Director Quantitative Genomics & Microarray Core Lab
Education & Training
- Postdoctoral Fellow
- Case Western Reserve University, 1985
- Stanford University, 1982
Areas of Interests
- Research Interest
- Signaling Pathways Involved in Endometrial Cancer
Signaling Pathways Involved in Endometrial Cancer
In general terms, my laboratory is interested in mechanisms that control gene expression and cell growth. Over the last few years, we have focused on identifying genes that are aberrantly expressed in endometrial cancer, which is the most common gynecologic cancer. To do this we employ several approaches including DNA and RNA microarray analysis of normal and malignant endometrium. We have determined that many signaling pathways can influence the rate of growth in the endometrium. One of these pathways is the wnt-signaling pathway. Wnts are glycoproteins that act a ligands; they interact with cell-surface receptors called frizzled that can produce downstream signals. This system is very complex: there are 19 wnts, 10 frizzleds, several antagonists such as sFRP, and a least 3 downstream pathways. The illustration depicts the “canonical” pathway that is mediated by wnt-induced stabilization of ß-catenin, but wnts can also induce signals via the “planar” polarity pathway, mediated by jun kinase, and the “calcium” pathway, mediated by NF-AT. Abnormal signals in any of these pathways can lead to disease. We have found that alteration of the canonical signals can leads to abnormal growth in the endometrium. We can detect early cancer by measuring the levels of expression of several genes. One of the best of these biomarkers is sFRP4 (secreted Frizzled-Related Protein). sFRP’s (there are 5 in humans, sFRP1-5). We have found that sFRP4 is expression is reduced nearly by 90% in tumors compared to normal endometrium. This lead us to examine the role of sFRP4 in regulating cell growth and we found that elevating expression of sFRP4 had a profound inhibitory effect on growth of a model endometrial cell line. We are currently performing studies to determine if sFRP is in fact a tumor-supressor.
- Berbée M, Fu Q, Boerma M, Sree Kumar K, Loose DS, Hauer-Jensen M. (2012). Mechanisms underlying the radioprotective properties of γ-tocotrienol: comparative gene expression profiling in tocol-treated endothelial cells. Genes Nutr., Jan;7(1):75-81. doi: 10.1007/s12263-011-0228-8. Epub 2011 Apr 24. PMID: 21516479.
- Hartig SM, He B, Newberg JY, Ochsner SA, Loose DS, Lanz RB, McKenna NJ, Buehrer BM, McGuire SE, Marcelli M, Mancini MA. (2012). Feed-forward inhibition of androgen receptor activity by glucocorticoid action in human adipocytes. Chem Biol., Sep 21;19(9):1126-41. doi: 10.1016/j.chembiol. 2012.07.020. PMID: 22999881.
- Weerasinghe P, Hallock S, Brown RE, Loose DS, Buja LM. (2012). A model for cardiomyocyte cell death: Insights into mechanisms of oncosis. Exp Mol Pathol., Feb;94(1):289-300. doi: 10.1016/ j.yexmp.2012.04.022. PMID: 22609242.
- Sceusi EL, Loose DS, Wray CJ. (2011). Clinical implications of DNA methylation in hepatocellular carcinoma. HPB (Oxford), 13(6):369-76. doi: 10.1111/j.1477-2574.2011. 00303.x. PMID: 21609368.
- Zhao Z, Miki T, Van Oort-Jansen A, Matsumoto T, Loose DS, Lee CC. (2011). Hepatic gene expression profiling of 5′-AMP-induced hypometabolism in mice. Physiol Genomics, 43(7):325-45. doi: 10.1152/ physiolgenomics. 00174.2010. PMID: 21224 422.
- Carmon KS and Loose DS. (2010). Development of a Bioassay for Detection of Wnt-Binding Affinities for Individual Frizzled Receptors. Anal Biochem., 401, 288-94.
- Garg S, Boerma M, Wang J, Fu Q, Loose DS, Kumar SK, Hauer-Jensen, M. (2010). Influence of sublethal total body irradiation on immune cell populations in the intestinal mucosa. Radiation Res., 173, 469-78.
- Guevara JG, Jr, Prashad N, Ermolinsky B, Gaubatz JW, Kang D, Schwarzbach AE, Loose DS, Guevara NV. (2010). Apo B100 similarities to viral proteins suggest basis for LDL-DNA binding and transfection capacity. J Lipid Res., 51, 1704-18.
- Nabilsi NH, Broaddus RR, McCampbell AS, Lu, KH, Lynch HT, Chen L and Loose, DS. (2010). Sex hormone regulation of survivin gene expression. J Endocrinol., [Epub ahead of print].
- Rosenfeld GC and Loose DS. (2010). Pharmacology (Board Review Series (BRS), 5th edition), Lippincott Williams and Wilkins, Baltimore.
- Westin SN, Broaddus RR, Deng L, McCampbell A, Lu KH, Lacour RA, Milam MR, Urbauer DL, Mueller P, Pickar JH, Loose DS. (2009). Molecular clustering of endometrial carcinoma based on estrogen-induced gene expression. Cancer Biol Ther. 8, 2126-2135.
- Nabilsi NH, Broaddus R, and Loose DS. (2009). DNA methylation inhibits p53 mediated survivin repression. Oncogene, 28, 2046-50.
- Izzat NN, Overturf M, Weisbrodt NW, Loose DS. (2009). Bile acid transport in hypercholesterolemic resistant rabbits. J Physiol Pharmacol., 60,79-84.
- Garg S, Boerma M, Wang J, Fu Q, Loose D S, Kumar S, Hauer-Jensen M. (2009). Influence of sublethal total body irradiation on immune cell populations in the intestinal mucosa. Radiation Research. in press.
- Xie R, Loose DS, Shipley GL, Xie S, Bassett RL, Jr, Broaddus RR. (2007). Hypomethylation Induced Expression of S100A4 in Endometrial Carcinoma. Modern Pathology.
- McCampbell AS, Bradduss RR, Loose DS, Davies PJA. (2006). Overexpression of the Insulin-Like Growth Factor I Receptor and Activation of AKT in Hyperplastic Endometrium. Clin Cancer Res., 12(21): 6373-6378.
- Deng L, Broaddus R, McCampbell A, Shipley GL, Loose DS, Stancel GM, Pickar JH, and Davies PJA. (2005). Identification of a Novel Estrogen Regulated Gene (EIG121) that is Induced by Hormone Replacement Therapy and Differentially Expressed in Type I and Type II Endometrial Cancer. Cancer Res., Dec 1;11(23):8258-64.