Mary Beth Martin

Mary Beth Martin

Professor

Research Building

3970 Reservoir Road, NW

Washington, DC 20007

Phone: 703-864-6877
IMG_9439
Research Disciplines: Diseases/Pathogens | Human Biology | Toxicology

Research Interests

Heavy metals and metalloids, endocrine disruption, metabolic disruption, steroid receptors, breast cancer

Biographical Sketch

I am a Professor in the Department of Oncology and the Department of Biochemistry and Molecular & Cellular Biology in the School of Medicine at Georgetown University. One of my research interests is in the role of estrogen receptor-alpha (ERa) and progesterone receptor in the etiology and treatment of breast cancer and focuses on the mechanisms that regulate expression and activity of the receptor in order to target the receptors for the treatment of ER positive breast cancer. My second research interest is in the activation of nuclear receptors by metals and metalloids as an underlying cause of breast cancer. My initial work in the field showed that estradiol and growth factors regulate the expression of ER through several mechanisms including regulation of transcription of the ERa gene, stability of the ERa transcript, and translation of ER mRNA. In addition to defining the mechanisms that regulate expression of ERa, my laboratory is interested in defining the mechanisms that regulate activity of the receptor. My laboratory was the first to show that growth factors activate ER through the AKT pathway and was the first to show that the bivalent metal cadmium activates ER through the ligand binding domain of the receptor. Subsequently, my laboratory showed that several bivalent metals and oxyanionic metalloids activate ERa. My laboratory also showed that the second messenger calcium, a bivalent metal, binds to the ligand binding domain and mediates the cross talk between growth factors and ERα suggesting that calcium is a physiological ligand of the receptor and explaining why heavy metals, that mimic calcium, are endocrine disruptors and contribute to hormone independent and resistant breast cancer. The Women’s Health Initiative and Million Women Study suggest that hormone replacement therapy with estrogen plus progestin increases the risk of developing breast cancer yet there are no known environmental progestins. As part of the Breast Cancer and Environment Research Program (BCERP), my laboratory studied the ability of metals and metalloids to activate the progesterone receptor. In addition to hormone replacement therapy, there is increasing evidence linking obesity to both ER positive and ER negative breast cancer, however, the molecular mechanisms underlying the association are not clearly understood and a focus of this grant. To address this question, my laboratory recently asked whether metals and metalloids disrupt metabolism by activating/inhibiting estrogen related receptors-alpha and -gamma, nuclear receptors that regulate the expression of metabolic genes. Our preliminary results show that cadmium and calcium activate estrogen related receptor-gamma and increase the expression of genes involved in gluconeogenesis. We are currently testing the novel hypothesis that higher lifetime environmental exposure to metals/metalloids with estrogen related receptor-like activity is associated with chronic metabolic dysfunction, high body weight, and an increased risk of developing breast cancer. Ongoing and recently completed projects that I would like to highlight include:

U01ES026132
Martin (contact PI); Byrne (MPI)
09/30/15-06/30/22(nce)
Impact of environmental metal/metalloid exposures on mammographic breast density, a marker of breast cancer

Citations:

  • Johnson M, Kenney N, Hilakivi-Clarke L, Singh B, Chepko G, Clarke R, Sholler PF, Lirio A, Foss C, Trock B, Paik S, Stoica A, Martin MB. (2003) Cadmium mimics the effects of estrogen in vivo in the uterus and mammary gland. Nature Med. 9:1081-1084. PMID 12858169
  • Divekar SD, Storchan GB, Sperle K, Veselik DJ, Johnson E, Dakshanamurthy S, Lajiminmuhip YN, Nakles RE, Huang L, Martin MB. (2011) The role of calcium in the activation of estrogen receptor-alpha. Cancer Research 71:1658-1668. PMID 2121417 PMC 3057389
  • Veselik DJ, Divekar S, Dakshanamurthy S, Storchan GB, Turner JMA, Graham KL, Huang L, Stoica A, Martin MB. (2008) Activation of estrogen receptor-alpha by the anion nitrite. Cancer Research 68:3950-8. PMID 18483281
  • Stoica A, Katzehellenbogen B, Martin MB. (2000) Activation of the estrogen receptor by the heavy metal cadmium. Mol. Endocrinol. 14: 545-553. PMID 10770491

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