Selected Journal Publications

Archived Web Publications

As promised at the inaugural launch of this web site, we will periodically publish scientific studies conducted in the McKnight laboratory at UT Southwestern Medical Center that, for one reason or another, are better suited for web dissemenation instead of conventional publication in a peer-reviewed scientific journal. Two such web publications have been posted to date, one written by Brandon Probst another by Andrew Pieper. The Probst paper describes a comprehensive search for substrates of a protein kinase enzyme, designated PAS kinase, first discovered in the McKnight lab about five years ago. These studies have been conducted in a thorough and comprehensive manner, leading not only to the identification of many putative PAS kinase substrates, but also to the amino acids directly modified by the enzyme in test tube reactions. The Probst manuscript also presents the results of a high throughput drug screen that sought to identify both synthetic organic compounds capable of either activating or inhibiting the PAS kinase enzyme. The Pieper et al manuscript lists the results of a screen for mutations that may predispose patients to mood disorders. Upwards of 500,000 individual DHPLC assays were conducted over a five year period in search for "smoking gun" mutations in one or more of the genes responsible for the control of circadian rhythm. Our idea was that mutations that would alter the robustness of circadian rhythm might cause humans to be susceptible to depression. Unlike the Probst study, conducted almost singlehandedly by Brandon himself, many people participated in the Pieper et al study - not only in the McKnight lab, but also the lab of John Rush, a distinguished psychiatrist here at UT Southwestern Medical Center. The Probst and Pieper manuscripts are similar in reporting thorough and extensive scientific observations for which all of us in the McKnight laboratory can be proud. In both cases, however, we have been unable to reach substantive conclusions regarding the scientific observations reported. As articulated, however, from the launch date of, we have chosen to use web-based dissemenation of these observations in hopes that they might help other scientists to "connect the dots" in a manner that has eluded us to date.

Depression Genetics Study (pdf format)

PASK High Throughput Screen (pdf format)