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

Center for Cancer Research
National Cancer Institute

Building 376, Room 225D
Frederick, MD 21702
301-228-4008

Dr. Schnermann and his group apply core expertise in modern synthetic chemistry and reaction discovery to the development of new approaches for cancer imaging and treatment. A particular focus is to develop small molecule-based techniques that take advantage of the low toxicity and high tissue penetration of light in the near-IR range. In this area, we focus on the identification of new imaging agents with improved properties and on new approaches for drug delivery. In addition, we are also pursuing the synthesis of natural products of relevance to cancer imaging and therapy.

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

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 (~centimeters). My group develops new single photon near-IR uncaging methods by defining and then taking advantage of photochemical reactions of long-wavelength fluorophores. We are using our methods towards two key unmet challenges in biology:  (1) the development of a general theranostic approach for  site-specific optical imaging and drug delivery and (2) the spatial and temporal regulation of gene expression to track and control cell fate.

Modern Synthetic Approaches for Small Molecule Imaging

Existing fluorophores, particularly those in the near-IR range, are prepared through inefficient classical synthetic methods that suffer from poor substrate scope and harsh reaction conditions. The limitations of existing methodologies dictate that researchers must choose from a small collection of probes whose   chemical and physical properties are not ideal. We are creating the chemistry needed to develop optimal near-IR fluorophores for several key cancer-related imaging 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.

Scientific Focus Areas:
Cancer Biology, Chemical Biology, Molecular Pharmacology
Selected Recent Publications
  1. Nani RR, Shaum JB , Gorka AP, and Schnermann MJ
    Org Lett. 17: 302-5, 2015. [ Journal Article ]
  2. Gorka AP, Nani RR, Zhu J, Mackem S, and Schnermann MJ
    J Am Chem Soc. 136: 14153-9, 2014. [ Journal Article ]
  3. Schnermann MJ, Overman LE.
    Angew. Chem. Int. Ed. Engl. 2012. [ Journal Article ]
  4. Schnermann MJ, Untiedt NL, Jiménez-Osés G, Houk KN, and Overman LE.
    Angew. Chem. Int. Ed. Engl. 2012. [ Journal Article ]
  5. Schnermann MJ, Beaudry CM, Egorova AV, Polishchuk RS, Sütterlin C, and Overman LE.
    Proc. Natl. Acad. Sci. U.S.A. 107: 6158-63, 2010. [ Journal Article ]

Dr. Schnermann attended Colby College and graduated in 2002 with degrees in Chemistry (honors with Prof. Dasan Thamattoor) and Physics. 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.

Name Position
Erin Anderson Ph.D. Postdoctoral Fellow (CRTA)
Alexander Gorka Ph.D. Postdoctoral Fellow (CRTA)
Megan Michie Postbaccalaureate Fellow
Rohini Nambiar Summer Student
Roger Nani Ph.D. Postdoctoral Fellow (CRTA)
Luxi Qiao Summer Student
James Blaine Shaum Postbaccalaureate Fellow

Summary

Dr. Schnermann and his group apply core expertise in modern synthetic chemistry and reaction discovery to the development of new approaches for cancer imaging and treatment. A particular focus is to develop small molecule-based techniques that take advantage of the low toxicity and high tissue penetration of light in the near-IR range. In this area, we focus on the identification of new imaging agents with improved properties and on new approaches for drug delivery. In addition, we are also pursuing the synthesis of natural products of relevance to cancer imaging and therapy.

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

Research

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 (~centimeters). My group develops new single photon near-IR uncaging methods by defining and then taking advantage of photochemical reactions of long-wavelength fluorophores. We are using our methods towards two key unmet challenges in biology:  (1) the development of a general theranostic approach for  site-specific optical imaging and drug delivery and (2) the spatial and temporal regulation of gene expression to track and control cell fate.

Modern Synthetic Approaches for Small Molecule Imaging

Existing fluorophores, particularly those in the near-IR range, are prepared through inefficient classical synthetic methods that suffer from poor substrate scope and harsh reaction conditions. The limitations of existing methodologies dictate that researchers must choose from a small collection of probes whose   chemical and physical properties are not ideal. We are creating the chemistry needed to develop optimal near-IR fluorophores for several key cancer-related imaging 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.

Scientific Focus Areas:
Cancer Biology, Chemical Biology, Molecular Pharmacology

Publications

Selected Recent Publications
  1. Nani RR, Shaum JB , Gorka AP, and Schnermann MJ
    Org Lett. 17: 302-5, 2015. [ Journal Article ]
  2. Gorka AP, Nani RR, Zhu J, Mackem S, and Schnermann MJ
    J Am Chem Soc. 136: 14153-9, 2014. [ Journal Article ]
  3. Schnermann MJ, Overman LE.
    Angew. Chem. Int. Ed. Engl. 2012. [ Journal Article ]
  4. Schnermann MJ, Untiedt NL, Jiménez-Osés G, Houk KN, and Overman LE.
    Angew. Chem. Int. Ed. Engl. 2012. [ Journal Article ]
  5. Schnermann MJ, Beaudry CM, Egorova AV, Polishchuk RS, Sütterlin C, and Overman LE.
    Proc. Natl. Acad. Sci. U.S.A. 107: 6158-63, 2010. [ Journal Article ]

Biography

Dr. Schnermann attended Colby College and graduated in 2002 with degrees in Chemistry (honors with Prof. Dasan Thamattoor) and Physics. 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.

Team

Name Position
Erin Anderson Ph.D. Postdoctoral Fellow (CRTA)
Alexander Gorka Ph.D. Postdoctoral Fellow (CRTA)
Megan Michie Postbaccalaureate Fellow
Rohini Nambiar Summer Student
Roger Nani Ph.D. Postdoctoral Fellow (CRTA)
Luxi Qiao Summer Student
James Blaine Shaum Postbaccalaureate Fellow