Heather LaMarca, Ph.D.
The ability of mammary stem cells to exist quiescently over long periods of time suggests an important role for these cells in breast cancer etiology. Mutations acquired by mammary stem cells have the potential to be passed on to progeny cells, rendering the tissue highly susceptible to tumor formation. Thus, it has been hypothesized that mammary gland stem cell populations are the primary targets for tumorigenesis. The objective of my project is to elucidate the role of CCAAT/enhancer binding protein beta (C/EBPß) in mammary stem cell self-renewal and cell fate determination. C/EBPß is a basic leucine zipper transcription factor whose expression is required for normal ductal morphogenesis and lobuloalveolar development. Previous studies in the laboratory demonstrated that germline deletion of C/EBPß alters murine mammary epithelial cell fate, as evident by the misexpression of multiple ductal cell markers. We hypothesize that C/EBPß controls mammary cell fate decisions through the regulation of multiple target genes that coordinate stem cell self-renewal as well as ductal and alveolar development. To test this hypothesis, a unique adenovirus-Cre-mediated recombination system will be exploited to target C/EBPß deletion to mammary stem/progenitor cells. Changes in cell fate will be identified by examining the expression of various mammary epithelial cell markers upon transplantation, and will be compared in germline and somatic C/EBPß knockout models. Defining the role of C/EBPß in stem cell function and mammary cell fate determination will greatly improve our understanding of the molecular mechanisms that regulate stem cell self-renewal and survival.
- Joined Lab: June 2005
- Position: Postdoctoral Fellow
- Degrees: BS, University of New Orleans, 1999 & Ph.D., Tulane University, 2005
- Awards: American Cancer Society Tricam Industries Postdoctoral Fellowship (2006-2009)
LaMarca HL, Visbal AP, Creighton CJ, Liu H, Zhang Y, Behbod F, Rosen JM. C/EBPbeta Regulates Stem Cell Activity and Specifies Luminal Cell Fate in the Mammary Gland. Stem Cells. 2010 Jan 6. [Epub ahead of print]PMID: 20054865 [PubMed - as supplied by publisher]Related articles
Coffelt SB, Marini FC, Watson K, Zwezdaryk KJ, Dembinski JL, LaMarca HL, Tomchuck SL, Honer zu Bentrup K, Danka ES, Henkle SL, Scandurro AB. The pro-inflammatory peptide LL-37 promotes ovarian tumor progression through recruitment of multipotent mesenchymal stromal cells. Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3806-11. Epub 2009 Feb 20.PMID: 19234121
Behbod F, Kittrell FS, LaMarca H, Edwards D, Kerbawy S, Heestand JC, Young E, Mukhopadhyay P, Yeh H-W, Allred DC, Hu M, Polyak K, Rosen JM, Medina D. An intraductal human-in-mouse transplantation model mimics the subtypes of ductal carcinoma in situ, Breast Cancer Res. 2009 Sep 7;11(5):R66. PMID: 19735549
LaMarca HL and Rosen JM. Minireview: hormones and mammary cell fate--what will I become when I grow up? Endocrinology. 2008 Sep;149(9):4317-21. PMID:18556345
LaMarca HL, Dash PR, Vishnuthevan K, Harvey E, Sullivan DE, Morris CA, Whitley GS. Epidermal growth factor-stimulated extravillous cytotrophoblast motility is mediated by the activation of PI3-K, Akt and both p38 and p42/44 mitogen-activated protein kinases. Hum Reprod. 2008 Aug;23(8):1733-41. Epub 2008 May 16.PMID: 18487214
LaMarca HL, Rosen JM.Estrogen regulation of mammary gland development and breast cancer: amphiregulin takes center stage. Breast Canc Res. 2007; 9:304-306.
Coffelt SB, Waterman RS, Florez L, zu Bentrup KH, Zwezdaryk KJ, Tomchuck SL, LaMarca HL, Danka ES, Morris CA, Scandurro AB. Ovarian cancers overexpress the antimicrobial protein hCAP-18 and its derivative LL-37 increases ovarian cancer cell proliferation and invasion.Int J Cancer. 2008 Mar 1;122(5):1030-9.
Shelby BD, LaMarca HL, McFerrin HE, Nelson AB, Lasky JA, Sun G, Myatt L, Offermann MK, Morris CA, Sullivan DE. Kaposi's sarcoma associated herpesvirus G-protein coupled receptor activation of cyclooxygenase-2 in vascular endothelial cells. Virol J. 2007 Sep 14;4:87.
Zwezdaryk KJ, Coffelt SB, Figueroa YG, Liu J, Phinney DG, LaMarca HL, Florez L, Morris CB, Hoyle GW, Scandurro AB. Erythropoietin, a hypoxia-regulated factor, elicits a pro-angiogenic program in human mesenchymal stem cellsExperimental Hematology 35 (2007) 640–652.
Lamarca HL, Morris CA, Pettit GR, Nagowa T, Puschett JB. Marinobufagenin Impairs First Trimester Cytotrophoblast Differentiation. Placenta. 2006 Jan 31
LaMarca HL, Nelson AB, Scandurro AB, Whitley GS, Morris CA.Human Cytomegalovirus-Induced Inhibition of Cytotrophoblast Invasion in a First Trimester Extravillous Cytotrophoblast Cell Line. Placenta. 2005 Nov;26(10):709-20.
LaMarca HL, CM Ott, K Höner zu Bentrup, CL LeBlanc, DL Pierson, AB Nelson, AB Scandurro, G St. J. Whitley, CA Nickerson and CA Morris
Three-dimensional growth of extravillous cytotrophoblasts promotes differentiation and invasion. Placenta. 2006 Feb-Mar;27(2-3):137-47.
Sainz B Jr, LaMarca HL, Garry RF, Morris CA. Synergistic inhibition of human cytomegalovirus replication by interferon-alpha/beta and interferon-gamma. Virol J. 2005 Feb 23;2(1):14.
LaMarca HL, Sainz B Jr, Morris CA. Permissive human cytomegalovirus infection of a first trimester extravillous cytotrophoblast cell line.Virol J. 2004 Nov 17;1(1):8.
McFerrin, HE, Sullivan, DE, Nelson, AB, LaMarca, HL, Shelby, BD, and Morris, CA Tat Induced Angiogenesis, p. 129-162. In R.R. Watson (ed.), AIDS and Heart Disease. Marcel Dekker, Inc., New York, 2004.