Overview of my current research work

In general, I am very interested in understanding the mechanism of biomolecule recognition, which plays central role in a variety of life activities, and hope to exploit its potential application in different area of biotechnology and biomedical applications.

(1)   Biomedical materials for blood purification treatment

One specific interest is to develop techniques that enable recognizing and separating some specific disease-related molecules directly from human blood circulation, for achieving blood purification treatment for a range of serious diseases. To this end, we have developed several strategies to design functional materials, including affinity ligand screening, camelid-derived single chain antibody or nanobody, and molecular imprinting et al. These techniques are used to synthesize selective adsorbents for removing pathogenic factors from the blood of patients suffering from autoimmune diseases, renal failure, sepsis, and even cancer. For example, we are using nanobody to develop blood purification materials to treat dialysis related amyloidosis (DRA) by selectively removing beta 2 microglobulin. Meanwhile we are also isolating nanobodies against cytokines for synthesizing selective adsorbents, which could be used to control “Cytokine Storm” by directly reducing circulating cytokines from the blood of critically-ill patients with deadly inflammation.

Currently, two of my patented blood purification adsorbents have been industrialized to develop medical appliances for treating autoimmune disease and DRA, respectively. The former has been in the stage of clinical trial in China.

(2)   Biomolecular engineering for bioprocessing and biohybrid materials

Other studies focus on engineering functional proteins and developing approaches for bioseparation, biosensing, and biofunctional device design, which are mainly based on the construction of biohybrid material system. Current work is centered at the application of engineering nanobody. The development of the methodologies involves production of engineered nanobody, specific tagging, multivalued complex, site-specific modification, bioconjugation, surface modification, as well as addressing issues such as stability, efficiency and activity rate in the process of applications.

We have been developing chemical and biological methods that could enable the immobilization of nanobody or other functional proteins in a controllable and efficient manner, to facilitate the preparation of affinity chromatography media, and biosensor surfaces. We used photochemical crosslinking of phenol groups to immobilize proteins and prepare all-protein nanoparticles. The reactions could be completed within seconds without loss of protein activity. Nanobody-based multiprotein complexes have been designed to form multifunctional protein assemblies.   

These technologies and methods are expected to be extended to other biomedical areas, such as assembly of targeted nanoparticles for drug delivery, disease detection and mechanistic studies.