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Liskin Swint-Kruse, Ph.D.

Liskin Kruse portrait
Department Chair, SOM-Kansas City, Biochemistry and Molecular Biology

Professor, Biochemistry and Molecular Biology

lswint-kruse@kumc.edu

Professional Background

University of Kansas Medical Center, Biochemistry and Molecular Biology
Assistant Professor, 2004 - 2009
Associate Professor, 2009 - 2017
Director of Graduate studies, 2009-2018
Professor, 2017- present
Interim Chair, 2018-2019
Chair, 2019-present

University of Kansas Medical Center, Interdisciplinary Program in Biomedical Sciences, Associate Director, 2011-2018

University of Kansas - Lawrence, Molecular Biosciences, Courtesy Appointment, 2009 - present

Education and Training
  • BS, Chemistry, Baylor University, Waco, TX
  • PhD, Biochemistry, University of Iowa, Iowa City, IA
  • Post Doctoral Fellowship, Computational Biology, W.M. Keck Center for Computational Biology, Rice University and The University of Houston, Houston, TX
  • Post Doctoral Fellowship, Biochemistry, Rice University, Houston, TX

Research

Overview

Areas of research emphasis: Protein structure-function for personalized medicine; protein engineering; protein evolution; transcription control of bacterial metabolism

1. Personalized medicine: Each patient genome can have as many as 10,000 varia­tions in protein coding regions. To filter for amino acid changes that alter protein function, and thus have potential to be medically-relevant, high-perform­ing computer algori­thms are needed. Although many algori­thms have been developed, improve­ments are urgently needed.

The approach of the Swint-Kruse lab is to improve the assumptions that underlie these algorithms. Most algorithms incorporate (i) se­quence alignments of evolutionarily-related proteins (homologs); and (ii) textbook, amino acid substitution “rules” derived from lab experiments. However, these rules were derived from experi­ments that were highly biased towards positions that do not change much during evolution (“conserved”).
In contrast, more than half of the amino acids do change during evolution (“nonconserved”) for most proteins. Further, we have identified a class of nonconserved amino acids that do not follow the textbook. Instead, these positions act as functional “rheostats” during evolution: Amino acid changes at these positions provide opportunities to “dial” protein function either up or down by various amounts. In patients, such changes could make an individual more or less susceptible to disease or drug interactions. We have also shown that computer algorithms correctly predict substitution outcomes for conserved positions but perform poorly for rheostat positions.

We are now assessing the prevalence of rheostatic positions in a range of different protein types and testing hypothe­ses about how to identify them. In addition, we are exploring the underlying physical properties that give rise to these com­plex mutational outcomes. Our work incorporates the disciplines of biochemistry, bioinformatics, and biophysics. Together, these studies will be used to improve algorithms for personalized medicine.

2. The Cra-FruK complex alters regulation of central metabolism of γ-proteobacteria:
For γ-proteobacteria, several key processes are regulated by the LacI/GalR homolog “Cra” (Catabolite Repressor Activator protein). We identified a novel interaction between Cra and a kinase that contributes to the bacteria's ability to switch among carbon sources. Results will identify new ways to perturb central metabolism in γ-proteobacteria, which might be exploited to target a select group of enteric bacteria.