Photo of Hak Soo Choi,  PhD

Hak Soo Choi, PhD

Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center
Phone: (617) 667-6024
Fax: (617) 667-0214


hchoi@bidmc.harvard.edu

Hak Soo Choi, PhD

Beth Israel Deaconess Medical Center

EDUCATIONAL TITLES

  • Associate Professor, Medicine, Harvard Medical School
  • Staff Scientist, Hematology-Oncology, Beth Israel Deaconess Medical Center

DF/HCC PROGRAM AFFILIATION

Research Abstract

My research focuses on the development of novel tissue- and organ-specific contrast agents for diagnosis, staging, and treatment of human diseases. Of particular interest is tumor-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 nanoparticles and small molecule contrast agents on in vivo biodistribution and clearance (Nature Biotech. 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 (Nature Biotech. 2010), human prostate cancers (Nature Nanotech. 2010), and human melanomas (Nature Biotech. 2013). Another project we have been working on is targeting of endocrine glands and their tumors. Currently we have achieved specific targeting on the thyroid/parathyroid glands (Nature Medicine, 2015), pancreas (Theranostics, 2014), thymus, pituitary gland (anterior/posterior separately), and adrenal glands (manuscripts in preparation/review). We have also developed other tissue-specific targeted fluorophores for lymph nodes (Theranostics, 2014), bone and cartilage (Angew Chem Int Ed. 2014), kidneys, liver, lungs, spleen, salivary glands, brown fat, seminal vesicle, and prostate (manuscripts in preparation).

Regenerative medicine with tissue-engineered scaffolds is another area of interest, and we have developed biodegradable NIR scaffolds and cellular trafficking systems for longitudinal monitoring of tissue regeneration (Sci Rep. 2013 and Biomed Mater. 2013). Using dual-channel intraoperative imaging systems, we are currently trying to target cancerous tissue/vasculature/nerve (tumors), cardiovascular diseases, and bone/cartilage/inflammation (rheumatoid arthritis) simultaneously with different colors, which lay the foundation for clinical translation to image-guided surgery.

