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Professor JIANG Hong Guest Lectures at Biomed-X Seminar, Sharing New Strategies for Pancreatic Cancer Immunotherapy

Professor JIANG Hong Guest Lectures at Biomed-X Seminar, Sharing New Strategies for Pancreatic Cancer Immunotherapy

On November 19th, 2025, the 142nd Biomed-X Research Seminar of the ZJE was successfully held in the Room 2A-203, ZJE Building.  At the invitation of Dr. James Qun Wang from the Centre for Cellular Biology and Signalling (CBS) of ZJE, Prof. JIANG Hong from Sichuan University delivered an academic report titled "Focal adhesion kinase in pancreatic cancer: from cell motility control to immunomodulation and beyond".Professor JIANG Hong's report focused on the multiple roles of Focal Adhesion Kinase (FAK) in pancreatic cancer, systematically elaborating on the research context of this kinase from its classical functions to innovative mechanisms. On one hand, it focused on the core role of FAK in regulating the motility of pancreatic cancer cells, revealing the molecular mechanism by which FAK affects tumor cell migration and invasion through mediating cell adhesion and cytoskeletal remodeling. On the other hand, it extended to the field of tumor immunomodulation, deeply analyzing how FAK participates in the remodeling of the tumor immune microenvironment and regulates immune cell functions as well as the formation of immunosuppressive networks. Meanwhile, the report also involved the extended exploration of this research in translational medicine, providing theoretical support and potential directions for the combined strategy of targeted therapy and immunotherapy for pancreatic cancer.During the event, faculty and students interacted actively, fully demonstrating the academic atmosphere of free discussion and critical thinking in the institute. Professor JIANG carefully and meticulously answered every question, enabling teachers and students to gain a deeper understanding of the cutting-edge progress, innovative directions and translational prospects in this field.As the 142nd session of the Biomed-X Seminar series, this report underscores the institute's commitment to fostering high-level academic exchanges through its academic brand building efforts. The institute will continue to provide a platform for faculty and students to engage in cutting-edge scientific discussions.
2025-11-25
ZJU-UoE Dual PhD Xinyu Xiang Reveals the Evolutionary Origin of the Mammalian piRNA Pathway

ZJU-UoE Dual PhD Xinyu Xiang Reveals the Evolutionary Origin of the Mammalian piRNA Pathway

