Pharmacology and Toxicology - Research

Lawrence Sowers, Ph.D.

Professor and Chair

John Sealy Distinguished Chair for MD/PhD Combined Degree Studies in Honor of Dr. Truman G. Blocker
Chair, Department of Pharmacology and Toxicology
Professor of Pharmacology and Medicine
Director, MD-PhD Combined Degree Program

Research Interests

His work has involved the chemistry and biology of DNA damage resulting from both carcinogens and cancer chemotherapy agents. More recently, he has focused upon damage to DNA resulting from reactive molecules generated by activated inflammatory cells including eosinophils and neutrophils. He has recently demonstrated how certain inflammation-mediated DNA damage products could mimic epigenetic signals, perhaps explaining how inflammation could result in heritable changes in genes expression important for the silencing of tumor suppressor genes in the development of cancer, and how early exposure to agents that trigger inflammation could influence disease susceptibility later in life. His laboratory has trained numerous Ph.D., M.D. and M.D./Ph.D. students over the years and he looks forward to training further students within the context of this translational and interdisciplinary program in Galveston.

Selected Publications

Kang, J., Burdzy, A., Liu, P., Sowers L.C.,: Synthesis and Characterization of Oligonucleotides containing 5-chlorocytosine. (2004) Chemical Research in Toxicology 17, 1236- 1244.

Valinluck, V. Liu, P. Kang, JI Jr., Burdzy, A., Sowers, L.C.:5-halogenated pyrimidine lesions within a CpG sequence context mimic 5-methlcytosine by enhancing the binding of the methyl-CpG-binding domain of methyl-CpG-binding protein 2 (MeCP2). (2005) Nucleic Acids Res. 33, 3057-64.

Valinluck, V., Wu, W., Lui, P., Neidigh, J., Sowers, L.C.: The impact of cytosine 5-halogens on the interaction of DNA with restriction endonucleases and methyltransferases. (2006) Chem Res Tox. 19, 556-62.

Valinluck, V., Sowers, L.C.: Endogenous cytosine damage products alter the site-selectivity of human DNA maintenance methyltransferase DNMT1. (2007) Cancer Research 67, 946-50.

Valinluck, V.V. and Sowers, L.C. Inflammation-mediated cytosine damage: a mechanistic link between inflammation and the epigenetic alterations in human cancers. (2007) Cancer Res. 67, 5583-6.

Kang, J., Sowers, L.C.: Examination of hypochlorous acid-induced damage to cytosine residues in a CpG dinucleotide in DNA. (2008) Chem Res Tox. 21, 1211-8.

Cui, Z., Theruvathu, J., Farrel, A., Sowers, L.C.: Characterization of synthetic oligonucleotides containing biologically important modified bases by MALDI-TOF mass spectrometry. (2008) Analytical Biochemistry 379, 196-207

Darwanto, A., Theruvathu, J., Sowers, J.L., Pascal, T., Goddard, W.A. III, and Sowers, L.C.: Mechanism of base selection by hSMUG1. (2009) J. Biol. Chem. 284, 885-93.

Lao, V.V., Herring, J.L., Kim, C.H., Darwanto, A., Soto, U., Sowers, L.C.: Incorporation of 5-chlorocytosine into mammalian DNA results in heritable gene silencing and altered cytosine methylation patterns. (2009) Carcinogenesis 30, 886-93.

Herring, J.L., Rogstad, D.K., Sowers, L.C.: Enzymatic methylation of DNA incultured human cells studied by stable isotope incorporation and mass spectrometry. (2009) Chem Res Toxicol 22, 1060-8.

Rogstad, D.K., Herring, J.L., Theruvathu, J.A., Burdzy A., Perry, C.C., Sowers, L.C.: Chemical decomposition of 5-asa-2'-deoxycytidine (Decitabine): kinetic analyses and identification of products by NMR, HPLC, and mass spectrometry. 2009) Chem Res Tox. 22, 1194-204.

Darwanto, A., Farrel, A., Rogstad, D.K., Sowers, L.C.: Characterization of DNA glycosylase activity by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. (2009) Analytical Biochem. 394, 13-23.

Theruvathu, J.A., Kim, C.H., Rogstad, D. K., Neidigh, J., Sowers, L.C.: Base pairing configuration and stability of an oligonucleotide duplex containing a 5-chlorouracil-adenine base pair. (2009) Biochemistry 48, 7539-46.

Theruvathu, J.A., Kim, C.H., Darwanto, A., Neidigh, J., Sowers, L.C.: pH-Dependent configurations of a 5-chlorouracil-guanine base pair. (2009) Biochemistry 48, 11312-8.

Williams, A.A., Darwanto, A., Theruvathu, J.A., Burdzy, A., Neidigh, J., Sowers, L.C.: Impact of sugar pucker on base pair and mispair stability. (2009) Biochemistry 48, 11994-2004.

Kim, C.H., Darwanto, A., Theruvathu, J.A., Herring, J.L., Sowers, L.C.: Polymerase Incorporation and Miscoding Properties of 5-Chlorouracil. (2010) Chem Res Tox. 23, 740-8.

Ito, S., D”Alessio, A.C., Taranova, O.V Hing, K., Sowers, L.C. and Zhang, Y. (2010) Role of Tet proteins in 5mc to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466, 1129-33.