment in our lab, and it is a challenge for both the experiment pipeline and bioinformatics analysis. Dr. Zhang in our department has experience analyzing Ribo-seq data when he was at Hudson Alpha Institute, and we are very happy to team up on this specific project.
How do you engage with the public regarding your research? What strategies do you use to make your work accessible and understandable, and how do you raise awareness about its impact on improving human health?
Su: This is a big question. We do this via publishing and sharing our research findings – nowadays it is not uncommon for scientists to post their recent research findings on social media and share the synopsis with the general public.
Xu: We mainly utilize digital platforms like social media, LinkedIn, or Lab website to share bite-sized, engaging content. Sometimes, we also accept interviews from social media, such as Onclive, Oncologytube, etc. We used to work with journalists to report research findings, meeting abstracts, and presentations accurately. Engaging with the public about our research is critical to ensuring that scientific work is both accessible and impactful. We try to use plain Language to communicate, avoid too much technical jargon, and reframe them into everyday language without losing accuracy. As breast cancer researchers, we also engage in breast cancer patients' community and join their breast cancer awareness activities, such as the Colors of Cancer 5K Run/walk hosted by O’Neal Comprehensive Cancer Center. I personally collaborate with patient advocacy to discuss research relevance and outcomes directly with those affected. These strategies aim to bridge the gap between researchers and the public, fostering a better understanding of how scientific discoveries contribute to health and well-being. We believe in effective strategies to make research understandable and to raise awareness about its contributions to human health. Engagement efforts tailored to specific audiences can maximize impact and encourage informed discussions about science in everyday life.
What inspired your interest in genetics? Can you share what initially drew you to your specific field of study and what continues to motivate you today?
Su: Chemical modifications occur naturally on almost all RNA subtypes, including rRNAs, tRNAs, mRNAs and small RNAs. They play important roles in RNA metabolism and gene regulation. RNA modifications are catalyzed by specialized enzymes - writers ("add" modifications) and erasers ("remove" modifications). Importantly, many RNA modifying enzymes have dysregulated expression in human disease, including cancers, neurodevelopmental disorders and mitochondria disorders. We are trying to understand how dysregulation of these RNA modification programs could contribute to human disease. For example, we found the writer enzyme TRMT6/61A and its enzymatic product 1-methyladenosine is up-regulated in bladder cancers and affects gene-silencing activity of small RNAs, which contributes to global gene regulation and unfolded protein response that is important for cancer cells to survive.
Xu: My inspiration is my postdoc mentor, Dr. Ramon Parsons. In the late 1990s, Dr. Parsons was an icon in the cancer genetics field because he discovered the PTEN tumor suppressor gene, a breakthrough in cancer biology. PTEN (phosphatase and tensin homolog) plays a critical role in regulating cell growth and preventing tumor formation by antagonizing the PI3K/AKT signaling pathway. It is among the highest mutated genes in multiple types of cancer. The discovery has provided foundational insights into the mechanisms underlying cancer and continues to influence therapeutic development. The discovery is unquestionably among the most important discoveries in the cancer field as it directly opened a whole research field. A search on databases like PubMed typically yields over 25,000 publications directly or indirectly related to PTEN, reflecting its importance in medical and biological research. After three decades, we are still working on the PTEN gene in various aspects, such as its genetic regulation, mutations, variations, cancer implications, and therapeutic potential. His discovery journey deeply inspired me in genetics. I wish I could follow his path to continue making more essential discoveries in genetics and make meaningful contributions to cancer diagnosis, treatment, or disease prevention. My passion for discovering great things continues to motivate me today.
How do you envision your research at UAB making a difference? Beyond contributing to our understanding of human health, how do you hope your work will lead to practical improvements in people’s lives?
Su: Short-term goals: building on our existing knowledge and methodology on small RNA modifications, understand the molecular mechanism of TRMT6/61A in GBM and bladder cancer. Expand our toolkit for site-specific manipulation of RNA modifications. Long-term goals: establish new collaborations at O’Neal Comprehensive Cancer Center with the shared objective to developing innovative strategies that target these disease-associated RNA modification factors.
Xu: I think the potential impact of our research can be profound, given its emphasis on addressing key challenges in human health through translational research. One of our interested genes is PTEN, which is mutated or lost in almost 40-60% of breast cancer and prostate cancer. In addition, PI3K/AKT/PTEN pathway mutations happen in almost 19% of all cancer patients, and it is arguably one of the most critical signaling pathways in cancer. Our research could advance a fundamental understanding of this signaling pathway. In addition, we also develop novel gene therapies, such as AAV or nanoparticles, to deliver tumor suppressor genes to tumors and inhibit tumor growth.