Cancer Institute

  • Damian G. Romero

    romero_damian.jpgAssociate Professor, Department of Biochemistry
    Tumor Cell Biology Program
    PhD, Molecular Biology, 2000, University of Buenos Aires, Argentina
    Postdoc, 2000-08, University of Mississippi Medical Center, Jackson, MS

    Contact information
    2500 N State St., Room G206
    Jackson, MS 39216
    Phone: (601) 984-1523

    Research interests

    • Regulator of G-protein signaling (RGS) proteins and breast cancer
    • Renin-Angiotensin-Aldosterone system and breast cancer

    Research synopsis

    Breast cancer is the most common cancer and the second leading cause of cancer related deaths in females. G-protein coupled receptors (GPCRs) have widespread fundamental roles in cellular signaling. Heterotrimeric G-proteins are the molecular switches that turn on intracellular signaling cascades in response to the activation of GPCRs by extracellular stimuli. Therefore, G proteins have a crucial role in defining the specificity and temporal characteristics of the cellular response. G-proteins are switched on by GTP binding, and intrinsic GTPase activity hydrolyzes G-protein bound GTP to GDP to return to the basal state. However, G-proteins GTPase activity is too low to account for the rapid changes in G-protein activation/deactivation status observed in vivo. Regulator of G-protein signaling (RGS) proteins increase G-proteins GTPase activity thousands of times. The RGS protein family is ubiquitously expressed and RGS proteins are involved in any intracellular signaling process in which GPCRs are involved.

    Although a highly attractive target, the role of RGS proteins in cancer is poorly understood. Screening for RGS proteins differentially expressed in MCF-7 breast cancer cells, which were grown in three dimensional extracellular matrixes that closely resemble the in vivo tumor microenvironment, we found that RGS22, the newest member of the RGS protein family, was significantly upregulated. Our studies have shown that RGS22 downregulation significantly decreases breast cancer cell proliferation, while RGS22 overexpression has the opposite effect. The recent development of specific RGS protein inhibitors makes RGS22 an exciting novel target to abolish or mitigate the exacerbated cell proliferation observed in breast cancers.

    Recent accomplishments and honors

    • 2008 Caroline tum Suden/Frances A. Hellebrandt Professional Opportunity Award, American Physiological Society
    • 2006 Mead-Johnson Research Award, American Physiological Society, Endocrinology and Metabolism Section

    Selected publications

    • Let-7i: lethal weapon against angiotensin ii-induced cardiac injury. Syed M, Ball JP, Romero DG. Hypertension. 2015 Oct;66(4):739-41. doi: 10.1161/HYPERTENSIONAHA.115.05659. Epub 2015 Aug 10.
    • 20-HETE and CYP4A2 ω-hydroxylase contribute to the elevated blood pressure in hyperandrogenemic female rats. Dalmasso C, Maranon RO, Patil CN, Moulana M, Romero DG, Reckelhoff JF.  Am J Physiol Renal Physiol. 2016 311(1):F71-7.
    • Regulation of nucleotide metabolism by mutant p53 contributes to its gain-of-function activities. Kollareddy M, Dimitrova E, Vallabhaneni KC, Chan A, Le T, Chauhan KM, Carrero ZI, Ramakrishnan G, Watabe K, Haupt Y, Haupt S, Pochampally R, Boss GR, Romero DG, Radu CG, Martinez LA. Nat Commun. 2015 Jun 12;6:7389. doi: 10.1038/ncomms8389.
    • p53 Modulates Notch Signaling in MCF-7 Breast Cancer Cells by Associating with the Notch Transcriptional Complex via MAML1. Yun J, Espinoza I, Pannuti A, Romero D, Martinez L, Caskey M, Stanculescu A, Bocchetta M, Rizzo P, Band V, Band H, Kim HM, Park SK, Kang KW, Avantaggiati ML, Gomez CR, Golde T, Osborne B, Miele L. J Cell Physiol. 2015 May 29. doi: 10.1002/jcp.25052. [Epub ahead of print]
    • TGIF Governs a Feed-Forward Network that Empowers Wnt Signaling to Drive Mammary Tumorigenesis. Zhang MZ, Ferrigno O, Wang Z, Ohnishi M, Prunier C, Levy L, Razzaque M, Horne WC, Romero D, Tzivion G, Colland F, Baron R, Atfi A.  Cancer Cell. 2015 Apr 13;27(4):547-60. doi: 10.1016/j.ccell.2015.03.002.
    • Identification of PHRF1 as a tumor suppressor that promotes the TGF-β cytostatic program through selective release of TGIF-driven PML inactivation. Ettahar A, Ferrigno O, Zhang MZ, Ohnishi M, Ferrand N, Prunier C, Levy L, Bourgeade MF, Bieche I, Romero DG, Colland F, Atfi A. Cell Rep. 2013 Aug 15;4(3):530-41. doi: 10.1016/j.celrep.2013.07.009. Epub 2013 Aug 1. PMID: 23911286
    • Angiotensin II- Regulated Transcription Regulatory Genes in Adrenal Steroidogenesis. Romero DG et al. Physiol Genomics 42A:259-66, 2010.
    • MicroRNA-21 increases aldosterone secretion and proliferation in H295R human adrenocortical cells. Romero DG et al. Endocrinology 149:2477-83, 2008.
    • RGS4 in adrenal gland: localization, regulation and role in aldosterone secretion. Romero DG et al.J Endocrinology 194:429-40, 2007.
    • RGS2 is regulated by angiotensin II and functions as a negative feedback of aldosterone production in H295R human adrenocortical cells.  Romero DG et al. Endocrinology 147:3889-97, 2006.