Martin J. Schnermann, Ph.D.

Martin J. Schnermann, Ph.D.
Senior Investigator
Head, Organic Synthesis Section

The Schnermann lab uses the tools and concepts of modern organic chemistry to discover new molecules for cancer diagnosis and therapy. We focus on the development of new drug delivery and imaging methodologies. In the context of drug delivery, we develop innovative chemical strategies to deliver bioactive payloads with high precision. In the area of imaging, we create novel fluorescent molecules with improved properties for in vivo optical imaging and microscopy. While our studies are enabled by core expertise in organic synthesis and molecular design, trainees in the lab are engaged in highly interdisciplinary research using techniques that range from in vitro characterization to in vivo imaging. In addition to our studies, we embrace a highly collaborative approach with extensive interactions with both intramural and extramural investigators.

Link to additional information about Dr Schnermann’s research.

Areas of Expertise

1) complex molecule synthesis, 2) synthetic methodology, 3) near-IR fluorescence,
4) natural product chemistry, 5) drug discovery, 6) drug delivery

Contact Info

Martin J. Schnermann, Ph.D.
Center for Cancer Research
National Cancer Institute
Building 376, Room 225D
Frederick, MD 21702
Ph: 301-228-4008
schnermannmj@mail.nih.gov

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.

NIH Scientific Focus Areas:
Cancer Biology, Chemical Biology, Molecular Pharmacology
  1. Gorka AP, Nani RR, Zhu J, Mackem S, and Schnermann MJ
    J Am Chem Soc. 136: 14153-9, 2014. [ Journal Article ]
  2. Nani RR, Gorka AP, Nagaya T, Kobayashi H, Schnermann MJ
    Angew. Chem. Int. Ed. Engl. 54: 13635-8, 2015. [ Journal Article ]
  3. Nani RR, Gorka AP, Nagaya T, Yamamoto T, Ivanic J, Kobayashi H, Schnermann MJ
    ACS Central Science. 3: 329–337, 2017. [ Journal Article ]
  4. Anderson ED, Gorka AP and Schnermann MJ
    Nature Communications. 7: 2016. [ Journal Article ]
  5. Michie MS, Götz R, Franke C, Bowler M, Kumari N, Magidson V, Levitus M, Loncarek J, Sauer M, Schnermann MJ
    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 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.

Name Position
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 (martin.schnermann@nih.gov) to express interest (please enclose a C.V. and a letter of support).