Recently, Prof. Donal O’Carroll’s group at the University of Edinburgh (UoE), together with Prof. Wanlu Liu (刘琬璐)’s group at ZJU-UoE Institute (ZJE) and Prof. Elly M. Tanaka’s group at the Research Institute of Molecular Pathology (IMP) in Vienna, published a collaborative study in The EMBO Journal titled “A mammalian-like piRNA pathway in Axolotl reveals the origins of piRNA-directed DNA methylation.” Using the axolotl as a model organism, the study uncovers for the first time the evolutionary origins of the mammalian nuclear piRNA pathway.Xinyu Xiang (相欣雨), a dual-degree ZJU-UoE PhD at ZJE, is the first author of this study. Her ZJU supervisor is Prof. Wanlu Liu, and her UoE supervisor is Prof. Donal O’Carroll FRS FRSE (corresponding author). Anni Gao (高安妮), an undergraduate student in the bioinformatics dual-degree program at ZJE, is the second author; she conducted research training in Prof. Liu’s lab during her undergraduate studies. This work highlights the strong strengths of the ZJU-UoE Institute in fostering high-level research collaboration and talent development, and exemplifies the impactful synergy and innovation arising from the international partnership between the two universities in the field of biomedical research.(1) piRNA-mediated transposon silencing is essential for germline integrityDuring the development of animal germ cells (such as sperm and oocytes), active transposonsbehave like “genomic time bombs.” As highly abundant mobile DNA elements, transposons can “jump” to new genomic locations, disrupt genes, induce DNA double-strand breaks, and consequently impair germ cell development and lead to infertility. The piRNA (PIWI-interacting RNA) pathwayfunctions as an efficient “demining system,” precisely recognizing and silencing active transposons 【1, 2】. It serves as a critical defense mechanism that safeguards genome integrity in the germline.(2) The nuclear piRNA pathway is believed to be bespoke to mammalspiRNAs are small non-coding RNAs that associate with PIWI proteins to silence transposons in germ cells, effectively defusing these “genomic time bombs.” The piRNA pathway consists of two parts: the cytoplasmic pathwayand the nuclear pathway. The cytoplasmic piRNA pathway is common to most animals 【3】 and functions by cleaving transposon transcripts, providing rapid and timely silencing. In contrast, the nuclear piRNA pathway acts as a “permanent seal,” guiding DNA methylation to stably silence transposons over the long term. For many years, this nuclear piRNA pathway was thought to be a mammal-specific mechanism 【1,2】.(3) Axolotl is an ideal model for studying transposons and the piRNA pathwayThe axolotl is a classic model organism in regenerative biology, well known for its remarkable tissue repair capacity, such as limb regeneration. Beyond its remarkable regenerative abilities, the axolotl also possesses an exceptionally large genome, as one of the largest among known animals (approximately 32 Gb, about ten times the size of the human genome) 【4】. This huge genome is largely result from extensive transposon expansion. Around 70% of the axolotl genome consists of transposons, compared with about 50% in humans. Its high transposon content and huge genome make the axolotl an ideal model for investigating transposon activity and their silencing mechanisms.(4) Axolotl has a mammalian-like piRNA pathwayTo trace the evolutionary origin of the mammalian piRNA pathway, we constructed a phylogenetic tree of key piRNA pathway genes across vertebrates. The analysis revealed that the core nuclear piRNA factors in mammals, such as PIWIL4, SPOCD1, C19ORF84, and TEX15, are found all together for the first time in the axolotl. Whereas these factors are partially missing in both lobe-finned and ray-finned fish. This suggests that the nuclear piRNA pathway may not have emerged in earlier vertebrate lineages. Furthermore, transcriptomic analyses show that these piRNA pathway genes exhibit germline-specific expressionin the axolotl, same as the mammalian expression pattern, thereby indicating their potential functional roles.