#  Eric Fischer 

Professor of Biological Chemistry and Molecular Pharmacology

 

 

 



   ![Eric Fischer](/sites/g/files/omnuum13191/files/styles/hwp_4_5__320x400/public/2026-07/Fischer%2C%20Eric4.jpg?itok=PrZVzt5R) 

 



 

 location\_on Dana-Farber Cancer Institute 360 Longwood Ave. Longwood Center 4th floor, LC-4312 Boston, MA 02215 

 email [eric\_fischer@dfci.harvard.edu](mailto:eric_fischer@dfci.harvard.edu) 

 laptop\_windows [Lab Website](http://fischerlab.dana-farber.org) 

 laptop\_windows [Publications](http://www.ncbi.nlm.nih.gov/sites/myncbi/1zk31-3n1A1AP/bibliography/40386965/public/?sort=date&direction=ascending) 

 

 



 

The Ubiquitin Proteasome System (UPS) is involved in virtually any cellular process and frequently implicated in human pathologies. Ubiquitin, through the action of a three-enzyme cascade (E1, E2 and E3), becomes attached to substrate proteins. The posttranslational modification with ubiquitin can serve a multitude of functions depending on the type and length of the ubiquitin chain attached to the substrate, including the control of protein abundance via proteasomal degradation. The human genome encodes for more than 600 E3 ligases, which confer specificity in the ubiquitin signaling cascade. While the process of ubiquitin transfer is well understood, the biological function and molecular mechanisms of the majority of ubiquitin ligases remain obscure.

We combine structural biology, cell biology and biochemical reconstitutions to address the molecular workings of these multi-component ubiquitin ligases. In particular, we are interested in protein complexes and pathways that contribute to the control of gene expression and are frequently associated with human disease and cancer. Intimate understanding of the structure allows us to dissect the complex mechanisms that underlie function and regulation of such molecules and to probe their biology in a cellular context. We seek to leverage our molecular understanding to propose and test new avenues of therapeutic intervention.

Another focus is on the use of small molecules for the targeted degradation of disease causing proteins, a new therapeutic modality now widely explored in academic research and the pharmaceutical industry. We helped establish many of the fundamental principles for how small molecules can redirect the activity of ubiquitin ligases for the controlled destruction of proteins. Using multi-disciplinary chemical biology (including X-ray crystallography, cryo-EM, proteomics, biochemistry and chemical synthesis), we define the mechanism of drugs such as thalidomide, lenalidomide, indisulam, etc. and leverage these findings to further refine approaches for the prospective development of small molecule degraders. We also develop computational methods to better understand and predict the molecular interations that comprise the activity of small molecule degraders.



 

 

 





 

 

- ## Person Categories
    
     [Faculty](/person-categories/faculty)
- ## Research Area
    
     [Biophysics](/research-area/biophysics) [Cancer biology](/research-area/cancer-biology) [Chromatin and epigenetics](/research-area/chromatin-and-epigenetics) [Computational biology / bioinformatics](/research-area/computational-biology-bioinformatics) [Gene regulation and transcription](/research-area/gene-regulation-and-transcription) [Genome Editing and Engineering](/research-area/genome-editing-and-engineering) [Medicinal chemistry / therapeutics](/research-area/medicinal-chemistry-therapeutics) [Protein function, modifications, and regulation](/research-area/protein-function-modifications-and-regulation) [Small molecule probe design and applications](/research-area/small-molecule-probe-design-and-applications) [Synthetic biology / bioengineering](/research-area/synthetic-biology-bioengineering) [Synthetic chemistry and natural products](/research-area/synthetic-chemistry-and-natural-products)