Laboratory of Pharmaceutical Chemistry and Engineering
A) Bacteria Responsible Materials for Bio-Fouling and Medical Device Infections. Any solid-liquid interfaces provide the environment for microorganism attachment and growth to cause bio-fouling. Bio-fouling occurs on a wide variety of surfaces, including industrial or potable water system piping, natural moist surfaces (bottom of boats and docks), living tissues (oral cavity), and biomedical devices, and is a growing global problem. Bio-fouling in industrial water-based process accounts for billions of dollars lost each year. In addition, as the wide use of biomedical devices and implants, indwelling device infections represent life-threatening circumstances account for the majority (> 80%) of hospital acquired infections. Because of the involvement of resistant mutants and biofilms, classical antibiotics are not effective. Current antibiotic impregnation is not an ideal approach which has many unsolved problems including short life-span, narrowed antibacterial spectrum, ineffectiveness towards resistant mutants, and the potential to hasten the antibiotic resistance process. We are working on polymeric antibacterial designed specifically for implants associated infections. Surfaces constructed from polymeric antibacterial can response bacteria attachment to kill bacteria by inducing autolysis. Biomedical (catheters, stents, orthopedic and dental implants, wound dressing, and antibacterial textiles/) and wide industrial applications of new antibacterial materials (metals and various polymers) are being explored.
B) Therapeutic Peptides. As biologically active molecule sand therapeutics, peptides have some many unique and unbeatable features in comparison with proteins. Bioactive peptides regulate many physiological processes, acting at some sites as endocrine or paracrine signals and at others as neurotransmitters or growth factors, and have positive impacts on human health, including antimicrobial, antifungal, antiviral, and antitumor activities. Over the last decade, there has been a rapid expansion in the study on peptides, and this is likely to continue. We are interested in new peptide design and delivery technology aiming at developing new therapeutic peptides for wide pharmaceutical applications. The two focuses of our current peptide project are: 1）Long life-span therapeutic peptides. All therapeutic peptides are sensitive to proteases and thus have very short life-span in the circulation which is usually insufficient for peptides to be fully exposed to the target tissue. Approaches such as amino acid replacement, polymer conjugation, and microparticulate encapsulation have been tried. Unfortunately, D-amino acid replacement and polymer conjugation may be associated with dramatic peptide activity drop while microparticulate encapsulations are accompanied by increased peptide retention in reticuloendothelial system (RES) to yield undesired toxicity to specific tissues and organs such as spleens and livers. We pioneered in utilizing self-assembly in peptides design and have successfully developed therapeutic peptides with greatly improved life-span; 2) Cell specific and permeable peptides. Due to the hydrophilicity nature and lack of defined structures, short peptides have no or extremely low cell targeting ability and cell permeability. Current conjugation approaches aiming at the poor cell selectivity and permeability will have dramatically and unavoidable effects on the biological activity of peptides. We have developed a single amino acid modification/mutation approach which can improve for selectivity or permeability of short therapeutic peptides with affecting their biological activities.
C) Nano-Technology Enabled Bacteria and Cancer Cell Sensing. Recently, we are working on a nano-patterning technology which can be used in biosensor and other analytic devices in combination with specific molecules (peptides and signaling massagers) for high sensitivity molecular and cell (bacteria and tumor) sensing. Meanwhile, a novel nano-crystalization technology with targeting and controlled release properties is being studied for drugs (anticancer drugs, antibiotics) with poor solubility and limited therapeutic effectiveness.
- Traba C, Chen L, Azzam R, Liang JF, “Insights into discharge argon-mediated biofilm inactivation”. Biofouling, 29:1205-13 (2013).
- Chen L, Liang JF, “Improved stability of bioactive peptides by controlling peptide assembling”. Biomacromolecules. 14:2326-31(2013).
- Chen L, Dong S, Liang JF, “The Effects of Metal Ions on the Cytotoxicity and Selectivity of a Histidine-Containing Lytic Peptides” Int. J. Pept Res Ther. 19: 611-623, (2013).
- Traba C, Chen L., Liang JF, “Low power gas discharge plasma mediated inactivation and removal of biofilms formed on biomaterials”. Cur. Appl. Phys, 13:12-18 (2013).
- Chen L., Patrone N., Liang JF, “Peptide self-assembly on cell membranes to induce cell lysis”, Biomacromolecules, 13(10):3327-33 (2012)
- Chen L, Tu Z Voloshchuk N, Liang JF, “Lytic peptides with improved stability and selectivity designed for cancer treatment”. J Pharm Sci. 101(4):1508-17 (2012).
- Chen L, Liang JF, “Metabolic monosaccharides altered cell responses to anticancer drugs”. Eur J Pharm Biopharm. 81(2):339-45 (2012).
- Kharidia R, Tu Z., Chen L., Liang JF, “Activity and Selectivity of Histidine-Containing Lytic Peptides to Antibiotic Resistant Bacteria”. Arch Microbiol . 194 (4) 579-685 (2012).
Postdoctoral and graduate student positions are available in our lab. Motivated students who are interested in our above research projects are encouraged to apply. Special consideration will be given to students with majors in Biochemistry, Microbiology, and Organic Chemistry. Applications will be reviewed as they come in, and may also be reviewed after the target date if the positions have not been filled.