(5) Axolotl possesses a functional cytoplasmic piRNA pathwayTo better understand transposon activity and silencing in the axolotl, we first predicted and annotated active transposons in axolotl genome, identifying a set of potentially active transposons. We then performed small RNA sequencing to profile piRNAs in axolotl germlines. The results revealed an abundantrepertoire of piRNAs in both male and female germlines (~88 million), with a substantial fraction derived from transposon sequences.The cytoplasmic piRNA pathway involves piRNA biogenesis and the classic ping-pong cycle, which mediates post-transcriptional silencing by cleaving transposon transcripts. These piRNAs are primarily generated from genomic piRNA clusters, which display clear sex-specific patterns in the axolotl. Moreover, transposon-targeting piRNAs exhibit hallmark features of the ping-pong cycle, providing strong evidences that a functional cytoplasmic piRNA pathway in the axolotl germline.(6) Evidence for an active nuclear piRNA pathway in axolotl is presentedThe nuclear piRNA pathway, or piRNA-directed DNA methylation, has been reported exclusively in mammals. This pathway is mediated by the piRNA-PIWIL4 complex together with associated nuclear factors, which recruit de novo DNA methyltransferases to specifically methylate the promoters of young and active transposons, ensuring their long-term silencing. During epigenetic reprogramming of the germline, the genome undergoes extensive DNA demethylation and is therefore particularly vulnerable to transposon activation, making piRNA-directed methylation silencing especially critical at this stage. The terminal outcome of this process is the high methylation levels of young transposons in sperm.Whole-genome bisulfite sequencing of axolotl sperm revealed an overall CpG methylation level of approximately 90%, higher than mammals (~75%-85%). Importantly, the entire transposon region, including promoter regions, exhibited tight methylation control. Moreover, young and potentially active transposons also showed significantly higherDNA methylation levels. Together, these findings provide the first evidence outside mammals that DNA methylation mediated transposon silencing, characteristic of the nuclear piRNA pathway, also exists in the axolotl. Overall, this study identifies a mammalian-like cytoplasmic and nuclear piRNA pathway in the axolotl. Small RNA sequencing and whole-genome methylation profiling together demonstrate that the axolotl possesses a functional cytoplasmic piRNA pathway for transposon transcript cleavage, as well as a nuclear piRNA pathway for long-term transposon silencing through DNA methylation. This work provides the first evidence that the mammalian piRNA pathway, particularly the piRNA-directed DNA methylation mechanism, can be traced back to the common ancestor of the axolotl and mammals, which are the early tetrapods. These findings not only fill a critical gap in the evolution of the piRNA pathway but also offer new insights into germline development, epigenetic reprogramming, and genome defense mechanisms.Original Publication:https://www.embopress.org/doi/full/10.1038/s44318-025-00631-w【1】 Wang X, Ramat A, Simonelig M, and Liu M-F Emerging roles and functional mechanisms of PIWI-interacting RNAs Nat Rev Mol Cell Biol 2023 24 123-141【2】 Ozata DM, Gainetdinov I, Zoch A, O’Carroll D, and Zamore PD PIWI-interacting RNAs: small RNAs with big functions Nat Rev Genet 2019 20 89-108【3】 Grimson A, Srivastava M, Fahey B, Woodcroft BJ, Chiang HR, King N, Degnan BM, Rokhsar DS, and Bartel DP Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals Nature 2008 455 1193-1197【4】 Nowoshilow S, Schloissnig S, Fei J-F, Dahl A, Pang AWC, Pippel M, Winkler S, Hastie AR, Young G, Roscito JG, et al. The axolotl genome and the evolution of key tissue formation regulators Nature 2018 554 50-55
2025-11-25
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Why Choose ZJE?

