Administration & Faculty
Brendan D. Stamper, PhD
2010-2012 Postdoctoral Fellow
Seattle Children’s Research Institute
2010 Doctor of Philosophy,
University of Washington
2002 Bachelor of Science,
Santa Clara University
Block coordinator for:
PHRM 580 GI/Nutrition/Natural Products
PHRM 586 Infectious Diseases
PHRM 560 Biochemistry I
PHRM 567 Pulmonary
PHRM 581 Endocrinology and Sex Hormones
Areas of Research & Specialization
My research is focused on projects that utilize comparative genomic, transcriptomic, and proteomic approaches to identify key pathways critical to propagating toxicologic and pathologic outcomes. The adaptability of ‘omic allows my lab to investigate pathologic mechanisms across a wide array of disease states, both inborn and drug-induced. Projects currently underway include mechanistic studies looking at acetaminophen-induced hepatotoxicity, hepatotoxicity associated with various natural products, and growth factor signaling in craniosynostosis.
Acetaminophen project: This project is an ongoing toxicogenomic study investigating the differential toxicity associated with acetaminophen and its regioisomer, 3-hydroxyacetanilide. Acetaminophen is a widely available analgesic and antipyretic, and while considered to be relatively safe at recommended doses, over 50,000 emergency room visits occur annually in the United States due to overdose. At therapeutic levels, the majority of an acetaminophen dose is metabolized to relatively non-toxic products via sulfation and glucuronidation reactions. A smaller percentage of the dose is metabolized to the reactive intermediate, N-acetyl-p-quinoneimine (NAPQI), which is conjugated to glutathione and safely cleared. In overdose situations, NAPQI concentrations rise, resulting in glutathione depletion, protein adduct formation, oxidative stress, and eventually liver injury. Using 3-hydroxyacetanilide as a comparative tool, gene expression profiling studies have been able to identify key biologic targets and pathways associated with the toxic response following acetaminophen overdose. Efforts are currently underway to understand of the role these targets play in signal transduction in hopes of gaining clearer insight into the cellular mechanisms that mediate drug-induced liver injury.
In other words: Acetaminophen and AMAP are structurally similar, yet only acetaminophen is toxic at high doses. While acetaminophen and AMAP trigger many of the same effects in cells, some cellular outcomes are different. It’s within these differences that we hope to clarify precisely why high-dose acetaminophen can lead to liver toxicity.
Craniosynostosis project: This project utilizes genomic and transcriptomic profiling to identify causal mechanisms associated with craniofacial disorders. Isolated craniosynostosis, which occurs in approximately 1/2500 births, is the pathologic fusion of calvarial bones that is associated with abnormal skull growth and increased intracranial pressure. There are more than one hundred well-established forms of craniosynostosis with known modes of inheritance, suggesting that genomic disposition plays an important role in this disease. The pathogenesis of craniosynostosis is poorly understood, and existing knowledge suggests no single gene, factor, or pathway is responsible. Rather, several independent mechanisms likely lead to the occurrence of several different forms of the disease, thus complicating the elucidation of these mechanisms. Large genomic and transcriptomic datasets using primary osteoblast cell lines derived from craniosynostosis patients have been generated by Dr. Michael Cunningham’s lab at the Seattle Children’s Research Institute. Probing these datasets has led to numerous insights into this complex disease, including key roles for signaling pathways associated with growth factors and the extracellular matrix.In other words: Craniosynostosis is a disease that leads to altered skull growth, which can have serious repercussions. It appears that numerous factors (both genetic and environmental) contribute to the disease state, making it a complex and interesting disease to study. By comparing the behavior of bone cells from the skulls of patients with and without craniosynostosis, we hope to identify the elusive factors that are responsible for causing this disease.
Stamper BD, Mecham B, Park SS, Wilkerson HW, Farin FM, Beyer RP, Bammler TK, Mangravite LM, Cunningham ML. Transcriptome correlation analysis identifies two unique craniosynostosis subtypes associated with IRS1 activation. Physiol Genomics 2012, 44(23):1154-63.
Stamper, B.D., Park, S.S., Beyer, R.P., Bammler, T.K., Cunningham, M.L. Unique sex-based approach identifies transcriptomic biomarkers associated with non-syndromic craniosynostosis. Gene Regul Syst Bio. 2012; 6:81-92.
Harrelson, J.P., Stamper, B.D., Chapman, J.D., Goodlett, D.R., Nelson, S.D. Covalent Modification and Time-Dependent Inhibition of Human CYP2E1 by the Meta Isomer of Acetaminophen. Drug Metab Dispos 2012, 40(8):1460-5.
Rieder, M.J., Green, G.E., Park, S.S., Stamper, B.D., Gordon, C.T., Johnson, J.M., Cunniff, C.M., Smith, J.D., Emery, S.B., Lyonnet, S., Amiel, J., Holder, M., Heggie, A.A., Bamshad, M.J., Nickerson, D.A., Cox, T.C., Hing, A.V., Horst, J.A., Cunningham, M.L. A human homeotic transformation resulting from mutations in PLCB4 and GNAI3 causes auriculocondylar syndrome. Am J Hum Genet. 2012 May 4; 90(5):907-14.
Stamper, B.D., Park, S.S., Beyer, R.P., Bammler, T.K., Farin, F.M., Mecham, B., Cunningham, M.L. Differential expression of extracellular matrix-mediated pathways in single-suture craniosynostosis. PLoS One. 2011;6(10):e26557.
Stamper, B.D., Mohar, I., Kavanagh, T.J., Nelson, S.D. Proteomic analysis of acetaminophen-induced changes in mitochondrial protein expression using spectral counting. Chem Res Toxicol 2011, 24(4):549-58.
Stamper, B.D., Bammler, T.K., Beyer, R.P., Farin, F.M., Nelson, S.D. Differential regulation of mitogen-activated protein kinase pathways by acetaminophen and its nonhepatotoxic regioisomer 3'-hydroxyacetanilide in TAMH cells. Toxicol Sci 2010, 116(1):164-73.