Barry M. Markaverich, Ph.D.
Department of Molecular and Cellular Biology
Ph.D.: University of Southern Mississippi, Hattiesburg
Postdoctoral training: Baylor College of Medicine, Houston
Bioflavonoids, Tetrahydrofurandiols, Leukotoxindiols, Cell Growth Regulation and Endocrine Disruption
Our research is directed towards understanding how estrogens and environmentally derived endocrine disrupters control reproductive function and cell proliferation. Although the interaction of estrogen agonists and antagonists with the estrogen receptor (ER) is a primary event in estrogen action, mammalian cells contain a second binding site for [3H]estradiol (type II site) that controls cell growth. Methyl-p-hydroxyphenyllactate (MeHPLA, a bioflavonoid metabolite) is the endogenous ligand for the type II sites that blocks estrogenic response and inhibits cell proliferation. We identified type II sites as ligand-binding domain on histones H3 and H4. These two core histones are components of nucleosomes associated with actively transcribed genes. Type II site ligands block the expression of Estrogen Signaling Pathway (ESP) and Cell Cycle Pathway (CCP) genes via inhibiting the acetylation of lysines in the N-terminus of histone H4. We are attempting to identify type II ligand-induced modifications in histones H3 and H4 that control ESP and CCP gene expression and to determine whether the ligands affect the recruitment of coregulators with histone acetytransferase (HAT) or histone deacetylase (HDAC) activity to the promoters of these genes.
We recently discovered that ground corncob and human food products contains mitogens that stimulate cancer cell proliferation and disrupt male and female sexual behavior and cyclicity in rats. The endocrine disruptive agents were identified as a pair of THF-diol isomers (9,12-oxy-10,13-dihydroxystearic acid and 10. 13-oxy-9,12-dihydroxystearic acid) and a leukotoxindiol (LTX-diol; 9,10-dihydroxy-12-octadecenoic acid). Synthetic THF-diols and LTX-diols are mitogenic in breast and prostate cancer cells and they block male and female sexual behavior and reproductive function. The compounds also regulate the expression of a number of genes involved in nitric oxide pathways controlling hypothalamic LH-RH release and cell cycle pathways in breast and prostate cancer cells. We are studying the mechanism of action of these compounds.
Baylor College of Medicine
One Baylor Plaza, Cullen 405A
Houston, TX 77030
- Markaverich BM, Crowley JR, Rodriguez M, Shoulars K and Thompson T. (2007). Tetrahydrofurandiol (THF-diol) Stimulation of Phospholipase A2 (PLA2), LOX and COX Gene Expression and MCF-7 Human Breast Cancer Cell Proliferation. Environmental Health Perspectives (in press; Available on-line).
- Markaverich BM, Alejandro M, Thompson T, Mani S, Reyna A, Portilo W, Turk J and Crowley J. (2007). Tetrahydrofuran-diols (THF-diols), Leukotoxindiols (LTX-diols) and Endocrine Disruption in Adult Rats. Environmental Health Perspectives 115:702-708.
- Markaverich BM, Shoulars K and Alejandro MA. (2006). Specific Nuclear Type II [3H]estradiol binding site ligands: Inhibition ER-Positive and ER-Negative Cell Proliferation and c-Myc and Cyclin D1 Gene Expression. Steroids 71:865-874.
- Shoulars K, Rodriguez MA, Crowley JR, Turk J, Thompson T and Markaverich BM. (2006). Reconstitution of Type II [3H]Estradiol Binding Sites with Recombinant Histones H4. J Steroid Biochemistry and Molecular Biology 99:1-8.
- Shoulars K, Rodrigues MA, Crowley JR, Turk J, Thompson T and Markaverich BM. (2005). Nuclear Type II [3H]Estradiol Binding Sites: A Histone H3-H4 Complex. J Steroid Biochemistry and Molecular Biology 96:19-30.
- Markaverich BM, Crowley JR, Shoulars K, Casajuna N, Mani S, Reyna A and Sharp J. (2005). Leukotoxinodiols Isolated from Gound Corn Cob Bedding Disrupt Estrous Cyclicity in Rats and Stumulate c-Myc and p27 and MCF-7 Cell Proliferation. Environmental Health Perspectives 113:1698-704.
- Shoulars, K, Brown T, Alejandro MA and Markaverich BM. (2002). Identification of Rat Uterine Nuclear Type II [3H]Estradiol Binding Sites as Histone H4. Biochem Biophys Res Commun 296:1083-90.
- Markaverich BM, Alejandro MA, Markaverich DM, Zitzow L, Casajuna N, Camarao N, Hill J, Bhirdo K, Faith R, Turk J and Crowley J. (2002). Identification of a Novel Endocrine Disrupting Agent in Corn Products that Stimulates Breast Cancer Cell Proliferation. Biochem Biophys Res Commun 291:692-700.