Matt Scaglione, PhD
K. Matthew Scaglione received his Bachelor of Science degree in Biology from McKendree University in 2001 and his Doctorate in Biochemistry from Saint Louis University School of Medicine in 2007 where his research focused on ubiquitin pathways in cancer. He performed postdoctoral studies at the University of Michigan School of Medicine from 2007 until 2013 investigating the role of protein quality control pathways in neurodegenerative diseases. During his postdoctoral studies Dr. Scaglione was awarded a F32 (Ruth L. Kirschstein National Research Service Award) and a NIH K99/R00 (Pathway to Independence Award). Dr. Scaglione joined the faculty of the Medical College of Wisconsin in 2013.
Phone: (414) 955-8416
Fax: (414) 955-6510
Neurodegenerative diseases are a diverse set of diseases including Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Polyglutamine expansion Diseases, Amyotrophic lateral sclerosis (ALS) and many others. While the clinical features and affected regions of the brain vary greatly between these neurodegenerative diseases they have one thing in common; the accumulation of neurotoxic proteins. The failure to fold or degrade toxic proteins ultimately leads to the accumulation of protein aggregates, a hallmark of neurodegenerative diseases. How neurons recognize and handle these toxic protein species is a major unresolved question in the field.
In the Scaglione lab we focus on understanding the how protein quality control machinery recognizes and handles aberrantly folded proteins. On one hand chaperones function to recognize and assist in refolding neurotoxic proteins, misfolded proteins. Conversely E3 ubiquitin ligases like CHIP (C-terminus of Hsc70 Interacting protein) bind chaperones and target misfolded proteins for degradation via the ubiquitin proteasome system.
Ongoing projects in the lab are:
Understanding how protein fate decisions are made by the chaperone and ubiquitin pathways. In this project we are utilizing biochemical reconstitution assays to understand how chaperones like HSP70 and HSP90 and the ubiquitin ligase CHIP “talk” to each other. These studies also involve structural studies to better understand the architecture of active ubiquitinating complexes.
Identifying the physiological role of Ube2w. We have recently identified Ube2w as the first ubiquitin conjugating enzyme to attach ubiquitin to the N-terminus of its substrates. The physiological significance of this is unclear. To address this we have developed a Ube2w knock-out mouse to study Ube2w function in vivo. Using the Ube2w knock-out mouse coupled with biochemical, cellular, and proteomic techniques we hope to identify what role Ube2w plays in vivo.
Determine the role of Ube2w in neuroprotection. Based on our preliminary work we hypothesize that Ube2w will play a neuroprotective role in vivo. To test this we are crossing Ube2w knockout mice with tau transgenic mice. This study will focus on understanding what if any role Ube2w plays in protecting against neurodegeneration in a mouse model of tauopathy.