Brown Laboratory Home Page

Laboratory of Cell Death, Differentiation, and Development

      *         Vital Statistics

               Contact Information

      *         Areas of Research

               Lab Personnel

               Recent Publications

 

Vital Statistics

 

 Faculty Position

Associate Professor

Department of Neuroscience, Cell Biology, and Physiology

 

Affliation

Wright State University  http://www.wright.edu

Wright State University School of Medicine http://www.med.wright.edu

Wright State Univ. College of Science and Math http://www.wright.edu/cosm

Wright State University Biomedical Sciences Ph.D. Program http://www.wright.edu/academics/biomed/Welcome.html

Wright State Univ. School of Graduate Studies http://www.wright.edu/sogs

 

Postgraduate Research

Cleveland Clinic Foundation, Lerner Research Institute, Dept. Cell Biology

http://www.lerner.ccf.org/

Cincinnati Children's Research Foundation, Division of Development Biology

http://www.cincinnatichildrens.org/chrf

University of Cincinnati College of Medicine, Dept of Environmental Health

http://www.med.uc.edu/

 

* Education

 

Van Wert High School, 1981, http://www.vanwertcougars.net/hs

The Ohio State University, B.S., Biochemistry, 1986 http://www.ohio-state.edu/

Univ. of Cincinnati, Developmental Biology, Ph.D., 1993 http://www.uc.edu/

 

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*  Contact Information

 

Thomas L. Brown, Ph.D.

Associate Professor

Wright State University Boonshoft School of Medicine

Department of Neuroscience, Cell  Biology, and Physiology

Laboratory of Cell Death, Differentiation, and Development

3640 Colonel Glenn Highway

042 Biological  Sciences Bldg.

Dayton, Ohio 45435

Phone: 937-775-3809

Fax: 937-775-3391

Email:mailto:thomas.l.brown@wright.edu

 

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Areas of Research

*    Apoptotic Cell Death and Cancer

Research on apoptosis involves the analysis of the molecular mechanisms that induce and inhibit apoptosis.  Apoptosis is a process of physiological cell death in which no inflammatory response occurs.  The laboratory analyzes how apoptosis impacts immune cell function.  In this past, we have studied apoptosis induced by transforming growth factor beta, a critical immune system regulating cytokine, as well as other transcriptional regulators in B cells in culture.  We also study the proinflammatory cytokine-induced (TNF alpha, IFN gamma, and FasL) cell death.  This system closely models the events that occur in the autoimmune disease SjogrenÕs Syndrome, also know as dry mouth /dry eye syndrome.  We are also currently evaluating new cell death regulators that can be used to promote or inhibit cell death to treat human diseases, such as cancer.

*    Reproductive Physiology & Placental Development

Research on placental development involves the analysis of the molecular mechanisms that control placental (trophoblast) lineage formation and function and proper development of the placenta.  Three types of trophoblast cells make up the placenta.  Our lab examines the critical regulators of placental development, on the growth and differentiation of trophoblast stem cells, trophoblast giant cells and labyrinthine trophoblast cells.  We are studying the signaling events that induce differentiation and the molecular mediators of the placental differentiation process. We are currently studying the mechanisms that control specific events in the development of the placenta and how this relates to infertility, placental development and problems associated with pregnancy, such as preeclampsia and intrauterine growth retardation.

*   Immunophysiology and Autoimmunity

Transforming growth factor beta (TGFb) is an essential growth regulatory cytokine critical in regulating the immune response. The establishment of immune tolerance is essential in preventing autoimmune disease and is tightly controlled by the process of apoptosis (cell suicide). We are analyzing the role of TGFb in the development of autoimmunity and control of apoptosis in systems that serve as models of the human autoimmune diseases Sjšgren's Syndrome and Type I diabetes.  We are currently analyzing the mechanisms that regulate female-predominant gender bias.

