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N. SHANE CUTLER

Research Assistant Professor of Pharmacology and Toxicology

Education and Training

B.S.,1995,University of Utah, Biology

Ph.D., 2000, Duke University, Genetics.

Postdoctoral Fellow 2000-2003, Vanderbilt University, Cancer

Research Interests

The cells of the respiratory tract are one of the primary sites of exposure to environmental toxins. These cells express a variety of cytochrome P450 molecules which are able to metabolize these compounds, often resulting in a less toxic, more easily eliminated compound. Unfortunately, in the process some of these compounds can become bioactivated and form highly reactive intermediates which can conjugate with cellular proteins and DNA causing cell damage or mutation.

The complement of cytochrome P450 molecules expressed by a given cell plays a large factor in how that cell will respond to environmental pollutants. In turn, the complement of P450 molecules expressed throughout an individual's cells play a major role in that individual's response to their environment. The variety and abundance of P450 molecules in a cell depends upon the genetic make-up of the individual and the induction or repression of these molecules in response to environmental cues. Using cell culture, human lung tissues, and genetic databases, Dr. Cutler seeks to identify transcription factors and genetic variation important in regulating P450 expression and cellular response to toxic pollutants. In addition to xenobiotic toxins, many P450 enzymes play important roles in metabolism of endogenous signaling molecules such as eicosanoids.  A new project in the lab involves investigating the role of Cytochrome P450 isoform 2J2 in generating epoxyeicosatrienoic acids and how this signaling molecule might affect the early stages of lung cancer.

Additionally, Dr. Cutler is interested in how the cells lining the airways and other organs respond to particulate matter.  Inhaled particulate matter has been definitively linked to adverse cardiovascular events.  With the proliferation of manufactured nano-sized particles, human exposure is becoming more and more common.  Understanding the cellular toxicity of these particles and the response of epithelial cells to their presence will allow us to better predict the risk of these particles being released into the environment.

Selected Publications

Stromal production of prostacyclin confers an antiapoptotic effect to colonic epithelial cells. N. Shane Cutler, Ramona Graves-Deal, Bonnie J. LaFleur, Zhenqiang Gao, Bruce M. Boman, Robert H. Whitehead, Erin Terry, Jason D. Morrow, Robert J. Coffey, Cancer Research 63:1748-1751, 2003.

Sp1 and Sp3 regulate basal transcription of the human CYP2F1 gene.
Jei Wan, Brian A. Carr, N. Shane Cutler, Diane L. Lanza, Ronald N. Hines, Garold S. Yost. Drug Metabolism & Disposition 33(8):1244-53, 2005.

Molecular mechanisms regulating human CYP4B1 lung-selective expression. Mark T. Poch, N. Shane Cutler, Garold S. Yost, Ronald N. Hines. Drug Metabolism & Disposition 33(8):1174-84, 2005.

Transcription Factor Binding to a Putative Double E-Box Motif Represses CYP3A4 Expression in Human Lung Cells. Jason S. Biggs, Jie Wan, N. Shane Cutler, Jukka Hakkola, Päivi Uusimäki, Hannu Raunio, and Garold S. Yost. Molecular Pharmacology 72(3):514-25,  2007.

Effects of Cell Type and Culture Media on Interleukin-6 Secretion in Response to Environmental Particles: An in Vitro Experimental Study. John M. Veranth, N. Shane Cutler, Erin G. Kaser, Garold S. Yost. Toxicology in Vitro, 2007 in press.

Pharmacology & Toxicology   College of Pharmacy   30 S. 2000 E., Rm 201, SLC  UT 84112  phone: 801-581-6287  fax: 801-585-5111 phtx@pharm.utah.edu