Savas, Jeffrey, PhD

Information

Name

Savas, Jeffrey, PhD

Title

Assistant Professor

Email

jeffrey.savas@northwestern.edu

Office Phone

312.503.3089

Office Fax

312.503.3951

Department

Neurology, Medicine, Neurological Surgery and Pharmacology

Office

Ward 12-101

Website

http://www.savaslab.com

Areas of Research

Cell Biology, Development, Learning & Memory, Mechanisms of Drug Action, Molecular Neuroscience, Neurobiology of Disease, Sensory Systems, Signal Transduction

Training Grants

Mechanisms of Aging and Demential Training Program (M.A.D)

NU Scholar Profile

https://www.scholars.northwestern.edu/en/persons/jeffrey-nicholas-savas

Recent Publications on PubMed

http://www.ncbi.nlm.nih.gov/pubmed/?term=jeffrey+savas+OR+Savas+JN

Current Research

Current Research

Research in the Savas lab is aimed at accelerating our understanding of the proteins and proteomes responsible for neurodevelopmental and neurodegenerative diseases. We use biochemistry with discovery-based mass spectrometry (MS) to identify the protein perturbations which drive synaptopathies and proteinopathies. Groups of perturbed proteins serve as pathway beacons which we subsequently characterizes in hopes of finding new pathogenic mechanisms and potential future therapeutic targets.
1. Anatomizing specific synaptic proteomes.
Synapses display complex electrophysiology and elaborate molecular diversity. We want to know which proteins are present at distinct mammalian synapses, how do they contribute to synapse specific properties, and how do synaptic proteomes change during development and disease? Through reductionist biochemical and molecular approaches, we explore the mammalian brain from the level of synaptic molecules to that of neuronal circuits. These efforts are aimed to investigate the molecular perturbations which drive synaptopathologies such as autism and schizophrenia.
2. Measuring synaptic perturbations in the auditory system.
Ribbon synapses perform precise, unusually fast, and sustained synaptic transmission which is essential for sensory perception in hearing and sight. Excess noise causes damage and eventual loss of cochlear hair cell / spiral ganglion neuron synapses but a detailed temporal understanding of the molecular perturbations are unknown. We aim to use biochemistry and quantitative proteomic analysis to characterize these perturbed synapses after noise exposure to gain a detailed understanding of these key noise sensitive structures.
3. Characterization of the protein decay dynamics during neurodegeneration.
Many neurodegenerative diseases including Alzheimer’s disease (AD), Huntington’s disease (HD), and Parkinson’s disease (PD) are characterized by impaired protein decay kinetics. We want to understand how altered protein degradation pathways contribute to each of these deadly diseases and impair neuronal function and cognition. Recently, we developed an approach that uses metabolic pulse-chase labeling of whole rodents with stable isotopes and proteomic analysis to monitor protein decay dynamics over long-time frames. We are particularly interested in determining how perturbed protein degradation pathways cause synapses collapse in AD

Selected Publications

Selected Publications

1. Savas JN, Ribeiro LF, Wierda KD, Wright R, DeNardo-Wilke LA, Rice HC, Chamma I, Wang YZ, Zemla R, Lavallée-Adam M, Vennekens KM, O'Sullivan ML, Antonios JK, Hall EA, Thoumine O, Attie AD, Yates JR 3rd, Ghosh A, de Wit J. (2015) The Sorting Receptor SorCS1 Regulates Trafficking of Neurexin and AMPA Receptors. Neuron. Aug 19;87(4):764-80.

2. Savas JN*, Toyama BH*, Xu T, Yates JR 3rd, Hetzer MW. (2012) Extremely long-lived nuclear pore proteins in the rat brain. Science. 335(6071):942.

3. Toyama BH*, Savas JN*, Park SK, Harris MS, Ingolia NT, Yates JR 3rd, Hetzer MW. (2013) Identification of long-lived proteins reveals exceptional stability of essential cellular structures. Cell. 154 (5): 971-82.

4. Savas JN*, de Wit J*, Comoletti D, Zemla R, Ghosh A, Yates JR 3rd. (2014) Ecto-Fc MS identifies ligand-receptor interactions through extracellular domain Fc fusion protein baits and shotgun proteomic analysis. Nat Protocols. 9(9):2061-74.
*Equal contribution.