Education
B.S. Mathematics, UT-Austin (2000)
Mentor:
Wah Chiu, Ph.D.
Joseph Bryan, Ph.D.
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David Ortiz
Baylor College of Medicine and PNRI
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Department: SCBMB
Address: Pacific Northwest Research Institute
720 Broadway
Seattle, WA 98122
Phone: (206) 726-1200
Fax:
Email: do148010@bcm.tmc.edu
Web:
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Honors
HAMBP Pre-doctoral Fellow 2005-2007
NSF GK-12 Fellow 2006-2007
GRC Travel Fellowship 2006 |
Research Topic
Structure/Function Study of ATP-Sensitive K+ Channel
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Research Description
I will study the structure and function of ATP-sensitive potassium channels. These channels, referred to as KATP channels, respond to changes in the metabolic state of cells and couple metabolism to membrane electrical activity. KATP channels are ~900 KDa in size and are heterooctamers composed of four subunits from the small inward rectifier family, either KIR6.1 or KIR6.2, that form a potassium selective pore, and four subunits of sulfonylurea receptors, either SUR1, SUR2 or SUR2b, that regulate the activity of the pore. SUR proteins are in the ATP-Binding Cassette, or ABC protein superfamily and other family members are usually ATP-hydrolyzing small molecule transporters. In pancreatic beta-cells KATP channels are involved in the regulation of insulin secretion. KATP channels are inhibited by ATP acting on the inward rectifier and activated by ADP acting through the SUR1. However, the coupling mechanism between SUR1 and Kir6.2 remains unknown. Furthermore it was recently found that heterozygous mutations in Kir6.2 cause permanent neonatal diabetes (PNDM) alone or neonatal diabetes with developmental delay, epilepsy or muscle weakness (DEND syndrome). I will express both wild type and mutated inward rectifier tetramers and KATP channel octamers, both His-tagged, in a pichia pastoris expression system, and purify via metal affinity chromotography. I will then perform biochemical assays on the purified inward rectifiers to quantify the variance of ATP affinity with and without the pathological mutations. Furthermore, I will work in parallel in Dr. Wah Chiu's cryo-em lab to solve the structure for the KATP channel with the goal of resolving the coupling mechanism between the two subunits.
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Selected Publications
- John B. Little, David Ortiz, Ricardo Ortiz-Rosado, Rebecca Pablo, Karen Ríos-Soto: Some remarks on Fitzpatrick and Flynn's Gröbner basis technique for Padé approximation. J. Symb. Comput. 35(4): 451-461 (2003)
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