I. Relevant Research in Animal Research Direction of Cell Biology Discipline

Team Members: Teng Chunbo, Sui Guangchao, Wang Yang, Wang Chunsheng, Shi Jinming, Liang Yang, Zheng Jian, Nie Yuzhe, and Li Dangdang.

(1) Research and Application of Forest-derived Bioactive Substances

China, particularly its vast forested Northeastern region, boasts abundant plant diversity. Many of these plants synthesize rich bioactive compounds, constituting critical medicinal plant resources and forming the foundation of China’s pharmaceutical development. Therefore, exploring and researching forest-derived bioactive components will enable more scientific and effective utilization of these extensive reserves. Our team employs advanced biochemical, molecular biological, cellular biological, and omics approaches to investigate the therapeutic applications of forest-derived bioactive substances in diseases such as diabetes and cancer. Key research focuses include the following:

1) Pharmacological Mechanism Research

Utilizing omics methodologies, we systematically analyze the targeted biological processes of bioactive substances within cells, elucidating their molecular mechanisms in inhibiting pathological progression and preventing diseases. This establishes a theoretical foundation for the clinical application of forest-derived bioactive substances.

2) Molecular Target Research

Through molecular fishing technology, we enrich and identify intracellular biomacromolecules that interact with bioactive substances. By resolving the molecular mechanisms of binding and associated biological functions between these substances and their targets, we provide fundamental data for the innovation and modification of pharmaceutical molecules.

3) Combination Drug Administration Research

Many forest-derived bioactive substances can selectively inhibit pathological cells while protecting normal cells, whereas existing clinical drugs often exhibit toxic side effects on the body. Therefore, combining forest-derived bioactive substances with clinical drugs achieves disease-inhibiting efficacy while reducing adverse effects on patients. We will integrate cell- and animal model-based approaches with omics methodologies to dissect the synergistic effects of combination drug administration and the pharmacodynamic mechanisms underlying disease-inhibiting activity.

4) Drug Delivery Research

Precise drug delivery is critically significant for disease treatment. Forest-derived bioactive substances can be developed into natural biomedical materials to assist drug delivery and control drug release, particularly in applications involving precision-controlled release of anticancer drugs, thereby enhancing therapeutic efficacy and targeting effects.

(2) Fundamental Research on the Molecular and Cellular Basis of Human Diseases Including Cancer and Diabetes

Aberrant gene expression and protein activity dysregulation within cells constitute the primary causative factors underlying various human diseases, including cancer and diabetes. Deciphering the biological processes governing gene expression and protein functionality and elucidating the molecular mechanisms driving disease onset and progression hold significant implications for preventing and treating human diseases. The Cell Biology discipline's fundamental research on human diseases encompasses the following aspects:

1) Regulatory Mechanisms of Tissue Stem Cell Proliferation and Differentiation

Using pancreatic and muscular systems as primary models, we investigate the regulatory mechanisms governing the proliferation and differentiation of stem/progenitor cells, conduct fundamental research on progenitor cell-based therapies for diabetes and muscular dystrophy, and explore the molecular mechanisms through which forest-derived bioactive substances and trace metal elements influence stem/progenitor cells and tumor cells.

2) Regulatory Mechanisms of Gene Expression in Cancer Cells

Employing breast cancer and liver cancer as experimental models, we study epigenetic molecular mechanisms that regulate the expression of proto-oncogenes and tumor suppressor genes. Key molecular regulatory mechanisms under investigation include: histone modifications, non-coding RNA functions, G-quadruplex formation, mRNA stability and precursor splicing, enhancer formation, phase separation of transcriptional regulatory proteins, etc.

II. Plant-Oriented Research in Cell Biology Discipline

Team Members:Zhan Yaguang, Zeng Fansuo, Niu Ben, Yin Jing, You Xiangling, Fan Guizhi, Qi Fenghui

The plant research focus of the Cell Biology discipline encompasses three primary areas:

(1) Centered on the overarching objectives of genetic improvement and cell engineering utilization, we conduct applied basic research, extending into both fundamental and applied research domains, using forest plants from China’s Northeastern region as primary study subjects.

(2)Targeting frontier scientific challenges and critical technologies, we systematically explore forest plant gene resources related to stress resistance, fast growth, cell wall development, wood quality, secondary metabolism, and ornamental traits. This includes investigating key trait formation's molecular basis and regulatory mechanisms, coupled with conventional and molecular breeding strategies to develop elite cultivars and novel plant varieties.

(3) Leveraging bioengineering technologies such as cell engineering and metabolic engineering, we mine valuable medicinal bioactive compounds (e.g., terpenoids, phenolics, and saponins) from forest plants, their symbiotic microbes, and other beneficial arboreal microorganisms. We follow this with high-efficiency synthesis, development, and utilization of these components.

