About the Fischer Lab

Proper protein function depends on flexibility and hydration. Our laboratory is focused on understanding the dynamic features of proteins using structural and chemical biology. We use a unique variable temperature approach to analyze protein conformations. Ultimately, our work will inform the design of better drugs to target cancer. 

Science Team

Our research summary

Our laboratory explores the protein conformational landscape to better understand and modulate protein function in health and disease. We employ a multidisciplinary approach to analyzing protein crystal structures obtained at variable temperatures to understand how ligands, mutations, and other factors perturb protein conformations. 

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Understanding the molecular underpinnings of proteins requires the generation of structural models.  The traditional method of collecting data on protein crystals involves freezing them at cryogenic temperatures. This convenient and common practice was applied for the collection of about 95% of all crystal structures but the process also freezes out different conformations that are often essential to a protein’s function.

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Our laboratory diverges from traditional crystal structure analysis by using a unique variable temperature X-ray crystallography approach to probe the protein conformation landscape. We aim to reveal protein conformations that are hidden in conventional approaches and gain insights into water networks that impact ligand binding. Our team uses this dynamic information to design specific ligands that would not be found in the static snapshot typically obtained with traditional X-ray crystallography methods. 

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Through collaboration with numerous experts at St. Jude, particularly in Department of Chemical Biology & Therapeutics, our laboratory has expanded its research to explore targeted protein degradation approaches. This interdisciplinary endeavor ties together elements of structural biology, chemical biology, molecular biology, and cell biology towards exploring new therapeutic modalities besides classic occupancy-based inhibition of protein function. 

Selected Publications

About Marcus Fischer

Dr. Marcus Fischer holds a dual appointment in the departments of Structural Biology and Chemical Biology & Therapeutics. He received his BSc and MSc from the University of Lübeck, Germany, and his PhD from the University of York, UK, and did his post-doctoral training under Prof. Brian Shoichet at the University of California San Francisco in the Department of Pharmaceutical Chemistry. Dr. Fischer also serves as an Adjunct Assistant Professor at the University of Tennessee Health Science Center in the Department of Pharmaceutical Sciences. Dr. Fischer has chosen to eschew the traditional cryogenic practices of crystallography in favor of a more complete view of the protein conformational landscape that includes protein flexibility and hydration.

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The team

Interdisciplinary team with expertise in structural, computational, and chemical biology

Explore Career Opportunities in Structural Biology

We are currently recruiting!

Contact us

Marcus Fischer, PhD
Chemical Biology and Therapeutics

MS1000, Room E9055
St. Jude Children’s Research Hospital

262 Danny Thomas Place
Memphis, TN, 38105-3678 USA
901-595-6269 Marcus.Fischer@stjude.org

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262 Danny Thomas Place
Memphis, TN, 38105-3678 USA
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