Publications

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  • Wada H, Hyun H, Vargas C, Genega EM, Gravier J, Gioux S, Frangioni JV, Choi HS. Sentinel Lymph Node Mapping of Liver. Ann Surg Oncol 2015. PubMed
  • Njiojob CN, Owens EA, Narayana L, Hyun H, Choi HS, Henary M. Tailored Near-Infrared Contrast Agents for Image Guided Surgery. J Med Chem 2015. PubMed
  • Hyun H, Park MH, Owens EA, Wada H, Henary M, Handgraaf HJ, Vahrmeijer AL, Frangioni JV, Choi HS. Structure-inherent targeting of near-infrared fluorophores for parathyroid and thyroid gland imaging. Nat Med 2015; 21:192-7. PubMed
  • Owens EA, Lee S, Choi J, Henary M, Choi HS. NIR fluorescent small molecules for intraoperative imaging. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2015. PubMed
  • Kim S, Jung UT, Kim SK, Lee JH, Choi HS, Kim CS, Jeong MY. Nanostructured multifunctional surface with antireflective and antimicrobial characteristics. 2015; 7:326-31. PubMed
  • Wada H, Hyun H, Vargas C, Gravier J, Park G, Gioux S, Frangioni JV, Henary M, Choi HS. Pancreas-targeted NIR fluorophores for dual-channel image-guided abdominal surgery. Theranostics 2015; 5:1-11. PubMed
  • Jee JE, Lim J, Hyun H, Oon J, Ong YS, Massif C, Chang YT, Choi HS, Lee SS. Investigating fluorescent dyes in fluorescence-assisted screenings. Chem Commun (Camb) 2014. PubMed
  • Inoue K, Gibbs SL, Liu F, Lee JH, Xie Y, Ashitate Y, Fujii H, Frangioni JV, Choi HS. Microscopic Validation of Macroscopic In Vivo Images Enabled by Same-Slide Optical and Nuclear Fusion. J Nucl Med 2014. PubMed
  • Salim MM, Owens EA, Gao T, Lee JH, Hyun H, Choi HS, Henary M. Hydroxylated near-infrared BODIPY fluorophores as intracellular pH sensors. Analyst 2014; 139:4862-73. PubMed
  • Chung JE, Tan S, Gao SJ, Yongvongsoontorn N, Kim SH, Lee JH, Choi HS, Yano H, Zhuo L, Kurisawa M, Ying JY. Self-assembled micellar nanocomplexes comprising green tea catechin derivatives and protein drugs for cancer therapy. Nat Nanotechnol 2014. PubMed
  • Hyun H, Wada H, Bao K, Gravier J, Yadav Y, Laramie M, Henary M, Frangioni JV, Choi HS. Phosphonated near-infrared fluorophores for biomedical imaging of bone. Angew Chem Int Ed Engl 2014; 53:10668-72. PubMed
  • Verbeek FP, van der Vorst JR, Tummers QR, Boonstra MC, de Rooij KE, Löwik CW, Valentijn AR, van de Velde CJ, Choi HS, Frangioni JV, Vahrmeijer AL. Near-Infrared Fluorescence Imaging of Both Colorectal Cancer and Ureters Using a Low-Dose Integrin Targeted Probe. Ann Surg Oncol 2014. PubMed
  • Choi HS. Nanoparticle assembly: building blocks for tumour delivery. Nat Nanotechnol 2014; 9:93-4. PubMed
  • Ashitate Y, Hyun H, Kim SH, Lee JH, Henary M, Frangioni JV, Choi HS. Simultaneous mapping of pan and sentinel lymph nodes for real-time image-guided surgery. Theranostics 2014; 4:693-700. PubMed
  • Park MH, Hyun H, Ashitate Y, Wada H, Park G, Lee JH, Njiojob C, Henary M, Frangioni JV, Choi HS. Prototype nerve-specific near-infrared fluorophores. Theranostics 2014; 4:823-33. PubMed
  • Yeo SJ, Huong DT, Hong NN, Li CY, Choi K, Yu K, Choi DY, Chong CK, Choi HS, Mallik SK, Kim HS, Sung HW, Park H. Rapid and Quantitative Detection of Zoonotic Influenza A Virus Infection Utilizing Coumarin-derived dendrimer-based Fluorescent Immunochromatographic Strip Test (FICT). Theranostics 2014; 4:1239-49. PubMed
  • Huang X, Zhang F, Zhu L, Choi KY, Guo N, Guo J, Tackett K, Anilkumar P, Liu G, Quan Q, Choi HS, Niu G, Sun YP, Lee S, Chen X. Effect of injection routes on the biodistribution, clearance, and tumor uptake of carbon dots. ACS Nano 2013; 7:5684-93. PubMed