Key research focuses include the following:

1. Multi-purpose Elite Cultivar Breeding, Propagation Technology Innovation, and Molecular Mechanism Research on Key Trait Formation in Precious Northeast Broadleaf Tree Species

We intensively explore gene resources related to stress resistance, fast growth, cell wall development, wood quality, and ornamental traits in the precious Northeast broadleaf tree species. Integrated with conventional breeding, we develop novel cultivars such as Fraxinus mandshurica (Manchurian ash), with particular emphasis on resolving bottleneck challenges in propagation through technological integration, innovation, and supporting mechanism studies. Specific research components include:

(1) Intraspecific and interspecific F1 hybridization to aggregate superior traits (fast growth, stress resistance, high quality, pest/disease resistance) for multi-purpose elite cultivar development. Concurrently, we employ mutagenesis and ploidy breeding combined with gene editing technologies for molecular breeding, accelerating germplasm innovation and shortening breeding/utilization cycles.

(2) We conduct integrated technological innovation in vegetative propagation and rejuvenation mechanism studies to address clonal propagation bottlenecks like age-related effects in Northeast broadleaf trees. This establishes scaled production systems for elite propagation materials to enhance the utilization rate of clonal elite cultivars and advance the elite cultivar development process.

(3) Investigating the molecular mechanisms and regulatory technologies that underlie critical trait formation (e.g., wood development, juvenile-to-mature phase transition) provides theoretical foundations and technical support for forest tree improvement and utilization. This enhances molecular-level research capabilities while accelerating advancements in elite cultivar breeding and propagation.

2. Synthesis Regulation and High-efficiency Utilization of Forest-derived Bioactive Substances

Using key forest and understory medicinal plants—including Betula platyphylla (white birch), Eleutherococcus senticosus, Panax notoginseng, Cannabis sativa (industrial hemp), and Apocynum venetum—we investigate the regulation of high-efficiency synthesis and the molecular regulatory mechanisms of anti-tumor bioactive components, such as terpenoids, phenolics, and saponins. Key research components include:

(1) Mining and identifying critical functional genes in the biosynthetic pathways of triterpenes, saponins, cannabidiol, and apocynin flavonoids. We use gene editing and pathway engineering technologies to genetically enhance medicinal plants and develop novel germplasm, providing innovative approaches and materials for efficiently utilizing forest-derived bioactive substances.

(2) Regulating high-efficiency biosynthesis of bioactive substances using plant tissues and cells while deciphering regulatory mechanisms involving environmental factors, nutrient components, and signaling molecules. Transcriptomic and metabolomic technologies are applied to resolve the regulatory networks of terpenoid and phenolic metabolism. Synthetic biology and metabolic engineering strategies are leveraged to synthesize bioactive compounds and their precursors, enhancing utilization efficiency.

(3) Isolating and characterizing endophytic fungi from stress-resistant forest trees and medicinal plants to explore their biological functions and medicinal value. To investigate their pharmaceutical and nutraceutical applications, we conduct large-scale fermentation and cultivation of macro-medicinal fungi such as Sanghuangporus sanghuang and Inonotus obliquus (Chaga).

3. Regulatory Mechanisms of Saponin Biosynthesis in Selected Araliaceae Plants and Bioreactor-based Large-scale Production Research

Araliaceae plants, including Panax notoginseng, Aralia elata, and Eleutherococcus senticosus, are critical traditional Chinese medicinal resources, with their primary bioactive constituents being pentacyclic triterpenoids. Investigating the saponin biosynthesis regulatory mechanisms in these three Araliaceae species and developing bioreactor-based large-scale production technologies will establish a theoretical foundation for the industrial biosynthesis of saponins from Araliaceae plants. This research also offers novel technical alternatives for producing pharmaceutically and nutraceutically active compounds such as ginsenosides.

4. Mining and Utilization of Beneficial Microbial Resources in Forest Trees

We conduct a systematic collection of disease-suppressive and growth-promoting microbial resources from ecologically and economically valuable forest trees, including Populus trichocarpa (black cottonwood), Xanthoceras sorbifolium, Pinus sylvestris var. mongolica (Mongolian pine), and Ricinus communis (castor bean). This research investigates the assembly mechanisms of symbiotic microbiomes and elucidates their molecular basis for enhancing growth, suppressing diseases, and conferring stress resistance. Concurrently, targeting devastating forest diseases such as pine wilt disease, we isolate and screen microbial strains with biocontrol potential, characterize their disease-suppression mechanisms, and develop high-efficiency microbial biocontrol agents for forest protection.