Martin J. Schnermann, Ph.D.
Chemical Biology Laboratory
Building 376, Room 225D
Frederick, MD 21702
Fluorescent Molecules for In Vivo Imaging
There is a significant need for fluorophores developed specifically for emerging imaging applications in fundamental and applied biomedical settings. A major component of our efforts is to discover chemical methodologies that enable the efficient preparation of previously inaccessible molecules. This approach allows us to access novel fluorophores, which are then optimized to address the limitations of existing agents. We have developed exceptionally bright, polycyclic pentamethine cyanines that are useful in a variety of advanced microscopy applications. We have also worked extensively to develop novel heptamethine cyanine dyes, which operate in the near-infrared (NIR) range making them compatible with in vivo use. We developed a highly modified heptamethine cyanine dye, FNIR-tag, that is uniquely resistant to aggregation. The properties of FNIR-Tag provide exceptionally bright bioconjugates (on both mAbs and nanoparticles). We have also sought to address specific challenges in the emerging field of fluorescence-guided surgery. We developed probes with rapid and exclusive renal or hepatobiliary clearance, making them useful for imaging during various abdominal surgeries. Finally, we are currently developing novel turn-on probes, which are being applied to quantitatively measure the utility of various drug delivery methods in live animal settings.
Novel Approaches to Drug Delivery
The targeted delivery of bioactive molecules requires the development of chemical strategies amendable to the complexity of in vivo biology. We have developed the first photocaging groups activated by single photon flux of NIR light – an uncaging method uniquely suitable for use in live animal and tissue settings. Our approach is to define and then take advantage of photochemical reactions of long-wavelength fluorophores. We have shown that the photooxidation of heptamethine cyanines can be used for small molecule drug delivery. Using these molecules, we have developed a general strategy for highly targeted in vivo drug delivery using antibody targeting. In addition to light-activated strategies, we are also using insights from our imaging studies to develop novel, biocompatible cleavable linkers. In particular, we are developing strategies to improve the in vivo properties of antibody drug conjugates.
Dr. Schnermann attended Colby College and graduated in 2002 with degrees in Chemistry and Physics. At Colby, he worked with Prof. Dasan Thamattoor in the areas of physical organic chemistry and photochemistry. After a year at Pfizer Research and Development (Groton, CT) as an associate in the medicinal chemistry division, he moved to the Scripps Research Institute. During his graduate studies, he performed research on the total synthesis and biological evaluation of anticancer natural products with Prof. Dale Boger and obtained a Ph.D. in 2008. He then completed an NIH-postdoctoral fellowship with Prof. Larry Overman at the University of California, Irvine. At Irvine, he developed light-mediated reactions to enable the synthesis of complex natural products. In addition, working with Prof. Christine Suetterlin, he pursued chemical biology and imaging studies of organelle specific probes. In 2012, Dr. Schnermann joined the Chemical Biology Laboratory at the National Cancer Institute, where his research focuses on the synthesis and development of new small-molecule imaging agents for cancer treatment and diagnosis. In 2018, Dr. Schnermann was promoted to Senior Investigator.
Nani RR, Gorka AP, Nagaya T, Yamamoto T, Ivanic J, Kobayashi H, Schnermann MJ. <i>In Vivo</i> Activation of Duocarmycin-Antibody Conjugates by Near-Infrared Light. ACS Cent Sci. 2017;3(4):329-337.
Nani RR, Shaum JB, Gorka AP, Schnermann MJ. Electrophile-integrating Smiles rearrangement provides previously inaccessible C4'-O-alkyl heptamethine cyanine fluorophores. Org Lett. 2015;17(2):302-5.
Nani RR, Gorka AP, Nagaya T, Kobayashi H, Schnermann MJ. Near-IR Light-Mediated Cleavage of Antibody-Drug Conjugates Using Cyanine Photocages. Angew Chem Int Ed Engl. 2015;54(46):13635-8.
Nani RR, Kelley JA, Ivanic J, Schnermann MJ. Reactive Species Involved in the Regioselective Photooxidation of Heptamethine Cyanines. Chem Sci. 2015;6(11):6556-6563.
Gorka AP, Nani RR, Zhu J, Mackem S, Schnermann MJ. A near-IR uncaging strategy based on cyanine photochemistry. J Am Chem Soc. 2014;136(40):14153-9.
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This page was last updated on June 2nd, 2020