Martin J. Schnermann, Ph.D.
Light provides a uniquely powerful stimulus to visualize and/or perturb biological systems. Tissue penetrant near-IR wavelengths can enable in vivo applications, however the identification of suitable molecules that function in this range remains a substantial challenge. We focus on the design and synthesis of the molecules needed to craft new near-IR optical drug delivery and imaging methods. Enabled by modern organic synthesis, the central element of our approach is to define and then use the reactivity of near-IR fluorophores. In the context of drug delivery, we develop novel reactions that release or “uncage” small molecules following irradiation with near-IR light. In the context of imaging, we prepare novel fluorophores with improved properties for in vivo optical imaging and microscopy.
1) complex molecule synthesis, 2) synthetic methodology, 3) near-IR fluorescence,
4) natural product chemistry, 5) drug discovery, 6) drug delivery
Near-IR Uncaging Chemistry: Discovery and Applications
Many key fundamental and applied questions in biology require unraveling issues relating to the spatial and temporal organization of multi-cellular systems. The combination of photocaged small molecule probes and the spatially controlled application of light could, in principle, provide key insights. However, existing photoremovable caging groups are often not suitable, particularly for organismal applications. This is due to the general requirement of UV or blue light, which suffers from associated toxicity and poor tissue penetration. By contrast, light between 650 and 900 nm, often referred to as the near-IR window, is cytocompatible and has significant tissue penetration. My group develops new single photon near-IR uncaging methods. The modest photonic energy of these wavelengths makes this a challenging chemistry problem. Our approach is to define and then take advantage of photochemical reactions of long-wavelength fluorophores. In our most advanced project, we have shown that the photooxidative reactivity of heptamethine cyanines can be used for small molecule drug delivery. Using these molecules, we are developing a general strategy for highly targeted in vivo drug delivery using antibody targeting. In a separate approach, we have also shown that the photoredox ligand exchange of silicon phthalocyanines can be used for hypoxia-selective near-IR uncaging.
Modern Synthetic Approaches for Small Molecule Imaging
There is a significant need for improved near-IR fluorophores for emerging applications in basic and applied biomedical science. Existing molecules are often prepared through inefficient classical synthetic methods that suffer from poor substrate scope and harsh reaction conditions. We create reactions that enable the efficient preparation of novel near-IR fluorophores. This new chemistry is used to develop molecules with improved stability and optical properties. We are particularly focused on developing compounds suitable for fluorescence-guided surgery applications. In related efforts, we are mining the structural diversity of natural products for light emitting scaffolds to develop broadly useful optical probes. Key to this work is the development of concise total syntheses to access compounds of interest.
View Dr. Schnermann's Google Scholar Bibliography.
Selected Key Publications
- J Am Chem Soc. 136: 14153-9, 2014. [ Journal Article ]
- Angew. Chem. Int. Ed. Engl. 54: 13635-8, 2015. [ Journal Article ]
- ACS Central Science. 3: 329–337, 2017. [ Journal Article ]
- Nature Communications. 7: 2016. [ Journal Article ]
- J Am Chem Soc. 139: 12406-12409, 2017. [ Journal Article ]
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 NCI where his research focuses on the synthesis and development of new small-molecule imaging agents for cancer treatment and diagnosis. He was awarded tenure in 2018.
|Donald Caldwell Ph.D.||Postdoctoral Fellow (CRTA)|
|Harrison C. Daly Ph.D.||Postdoctoral Fellow (Visiting)|
|Ivan Dingle||Postbaccalaureate Fellow (CRTA)|
|Michael P. Luciano Ph.D.||Postdoctoral Fellow (CRTA)|
|Siddharth Matikonda Ph.D.||Postdoctoral Fellow (Visiting)|
|Ryan R. McLaughlin||Postbaccalaureate Fellow (CRTA)|
|Meredith N. Nix||Postbaccalaureate Fellow (CRTA)|
|Ek Raj Thapaliya Ph.D.||Postdoctoral Fellow (Visiting)|
A funded postdoctoral position is available within the Chemical Biology Laboratory at the National Cancer Institute, Frederick, Maryland. Research projects center on the development of new approaches for cancer imaging and drug delivery. The lab is focused on the synthesis and development of small molecules, with a specific interest on methods that function in complex organisms. The NCI is an excellent environment for postdoctoral study. Postdoctoral scholars will have access to first-rate scientific resources, strong training opportunities, and a close community of researchers working on critical problems that link chemistry to cancer biology. Prospective candidates should have a strong background in synthetic organic chemistry, photochemistry, and/or chemical biology and be motivated to actively contribute to interdisciplinary projects. Potential applicants should contact Dr. Martin Schnermann (firstname.lastname@example.org) to express interest (please enclose a C.V. and a letter of support).