Dr. Shaun Sanders

I first became interested in science during my BSc at the University of British Columbia when I volunteered in a research lab and quickly realized that I love biomedical research. I was always fascinated by the brain and with brain diseases. This was further strengthened by my undergraduate research when I worked on developing strategies for delivery of therapeutics across the blood brain barrier in Sandhoff and Tay-Sachs diseases, which are devastating, fatal neurodegenerative disorders that primarily affect young children. After obtaining my BSc, I worked as a research technician in Dr. Michael Hayden’s lab researching the adult-onset neurodegenerative disease, Huntington disease (HD). There, I became fascinated with how the protein-lipid modification known as palmitoylation regulates protein trafficking in neurons and how that goes wrong in neurological disorders. I quickly decided that I wanted to pursue a PhD with Dr. Hayden investigating the role palmitoylation plays in HD and identified the HTT palmitoylating enzyme ZDHHC17 as an essential protein crucial for neuronal integrity. This led to a postdoctoral fellowship supported by the Brody Foundation Medical Trust Fund in the lab of Dr. Gareth Thomas in Philadelphia. During my PDF I combined biochemical and cell biological studies with viral-mediated approaches in neurons to identify a new role for palmitoylation in targeting voltage-gated potassium ion channels to the neuronal axon initial segment, the site of action potential initiation. I joined the Department of Molecular and Cellular Biology at the University of Guelph June 2020. My group will use cutting edge genetic, biochemical, and cell biological approaches to understand how neurons use palmitoylation to target proteins to specific subcellular locations in neurons and to define how palmitoylation-dependent targeting contributes to physiological neuronal function and neuropathological conditions.

BSc – Biology, Cell Biology and Genetics Option; University of British Columbia, Vancouver, BC, Canada

PhD – Neuroscience; University of British Columbia, Vancouver, BC, Canada

PDF – Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA

The Sanders lab is interested in how neurons use the protein-lipid modification palmitoylation to target proteins to specific subcellular locations in and to define how palmitoylation-dependent targeting contributes to physiological neuronal function and neuropathological conditions. Precise control of neuronal excitability, or whether or not a neuron fires a nerve impulse to its neighbours, is essential for normal behaviour and cognition, while aberrant excitability is a hallmark of many neurological diseases, including epilepsy, bipolar disorder, Schizophrenia, and autism spectrum disorder. The key factor that controls the threshold of excitability is the clustering of ion channels and receptors at sites of excitability, including synapses, axon initial segments (AIS), and nodes of Ranvier; but how such clustering is regulated is not fully understood. Current areas of research in the Sanders lab include:

• How does palmitoylation control voltage-gated sodium and potassium channel targeting and function at the AIS and nodes of Ranvier?
• How do physiological and pathological changes in neuronal activity impact potassium and sodium channel palmitoylation and targeting to the AIS?
• What palmitoyl acyltransferase and palmitoyl protein thioesterase enzymes palmitoylate and depalmitoylate, respectively, sodium and potassium ion channels and how are they regulated by physiological and pathological changes in neuronal activity?
• Do human mutations in ion channels that cause ataxia and seizure disorders alter channel palmitoylation and targeting to sites of excitability?
• How does palmitoylation regulate axonal trafficking of cargo to sites of neuronal excitability?

We use cutting edge genetic, biochemical, and cell biological approaches to answer these questions, including CRISPR-mediated gene knockout and mutation, shRNA-mediated knockdown and rescue, specialized palmitoylation assays, and live and fixed confocal microscopy in neuronal cultures grown in conventional culture and in microfluidic devices.

• Petropavlovskiy AA, Kogut JA, Leekha A, Townsend CA, Sanders SS. A Sticky Situation: Roles of Palmitoylation in the Axon and Axon Initial Segment. Neuronal Signaling. Provisionally accepted pending minor revisions.
• Sanders SS, Hernandez LM, Soh H, Karnam S, Walikonis RS, Tzinhounis AV, Thomas GM. The palmitoyl acyltransferase ZDHHC14 controls K_v1 family potassium channel clustering at the axon initial segment. eLife. 2020. 2020: 9: e56058.
• Niu J*, Sanders SS*, Jeong HK*, Holland SM, Sun Y, Collura KM, Hernandez LM, Huang H, Hayden MR, Smith GM, Hu Y, Jin Y, Thomas GM. Coupled Control of Distal Axon Integrity and Somal Responses to Axonal Damage by the Palmitoyl Acyltransferase ZDHHC17. Cell Reports. 2020: 33: 108365.
• Sanders SS, DeSimone FI, Thomas GM. mTORC1 signaling is palmitoylation-dependent and involves dynamic palmitoylation of LAMTOR1 and mTOR. Front Cell Neurosci. 2019: 13: 115.
• Skotte NH*, Sanders SS*, Singaraja RR*, Ehrnhoefer DE, Vaid K, Qui X, Kannan S, Verma C, Hayden MR. Palmitoylation of caspase-6 by HIP14 regulates its activation. Cell Death and Dif 2017: 24: 433. *equal contribution.
• Sanders SS, Parsons MP, Mui KKN, Southwell AL, Franciosi S, Cheung D, Waltl S, Raymond LA, Hayden MR. Sudden death due to paralysis and synaptic and behavioral deficits when Hip14/Zdhhc17 is deleted in adult mice. BMC Biology 2016: 14: 108.
• Sanders SS*, Martin DDO*, Butland SL, Lavallee-Adam M, Calozari D, Kay C, Yates III JR, Hayden MR. Curation of the mammalian palmitoylome indicates a pivotal role for palmitoylation in diseases and disorders of the nervous system. PLOS Comp Bio 2015: 11: e1004405-20. *equal contribution.
• Sanders SS, Hou J, Sutton LM, Garside VC, Mui KKN, Singaraja RR, Hayden MR, Hoodless PA. Huntingtin interacting proteins 14 and 14-like are required for chorioallantoic fusion during early placental development. Dev Biol 2015: 387: 257-66.
• Sanders SS, Sutton LM, Mui KKN, Hayden MR. Identification of a binding site in Huntingtin for the Huntingtin interacting proteins HIP14 and HIP14L. PLoS One 2014: 9: 90669.

A complete list of publications can be found here