To enhance the development of the research team in Shenzhen Bay Laboratory (SZBL), support innovative research, and encourage interdisciplinary cooperation, the SZBL launched the Shenzhen Bay Scholars Programme in 2021. The Shenzhen Bay Scholars Programme comprises three categories: “Shenzhen Bay Distinguished Scholar”, “Shenzhen Bay Scholar”, and “Shenzhen Bay Fellow”, in which, the “Shenzhen Bay Fellow” is designed to cultivate and support a group of young scholars with strong academic foundations, exceptional innovative ability, and significant potentials of growth, promote the talent pipeline of the SZBL across various institutes/centers academic echelons and research teams, and encourage bold and original scientific research and exploration.
At Peking University’s School of Life Sciences, where nearly 90% of doctoral candidates would require extensions for graduation, Feng Yin never envisioned herself among the few who would finish on time. “While hard work doesn’t always guarantee good results, not working hard guarantees no results. In short, I‘ve tried my best.” she reflected with a smile.
At that time, her supervisor, based in the United States, assigned her several projects aligned with their original research focus. As she worked on them, Feng Yin began to sense that something wasn’t right—continuing on this path might jeopardize her timely graduation. Resolutely, she decided to take on a few more projects to ensure her progress.
In addition to continuing her assigned projects, Yin actively engaged with other faculty members and peers to explore new ideas and directions. This proactive approach led to a breakthrough while she was conducting fundamental research in epigenetics: she identified that two enzymes, LSD1 (lysine-specific demethylase 1) and HDAC1 (histone deacetylase 1), whose enzymatic activities influenced one another and collectively regulated the initiation and progression of cancer stem cells. Further investigations unveiled a novel histone modification substrate for HDAC1. Within five years, this result was published in Molecular Cellular Biology, a leading journal in molecular biology, establishing it as one of her landmark achievements during her doctoral studies.
Graduating on time—or even ahead of schedule—may seem impressive to others. Still, for Yin, those five years were marked by countless Sisyphean struggles: facing setbacks, reflecting on failures, and rising stronger each time. Reflecting on her journey, Yin shared, “Attitude determines altitude. Regardless of the challenges or outcomes, insisting on finishing a project with diligence and excellence has been my guiding principle in my life. In those years, numerous arduous have strengthened my fundamental research skills and sharpened my independent thinking ability, paving the way for my later scientific career.”
Following her Ph.D., Yin pursued postdoctoral research at Nanyang Technological University (NTU) in Singapore, transitioning from cellular epigenetic mechanisms to the application of nanomaterials—a completely new field that also
means a new challenge for her.
"I greatly admire Steve Jobs; he was not just a successful entrepreneur, but also a profound thinker and educator. I am inspired by his great passion for his career, his perseverance, and his indomitable spirit whenever I face difficulties,” said Feng Yin. During her postdoctoral research, she leveraged her cell biology expertise to integrate various disciplines, collaborating closely with her mentors and colleagues. Despite starting with no knowledge of inorganic nanomaterials, she became proficient in their preparation and modification, eventually extending their biomedical applications. "This challenging start laid a solid foundation for my later work in the fields of chemical biology and peptide biomedical research,” she added.
In 2015, Feng Yin returned to the Peking University Shenzhen Graduate School, joining Professor Zigang Li's research group to work on the methodologies for stabilizing peptides and conducting biomedical research. Drawing from her extensive experience in cell biology and nanomedicine, she excelled in peptide drug research. Peptide molecules offer numerous advantages, for instance, they have high binding affinity and target selectivity, lower off-target effects compared to small-molecule drugs, and amino acids as their metabolic byproducts can greatly minimize the toxicity. Additionally, peptides are less costly with weaker immunogenicity compared to biological macromolecules, and can easily penetrate tissues due to their smaller molecular size.
