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Home > Research > NIBIB Intramural Labs > Staff Page: Xiaoyuan Chen Biological Molecular Imaging GroupContentsResearchMolecular imaging will continue to play an increasingly important role in the study of disease initiation, progression and therapeutic response. The emphases of the Biological Molecular Imaging group are to identify diseases specific markers; to develop new probes with cellular and molecular biology oriented techniques and methods; to apply the developed probes into multiple modality imaging; and to collaborate and support other groups to characterize novel imaging or therapeutic agents both in vitro and in vivo.
Target Identification and Probe Development
Molecular imaging allows detection of specific targets in vivo, including visualization of the presence of targets, as well as the quantification of their spatial and temporal distribution. A target may be a single key protein or a particular pathway related to certain pathological processes. We will develop probes of small organic molecules, polypeptides, proteins, antibodies or aptamers by phage peptide display library screening, single chain antibody library screening, and systematic evolution of ligands by exponential enrichment (SELEX). The newly developed probes will be modified and optimized for in vivo molecular imaging application.
Protein Engineering and Site-specific Labeling
Fluorophores, isotopes, and other detectable labels are most commonly introduced into a protein through in vitro modifications with suitable amine or thiol reactive reagents. Non-specific labeling of protein probes will cause heterogeneity and inaccuracy of quantification in imaging process. We will engineer protein probes to accomplish sit-specific modification. For example, with a system utilizing an mRNA template with an amber codon (UAG) instead of a normal initiating codon (AUG) and a complementary misaminoacylated initiator suppressor tRNA capable of initiating protein synthesis from the UAG codon, an artificial amino acid can be introduced into the N-terminal of synthesized proteins. Enzymatic posttranslational modification of proteins utilizing inteins mediated protein splicing is an alternative approach for site-specific labeling.
Therapeutic Response Monitoring
Therapeutic efficacy is one of the key questions need to be answered for each drug or drug candidate. Molecular imaging is able to provide information to evaluate pharmacological effects. For instance, solid tumors are often characterized by having high glucose utilization, tumor cell proliferation, hypoxia with sustained angiogenesis and evasion of apoptosis. The influence of compounds targeting these characteristics of cancer biology can be selectively visualized by molecular imaging techniques. Examples include that FDG PET to image glucose transport and metabolism, FLT PET to evaluate the proliferating status. In addition, some imaging strategies can focus on one particular pathway such as apoptosis and hypoxia or single molecular target to access specific drugs.
Reporter Gene Based Imaging
As a unique branch of molecular imaging, various reporter genes have been developed and expression of reporter genes can be evaluated by multiple imaging modalities including optical imaging, SPECT/PET or MRI. With split reporter gene or bioluminescence resonance energy transfer (BRET) system, protein-protein interaction can be visualized in living organisms. We will develop and apply the reporter gene imaging to corroborate probe based non-invasive imaging.The PET radiochemistry section has research interests in the development of novel methods for incorporation of radionuclides into tracers for the study of biologically important processes. Our research efforts are driven by the desire to translate our work into clinically relevant human diseases. Thus, we seek to collaborate with clinicians that share our goal of providing new imaging tools with utility in patients. We contributed to the preparation of INDs of compounds now used at the NIH Clinical Center (FC-WAY and FPTZTP) and an RGD based peptide agent at Stanford University.StaffBiological Molecular Imaging Group Leader/ISTP Research Fellow
Telephone: 650-336-4495 Telephone: 301-402-4896 |
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Department of Health and Human Services |
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National Institutes of Health |
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