Faculty » Research Information
Heather L. Machado, PhD
Department of Biochemistry and Molecular Biology
Tulane University School of Medicine
1430 Tulane Avenue, #8643
New Orleans, LA 70112
Research Interests: Mammary Gland Biology, DCIS and Breast Cancer Progression, Inflammation and Cancer, Cancer Stem Cells
Summary: Inflammation has emerged as a critical component of the tumor microenvironment that is required for tumor progression. Infiltrating inflammatory cells, including tumor-associated macrophages (TAMs), have been shown to promote breast cancer cell invasion and have been correlated with metastasis and poor prognosis. However, very little is known about the mechanisms regulating macrophage recruitment to the tumor microenvironment. Gene profiling studies of both pre-malignant DCIS (ductal carcinoma in situ) and invasive breast cancer have resulted in the classification of various subtypes, which largely dictate patient outcome. It has been proposed that different breast cancer subtypes contain distinct cancer stem cell populations, which interact within a niche environment to enhance malignant progression. These stem cell populations have been shown to be radio- and chemo-resistant, and are postulated to contribute to disease recurrence.
My laboratory utilizes unique mouse models to study the molecular mechanisms that regulate the switch from premalignant to invasive breast cancer. Specifically, we are interested in delineating the interactions between cancer stem cells and tumor-associated macrophages, and dissecting the molecular pathways between these cell types that promote tumor cell invasion.
Representative and Recent Publications:
Sainz, B., Carron, E., Vallespinós, M., and Machado, H.L. Cancer stem cells and macrophages: implications in tumor biology and therapeutic strategies. Mediators of Inflammation; 2016:9012369. 2016. (PMC4769767)
Rahal, O.M., Machado, H.L., Montales, M.E., Pabona, J.P., Heard, M.E., Nagarajan, S., and Simmen, R.C.M. Dietary suppression of the mammary CD29hiCD24+ epithelial subpopulation and icytokine/chemokine transcriptional signatures modifies mammary tumor risk in MMTV-Wnt1 transgenic mice. Stem Cell Research; 11(3):1149-1162. 2013.
Machado, H.L., Kittrell, F.S., Edwards, D., White, A.N., Atkinson, R.L., Rosen, J.M., Medina, D., and Lewis, M.T. Separation by cell size enriches for mammary stem cell repopulation activity. Stem Cell Translational Medicine; 2(3):199-203. 2013 (PMC3659766)
Batts, T.D., Machado, H.L., Zhang, Y., Creighton, C.J., Li, Y., and Rosen, J.M. Stem cell antigen-1 (Sca1) regulates mammary tumor development and cell migration. PLoS One; 6(11):e27841, 2011. (PMID: 22140470)
Visbal, A.P., LaMarca, H.L., Villanueva, H., Toneff, M.J., Li, Y., Rosen, J.M., and Lewis, M.T. Altered differentiation and paracrine stimulation of mammary epithelial cell proliferation by conditionally activated Smoothened. Developmental Biology; 352 (1):116-27, 2011. (PMID: 21276786)
Long, W., Yi P., Amazit, L., LaMarca, H.L., Kuma, R., Mancini, M.A., Tsai, S.Y., Tsai, M., and O’Malley, B.W. SRC-3Δ4 mediates the interaction of EGFR with FAK to promote cancer cell migration and metastasis. Molecular Cell; 37:321-332, 2010. (PMID: 20159552)
LaMarca, H.L., Visbal, A.P., Creighton, C.J., Liu, H., Zhang, Y., Behbod, F., and Rosen, J.M. C/EBPβ regulates stem cell activity and specifies luminal cell fate in the mammary gland. Stem Cells; 28(3):535-44, 2010. (PMID: 20054865)
Behbod, F., Kittrell, F.S., LaMarca, H., Edwards, D., Kerbawy, S., Heestand, J.C., Young, E., Mukhopadhyay, P., Yeh, H., Allred, D.C., Hi, M., Polyak, K., Rosen, J.M., and Medina, D. An intraductal human-in-mouse transplantation model mimics the subtypes of ductal carcinoma in situ. Breast Cancer Research; 11(5):R66, 2009. (PMID: 19735549)
Coffelt, S.B., Marini, F.C., Watson, K., Zwezdaryk, K.J., Dembinski, J.L., LaMarca, H.L., Tomchuck, S.L., Höner zu Bentrup, K., Danka, E.S., Henkle, S.L., and Scandurro, A.B. The pro-inflammatory peptide LL-37 promotes ovarian tumor progression through recruitment of multipotent mesenchymal stromal cells. PNAS; 106(10):3806-11, 2009. (PMID: 19234121)
LaMarca, H.L. and Rosen, J.M. Minireview: hormones and mammary cell fate—what will I become when I grow up? Endocrinology; 149(9):4317-21, 2008. (PMID: 18556345)
Coffelt, S.B., Waterman, R.S., Florez, L., Höner zu Bentrup, K., Zwezdaryk, K.J., Tomchuck, S.L., LaMarca, H.L., Danka, E.S., Morris, C.A., and Scandurro, A.B. Ovarian cancers overexpress the antimicrobial protein hCAP-18/LL-37 and the LL-37 peptide increases ovarian cancer cell proliferation and invasion. Int J Cancer; 122(5):1030-9, 2008. (PMID: 17960624)
LaMarca, H.L. and Rosen, J.M. Estrogen regulation of mammary gland development and breast cancer: amphiregulin takes center stage. Breast Cancer Research; 9:304, 2007. (PMID:17659070)
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