Professional Education


  • Doctor of Philosophy, University of Akron (2021)
  • Master of Science, University of Science and Technology Beijing (2017)

Stanford Advisors


All Publications


  • Antimicrobial alpha-defensins as multi-target inhibitors against amyloid formation and microbial infection CHEMICAL SCIENCE Zhang, Y., Liu, Y., Tang, Y., Zhang, D., He, H., Wu, J., Zheng, J. 2021; 12 (26): 9124-9139

    Abstract

    Amyloid aggregation and microbial infection are considered as pathological risk factors for developing amyloid diseases, including Alzheimer's disease (AD), type II diabetes (T2D), Parkinson's disease (PD), and medullary thyroid carcinoma (MTC). Due to the multifactorial nature of amyloid diseases, single-target drugs and treatments have mostly failed to inhibit amyloid aggregation and microbial infection simultaneously, thus leading to marginal benefits for amyloid inhibition and medical treatments. Herein, we proposed and demonstrated a new "anti-amyloid and antimicrobial hypothesis" to discover two host-defense antimicrobial peptides of α-defensins containing β-rich structures (human neutrophil peptide of HNP-1 and rabbit neutrophil peptide of NP-3A), which have demonstrated multi-target, sequence-independent functions to (i) prevent the aggregation and misfolding of different amyloid proteins of amyloid-β (Aβ, associated with AD), human islet amyloid polypeptide (hIAPP, associated with T2D), and human calcitonin (hCT, associated with MTC) at sub-stoichiometric concentrations, (ii) reduce amyloid-induced cell toxicity, and (iii) retain their original antimicrobial activity upon the formation of complexes with amyloid peptides. Further structural analysis showed that the sequence-independent amyloid inhibition function of α-defensins mainly stems from their cross-interactions with amyloid proteins via β-structure interactions. The discovery of antimicrobial peptides containing β-structures to inhibit both microbial infection and amyloid aggregation greatly expands the new therapeutic potential of antimicrobial peptides as multi-target amyloid inhibitors for better understanding pathological causes and treatments of amyloid diseases.

    View details for DOI 10.1039/d1sc01133b

    View details for Web of Science ID 000659476200001

    View details for PubMedID 34276942

    View details for PubMedCentralID PMC8261786

  • Design and Engineering of Amyloid Aggregation-Prone Fragments and Their Antimicrobial Conjugates with Multi-Target Functionality ADVANCED FUNCTIONAL MATERIALS Zhang, Y., Tang, Y., Liu, Y., Zhang, D., Zheng, J. 2021; 31 (32)
  • Dual amyloid cross-seeding reveals steric zipper-facilitated fibrillization and pathological links between protein misfolding diseases JOURNAL OF MATERIALS CHEMISTRY B Zhang, Y., Zhang, M., Liu, Y., Zhang, D., Tang, Y., Ren, B., Zheng, J. 2021; 9 (15): 3300-3316

    Abstract

    Amyloid cross-seeding, as a result of direct interaction and co-aggregation between different disease-causative peptides, is considered as a main mechanism for the spread of the overlapping pathology across different cells and tissues between different protein-misfolding diseases (PMDs). Despite the biomedical significance of amyloid cross-seeding in amyloidogenesis, it remains a great challenge to discover amyloid cross-seeding systems and reveal their cross-seeding structures and mechanisms. Herein, we are the first to report that GNNQQNY - a short fragment from yeast prion protein Sup35 - can cross-seed with both amyloid-β (Aβ, associated with Alzheimer's disease) and human islet amyloid polypeptide (hIAPP, associated with type II diabetes) to form β-structure-rich assemblies and to accelerate amyloid fibrillization. Dry, steric β-zippers, formed by the two β-sheets of different amyloid peptides, provide generally interactive and structural motifs to facilitate amyloid cross-seeding. The presence of different steric β-zippers in a variety of GNNQQNY-Aβ and GNNQQNY-hIAPP assemblies also explains amyloid polymorphism. In addition, alteration of steric zipper formation by single-point mutations of GNNQQNY and interactions of GNNQQNY with different Aβ and hIAPP seeds leads to different amyloid cross-seeding efficiencies, further confirming the existence of cross-seeding barriers. This work offers a better structural-based understanding of amyloid cross-seeding mechanisms linked to different PMDs.

    View details for DOI 10.1039/d0tb02958k

    View details for Web of Science ID 000641964200013

    View details for PubMedID 33651875

  • Design principles and fundamental understanding of biosensors for amyloid-beta detection JOURNAL OF MATERIALS CHEMISTRY B Zhang, Y., Ren, B., Zhang, D., Liu, Y., Zhang, M., Zhao, C., Zheng, J. 2020; 8 (29): 6179-6196

    Abstract

    Alzheimer's disease (AD), as an age-related, progressive neurodegenerative disease, poses substantial challenges and burdens on public health and disease research. While significant research, investment, and progress have been made for the better understanding of pathological mechanisms and risk factors of AD, all clinical trials for AD treatment and diagnostics have failed so far. Since early and accurate diagnostics of AD is key to AD prevention and treatment, the development of probes for AD-related biomarkers is highly important but challenging for AD diagnosis. In this review, emerging evidence highlights the importance of the Aβ cascade hypothesis and indicates a significant role of Aβ and its aggregates as biomarkers in the pathogenesis of AD; we present an up-to-date summary on Aβ-based biosensor systems. Four typical biosensor systems for Aβ detection and representative examples from each type of biosensor are carefully selected and discussed in terms of their sensing strategies, materials, and mechanisms. Finally, we address the remaining challenges and opportunities for the development of future sensing platforms for Aβ detection and Aβ-based diagnostics of AD.

    View details for DOI 10.1039/d0tb00344a

    View details for Web of Science ID 000553658200010

    View details for PubMedID 32355946