  • Huang X, Zhang F, Wang H, Niu G, Choi KY, Swierczewska M, Zhang G, Gao H, Wang Z, Zhu L, Choi HS, Lee S, Chen X. Mesenchymal stem cell-based cell engineering with multifunctional mesoporous silica nanoparticles for tumor delivery. Biomaterials 2012; 34:1772-80. PubMed
  • Owens EA, Hyun H, Kim SH, Lee JH, Park G, Ashitate Y, Choi J, Hong GH, Alyabyev S, Lee SJ, Khang G, Henary M, Choi HS. Highly charged cyanine fluorophores for trafficking scaffold degradation. 2013; 8:014109. PubMed
  • Kim SH, Park G, Hyun H, Lee JH, Ashitate Y, Choi J, Hong GH, Owens EA, Henary M, Choi HS. Near-infrared lipophilic fluorophores for tracing tissue growth. 2013; 8:014110. PubMed
  • Choi HS, Gibbs SL, Lee JH, Kim SH, Ashitate Y, Liu F, Hyun H, Park G, Xie Y, Bae S, Henary M, Frangioni JV. Targeted zwitterionic near-infrared fluorophores for improved optical imaging. Nat Biotechnol 2013; 31:148-53. PubMed
  • Kim SH, Lee JH, Hyun H, Ashitate Y, Park G, Robichaud K, Lunsford E, Lee SJ, Khang G, Choi HS. Near-infrared fluorescence imaging for noninvasive trafficking of scaffold degradation. Sci Rep 2013; 3:1198. PubMed
  • Lee JH, Park G, Hong GH, Choi J, Choi HS. Design considerations for targeted optical contrast agents. Quant Imaging Med Surg 2013; 2:266-73. PubMed
  • Ashitate Y, Kim SH, Tanaka E, Henary M, Choi HS, Frangioni JV, Flaumenhaft R. Two-wavelength near-infrared fluorescence for the quantitation of drug antiplatelet effects in large animal model systems. J. Vasc. Surg. 2012; 56:171-80. PubMed
  • Huang X, Zhang F, Lee S, Swierczewska M, Kiesewetter DO, Lang L, Zhang G, Zhu L, Gao H, Choi HS, Niu G, Chen X. Long-term multimodal imaging of tumor draining sentinel lymph nodes using mesoporous silica-based nanoprobes. Biomaterials 2012; 33:4370-8. PubMed
  • Ashitate Y, Lee BT, Laurence RG, Lunsford E, Hutteman M, Oketokoun R, Choi HS, Frangioni JV. Intraoperative Prediction of Postoperative Flap Outcome Using the Near-Infrared Fluorophore Methylene Blue. Ann Plast Surg 2012. PubMed
  • Liu F, Lunsford EP, Tong J, Ashitate Y, Gibbs SL, Yu J, Choi HS, Henske EP, Frangioni JV. Real-time monitoring of tumorigenesis, dissemination, & drug response in a preclinical model of lymphangioleiomyomatosis/tuberous sclerosis complex. PLoS ONE 2012; 7:e38589. PubMed
  • Zhu L, Guo N, Li Q, Ma Y, Jacboson O, Lee S, Choi HS, Mansfield JR, Niu G, Chen X. Dynamic PET and Optical Imaging and Compartment Modeling using a Dual-labeled Cyclic RGD Peptide Probe. Theranostics 2012; 2:746-56. PubMed
  • Ashitate Y, Stockdale A, Choi HS, Laurence RG, Frangioni JV. Real-Time Simultaneous Near-Infrared Fluorescence Imaging of Bile Duct and Arterial Anatomy. J Surg Res 2011. PubMed
  • Choi HS, Nasr K, Alyabyev S, Feith D, Lee JH, Kim SH, Ashitate Y, Hyun H, Patonay G, Strekowski L, Henary M, Frangioni JV. Synthesis and in vivo fate of zwitterionic near-infrared fluorophores. Angew Chem Int Ed Engl 2011; 50:6258-63. PubMed
  • Ashitate Y, Tanaka E, Stockdale A, Choi HS, Frangioni JV. Near-infrared fluorescence imaging of thoracic duct anatomy and function in open surgery and video-assisted thoracic surgery. J Thorac Cardiovasc Surg 2011; 142:31-8.e1-2. PubMed
  • Lee JH, Choi HS, Nasr KA, Ha M, Kim Y, Frangioni JV. High-throughput small molecule identification using MALDI-TOF and a nanolayered substrate. Anal Chem 2011; 83:5283-9. PubMed
  • Hutteman M, Choi HS, Mieog JS, van der Vorst JR, Ashitate Y, Kuppen PJ, van Groningen MC, Löwik CW, Smit VT, van de Velde CJ, Frangioni JV, Vahrmeijer AL. Clinical translation of ex vivo sentinel lymph node mapping for colorectal cancer using invisible near-infrared fluorescence light. Ann Surg Oncol 2011; 18:1006-14. PubMed
