Our research focuses on molecular and cellular engineering for gene therapy, biomaterials, biopharmaceuticals, and stem cell bioengineering.
Proteins play important roles in all kinds of biological systems from viruses to human beings. Therefore, understanding the function and structure of proteins in biological systems is a very interesting and challenging area for engineers as well as scientists. Recent advances in protein engineering tools with the aid of genetic engineering, such as rational design, unnatural amino acid mutagenesis and high-throughput screening of and proteins, facilitate design of proteins with novel structures and functions. Recombinant DNA techniques open a door to produce a genetically engineered protein from living cells. Chemical engineering approaches combined with protein engineering and metabolic engineering facilitate design and optimization of biosynthetic processes of the engineered proteins from living cells, and design of even living cells themselves. Our research will focus on design of novel genetically engineered proteins and living cells that will be used to cure diseases, deliver drugs, produce novel biomaterials, produce renewable energy, and monitor cellular processes.
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| Research Projects |
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 1. Modulation of amyloid-beta aggregation by small molecules and peptides
Alzheimer’s disease (AD) is a degenerative illness that impairs memory, thinking and behavior. The accumulation of insoluble amyloid aggregates, composed primarily of the neurotoxic amyloid-beta peptide, is a hallmark of AD. Although amyloid-beta monomer is soluble and non-toxic, soluble amyloid-beta oligomers are known to be primary toxic species in AD. Therefore, modulation of amyloid-beta oligomerization is considered a promising therapeutic strategy to prevent or treat AD. Beyond therapeutic impact, recently discovered aggregation modulators have also enhanced our understanding of AD pathogenic mechanism. Despite these advances, an effective therapeutic to AD is still unavailable. Therefore, there remains a need to discover new chemical classes of safe and effective modulators. In order to search for inhibitors, we are screening a family of small molecules and peptides that can modulate amyloid-beta aggregation and toxicity. |
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 2. Site-specific antibody conjugation to viral gene delivery vehicle for cell targeting
Adeno-associated virus (AAV) has a 10-nm diameter of icosahedral shell structure co ntaining genetic materials (genes) inside. AAV can carry genes to broad range of cells or tissue. However, selective delivery of a gene to a specific cell or tissue, except liver, is very challenging. Even some cells including cancer cells are resistant to infection of AAV. Targeted gene delivery to cancer cells has great therapeutic benefit. Several antibodies, which selectively bind to their target molecules, are available to target cancer cells. However, conjugation of an antibody to random positions of AAV coat protein often results in compromise of its cell entry, most likely due to blocking receptor binding of AAV. Therefore, our research will focus on site-specific conjugation of an antibody at a permissive site of virus particles to enhance gene delivery. |
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 3. Site-specific PEG conjugation to multiple sites of therapeutic proteins for enhanced stability in vivo.
Therapeutic applications of human growth hormone (hGH) are limited by its relatively short lifetime in serum. Enhancing the stability of hGH or the hGH receptor antagonist via random polyethylene glycol (PEG) conjugation through lysine residues decreases the receptor binding affinity by two to three orders of magnitude, which is due, at least in part, to hindrance of receptor binding by PEG molecules conjugated to nonpermissive positions. Phenylalanine analogs with reactive functional groups will be introduced into hGH at permissive positions for “chemically orthogonal” PEGylation, which may reduce the reduction in receptor binding affinity and enhance the stability of hGH in serum.
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