Research Direction
Our International Collaboration
At our Cancer Discovery Network, we believe that the key to progress in the fight against cancer lies in nurturing the potential of young researchers. Our mission is to provide a dynamic platform where emerging talents can shine, collaborate, and make a significant impact on the world of oncology.
Single-cell RNA-seq analysis reveals the distinctive functional composition of immune cells. (Source: 10.1158/2159-8290.CD-20-1500)
New Discovery
c-MET, also known as hepatocyte growth factor receptor (HGFR), is a receptor tyrosine kinase that plays a crucial role in various solid tumors like lung, breast, and liver cancers. Recent single-cell analysis has revealed that c-MET significantly impacts the composition of immune cells within the tumor microenvironment. It promotes an immunosuppressive environment by transforming anti-cancer M1 macrophages into tumorigenic M2 macrophages and converting CD4+Th cells into Treg cells by upregulating PD-L1, TGF-β, and IL-10. Our current research explores the potential of targeting c-MET as an immunotherapeutic strategy.
Traditionally, c-MET was known to have a single ligand, HGF. However, our recent research has discovered new ligands for c-MET in breast cancer. These newly identified ligands can potentially disrupt anticancer immunotherapy efforts by altering the immune cell composition within the tumor microenvironment, ultimately hindering the body's ability to combat cancer effectively. This discovery highlights the need for a deeper understanding of c-MET's role in breast cancer and its implications for immunotherapeutic approaches.
In our future team, we plan to jump much deeper into c-MET mechanism and the functional roles of interactions of c-MET with its novel ligands. The results have yet to be published.
c-MET discovery subgroup
The c-MET Discovery Subgroup represents a specialized research community dedicated to unraveling the intricacies of c-MET, a protein that has emerged as a pivotal player in cancer biology. This subgroup is deeply invested in understanding how c-MET influences the resistance mechanisms that cancer cells employ against targeted therapies and immunotherapies. They recognize the significance of c-MET in shaping the immunosuppressive microenvironment within tumors, which enables cancer cells to evade the body's natural defense mechanisms.
Studies reviewed by this subgroup highlight several critical aspects of c-MET's role in cancer progression. They emphasize that c-MET's overexpression and hyperactivity are closely linked to the expression of PD-L1, a protein cancer cells use to shield themselves from the immune system. Moreover, c-MET activation appears to foster the transition of immune cells from an antitumor (M1) phenotype to a pro-tumor (M2) phenotype. It promotes the expansion of immunosuppressive T cells in the tumor microenvironment.
(left) When human HGF (hHGF) binds to the Met ectodomain, it forms a 2:2 dimerization complex, bringing intracellular tyrosine kinase domains into close proximity and inducing trans-phosphorylation. Met activation transduces major signals through the adaptor protein Gab1. Activation of downstream cytoplasmic kinases such as Akt and Erk1/2 (mitogen-activated protein kinase (MAPK)) eventually promote cellular phenotypic changes. (right) Using the RaPID system, we can select artificial macrocycles fused to the respective mRNAs against a target: in this case, the human Met ectodomain.(Source: https://doi.org/10.1038/ncomms7373 )
Perhaps most intriguingly, the subgroup delves into the potential therapeutic implications of their findings. They have examined a bispecific antibody called amivantamab, which targets both c-MET and EGFR. This antibody has shown promise in enhancing the immune system's ability to combat cancer by engaging immune cells through an Fc-dependent mechanism. This discovery has paved the way for new therapeutic approaches that combine c-MET inhibition with immunotherapy, potentially offering a dual-pronged attack on tumorigenesis and immunosuppression.
Overall, the c-MET Discovery Subgroup's research endeavors are instrumental in shedding light on the multifaceted roles of c-MET in cancer, offering hope for more effective treatments and personalized therapies for cancer patients. Their dedication to unraveling the complexities of c-MET's function in the context of cancer is paramount in advancing our understanding of this critical protein and its therapeutic potential.
Antibody subgroup
This specialized subgroup is dedicated to pioneering the development of monoclonal antibodies (mAbs) tailored for innovative targets in cancer research. We embark on a journey of discovery, identifying novel biomarkers and signaling pathways specific to various cancer types. Leveraging cutting-edge technologies, we engineer mAbs with unprecedented precision and affinity to selectively target these unique markers. Through rigorous preclinical assessments and clinical trials, we aim to revolutionize cancer therapy by introducing a new class of highly targeted treatments. Our commitment lies in reshaping the landscape of cancer research and therapeutics, offering hope for more effective, personalized, and less toxic interventions in the fight against this complex disease.
FDA watch subgroup
The FDA watch subgroup monitors and analyzes decisions made by the U.S. Food and Drug Administration (FDA) regarding the approvals and withdrawals of pharmaceutical drugs. Their responsibility is to closely observe FDA actions and assess the implications of these decisions, particularly in the context of cancer therapy and immunotherapeutic interventions.
This subgroup focuses on monitoring FDA actions related to immunotherapeutic drugs such as atezolizumab and nivolumab. When the FDA withdraws approvals for these drugs, the subgroup investigates the structural and clinical factors that influenced these decisions. They consider the impact of these withdrawals on patients, healthcare providers, and the pharmaceutical industry, recognizing the potential consequences for individuals suffering from specific cancers like TNBC and HCC.
Furthermore, the FDA watch subgroup is critical in emphasizing the importance of continuous drug safety and efficacy evaluation, especially concerning immunogenicity and pharmacokinetics. Their work underscores the need for ongoing research to understand how these factors affect clinical outcomes. Additionally, they stay informed about advancements in cancer therapy, including developments in protein engineering and targeted protein degradation strategies, which could hold promise for future treatments.
Our cutting-edge subgroup
Welcome to our High-Tech Bioinformatics Subgroup! In 2024, our research endeavors are fueled by innovation and focused on cutting-edge technologies. We have identified three priority areas that drive our projects and shape the future of bioinformatics.
1) AI-based Bioinformatics: Artificial Intelligence (AI) is revolutionizing the field of bioinformatics. We're at the forefront of harnessing AI's power to analyze biological data. By employing machine learning algorithms, we can uncover hidden patterns, make predictions, and gain profound insights into complex biological processes.
2) Single-Cell Analytic Study: Understanding biology at the single-cell level is crucial. Our research delves into single-cell analytics, a field that allows us to dissect and analyze individual cells with precision. This approach unveils intricate details of cellular behavior, aiding in disease understanding, drug development, and personalized medicine.
3) Transferrable AI Models: Collaboration and knowledge sharing are essential in today's scientific landscape. We're seeking individuals well-versed in building transferrable AI models. These models can be applied across various biological datasets and domains, enhancing the efficiency and effectiveness of research.
Join us on this exciting journey into the future of bioinformatics. Together, we'll push the boundaries of knowledge, advance scientific discovery, and make a lasting impact on the world of biology.