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Pepper J. Schedin

Ph.D. (1988) University of Colorado Boulder



Department of Medicine
Division of Medical Oncology
 
Campus Box 8117
RC1 South, L18-8114
Phone: 303-724-3873

Pepper.Schedin@UCDenver.edu

The long term objective of the Schedin Lab research program is to develop breast cancer chemopreventive strategies that are targeted to specific windows of breast development. By understanding normal mammary gland development and homeostasis, it should possible to identify both mammary specific and life cycle specific chemopreventive strategies. The focus of my lab is on characterizing extracellular matrix (ECM) proteins that mediate mammary epithelial cell death during key windows of normal mammary gland differentiation, such as adolescent mammary gland development, the estrous cycle, and the pregnancy/lactation/involution cycle. Major areas of investigation include adolescent mammary development, mammary epithelial cell-stromal interactions, tissue remodeling, mammary carcinogenesis, and chemoprevention in rodent models.

Current Research Projects Include:

Determine the mechanism of pregnancy-associated breast cancer. I have proposed that the natural tissue remodeling that occurs in the mammary gland following pregnancy and lactation promotes breast cancer progression, accounting for 'the dual effect' of pregnancy. I propose that the tumor promoting activity of physiologic mammary gland regression is due to an inflammation-like microenvironment that is present during gland regression. The hypothesis that mammary stroma from an actively involuting mammary gland promotes tumor progression is being evaluated using both in vivo and in vitro model systems. ECM proteins that activate tumor cells invasion are being identified using proteomic approaches.

Identify the ECM proteomes of the 'breast-cancer protected' and 'at-risk' mammary gland. For these studies, we are isolating mammary ECM proteins from mammary glands of female rats at reduced risk of developing breast cancer due to tamoxifen treatment or parity, and from control, 'at-risk' rats. The ECM proteins will be identified by proteomics and proteins in common to the 'protected-glands', but absent or reduced in the 'at-risk' glands, will be candidates for ECM proteins that mediate protection.

The identification of dietary interventions that result in the development of mammary tissue that is resistant to carcinogenic insult. To this end, we are currently evaluating how vitamin A modifies adolescent mammary development, mammotrophic hormone signaling, and subsequent risk for carcinogenesis.

Lyons, T.R.*, O’Brien, J.*, Borges, V., Conklin, M.W., Keely, P.J., Elicieri, K.W., Marusyk, A., Tan, A.C., and Schedin, P. Postpartum mammary gland involution drives DCIS progression through collagen and COX-2, Nature Medicine 17: 1109-1116; doi:10:1038/nm.2416
Commentary: T. Tlsty, Cancer Cell, 20: 285-286, September 13, 2011.

O’Brien, J., Hansen, K., Barkan, D., Green, J., and Schedin, P. NSAIDs target pro-tumorigenic extracellular matrix of the postpartum mammary gland, International Journal of Developmental Biology, doi:10.1387/ijdb.113379j0, In press, 9/2011.

Shim YJ, Kang BH, Jeon HS, Park IS, Lee KU, Lee IK, Park GH, Lee KM, Schedin P, Min BH. Clusterin induces matrix metalloproteinase-9 expression via ERK1/2 and PI3K/Akt/NF-κB pathways in monocytes/macrophages. J Leukoc Biol. 2011 Oct;90(4):761-9. Epub 2011 Jul 8.PMID:21742938

Schedin P and Keely, PJ. Mammary Gland ECM Remodeling, Stiffness, and the Role of Force in Normal Development and Tumor Progression. The Biology of The Mammary Gland, Cold Spring Harb Perspect Biol. 2011 Jan 1;3(1):a003228. 

McDaniel, S., Rumer, K., Biroc, S., Metz, R., Singh, M., Porter, W., and Schedin, P. Remodeling of the mammary microenvironment following lactation promotes breast tumor cell metastasis. American Journal of Pathology, 168 2):608-620, 2006. 
Highly Accessed, and Commentary: N. Polyak, Cancer Cell, March 2006, 152-153, and C. Sonnenschein and A. Soto, American Journal of Pathology, 168 2):363-366, 2006.

O'Brien J, Lyons T, Monks J, Lucia MS, Wilson RS, Hines L, Man YG, Borges V, and  Schedin P. Alternatively activated macrophages and collagen remodeling characterize the postpartum involuting mammary gland across species. Am J Pathol 2010;176(3):1241-55.

MacLean PS, Giles ED, Johnson GC, McDaniel SM, Fleming-Elder BK, Gilman KA, Andrianakos AG, Jackman MR, Shroyer KR, and Schedin PJ. A surprising link between the energetics of ovariectomy-induced weight gain and mammary tumor progression in obese rats. Obesity 2010;18(4):696-703.

Hansen KC, Kiemele L, Maller O, O'Brien J, Shankar A, Fornetti J, and Schedin P.. An in-solution ultrasonic assisted digestion method for improved extracellular matrix proteome coverage. Mol Cell Proteomics 2009; 8(7):1648-57. 

Billups SC, Neville MC, Rudolph M, Porter W and Schedin P. Identifying significant temporal variation in time course microarray data without replicates. BMC Bioinformatics 2009; 26; 10:96, Highly accessed.

Hattar R, Maller O, McDaniel S, Hansen KC, Hedman KJ, Lyons T, Lucia, Jr Wilson RS, and Schedin P. Tamoxifen induces pleiotrophic changes in mammary stroma resulting in extracellular matrix that suppresses transformed phenotypes. Breast Cancer Res 2009;11(1):R5. Epub 2009 Jan 27, Highly Accessed

McDaniel SM, O'Neill C, Metz R, Tarbutton E, Sapuntzakis M, Heimendinger J, Wolfe P, Thompson H, and Schedin P. Whole food sources of vitamin A more effectively inhibit female rat sexual maturation, mammary gland development, and mammary carcinogenesis than retinyl palmitate.  J Nutrition 2007;137(6):1415-1422. 

Schedin P.  Pregnancy-associated breast cancer and metastasis. Nature Reviews Cancer 2006; 6:281-291. 


Latest Publications in PubMed