Ralf Weiskirchen1, Jin Ye Yeo2
1Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC) at the RWTH University Hospital Aachen, Aachen, Germany; 2ATM Editorial Office, AME Publishing Company
Correspondence to: Jin Ye Yeo. ATM Editorial Office, AME Publishing Company. Email: editor@atmjournal.org
Expert introduction
Prof. Ralf Weiskirchen (Figure 1) is currently the head of the Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC) in Aachen. His primary research focus is analysing the molecular mechanisms underlying the pathogenesis of hepatic fibrosis. In the past, he has extensively studied general aspects of cytokine and chemokine activities, as well as their signalling pathways. He has also established novel biomarkers and predisposition traits (SNPs, haplotypes) that allow for determining the outcome of liver disease. The long-term goal of Prof. Weiskirchen’s studies is to translate experimental findings into new diagnostic or therapeutic strategies. In recent years, he has also developed innovative protocols for measuring and profiling metal concentrations in both experimental and clinical samples.
Prof. Weiskirchen has authored over 550 articles in peer-reviewed journals, which are frequently cited, resulting in a current h-index of 65 and the inclusion in the 2024 Highly Cited Researchers list from Clarivate. He has given numerous presentations and lectures at medical and scientific conferences. Additionally, he serves as an editorial board member for several journals and is an active member of the German Association for the Study of the Liver (GASL) and the European Association for the Study of the Liver (EASL). His scientific studies are part of a close network of national and international collaborations with many other laboratories and industrial partners. These studies are supported by the German Research Foundation (DFG) and the Interdisciplinary Center for Clinical Research (IZKF), and the German Cancer Aid.
Figure 1 Prof. Ralf Weiskirchen
Interview
ATM: What motivated you to focus your research on molecular mechanisms underlying the pathogenesis of hepatic fibrosis?
Prof. Weiskirchen: My motivation to focus my research on the molecular mechanisms underlying the pathogenesis of hepatic fibrosis stems from the significant impact this condition has on global health. Hepatic fibrosis is a progressive disease that can lead to cirrhosis and liver failure, yet its underlying mechanisms remain poorly understood. I am driven by a desire to uncover the intricate biological pathways involved in fibrogenesis, which could ultimately inform novel therapeutic strategies and improve patient outcomes. Particularly, I am interested in unraveling how members of the transforming growth factor-β and the platelet-derived growth factor family drive fibrosis. Additionally, the intersection of cellular signaling, inflammation, and extracellular matrix remodeling in hepatic fibrosis presents a fascinating area for exploration, allowing me to contribute to both scientific knowledge and clinical advancements in hepatology.
ATM: In the past few years, you developed novel protocols to measure metal concentrations in samples. Could you share the significance of developing these protocols, and how they have impacted experimental and clinical practices?
Prof. Weiskirchen: The development of new protocols to measure metal concentrations in samples has significant implications for both experimental and clinical practices. Accurate measurement of trace metals in tissues is crucial for understanding their roles in biological systems, as imbalances can lead to various health issues and influence disease progression. For example, metals play a crucial role in the pathogenesis of hemochromatosis and Wilson's disease. Excessive iron accumulation in hemochromatosis leads to oxidative stress and tissue damage, while impaired copper metabolism in Wilson's disease results in toxic copper buildup, both contributing to liver dysfunction and other systemic complications. By refining protocols based on laser ablation-inductively coupled plasma mass spectrometry (LA-ICP-MS), we have enhanced the sensitivity and specificity of metal detection in tissues. This improvement enables researchers to obtain more reliable data from complex biological matrices with spatial resolution. These advancements not only facilitate a better understanding of metal-related pathologies but also support clinical diagnostics by providing precise assessments that can inform treatment decisions. Ultimately, these protocols contribute to improved patient care and a deeper comprehension of the biochemical pathways influenced by metals, paving the way for innovative therapeutic approaches.
ATM: Could you share the challenges of developing these novel protocols? How do you overcome them?
Prof. Weiskirchen: Developing novel protocols to measure metal concentrations presents several challenges, including the need for high sensitivity and specificity in complex biological samples, potential interference from other substances, and the variability inherent in sample preparation techniques. Additionally, ensuring reproducibility across different laboratories can be difficult. To overcome these challenges, I focus on optimizing each step of the protocol, from sample collection and storage to analytical methods. Rigorous validation processes are implemented to assess accuracy and precision while incorporating controls to mitigate interference effects. Collaborating with interdisciplinary teams also plays a crucial role; by leveraging expertise from chemists and biologists, we can refine methodologies and troubleshoot issues more effectively. Continuous iteration based on feedback and emerging technologies further enhances the robustness of these protocols, ensuring they meet both research and clinical needs.
ATM: In 2021, you led a special series on ‘Unresolved basic issues in hepatology’ in ATM. Could you share the progress that has been made in hepatology research since then? To what extent have the issues mentioned in the special issue been resolved?