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Jin Yinhua, Rush towards every passion

She is a lovely girl from Northeast China, gentle towards all things in the world. She approaches science with reverence, delving into the mysteries of life. Using her soul to ignite the fireworks in her aspirations, she decorates the joys of life with her actions. In this edition, we introduce Dr. Jin Yinhua, a researcher and doctoral supervisor at ZJE."Dr. Jin YinhuaResearcher, PhD Supervisor, Tenure-Track Assistant ProfessorDr. Jin Yinhua graduated from the University of Heidelberg in Germany under the guidance of Prof. Dr. Bruce A. Edgar. She subsequently pursued postdoctoral training at Stanford University School of Medicine in the United States, mentored by Prof. Dr. Roel Nusse, a fellow of the National Academy of Sciences and an HHMI investigator. During this period, her research focused on elucidating the mechanisms by which signals from the stem cell microenvironment regulate tissue homeostasis and regeneration.By establishing a unique set of genetic, cellular, and molecular biology tools, she first revealed the mechanisms through which microenvironmental signals such as EGF and Wnt control the potential of stem cells, as well as the roles of these mechanisms in tissue regeneration and repair. In May 2023, Dr. Jin Yinhua joined Zhejiang University-University of Edinburgh Institute as a researcher and PhD supervisor. She formed the Stem Cell Microenvironment and Tissue Regeneration research group, where she primarily investigates how microenvironmental signals control cell behavior and cell interactions during tissue development and regeneration.ACADEMIC CAREERThe journey of learning began in 2003 when the Human Genome Project was nearing completion, planting the seeds of ideals in the young and tender heart. The seeds, imbued with vibrant vitality, quickly took root and sprouted, breaking through the soil, fueled by curiosity, exploration, and the quest for knowledge. Starting with the study of biotechnology at China Agricultural University, focusing on the application of technology in production, to researching plant stem cells at Seoul National University, and further delving into adult stem cells and understanding the regulation of intestinal stem cells by growth factors at the University of Heidelberg. Then, journeying to Stanford University to continue in this field, Dr. Jin, like a helmsman, held the oar, steered the course, adjusted the direction, cut through waves, and sailed towards the ideal shore.In the pursuit of biology, Dr. Jin Yinhua's journey began with interest, and she consistently nurtured that interest with the purest passion, focusing single-mindedly on watering and cultivating it. Over the years, that initial interest quietly shed its youthfulness and transformed into a deep-seated aspiration.During her academic journey, Dr. Jin Yinhua was influenced by the diligent efforts of Korean students, admired the rigorous, meticulous, and high-standard work attitude of German researchers, and was amazed by the active thinking, daring spirit, and courage to tackle cutting-edge work displayed by American researchers. Under the influence of a multicultural environment, Dr. Jin Yinhua embraced the strengths of various cultures, developed her style, and explored infinite truths in the endless river of the universe.Behind Dr. Jin Yinhua's calm and easygoing narrative, there ripples the unknown hardships and challenges. Cultural clashes, language barriers, and unfamiliar environments are tests that every international student must face. The comforting language rules, habits, and ways of thinking in one's native tongue can become barriers and misunderstandings in cross-cultural communication. In other words, what was once familiar and understood has turned into confusion.Courage is the belief that life holds onto in difficult times, a belief that time endows with enduring resilience. On this note, Dr. Jin Yinhua also provides advice: bravely step out of the comfort zone of the Chinese community, communicate more with locals, and embrace each other's cultural habits. This is indeed something that takes time and effort, but it is worth doing.SCIENTIFIC RESEARCH JOURNEY"Passionate, enjoyable, challenging" is Dr. Jin Yinhua's summary of her journey in scientific research. Maintaining a childlike curiosity is the driving force for researchers. The pursuit originates from love, and love achieves the pursuit. The scientific research career begins with curiosity and passion, and what is most precious is retaining the initial expectation after experiencing numerous challenges. In our conversation with Dr. Jin Yinhua, we can feel her passion for research and enjoyment of the process. She attributes this to the influence of two mentors.Her American mentor, despite being elderly, left a deep impression on Dr. Jin with his pure passion. His relentless pursuit of truth, continuous progress, and unwavering commitment inspired her. "Life gains value when you can find joy in your profession," he once said. Scientific research is challenging, but we can still find enjoyment in it.Her German mentor, on the other hand, is someone who truly enjoys scientific research. He finds pleasure in the seriousness of research, immersing himself in the process with a philosophical mindset and a comfortable and relaxed state. Despite the difficulties of scientific research, he manages to derive enjoyment from it, showcasing a unique approach to the scientific journey.THE JOURNEY OF LIFE Andrew Carnegie once said, "Everyone should have a strong interest or hobby to enrich the soul and add flavor to life." Wise individuals can make ordinary lives vibrant and colorful. Volleyball, comics, books, movies, travel, and everyday meals and seasons are all cherished as the most beautiful scenery in Dr. Jin Yinhua's heart, enriching her life beyond scientific research. Dr. Jin enjoys playing volleyball, having been a member of the university team at China Agricultural University, and participating in intercollegiate volleyball competitions with friends, a joyful and satisfying experience.What stands out most in Dr. Jin Yinhua's memories? Undoubtedly, it's travel. Leafing through the pages of her life, she realizes that many unforgettable memories are closely tied to her travels. Whether it's reaching for the stars in accessible Alaska, the romantic encounter with the aurora and snow near the Arctic Circle, or personally visiting the small village mentioned in the textbook's "The Last Lesson" and experiencing the wonderful overlap of reality and memory. Dr. Jin particularly emphasizes that compared to short-term tourist visits, the long-term immersive travel experienced during her overseas studies made it easier to discover vibrant corners and encounter unexpected beauty.For undergraduate students, Dr. Jin Yinhua's message is: "The guidance of good mentors is like a lighthouse at sea, guiding lost ships. Dr. Jin Yinhua wants to say to our undergraduate classmates, 'It should be a fun journey, enjoy it.' She plainly states that looking back on her academic journey, the undergraduate phase was undoubtedly the most interesting. Therefore, undergraduate students should wholeheartedly enjoy this period, striking a balance between diligent learning and embracing the pleasures of life. Fear not the length of youth, and let's explore new horizons while the fire is still burning, sipping poetry and wine in the bloom of our time!"

