2021 Theses Doctoral
Developing a ‘ubiquitous’ toolkit for modulating ion channel expression in health & disease
Protein stability is critical for the proper function of all proteins in the cell. Ubiquitin is a key post-translational modification that serves as a universal regulator of protein turnover and has emerged as a highly sought-after signal for biological inquiry and drug development. Yet the pervasive role of ubiquitin signaling has given rise to the fundamental challenge of selectively manipulating a widespread signal: current pharmacological and genetic tools that target the ubiquitin-proteasome system (UPS) broadly alter cellular proteostasis with confounding side effects. Ion channels are essential proteins that regulate fundamental cellular properties including; electrical activity, fluid homeostasis, muscle contraction, neuronal firing, gastric acidification, and gene expression. Enhanced or reduced ion channel expression represents a pathological signature for a myriad of disease states, from chronic pain to cardiac arrhythmias, epilepsy, and cystic fibrosis. Although ubiquitin represents a critical mediator of ion channel expression, the inability to precisely manipulate ubiquitin modifications in situ has limited mechanistic insight and opportunities for therapeutic intervention. To address this barrier, I developed a novel nanobody-based toolset to selectively – and bidirectionally – manipulate the ubiquitin status and functional expression of target ion channels for basic study and therapeutic rescue.
Subjects
Files
- Kanner_columbia_0054D_16371.pdf application/pdf 5.13 MB Download File
More About This Work
- Academic Units
- Neurobiology and Behavior
- Thesis Advisors
- Colecraft, Henry M.
- Degree
- Ph.D., Columbia University
- Published Here
- February 23, 2021