Prof. Weiskirchen: Since leading the special series on ‘Unresolved Basic Issues in Hepatology’ in 2021, significant progress has been made in addressing several key challenges within the field. Research has advanced our understanding of liver diseases, particularly through the elucidation of molecular pathways involved in fibrosis and inflammation. New insights into the microbiome's role in liver health have also emerged, highlighting its potential as a therapeutic target. While some issues raised in the special issue remain unresolved, such as the complexities of metabolic dysfunction-associated steatotic liver disease (MASLD) and its progression to more severe forms, ongoing studies are yielding promising results that may lead to effective treatment strategies. Collaborative efforts among researchers and clinicians have fostered a more integrated approach to hepatology, facilitating advancements in diagnostics and personalized medicine. Overall, while challenges persist, there is renewed optimism regarding the future trajectory of hepatology research as we continue to build upon these foundational insights. The special issue has summarized cutting-edge findings and highlighted emerging trends, unresolved questions, and innovative methodologies, which might have inspired researchers to explore new avenues in their research. As such, it has set benchmarks for future studies, ultimately driving the field forward.
ATM: With a long-term objective of translating experimental findings into novel diagnostic or therapeutic strategies, what are some of your current or upcoming research plans? How will they contribute to your long-term objective?
Prof. Weiskirchen: In pursuit of my long-term goal to translate experimental findings into new diagnostic or therapeutic strategies, I am currently focused on several key research initiatives. One major plan involves investigating the role of specific biomarkers in the early detection of hepatic fibrosis, which could lead to more timely interventions and improved patient outcomes. Additionally, I aim to explore innovative therapeutic approaches targeting the molecular pathways involved in liver inflammation and fibrosis, including the use of small molecules and gene editing technologies. Collaborating with clinical partners from around the world will be crucial in these endeavors, as it allows for the integration of laboratory findings with real-world applications. By bridging the gap between the bench and the bedside, these research plans not only advance our understanding of liver diseases but also pave the way for developing effective tools that can enhance diagnosis and treatment, ultimately fulfilling my goal of improving patient care in hepatology.
ATM: Having presented at a large number of presentations and lectures at medical and scientific conferences, what impact have you made, and what is your biggest takeaway from these interactions?
Prof. Weiskirchen: Having presented at numerous medical and scientific conferences, I believe I have made a meaningful impact by fostering dialogue around crucial topics in hepatology and sharing insights from my research. These interactions have allowed me to connect with a diverse audience of professionals, facilitating knowledge exchange that can drive innovation in the field. My biggest takeaway from these experiences is the importance of collaboration; engaging with fellow researchers and clinicians has highlighted the value of multidisciplinary approaches in addressing complex health issues. Additionally, I have learned that effective communication is key to translating scientific findings into practical applications, as it helps bridge gaps between research and clinical practice. Overall, these presentations have not only enriched my own understanding but also contributed to building a community focused on advancing liver health through shared knowledge and collaborative efforts.
ATM: How has your experience been as a longstanding Editorial Board Member of ATM?
Prof. Weiskirchen: My experience as a longstanding Editorial Board Member of ATM has been both rewarding and enriching. It has provided me with a unique opportunity to engage deeply with cutting-edge research in hepatology, allowing me to stay at the forefront of advancements in the field. Collaborating with fellow board members and contributing to the peer-review process has sharpened my critical thinking skills and enhanced my ability to evaluate scientific work rigorously. Additionally, this role has enabled me to influence the direction of research published in the journal, advocating for high-quality studies that address pressing issues in hepatology. The interactions with authors and researchers have also expanded my professional network, fostering collaborations that can lead to innovative projects. Overall, serving on the editorial board has not only contributed to my personal growth but also reinforced my commitment to advancing knowledge and improving practices within hepatology.
ATM: As an Editorial Board Member, what are your aspirations for the future of ATM?
Prof. Weiskirchen: As an Editorial Board Member, my aspirations for the future of ATM focus on enhancing its role as a leading platform for innovative research in hepatology and other research areas. I envision expanding the journal's reach by encouraging submissions that explore emerging areas such as personalized medicine, the microbiome's influence on liver health, and novel therapeutic approaches. Additionally, I aim to foster greater collaboration with researchers from diverse disciplines to enrich content and broaden perspectives. Promoting open access and increasing visibility for high-quality studies published in ATM will also be priorities, ensuring vital findings are accessible to clinicians and researchers worldwide. Ultimately, I hope to help position ATM not only as a repository of knowledge but also as a catalyst for transformative advancements in liver health research and clinical practice. I am confident that ATM's future impact will be profound, serving as a vital platform for disseminating groundbreaking research, fostering collaboration among scientists and clinicians, and shaping innovative discoveries that can transform our understanding of complex diseases. I am delighted to be part of the editorial board of ATM, contributing to advancing knowledge in our field.