However, developing peptides into viable drugs presents significant challenges. For example, peptide-based molecules, typically composed of natural amino acids, are easily recognized and degraded by proteases, resulting in poor stability in the body. They are also rapidly metabolized by the liver and kidneys, leading to poor pharmacokinetics. Furthermore, their oral bioavailability and cell penetrability are limited by their inherent biophysical properties. Traditional peptide drugs, with a limited number of amino acid residues, cannot effectively form complex secondary structures, remaining highly flexible with disordered linear states in physiological solutions. This reduces their specificity and makes them susceptible to protease degradation.
Since the 1980s, chemists have explored various chemical modifications to extract and enhance secondary structural units involved in protein-protein interactions. These modifications do not just stabilize their secondary conformations to mimic original protein interactions but also allow these units to penetrate cell membranes, thereby targeting intracellular interactions and expanding the possibilities for molecular targeting. Under the guidance of Professor Zigang Li, Yin, and her team quickly developed several groundbreaking strategies, including the "Chiral Induced Helix Concept”, "Photo-induced Thiol-yne Click Strategy”, "TD Terminal Aspartic Acid Strategy”, and the "Intracellularly Reducible Bis-alkylated Peptide Modification Strategy". They successfully applied these strategies in biomedical research. In studies focusing on protein interactions of important disease targets, they created stable peptide regulators for critical epigenetic targets such as HDACs, LSD1, and USP30. These advancements provided new insights and foundations for anticancer peptide drug research (Journal of Medicinal Chemistry, 2022, 65, 18, 12188–12199; ACS Chemical Biology, 2022, 17, 3, 521-528; Autophagy, 2022, 18(9):2178-2197; Journal of Medicinal Chemistry, 2022, 65, 1, 876-884; Cancer Research, 2019, 79(8): 1769-1783). In the field of nucleic acid drug delivery, they developed the world's shortest stable 9-peptide delivery system (ACS Nano, 2022, 16, 11, 19509–19522; Materials Horizons, 2018, 5(4): 745-752), capable of efficiently delivering nucleic acid drugs or tumor neoantigen peptides, potentially overcoming the limitations of lipid nanoparticles (LNP). Additionally, this short peptide exhibits adjuvant properties, suitable for various vaccines (e.g., hepatitis B vaccine, influenza vaccine), showing significant potential for clinical translation. Currently, this project has completed preclinical data integration and is actively moving towards clinical trial applications.
In 2019, Feng Yin joined the SZBL and became a pivotal figure at the Pingshan Translational Medicine Center. She is currently leading two key peptide projects that have achieved notable interim results:
(1) Innovative Cyclic Peptide Radionuclide Conjugate Drugs. Positron emission tomography (PET) imaging has progressively become an essential tool for evaluating lesions, diagnosing tumor progression, and providing radiological evidence for severe diseases. The core evaluation criteria for PET radionuclides include stability, receptor affinity, and imaging signal quality. Yin's team developed a novel cyclic peptide system to create analogs of commercial disulfide-bond peptides. In preclinical tests, these new cyclic peptides demonstrated superior tumor-homing abilities and pharmacokinetics compared to disulfide-bond peptides. By combining positron emission radionuclides with therapeutic radionuclides, they developed several targeted radioactive diagnostic and therapeutic drugs. Compared to traditional peptide radionuclide conjugate drugs (such as Dotadate, approved in the US in 2016), the new cyclic peptides offer higher signal-to-noise ratios, longer tumor retention times, better therapeutic outcomes, and reduced radiation exposure to normal tissues. These drugs are designed for the early diagnosis and treatment of neuroendocrine tumors, allowing for image-guided precision therapy. Clinical research initiated by Japan's National Institute for Quantum and Radiological Science and Technology is in progress, with crucial clinical data expected by 2023. Collaboration agreements with several domestic hospitals and peptide companies (Hybio Pharmaceutical, JYMed) have been established, with an IND application anticipated in 2023, indicating strong transferability and potential for drug development.
