Jeroen Roelofs, PhD
University of Wageningen, Wageningen, The Netherlands, Master degree in Molecular Sciences, 1996
University of Groningen, The Netherlands, PhD degree, Summa cum Laude, 2001
Harvard Medical School, Boston, MA, Postdoctoral Research Fellow, 2001-1009
Kansas State University, Manhattan, KS, Assistant Professor, 2009-2016
Kansas State University, Manhattan, KS, Associate Professor, 2016-2019
University of Kansas Medical Center, Kansas City, KS, Associate Professor, 2019-present
Interests: Protein degradation in the cell. Biochemical and cell biological analyses of assembly, regulation, and localization of proteasomes and their autophagic degradation.
Education and Training
- MS, Molecular Sciences, University of Wageningen, Wageningen, Netherlands
- PhD, Biochemistry, University of Groningen, Groningen, Netherlands
- Post Doctoral Fellowship, Biochemistry / Cell Biology, Harvard Medical School, Boston, MA
- Post Doctoral Fellowship, Biochemistry / Cell Biology, Haravrd Medical School, Boston, MA
The Roelofs Lab is fascinated by the proteasome, a large and abundant 66-subunit protein complex. As one of the cell's major degradation machines, proteasomes play an important role in cellular processes where the timely and coordinated turnover of proteins is required, such as the cell cycle and DNA repair. As a regulator of such cellular processes, the proteasome is associated with various cancers; inhibitors of the proteasome are, for example, FDA-approved drugs used in the treatment of multiple myelomas. The proteasome is also important for general protein homeostasis and quality control of proteins (proteostasis). This is important with respect to neurodegenerative diseases characterized by toxic protein accumulation, like the Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS).
Our lab is particularly interested in the "life cycle" of the proteasome itself. Proteasomes consist of 66 individual polypeptides which are assembled in a precise temporal and spatial manner to form an intricate and complex molecular machine. Here, we aim to understand the mechanisms that ten proteasome-specific chaperones use to guide and regulate this assembly process. Furthermore, we are interested in understanding how the cell monitors correct assembly of this complex. We have identified a protein that acts as a quality control factor for proper assembly, but the molecular mechanisms that govern proteasome quality control remain poorly understood. Finally, we found that proteasomes themselves can be degraded or stored for future use. Proteasomes, normally abundant in the nucleus, can be exported to the cytosol and targeted to storage granules or turned over by targeting them for autophagic degradation in the lysosome/vacuole. These processes are induced under certain environmental conditions and depend on the state of the complex.
Our goal is to identify factors that control the nuclear export of proteasomes or regulate the subsequent targeting of the proteasomes. For degradation, it depends on autophagic machinery to deliver proteasomes to lysosomes, while no clear mechanism for the formation and targeting to proteasome storage granules is known. We use a variety of biochemical and cell biological approaches in yeast and mammalian cells to address these questions.