  • Mieog JS, Troyan SL, Hutteman M, Donohoe KJ, van der Vorst JR, Stockdale A, Liefers GJ, Choi HS, Gibbs-Strauss SL, Putter H, Gioux S, Kuppen PJ, Ashitate Y, Löwik CW, Smit VT, Oketokoun R, Ngo LH, van de Velde CJ, Frangioni JV, Vahrmeijer AL. Toward Optimization of Imaging System and Lymphatic Tracer for Near-Infrared Fluorescent Sentinel Lymph Node Mapping in Breast Cancer. Ann Surg Oncol 2011. PubMed
  • Choi HS, Frangioni JV. Nanoparticles for biomedical imaging: fundamentals of clinical translation. Mol Imaging 2010; 9:291-310. PubMed
  • Choi HS, Ashitate Y, Lee JH, Kim SH, Matsui A, Insin N, Bawendi MG, Semmler-Behnke M, Frangioni JV, Tsuda A. Rapid translocation of nanoparticles from the lung airspaces to the body. Nat Biotechnol 2010; 28:1300-3. PubMed
  • Gioux S, Choi HS, Frangioni JV. Image-guided surgery using invisible near-infrared light: fundamentals of clinical translation. Mol Imaging 2010; 9:237-55. PubMed
  • Matsui A, Tanaka E, Choi HS, Kianzad V, Gioux S, Lomnes SJ, Frangioni JV. Real-time, near-infrared, fluorescence-guided identification of the ureters using methylene blue. Surgery 2010; 148:78-86. PubMed
  • Winer JH, Choi HS, Gibbs-Strauss SL, Ashitate Y, Colson YL, Frangioni JV. Intraoperative localization of insulinoma and normal pancreas using invisible near-infrared fluorescent light. Ann Surg Oncol 2010; 17:1094-100. PubMed
  • Matsui A, Tanaka E, Choi HS, Winer JH, Kianzad V, Gioux S, Laurence RG, Frangioni JV. Real-time intra-operative near-infrared fluorescence identification of the extrahepatic bile ducts using clinically available contrast agents. Surgery 2010. PubMed
  • Choi HS, Liu W, Liu F, Nasr K, Misra P, Bawendi MG, Frangioni JV. Design considerations for tumour-targeted nanoparticles. Nat Nanotechnol 2009; 5:42-7. PubMed
  • Choi HS,Ipe BI,Misra P,Lee JH,Bawendi MG,Frangioni JV. Tissue- and Organ-Selective Biodistribution of NIR Fluorescent Quantum Dots. Nano Lett 2009; 9:2354-9. PubMed
  • Yuan TL,Choi HS,Matsui A,Benes C,Lifshits E,Luo J,Frangioni JV,Cantley LC. Class 1A PI3K regulates vessel integrity during development and tumorigenesis. Proc Natl Acad Sci U S A 2008; 105:9739-44. PubMed
  • Tanaka E,Choi HS,Humblet V,Ohnishi S,Laurence RG,Frangioni JV. Real-time intraoperative assessment of the extrahepatic bile ducts in rats and pigs using invisible near-infrared fluorescent light. Surgery 2008; 144:39-48. PubMed
  • Gioux S, Kianzad V, Ciocan R, Choi HS, Nelson C, Thumm J, Filkins RJ, Lomnes SJ, Frangioni JV. A low-cost, linear, DC - 35 MHz, high-power LED driver for continuous wave (CW) and fluorescence lifetime imaging (FLIM). Proc Soc Photo Opt Instrum Eng 2010; 6848:684807. PubMed
  • Liu W, Choi HS, Zimmer JP, Tanaka E, Frangioni JV, Bawendi M. Compact cysteine-coated CdSe(ZnCdS) quantum dots for in vivo applications. J Am Chem Soc 2007; 129:14530-1. PubMed
  • Tanaka E, Ohnishi S, Laurence RG, Choi HS, Humblet V, Frangioni JV. Real-time intraoperative ureteral guidance using invisible near-infrared fluorescence. J Urol 2007; 178:2197-202. PubMed
  • Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Itty Ipe B, Bawendi MG, Frangioni JV. Renal clearance of quantum dots. Nat Biotechnol 2007; 25:1165-70. PubMed
  • Tanaka E, Choi HS, Fujii H, Bawendi MG, Frangioni JV. Image-guided oncologic surgery using invisible light: completed pre-clinical development for sentinel lymph node mapping. Ann Surg Oncol 2006; 13:1671-81. PubMed