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*   The Brown Lab – 2006

Tom Brown, Ph.D., Principal Investigator

Kashmira Kulkarni, Ph.D. Candidate- Biomedical Sciences Ph.D. Program

Diane Doran-M.S. Candidate in Microbiology and Immunology

Amanda Vince-Honors Undergraduate in Biological Sciences

Sarah Wilson- Honors Undergraduate in Biological Sciences

Christopher Weaver-Work Study Program

 

*   Good Luck to Former Lab Members

Kaisa Selesniemi, Ph.D.; Postdoc @ Harvard Medical School, Vincent Ctr for Reproductive Biology

Amy Gultice, Ph.D.; Postdoc @ Wright State University, Dept. of Biochemistry and Molecular Biology

Meredith Reedy, M.S.; Instructor @ Wright State University, Dept. of Biological Sciences

Hiloni Bhasvar; Medical Student @ Wright State University Boonshoft School of Medicine

Tina Caserta, M.S.; Research Associate @ Wright State University Boonshoft School of Medicine

April Smith, M.S.; Senior Research Associate @ Cincinnati ChildrenÕs Hosptial Medical Center

Eric Harris, B.S.; Wright State University, Registered Nurse

Shanedah Williams, M.S.; Scientist  @ Florida State University, Taxolog, Inc.

Quincy Carter, M.S.; Scientist @ Eli Lilly Pharmaceuticals

 

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*        Recent Publications

Lauf PK, Warwar, R, Brown TL, and Adragna NC. Regulation of Potassium Transport in Human Lens Epithelial Cells. Experimental Eye Research  82(1):55-64   2006 http://www.sciencedirect.com/science?_ob=IssueURL&_tockey=%23TOC%236792%232006%23999179998%23614879%23FLA%23&_auth=y&view=c&_acct=C000061256&_version=1&_urlVersion=0&_userid=3742306&md5=110a2463b1ff7c8ed41ee6c6561743f2

Gultice AD, Selesniemi KL, and Brown TL.  Hypoxia inhibits differentiation of lineage-specific Rcho-1 trophoblast giant cells.  Biology of Reproduction 74(6):1041-1050 2006 June Cover Photo http://www.biolreprod.org/content/vol74/issue6/

Selesniemi KL, Reedy MA, Gultice AD, Guilbert LJ, Brown TL.  TGF-§ induces differentiation of the labyrinthine trophoblast stem cell line, SM10.  Stem Cells and Development  14(6):697-711  2005 http://www.liebertonline.com/toc/scd/14/6

Selesniemi KL, Reedy MA, Gultice AD, Brown TL. Identification of Committed Placental Stem Cell Lines for Studies of Differentiation. In Press.  Stem Cells and Development  14(5):535-547    2005 http://www.liebertonline.com/toc/scd/14/5

Muller S, Zhao Y, Brown TL, Morgan AC, and Kohler H.  TransMabs: Cell-penetrating antibodies, the next generation.  Expert Opinion on Biological Therapy,  5(2):237-241   2005  http://www.ingentaconnect.com/content/apl/ebt/2005/00000005/00000002

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 SjšgrenÕs Syndrome, Annales de Genetique   47:359-363   2004  http://www.sciencedirect.com/science?_ob=IssueURL&_tockey=%23TOC%236607%232004%23999529995%23534526%23FLA%23&_auth=y&view=c&_acct=C000061256&_version=1&_urlVersion=0&_userid=3742306&md5=588b6a02ad31c316ac6045e776aa648b

Selesniemi K and Brown TL. High Rate of transfection achieved with Metafectene  transfection in the rodent placental giant cell line, Rcho-1.  Biontex, Inc., Application Note.  http://www.biontex.com  2004

Brown TL. Q-VD-OPh, A next generation caspase inhibitor.   Cell Volume and Signaling:Proceedings  of the Dayton International Symposium on Cell Volume and Signal Transduction.  Eds PK Lauf and NC Adragna  559:293-300  Kluwer/Plenum Publishing. 2004

