Postdoctoral Fellow – Oncology and Inflammation Research - United States
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Dr. J Russell Lipford in the Oncology and Inflammation Research department at Amgen, Inc. is seeking a Postdoctoral Fellow in the area of molecular cellular biology, chemical biology and protein biochemistry.
This postdoctoral project will focus on the development of additional small-molecules to alter the function of the ubiquitin-proteasome system (UPS). This will include:
1. Further development of the first-in-class proteasome inhibitors targeting the 19S deubiquitinase Rpn11. Structural biology techniques will be used to optimize these compounds and improve their potency and selectivity. The eventual goal will be to test RPN11 inhibitors in pharmacodynamic and efficacy models in vivo.
2. Identification of novel small-molecule inhibitors of proteasome activities other than the proteases (e.g. ATPases and deubiquitinases). This will involve the development of novel proteasome substrates to screen for proteasome inhibitors that affect discreet substrate classes (eg K48-ub-linked substrates vs K63-linked substrates).
3. Investigation of inhibitors of the HSP90 chaperone system to study the connection of chaperone assisted protein folding and degradation. Specifically we wish to elucidate the role that chaperones play in proteasome assembly, in interactions with ubiquitin-ligases and in delivery of substrates to the proteasome for degradation.
The assignment length is expected to be 3 years.
PhD at the time of appointment
Molecular cellular biology and protein biochemistry expertise
UPS expertise especially with the proteasome, deubiquitinases, and their inhibitors
HSP90 chaperone system expertise
Chemical biology experience
Small-molecule inhibitor screening and SAR experience
Amgen is an Equal Opportunity employer and will consider all qualified applicants for employment without regard to race, color, religion, sex, sexual orientation, gender identity, national origin, protected veteran status, or disability status.