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Thomas L. Brown, Ph.D.
Associate Professor
Director, Laboratory of Cell Death, Differentiation, and Development
Address: 011F Medical Sciences Building
Phone: (937) 775-3809
E-mail: thomas.L.brown@wright.edu
President and CEO, Apoptrol, LLC
Ph.D., University of Cincinnati, 1993
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Research Interests
Cell death (apoptosis)
Apoptosis is an evolutionarily-conserved, normal physiologic process that occurs to maintain homeostasis. The majority of human diseases have an altered cell death program that can result in to much (autoimmune, neurological disorders) or to little cell death (cancer). We are looking at therapeutics designed to specifically control the apoptosis process.
Cancer - Overcoming tumor resistance
In the early stages of cancer, tumorigenic cells routinely undergo physiologic cell death as a normal means to control its spread; however, over time cancer cells can often become resistant to the normal induction of apoptosis. Examining how to sensitize chemotherapeutic resistance may lead to new insights in the fight against cancer.
Oxygen regulation and placental differentiation
Many pregnancy-associated disorders (such as preeclampsia) stem from abnormal placental development. Babies born from these pregnancies are at increased risk of hypertension, cardiovascular diseases, and stroke later in life. Placental stem cells grow in very low levels of oxygen and differentiate as oxygen levels rise during development. We are using state of the art gene targeting approaches to investigate the role of oxygen in placental stem cell differentiation.
Our understanding of the cellular and molecular events that control apoptosis and differentiation may contribute to future treatments for numerous diseases and pregnancy associated disorders.
Selected Publications
(Out of 47)
Doran DM, Kulkarni-Datar K, Cool DR, and Brown TL. Hypoxia Activates Constitutive Luciferase Reporter Constructs. (In Press 2010) Biochimie
Sahu R, Batra S, Prabodh K, Brown TL*, Srivastava S*. The role of K-Ras gene mutation in TRAIL-induced apoptosis in pancreatic and lung cancer cell lines. (In Press 2010) Cancer Chemotherapy and Pharmacology.
Southerland B, Kulkarni-Datar K, Keoni C, Bricker R, Grunwald WC, Ketcha DM, Hern E, Cool DR and Brown TL. Q-VE-OPh, a negative control for O-phenoxy-conjugated caspase inhibitors. (2010) 3:33-40 Journal of Cell Death
Davoli A, Hocevar B, and Brown TL. Progression and Treatment of HER2-Positive Breast Cancer. (2010) 65:611-23 Cancer Chemotherapy and Pharmacology.
Wicker CA, Sahu RP, Kulkarni-Datar K, Srivistava SK*, and Brown TL*. BITC sensitizes pancreatic adenocarcinomas to TRAIL-induced apoptosis. (2009) Cancer Growth & Metastasis 2:45-55
Gultice AD, Kulkarni-Datar K, Brown TL. HIF1alpha Mediates Distinct Steps of Rat Trophoblast Differentiation in Gradient Oxygen. (2008) Biology of Reproduction. 80:184-193
Hemberger M, Yang, W, Natale D, Brown TL, Dunk C, Gargett CE, and Tanaka S. Subtype-Specific Trophoblast Cell Lines. Stem Cells from Fetal Membranes, Placenta (2007), 29 Supp: Trophoblast Research 17-19
Kulkarni K, Selesniemi K, Brown TL. Interferon-gamma Sensitizes the Human Salivary Gland Cell Line, HSG, to Tumor Necrosis Factor-alpha Induced Activation of Dual Apoptotic Pathways. (2006) Apoptosis. 11:2205-2215
Gultice AD, Selesniemi KL, and Brown TL. Hypoxia inhibits differentiation of lineage-specific Rcho-1 trophoblast giant cells. (2006) Biology of Reproduction 74:1041-1050.
Lauf PK, Warwar, R, Brown TL, and Adragna NC. Regulation of Potassium Transport in Human Lens Epithelial Cells. (2006) Experimental Eye Research 82:55-64
Selesniemi KL, Reedy MA, Gultice AD, Guilbert LJ, Brown TL. TGF-ß induces differentiation of the labyrinthine trophoblast stem cell line, SM10. (2005) Stem Cells and Development 14:697-711
Caserta TM, Knisley AA, Tan FK, Arnett FC and Brown TL. Genotypic Analysis of the TGF beta -509 Allele in Patients with Systemic Lupus Erythematosus and Sjögren's Syndrome, Annales de Genetique (2004) 47:359-363
Caserta TM, Smith AN, Gultice AD, Reedy MA, and Brown TL. Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties. Apoptosis (2003) 8:345-352.
Williams S, Smith AN, Cianci C, Morrow JS, and Brown TL. Identification of the Primary Caspase 3 Cleavage Site in alpha II-Spectrin during Apoptosis. Apoptosis (2003) 8:353-361
Zhao Y., Brown TL, Kohler H, Müller S. Transmembrane-Antibody Induced Inhibition of Cell Suicide. Apoptosis (2003) 8:631-637
Kadakia M, Brown TL, McGorry M and Berberich S. MdmX mediates Smad transactivation. Oncogene (2002) 21:8776-8785
LePoole IC, Sarangarajan R, Zhao Y, Stennett LS, Brown TL, Sheth P, Miki T, Boissy RE. "VITI", a novel gene associated with vitiligo. Pigment Cell Research (2001) 14:475-484
Patil S, Wildey GM, Brown TL, Choy L, Derynck R, Howe PH. Smad 7 is induced by CD40 and protects WEHI 231 B-lymphocytes from TGFbeta-induced growth inhibition and apoptosis. J. Biol.Chem. (2000) 275:38363-38370
Brown TL, Patil S., Cianci C., Morrow JS, and Howe PH. TGF beta Induces Caspase 3 Independent Cleavage of alpha II-Spectrin/alpha-Fodrin) Coincident With Apoptosis. J. Biol. Chem (1999) 274:23256-23263.
Hocevar, BA, Brown, TL, and Howe, PH. TGFbeta induces fibronectin synthesis through a c-Jun N-terminal kinase -dependent, Smad 4 independent pathway. EMBO J. (1999) 18:1345-1356.
Brown, TL, Patil, S, Basnett, R, and Howe, P. Caspase Inhibitor, BD-fmk, Distinguish TGFb-Induced Apoptosis From Growth Inhibition. Cell Growth and Diff. (1998) 9:869-875.
Moulton BC, Akcali KC, Ogle TF, Brown TL, Motz J, Khan SA., Control of Apoptosis in the Uterus During Decidualization. Serono Symposia (ed. JL Tilly, JF Strauss III, M. Tenniswood) "Cell Death in Reproductive Physiology." Springer-Verlag, New York (1997) p48-66.
Zhou A., Paranjapoe J., Brown TL, Nie H., Naik S, Dong B., Chang A, Trapp B, Fairchild R., Colmenares C., Silverman RH. Interferon Action and Apoptosis are Defective in Mice Devoid of 2',5'-Oligoadenylate Dependent RNAse L. EMBO J. (1997) 16:6355-6363.
Brown TL., Moulton BC., Swertfeger DK., Witte DP., Harmony, J.A.K. Apolipoprotein J/Clusterin Expression Defines Distinct Stages of Blastocyst Implantation in the Mouse Uterus. Biol. Reprod. (1996) 55:740-747.
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