Brenda A. Schulman

Max Planck Institute of Biochemistry

Election Year: 2014
Primary Section: 21, Biochemistry
Membership Type: Member


Brenda Schulman is an Investigator of the Howard Hughes Medical Institute, and the Joseph Simone Chair in Basic Research at St. Jude Children’s Research Hospital. Schulman is a structural biologist and biochemist. She is recognized for her studies of eukaryotic regulatory mechanisms involving protein modification by the family of small ubiquitin-like proteins. Schulman is particularly interested in understanding how a wide range of different ubiquitin-like protein modifications lead to extraordinary changes in fates of their targets, such as altered subcellular localization, intermolecular interactions, conformation, and/or stability. Schulman was born and raised in Tucson, Arizona. She graduated from Johns Hopkins with a degree in Biology in 1989, and in 1996 with a PhD in biology from MIT where she studied with Peter Kim. After postdoctoral studies with Ed Harlow at MGH and Nikola Pavletich at Sloan-Kettering, she joined the faculty in 2001. Schulman has been named a Pew Scholar in the Biomedical Sciences and a Beckman Young Investigator, and received a Presidential Early Career Award for Scientists and Engineers. She was a joint winner of The Protein Society’s Dorothy Crowfoot Hodgkin Award, and is a member of American Academy of Arts and Sciences and the National Academy of Sciences.

Research Interests

I am fascinated by how protein functions are dynamically switched to drive regulatory pathways. In eukaryotes, a major form of regulation involves covalent protein modification by a diverse array of ubiquitin-like proteins (UBLs), which impart extraordinary changes in the fates of their targets. As examples, some polyubiquitin chains mediate proteasomal degradation, whereas ubiquitin’s closest relative, NEDD8, has the distinct function of activating hundreds of ubiquitinating enzymes. By contrast, Atg8 is ligated to a lipid, regulating numerous features of bulk degradation via autophagy. We are interested in how dedicated cascades of E1 activating, E2 conjugating, and E3 ligase enzymes direct these UBLs to their targets to regulate the cell cycle, autophagy, and other processes. Regulation depends on numerous E2 and E3 enzymes (roughly 30 and 600, respectively, in humans) coordinately matching particular UBLs and substrates in a highly specific manner. My lab has determined a series of crystal structures that serve as molecular “snapshots” revealing how UBLs are activated by E1 enzymes, transferred between E1s, E2s and different types of E3 enzymes to particular target proteins, and how UBL attachment can transform the functions of modified proteins. Our current research focuses on understanding how E3 ligases are regulated to ensure that targets are modified under the right circumstances to mediate proper regulation, how UBL modifications alter the functions of targets, and consequences of defects in UBL pathways associated with certain cancers and neurodegenerative disorders.

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