Georgia State University, Ph.D. (1997-2000)
Georgia Institute of Technology, Postdoctoral Research Fellow (2001-2004)
Visiting Lecturer, Georgia State University (2005-2006)
Lecturer, Georgia State University (2007-2010)
Assistant Professor, Georgia State University (2011-present)
Research in the Henary Laboratory focuses on synthetic organic chemistry. Our group is interested in the design, synthesis and development of small molecules for biomedical application and other chemical entities suitable for therapeutic use and imaging technology, such fluorophores for in vivo imaging of native and diseased tissues and DNA targeted agents with anticancer activity. We have established several collaborations with biologists, biochemists, and physicians to facilitate the design and developmental process of small molecules with significant biological activity.
Our group has developed near infrared fluorophores for use in medical imaging of healthy tissue (top left), diseased tissue including tumors (bottom left), duplex DNA probes (top right) and antitumor agents which act on G-quadruplex DNA to selectively target cancerous cells (bottom right).
Synthesis of Endocrine Specific Near-Infrared Fluorophores (ESNFs)-
Through collaboration with the Center of Molecular Imaging at Harvard Medical School, specifically the Choi and Frangioni Laboratories, we are working to design, synthesize and analyze NIR fluorophores that successfully image endocrine glands for intraoperative use.
Identification of normal endocrine glands and their tumors are of critical importance to preserve normal tissue, and to remove diseased tissue, respectively.
There are no contrast agents available to highlight normal tissue, such as the thyroid gland, which needs to be avoided for example, during head and neck surgery.
Through extensively modifying the pentacyanine structure (utilizing Log(P) values) we have developed several ESNFs for image-guided surgery of various glands.
Synthesis of Tri- and Pentamethine Cyanine Dyes for Selectively Binding G-Quadruplex DNA
Telomerase is overactive in cancer cells and provides endless replication processes to the mutated cells. Inhibition of telomerase has been recognized as a viable strategy to prevent growth of tumors. This chemotherapeutic strategy to specifically target G-quadruplex DNA in cancer cells with no apparent side effects is being heavily investigated. To date, no small molecules have been reported that satisfy the conditions needed for medicinal use.
BRACO-19 was identified as the lead compound in this field and was removed from clinical trials due to cytotoxicity from Duplex DNA binding. Our data strongly suggest a) an increase in G-quadruplex binding with certain carbocyanine dyes, b) active compounds have a net positive charge, c) strong binding properties to G-quadruplex structures while sparing duplex DNA.
This suggests the potential usefulness of these carbocyanine compounds as novel anti-cancer agents. Our goal is to design and synthesize additional condensed and positively charged tri- and pentacarbocyanine dyes as G-quadruplex targeting compounds for use as anti-cancer therapeutic agents.
1. Ma, Xio., Laramie, M., Henary, M. Synthesis, Optical Properties and Cytotoxicity of Meso-Heteroatom Substituted IR-786 Analogs. Bioorg. & Med. Chem. Let., 2018. In Press. DOI: 10.1016/j.bmcl.2017.12.001
2. Levitz, A., Holder, C., Soriano, E., Henary, M. Turn on Fluorescence Response of Monomethine Cyanines Caused by Noncovalent Binding to ct-DNA. Dyes and Pigments, 2017; 145: 202-207. DOI: 10.1016/j.dyepig.2017.05.051.
3. Ashitate, Y., Levitz, A., Park, M. H., Hyun, H., Venugopal, V., Park, G. L., El Fakhri, G., Henary, M., Gioux, S., Frangioni, J. V., Choi, H. Endocrine-Specific NIR Fluorophores for Adrenal Gland Targeting. Chem. Comm., 2016; 52: 10305-10308.
4. Owens, E., Hyun, H., Dost, T., Lee, J.-H., Park, J., Pham, D. Park, M., Choi, H., Henary, M. Near-Infrared Illumination of Native Tissues for Image-Guided Surgery. J. Med. Chem., 2016; 59 (11): 5311–5323.
5. Owens, E., Henary, M., El Fakhri, G., Choi, H. Tissue-Specific Near-Infrared Fluorescence Imaging. Acc. Chem. Res., 2016; 49(9): 1731–1740.
6. Martinez, V., Henary, M. Nile Red and Nile Blue: Applications and Syntheses of Structural Analogues. Chem. Eur. J. 2016; 22: 1-20.