Page 26 - CBAC Newsletter 2014

August 2009. In the Cui lab, we study the structure, function focused, at least part of the time.
and regulation of voltage-gated ion channels. Voltage-gated
ion channels generate the electrical signals that make mus- My most important significant personal achievement is
cle tissue contract, encode information in the nervous sys- meeting and marrying my wife Amanda. We have built a
tem, and trigger hormone release. A fundamental feature of great life together, and her support has carried me through.
their function is the ability to detect and react to changes in
transmembrane voltage. This is achieved by the interaction After completing medical school I plan to continue my scien-
between two distinct domains, the voltage-sensing domain, tific training in the form of a post-doctoral position. During
which detects changes in membrane voltage, and the pore my thesis work, I learned to work through a very basic prob-
domain, which opens and closes to modulate the mem- lem. During my post-doc, I intend to expand my toolkit to
brane conductance. In my thesis work, I have been studying problems at the tissue, organ or organism level so that I can
the fundamental mechanisms through which the functions ultimately run a lab of my own that works on the mechanistic
of the voltage-sensing and pore domains are coupled. We underpinnings of human diseases.
have discovered that lipid molecules play a central role in
communicating voltage-sensor activation to pore opening As ion channel biophysicists in the biomedical engineering
and the two domains couple through unique protein-protein department we are a bit of an oddity. CBAC has provided me
and protein-lipid interactions at every stage in the gating a sense of community and belonging on the Danforth Cam-
pathway. This work has direct relevance to cardiac elec- pus. Also, the CBAC invited seminar speakers have been
trophysiology where, we have discovered, modulation of amazing. This series of lectures has provided me first hand
these coupling interactions is the major mechanism through access to current experts in the field.
which the accessory subunit KCNE1 modulates the func-
tion of the KCNQ1 voltage-gated potassium channel. In the Papers that Mark has authored along with other CBAC
heart, channels formed by KCNQ1 and KCNE1 generate the members include:
IKs current, which plays a critical role in regulating action
potential duration. Patients with inherited mutations that Zaydman MA, Silva JR, Delaloye K, Li Y, Liang H, Lars-
decrease IKs are predisposed to sudden cardiac death. Our son HP, Shi J, Cui J. (2013) Kv7.1 ion channels require a
studies provide novel therapeutic strategies for targeting lipid to couple voltage sensing to pore opening. Proc Natl
these abnormal channels. Acad Sci USA. 2013 Aug 6;110(32):13180-5. doi: 10.1073/
pnas.1305167110. Epub 2013 Jul 16.
The work itself is extremely motivating for me. It is both cre-
ative and challenging, and I feel that the work we have done Zaydman MA, Silva JR, Cui J. (2012) Ion channel associat-
is significant. I am thrilled that we have made fundamental ed diseases: overview of molecular mechanisms. Chem Rev.
contributions to the understanding of voltage-dependent 2012 Dec 12; 112(12):6319-33. doi: 10.1021/cr300360k.
gating, and we are extending this work to clinically relevant Epub 2012 Nov 14.
questions. I hope that this work provides a useful, concep-
tual framework for others studying voltage-dependent ion Sun X, Zaydman MA, Cui J. (2012) Regulation of Voltage-Ac-
channels and their associated diseases. tivated K(+) Channel Gating by Transmembrane β Sub-
units. Front Pharmacol. 2012 Apr 17; 3:63. doi: 10.3389/
I am very proud of the paper I published in PNAS in 2013 fphar.2012.00063. eCollection 2012
[See: “Kv7.1 ion channels require a lipid to couple voltage
sensing to pore opening” at http://www.pnas.org/content/ Li Y, Zaydman MA, Wu D, Shi J, Guan M, Virgin-Downey B,
early/2013/07/16/1305167110.short]. It was a real jour- Cui J. (2011) KCNE1 enhances phosphatidylinositol 4, 5-bi-
ney, but in the end the story came together beautifully. Of sphosphate (PIP2) sensitivity of IKs to modulate channel ac-
course, I am now obsessed with my current work that is a di- tivity. Proc Natl Acad Sci USA. 2011 May 31; 108(22):9095-
rect continuation of that paper. I guess in research your new 100. doi: 10.1073/pnas.1100872108. Epub 2011 May 16.
most important achievement may always be just around the
corner. Wu D, Delaloye K, Zaydman MA, Nekouzadeh A, Rudy Y,
Cui J. (2010) State-dependent electrostatic interactions of
Time goes by so quickly, I feel like I just moved here yester- S4 arginines with E1 in S2 during Kv7.1 activation.
day. I have learned that you can achieve a lot with good peo- J Gen Physiol. 2010 Jun; 135(6):595-606. doi: 10.1085/
ple and hard work, but I also learned that time and energy jgp.201010408. Epub 2010 May 17. PMID: 20479111
are limited resources. It does a lot of good to be realistic and

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