  • Loethen S, Ooya T, Choi HS, Yui N, Thompson DH. Synthesis, characterization, and pH-triggered dethreading of alpha-cyclodextrin-poly(ethylene glycol) polyrotaxanes bearing cleavable endcaps. Biomacromolecules 2006; 7:2501-6. PubMed
  • Choi HS, Takahashi A, Ooya T, Yui N. Molecular-recognition and binding properties of cyclodextrin-conjugated polyrotaxanes. 2006; 7:1668-70. PubMed
  • Choi HS, Hirasawa A, Ooya T, Kajihara D, Hohsaka T, Yui N. pH-sensitive locomotion of cyclodextrins in a block-selective mobile polyrotaxane. 2006; 7:1671-3. PubMed
  • Ooya T, Inoue D, Choi HS, Kobayashi Y, Loethen S, Thompson DH, Ko YH, Kim K, Yui N. pH-responsive movement of cucurbit[7]uril in a diblock polypseudorotaxane containing dimethyl beta-cyclodextrin and cucurbit[7]uril. Org Lett 2006; 8:3159-62. PubMed
  • Choi HS, Ooya T, Yui N. One-pot synthesis of a polyrotaxane via selective threading of a PEI-b-PEG-b-PEI copolymer. 2006; 6:420-4. PubMed
  • Ooya T, Choi HS, Yamashita A, Yui N, Sugaya Y, Kano A, Maruyama A, Akita H, Ito R, Kogure K, Harashima H. Biocleavable polyrotaxane-plasmid DNA polyplex for enhanced gene delivery. J Am Chem Soc 2006; 128:3852-3. PubMed
  • Yamashita A, Choi HS, Ooya T, Yui N, Akita H, Kogure K, Harashima H. Improved cell viability of linear polyethylenimine through gamma-cyclodextrin inclusion for effective gene delivery. Chembiochem 2006; 7:297-302. PubMed
  • Choi HS, Yamashita A, Ooya T, Yui N, Akita H, Kogure K, Ito R, Harashima H. Sunflower-shaped cyclodextrin-conjugated poly(epsilon-lysine) polyplex as a controlled intracellular trafficking device. Chembiochem 2005; 6:1986-90. PubMed
  • Choi HS, Yamamoto K, Ooya T, Yui N. Synthesis of poly(epsilon-lysine)-grafted dextrans and their pH- and thermosensitive hydrogelation with cyclodextrins. 2005; 6:1081-6. PubMed
  • Choi HS, Ooya T, Sasaki S, Yui N, Kurisawa M, Uyama H, Kobayashi S. Spontaneous change of physical state from hydrogels to crystalline precipitates during poly-pseudorotaxane formation. 2004; 5:1431-4. PubMed
  • Choi HS, Huh KM, Ooya T, Yui N. pH- and thermosensitive supramolecular assembling system: rapidly responsive properties of beta-cyclodextrin-conjugated poly(epsilon-lysine). J Am Chem Soc 2003; 125:6350-1. PubMed
  • Seo SA, Choi HS, Khang G, Rhee JM, Lee HB. A local delivery system for fentanyl based on biodegradable poly(L-lactide-co-glycolide) oligomer. Int J Pharm 2002; 239:93-101. PubMed
  • Choi HS, Seo SA, Khang G, Rhee JM, Lee HB. Preparation and characterization of fentanyl-loaded PLGA microspheres: in vitro release profiles. Int J Pharm 2002; 234:195-203. PubMed
  • Hyun H, Bordo MW, Nasr K, Feith D, Lee JH, Kim SH, Ashitate Y, Moffitt LA, Rosenberg M, Henary M, Choi HS, Frangioni JV. cGMP-Compatible preparative scale synthesis of near-infrared fluorophores. Contrast Media Mol Imaging 2012; 7:516-24. PubMed
  • Ashitate Y, Vooght CS, Hutteman M, Oketokoun R, Choi HS, Frangioni JV. Simultaneous assessment of luminal integrity and vascular perfusion of the gastrointestinal tract using dual-channel near-infrared fluorescence. 2012; 11:301-8. PubMed
  • Gioux S, Lomnes SJ, Choi HS, Frangioni JV. Low-frequency wide-field fluorescence lifetime imaging using a high-power near-infrared light-emitting diode light source. J Biomed Opt 2010; 15:026005. PubMed
  • Choi HS, Ooya T, Huh KM, Yui N. pH-triggered changes in assembling properties of beta-cyclodextrin-conjugated poly(epsilon-lysine) complexes. Biomacromolecules 2005; 6:1200-4. PubMed
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