(2) "Sulfonium-based " Staple Peptide Carrier. Facing the challenges of ineffectively treating solid tumors with immune checkpoint inhibitors and adoptive cell therapies, personalized precision immunotherapy using tumor neoantigens provides new opportunities for modulating the tumor microenvironment. However, the low expression and immune response of neoantigen peptides on cell surfaces severely limit the clinical application of neoantigen peptide vaccines. Developing new vaccine adjuvants and nanocarriers is essential for advancing tumor neoantigen vaccines. To address this, Yin Feng's team collaborated with Shenzhen BioKangtai Co., Ltd., and developed the "Sulfonium-based " Staple peptide carrier that is compatible with adjuvant activity with only nine amino acids. This innovative carrier enhances the membrane penetration, stability, and immune activation of neoantigen peptides, effectively inhibiting the growth of various tumor cells, such as melanoma and colon cancer, without significant physiological toxicity. Additionally, this peptide also functions as an RNA carrier, with potential applications in various vaccine types (e.g., mRNA vaccines), demonstrating substantial clinical translation potential. The project has completed preclinical data integration and is actively moving towards clinical trial applications.
"Currently, the immune mechanisms of the stable peptide adjuvants we are developing are still unknown and under investigation. I am optimistic about finding breakthroughs using the advanced research facilities at Shenzhen Bay Laboratory, including multi-omics analysis, AI prediction, detailed cell biology studies, and high-dimensional imaging technologies,” said Yin Feng. "We aim to complete GMP production and submit the IND application for our PET imaging agents and stable peptide adjuvants by 2023. Additionally, one little wish of mine is to develop the world’s first peptide-based adjuvant and facilitate the clinical application of 3-4 vaccines combined with new adjuvants, making a substantial contribution to the global healthcare industry."
Biography
Feng Yin is a researcher at the PKU-Princeton Research Center of Shenzhen Bay Laboratory (SZBL) and serves as the Head of the Biology and Collaboration Departments at the Pingshan Translational Medicine Center. She has been recognized among the Top 100 Innovative Doctorate/Postdoctoral Talents in Guangdong Province, designated as an Outstanding Young Scientist of Guangdong Province, a Shenzhen Overseas High-Level Talent, a Nanshan District Leading Talent, and an Outstanding Postdoctoral Fellow at the Center for Life Sciences (CLS) of Peking University and Tsinghua University. Dr. Yin earned her Ph.D. in Cell Biology from Peking University in 2014. Her research spans several areas, including the induction and differentiation of induced pluripotent stem cells (iPS), the design and development of Plk1 kinase small molecule inhibitors, the design and development of LSD1 small molecule inhibitors, and the role of epigenetics in tumor and tumor stem cell occurrence. From 2014 to 2015, she pursued postdoctoral research in nanomedicine at Nanyang Technological University in Singapore. In late 2015, Dr. Yin joined Professor Zigang Li's team at the Shenzhen Graduate School of Peking University, where she focused on the chemical biology and biomedical applications of novel stable peptides. She joined the SZBL at the end of 2019 to further develop the biomedical applications of these stable peptides. In 2022, she attained the title of Senior Principal Engineer. As a project leader, Dr. Yin has spearheaded over ten projects, including the General Program and Youth Program of the National Natural Science Foundation of China (NSFC), the Postdoctoral General Fund, the Guangdong Provincial General Fund, and the Shenzhen Free Exploration Fund. As a core team member, she has contributed to over ten national and provincial projects, including the National Key R&D Program. Over the past five years, Dr. Yin has published more than 80 papers as the first author and corresponding author in esteemed international journals such as Autophagy, Cancer Research, Nano Letters, Chemical Science, Coordination Chemistry Reviews, and Journal of Medicinal Chemistry. She is an invited reviewer for several internationally recognized SCI journals and serves as a guest editor for the Journal of Peptide Science and a young editorial board member for Chinese Chemical Letters.
