The goal of my research program is to develop inhibitors selective for ion channel subtypes, particularly voltage-gated potassium (Kv) channels, such that researchers may use them to identify channel subunits that generate native currents. Establishing the molecular identity of Kv channels has been a particularly challenging problem: mammalian Kv channels arise from a family of more than 40 genes, and Kv pore-forming subunits can assemble as heterotetramers. Despite substantial and enduring efforts, few modulators of Kv channel activity have been discovered that are highly selective between individual channel subtype. This is perhaps due to a high degree of sequence conservation between subfamily members in the transmembrane segments that are important for function.
[[Image:sackshot.jpg|thumb|right]]
Jon Sack, Ph.D.
==Education==
===Research interests===
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* 2003 PhD, Stanford University, Department of Biological Sciences
* 1997, BA, Reed College, Major in Biochemistry
==Institutional Affiliations==
In living cells, electrical signals control a cornucopia of important physiological processes including neurotransmission, insulin secretion, and heartbeat. Electrophysiological signals are generated by proteins known as ion channels. Different cell types harbor distinct complements of channels, tuned to serve the particular functions of a cell. Establishing the identity of proteins underlying endogenous ionic currents in any particular cell type has been particularly challenging problem. Mammalian voltage-gated potassium channels are exemplars of protein diversity. They arise from a family of more than 40 genes encoding pore-forming subunits, many of which can co-assemble into functionally distinct heterotetramers, which then recruit a variety of modulatory subunits. There are no selective inhibitors for most of these proteins, and more advanced tools are needed to identify the channels underlying endogenous potassium currents. The Sack laboratory is developing serial strategies to molecularly identify the channels that underlie important yet unidentified ionic currents. By using engineering biologic macromolecules and implementing ligand evolution strategies, we are developing novel means to target specific potassium channel gene products. The new biochemical tools are being used to probe the physiological function of specific ion channel proteins, and modulate cellular electrical signaling.
Founder
Institute for Design of Intelligent Drugs
===Education===
Protean Research
Ph.D., Stanford University, Department of Biological Sciences
In living cells, electrical signals control a cornucopia of important physiological processes including neurotransmission, insulin secretion, and heartbeat. Electrophysiological signals are generated by proteins known as ion channels. Different cell types harbor distinct complements of channels, tuned to serve the particular functions of a cell. Establishing the identity of proteins underlying endogenous ionic currents in any particular cell type has been particularly challenging problem. Mammalian voltage-gated potassium channels are exemplars of protein diversity. They arise from a family of more than 40 genes encoding pore-forming subunits, many of which can co-assemble into functionally distinct heterotetramers, which then recruit a variety of modulatory subunits. There are no selective inhibitors for most of these proteins, and more advanced tools are needed to identify the channels underlying endogenous potassium currents. The Sack laboratory is developing serial strategies to molecularly identify the channels that underlie important yet unidentified ionic currents. By using engineering biologic macromolecules and implementing ligand evolution strategies, we are developing novel means to target specific potassium channel gene products. The new biochemical tools are being used to probe the physiological function of specific ion channel proteins, and modulate cellular electrical signaling.
Education
Ph.D., Stanford University, Department of Biological Sciences