Hak Soo Choi, PhD
Assistant Professor, Department of Medicine, Harvard Medical School
Staff Scientist, Hematology-Oncology, Beth Israel Deaconess Medical Center
DF/HCC Program AffiliationProstate Cancer
Lab WebsiteBIDMC Center for Molecular Imaging
Research AbstractMy research focuses on the development of novel optical contrast agents for tissue- and organ-specific targeting and diagnosis. Of particular interest is targeted fluorophores, which can be used for image-guided surgery by specifically visualizing target tissue with high optical properties and by avoiding nonspecific uptake in normal background tissues.
During the past decade, we have been systematically probing the relationship among the hydrodynamic diameter, shape, charge, and hydrophobicity of contrast agents on in vivo biodistribution and clearance (Nat Biotechnol. 2007, Nano Lett. 2009, Angew Chem Int Ed. 2011). Using invisible near-infrared (NIR) fluorescence and 3D molecular modeling, we have defined the relationship among the key independent variables that dictate biodistribution and tissue-specific targeting such as lung and sentinel lymph nodes (Nat Biotechnol. 2010), human prostate cancers (Nat Nanotechnol. 2010), and human melanomas (Nat Biotechnol. 2013). Another project we have been working on is targeting of endocrine glands and their tumors including insulinoma. Currently we could achieve specific targeting on the pituitary gland (anterior/posterior separately), thyroid gland, thymus, adrenal gland, and pancreas (manuscripts in preparation). We have also developed organ-specific targeted fluorophores for kidneys, liver, lungs, spleen, lymph nodes, salivary glands, brown fat, bone, cartilage, seminal vesicle, and prostate (manuscripts in preparation).
Most recently, we have also developed biodegradable NIR scaffolds and cellular trafficking systems for longitudinal monitoring in tissue engineering and regenerative medicine (Biomed Mater. 2013). Using the dual-channel intraoperative FLARE imaging system, we are currently trying to target cancerous tissue and vasculature/nerve, bone and cartilage, thyroid and cartilage, vasculature and bone, or nerve and cartilage/bone simultaneously, which lay the foundation for clinical translation to image-guided surgery.
Armed with the ability to a priori engineer small molecules, my laboratory also focuses on the discovery of lead compounds that bind specifically to living cancer cells. The Robotic Chemistry Group at the Center for Molecular Imaging has developed a system of technology that is capable of quickly screening thousands of small molecules against dozens of types of living cancer cells. With this system, and combinatorial chemical libraries designed specifically for the target cell of interest, he is seeking to discover cancer cell-specific small molecules. The system is quite flexible and permits any type of cell (cancer, endothelial, or other) to be screened.