Faculty Summaries
Eileen K. Jaffe, PhD
Eileen K. Jaffe, PhD
  • Adjunct Professor, Bichemistry, University of Pennsylvania School of Dental Medicine
  • Adjunct Professor, Biochemistry & Molecular Biology, Drexel University College of Medicine
  • Adjunct Professor, Department of Medical Genetics and Molecular Biochemistry, Temple University School of Medicine
Office Phone: 215 728-3695
Lab Phone: 215 728-5268
Fax: 215 728-2412
Office: R455
Lab: R452
  • Lab Overview

    The Jaffe laboratory studies protein structure-function relationships using both biochemical and biophysical approaches. We are focused on the roles of protein quaternary structure dynamics in the control of protein function.  This follows our discovery that multimeric proteins can come apart, the dissociated units can change conformation, and these altered conformations can come back together differently to form a structurally and functionally distinct  assembly. Unlike amyloid, the changes in subunit structure are subtle, such as a hinge movement between folded domains, the oligomeric stoichiometry is finite, and the process is freely reversible. This structural dynamic can be the basis for allosteric regulation of protein function (the morpheein model of protein allostery).  Disregulation of the equilibrium of assemblies is responsible for some human disease.  Designed regulation of the equilibrium of assemblies provides a basis for allosteric drug discovery. The now well established structural dynamic was originally unexpected, but new examples are being discovered regularly, as in the Ebola virus VP40 protein (E. Ollmann-Saphire, Scripps Institute). Although we coined the term morpheein to describe proteins that could reversibly dissociate, change conformation, and assemble differently with finite stoichiometry, the term transformers has also been used. What we have learned from the prototype morpheein, porphobilinogen synthase, allows us to mine the literature and protein structure databases in search of other proteins that function as morpheeins. A family of putative morpheeins includes many drug targets, including cancer chemotherapeutic targets.  The putative morpheein currently under most active investigation in the laboratory is phenylalanine hydroxylase, where the dysregulation of the interchange between various multimers is proposed to account for phenylketonuria in some patients.