Biological Molecular Imaging Section

Contents

• Research and Facilities
• Staff

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Research

The Biological Molecular Imaging Section focuses on identification of disease-specific biomarkers; development of new molecular imaging probes with cellular and molecular biology oriented techniques and methods; application of the developed probes into multimodality imaging; and collaborates with the other two LOMIN sections 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 site-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 post-translational 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 that needs 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 FDG PET to image glucose transport and metabolism, and FLT PET to evaluate the proliferating status. Additionally, some imaging strategies can focus on one particular pathway such as apoptosis and hypoxia or a 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.

Facilities

The Biological Molecular Imaging Section is physically located in building 9. The laboratory is equipped with instruments to perform cell biology and molecular biology experiments, such as cell culture, western blot, PCR, and gene and protein engineering. An Olympus X-81 epifluorescent microscope allows us to investigate fluorphores label probes in tissue section or live cells.

The group has significant experience in conducting phage display, protein expression and purification, transient and stable transfection, cell-based probe characterization, cell and tissue HE, Prussian blue, and immunofluorescence staining. We are proficient in small animal handling, including subcutaneous and orthotopic tumor xenograft model and infarction model development, small animal imaging with newly installed Simens Inveon PET/CT and CRI maestro within the group. We also access the NIH/MIF (Mouse Imaging Facility) to perform MRI and BLI imaging.

Staff 

Gang Niu, Ph.D.
Group Leader, Biological Molecular Imaging Section
Telephone: 301-402-4486

Naoki Hida, Ph.D.
Visiting Fellow
Telephone: 301-594-0306

Shuo Hu, M.D., Ph.D.
Visiting Scholar
Telephone: 301-594-0306

Zhe Wang, Ph.D.
Visiting Fellow
Telephone: 301-402-2574

Lei Zhu, M.S.
Predoctoral Visiting Fellow
Telephone: 301-402-2711

Peng Huang, Ph.D.
Visiting Fellow
Telephone: 301-594-0310

Jie Lu, Ph.D.
Research Fellowship
Telephone: 301-402-0775

Zhongchan Sun, M.D.
Predoctoral Visiting Fellow
Telephone: 301-594-0306

Jinxia Guo, B.S.
Predoctoral Visiting Fellow
Telephone: 301-594-0306

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