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Aaron Irving, Befriending Biology, Keeping up with Interests

Aaron IrvingAaron Irving, Assistant Professor at the Zhejiang University-University of Edinburgh Institute (ZJE). His journey into the world of life sciences began with a movie and a deep connection to China.Dr. Aaron Irving, an Assistant Professor at ZJE, brings a wealth of academic and research experience from his training at institutions like the University of Queensland (Australia), Diamantina Institute (UQ Australia), Monash Biomedicine Discovery Institute (Melbourne), and the Duke-NUS Medical School (Singapore).Dr. Irving's focus lies in newly emerging zoonotic viral infections and the host-pathogen interactions they trigger. He uses bats as a model organism, exploring key factors in bat immune responses that could be harnessed to enhance human immunity against pathogens. His lab also works on new diagnostic techniques to identify wildlife infections with zoonotic viruses like SARS-CoV-2 and factors contributing to the potential for zoonotic diseases.But what led Aaron to this fascinating field of virology? It all started with a childhood fascination with viruses, but it was a movie that changed the course of his life. The film "Outbreak," which tells the story of the Ebola virus jumping from monkeys to humans and spreading among the population, convinced him to become a research scientist. With curiosity about viruses and a concern for human health, he embarked on the path of scientific research.During his undergraduate years, Aaron pursued a Bachelor of Science degree, allowing him to freely explore his interests and build a solid foundation in biology. He worked diligently, fueled by passion and guided by his interests, eventually earning dual degrees in molecular biology and cell biology.After his undergraduate studies, he continued for an additional year of research (known as an Honours degree in Australia) and achieved the highest honors (Class I). During this time, he delved into the study of the herpes simplex virus (HSV1), which causes cold sores, and how it evades the human immune system. This research laid the groundwork for his future career in host-pathogen interactions.When it comes to bats, Aaron's eyes light up with excitement. "Bats are truly fascinating creatures," he says. What makes Aaron so enamored with these flying mammals?Initially, Aaron was not well-acquainted with the mysteries of bats. However, he stumbled upon a new world that captured his interest. Bats have undergone many evolutionary adaptations, making them exceptionally healthy, robust, and resilient animals with strong immune systems, immunity to aging, cancer resistance, inflammation prevention, and autoimmune disease avoidance. Aaron's research on bats aims to uncover the secrets of their exceptional health and apply that knowledge to benefit human health.Today, Aaron is involved in various projects, including those related to coronaviruses. His primary focus is on understanding the different genes that bats activate in their immune responses and comparing them to humans.One of his most intriguing projects examines the differences between bat and human aging. According to Aaron, wild-caught bats show no signs of aging, with 20-year-old bats appearing as youthful as 1-year-olds. He hopes to compare this phenomenon with research on human aging and humorously suggests that the findings could potentially be applied to skincare products to prevent human skin aging.Before joining ZJE, Aaron had already established a connection with China. He had previously visited Yunnan, known as the "Kingdom of Flora and Fauna," and collaborated with a local organization. He describes Yunnan as an incredible place with diverse biological species, making bat capture relatively easy due to the vast bat populations in a small area.When asked why he chose ZJE, Aaron believes that science in China is rapidly growing, offering abundant opportunities and possibilities. ZJE warmly welcomes fresh talent and provides excellent research facilities and an environment conducive to teaching. Additionally, the international platform at ZJE allows him to adapt and integrate into a foreign culture. Despite being a newcomer, he appreciates the students' critical thinking abilities and their knack for posing thought-provoking questions, which continually surprise him. He encourages students to express their opinions boldly and actively participate in the classroom.

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