Selesniemi K and Brown TL. Efficiency of Metafectene  transfection in a murine labyrinthine placental trophoblast cell line.  Biontex, Inc., Application Note.  http://www.biontex.com  2004

Brown, TL.  Steroid Hormones, Encyclopedia of Genetics, 2nd Ed., (Ed. B. Ness) Salem Press, 2004

Brown, TL.  SjogrenÕs syndrome.  MagillÕs Medical Guide, 3rd Ed. (T. Irons-George Ed.), Salem Press, 2004

Brown, TL.  Placenta.  MagillÕs Medical Guide, 3rd Ed. (T. Irons-George Ed.), Salem Press, 2004

Zhao Z., Brown TL, Kohler H, MŸller S. Transmembrane-Antibody Induced Inhibition of Cell Suicide.  Apoptosis.  (2003)  8(6):631-637  http://journals.ohiolink.edu/cgi-bin/sciserv.pl?collection=journals&journal=13608185&issue=v08i0006

 

Selesniemi K and Brown TL.  Metafectene transfection in HSG human salivary gland cells.  Biontex, Inc., Application Note.  http://www.biontex.com  2003

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(4):345-352  http://journals.ohiolink.edu/cgi-bin/sciserv.pl?collection=journals&journal=13608185&issue=v08i0004

Williams ST, Smith AN, Cianci CD, Morrow JS, and Brown TL.  Identification of the Primary Caspase 3 Cleavage Site in alpha II-Spectrin during Apoptosis.  Apoptosis (2003)  8(4):353-361  http://journals.ohiolink.edu/cgi-bin/sciserv.pl?collection=journals&journal=13608185&issue=v08i0004

Kadakia M, Brown TL, McGorry M and Berberich S.  MdmX mediates Smad transactivation. Oncogene   2002 21:8776-8785 http://www.nature.com/onc/journal/v21/n57/index.html

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  14:475-484  2001  http://www.blackwell-synergy.com/toc/pcr/14/6

Smith AN, Carter QC, Kniss DA and Brown TL.  Identification of a TGF beta-responsive human trophoblast derived cell line. Placenta 2001(5) 22:425-431   http://www.sciencedirect.com/science?_ob=IssueURL&_tockey=%23TOC%236988%232001%23999779994%23286644%23FLP%23&_auth=y&view=c&_acct=C000061256&_version=1&_urlVersion=0&_userid=3742306&md5=4d0ca4b5e9cbbb8bce3fdfebee5e3904

Brown TL, Howe PH. Analysis of TGFb-Induced Apoptosis, (Transforming Growth Factor Beta protocols) Methods in Mol.Biol. 2000 (ed. PH Howe), Humana Press, Totowa NJ  142:149-167

Patil S, Wildey GM, Brown TL, Choy L, Derynck, and Howe PH.  Smad 7 is induced by CD40 and protects WEHI 231 B-lymphocytes from TGF beta induced growth inhibition and apoptosis. J. Biol.Chem. (2000)  275(49):38363-38370 http://www.jbc.org/content/vol275/issue49/index.shtml

Brown, TL, Patil S., Cianci C., Morrow JS, and Howe PH. TGFb Induces Caspase 3 Independent Cleavage of aII-Spectrin (a-Fodrin) Coincident With Apoptosis. J.Biol. Chem (1999) 274(33):23256-23263.  http://www.jbc.org/content/vol274/issue33/index.shtml

Hocevar, BA., Brown, TL., and Howe, PH. TGFb induces fibronectin synthesis through a c-Jun N-terminal kinase -dependent, Smad 4 independent pathway. EMBO J. (1999) 18:1345-1356.  http://www.nature.com/emboj/journal/v18/n5/index.html

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.  http://cgd.aacrjournals.org/content/vol9/issue10/

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.  http://www.nature.com/emboj/journal/v16/n21/index.html

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) 48-66.

 

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Wright State University

 

 

Last Revised: 6/29/06