Breast cancer is the most common cancer as well as the leading cause of death from cancer among women worldwide. The Chodosh laboratory uses genetically engineered mouse models to study the genes and mechanisms that cause breast cancer and that regulate normal mammary gland development. Particular areas of interest include: the function of oncogenes and tumor suppressor genes in breast cancer, metastasis, tumor dormancy and recurrence; the role of stem cells in cancer and the normal development of the mammary gland; the use of genomics and computational approaches to understand genetic programs in mammary development and breast cancer; the mechanisms by which pregnancy protects against breast cancer; and the use of non-invasive imaging approaches such as PET, MRI, and bioluminescence to study tumor biology. These approaches employ a broad array of molecular, cellular, animal, human, and in silico model systems to study the function of key regulatory molecules in mammary gland and tumor biology.
The Chodosh laboratory uses genetically engineered mouse models to study the genes and mechanisms that cause breast cancer and that regulate normal mammary gland development. The relationship between mammary development and breast cancer susceptibility is illustrated by the observation that women who have their first child early in life have a significantly lower lifetime risk of developing breast cancer.
Understanding the molecular biology of breast cancer susceptibility requires a thorough understanding of the normal developmental biology of the mammary gland, the mechanisms by which breast cancers arise, and the role played by key regulatory molecules in each of these processes. Current experimental approaches towards these goals in the Chodosh laboratory include:
1. Creating genetically engineered mouse models in which specific oncogenic pathways can be inducibly activated or repressed;
2. Using inducible animal models to analyze the effect of developmental events on the mammary gland's response to a defined oncogenic stimulus;
3. Using inducible animal models to dissect the process of carcinogenesis;
4. Defining the molecular and cellular changes that occur in the mammary glands of mice, rats, and humans during stages of development that influence breast cancer risk;
5. Using genomic and computational approaches to investigate genetic programs in mammary development and carcinogenesis; and
6. Studying the function of three novel serine/threonine kinases in mammary development and carcinogenesis. These approaches employ a variety of molecular, cellular, animal, human, and in silico model systems to study the function of key regulatory molecules in mammary gland biology.
Department of Cancer Biology
421 Curie Boulevard
627 BRB II/III
Philadelphia, PA 19104-6160
Ph: (215) 898-0006
Fax: (215) 573-6725
01. Moody SE, Sarkisian CJ, Hahn KT, Gunther EJ, Pickup S, Dugan KD, Innocent N, Cardiff RD, Schnall MD, and Chodosh LA. Conditional activation of Neu in the mammary epithelium of transgenic mice results in reversible pulmonary metastasis. Cancer Cell, 2:451-461, 2002.
02. Gunther EJ, Moody SE, Belka GK, Hahn KT, Innocent N, Dugan KD, Cardiff RD, and Chodosh LA. Impact of p53 loss on reversal and recurrence of conditional Wnt-induced tumorigenesis. Genes & Development 17:488-501, 2003.
03. Boxer RB, Jang JW, Sintasath L, and Chodosh LA. Lack of sustained regression of c–MYC-induced mammary adenocarcinomas following brief or prolonged MYC inactivation. Cancer Cell, 6:577-586, 2004.
04. Moody SE, Perez D, Pan TC, Sarkisian CJ, Portocarrero C, Sterner CJ, Notarfrancesco K, Cardiff RD, and Chodosh LA. The transcriptional repressor, Snail, promotes mammary tumor recurrence. Cancer Cell, 8:197-209, 2005.
05. Boxer RB, Stairs DB, Dugan KD, Notarfrancesco KL, Portocarrero CP, Keister BA, Belka GK, Cho H, Rathmell J, Thompson CB, Birnbaum MJ, and Chodosh LA. Isoform-specific requirement for Akt1 in the developmental regulation of cellular metabolism during lactation. Cell Metabolism, 4:475-490, 2006.
06. Blakely CM, Stoddard AJ, Belka GK, Dugan KD, Notarfrancesco KL, Moody SE, D’Cruz CM, and Chodosh LA. Hormone-induced protection against mammary tumorigenesis is conserved in multiple rat strains and identifies a core gene expression signature induced by pregnancy. Cancer Res, 66:6421-6431, 2006.
07. Wang M, Master SR, and Chodosh LA. Computational expression deconvolution in a complex mammalian organ. BMC Bioinformatics, 7:328-341, 2006.
08. Liu Z, Wang M, Alvarez JV, Bonney ME, Chen CC, D'Cruz C, Pan TC, Tadesse MG, and Chodosh LA. Singular value decomposition-based regression identifies activation of endogenous signaling pathways in vivo. Genome Biology, 9:R180, 2008. PMC2646284
09. Wertheim GBW, Yang TW, Pan TC, Ramne A, Liu Z, Gardner HP, Dugan KD, Kristel P, Kreike B, Vijver MJ, Cardiff RD and Chodosh LA. The Snf1-related kinase, Hunk, is essential for mammary tumor metastasis. Proceedings of the National Academy of Sciences USA, 106:15855-15860, 2009. PMC2734880
10. Chen CC, Boxer RB, Stairs DB, Portacarrero CP, Horton RH, Alvarez JV, Birnbaum MJ, Chodosh LA. Akt is required for Stat5 activation and mammary differentiation. Breast Cancer Research, 17;12:R72, 2010.
Amelie Raz - Research Specialist
Ania Warczyk - Graduate Student
Ann Elizabeth Vernon-Grey - Postdoctoral Researcher
Caroline Kitzmiller - Administrative Coordinator
Chien-Chung Chen - Manager Research Project
Chris Sterner - Research Specialist
Daniel Abravanel - Graduate Student
Deborah Whitehouse - Research Specialist
Dhruv Pant - Data Analyst
George Belka - Research Project Manager
Hans Seidel - Research Specialist
Heather Martin - Postdoctoral Fellow
James Alvarez - Manager Research Project
Jason Jung - Graduate Student
Jason Ruth - Graduate Student
Judith Smith - Lab Manager
Judy Farrell - Associate Director
Katelyn Wichert - Administrative Assistant
Lauren Smith - Graduate Student
Lauren Vaught - Research Specialist
Liz Yeh - Postdoctoral Fellow
Sam Getchell - Graduate Student
Samantha Eberle - Graduate Student
Tien-chi Pan - Senior Data Analyst
Xiaoxuan (Farrah) Wu - Research Specialist
Yan Chen - Research Specialist
Yi Feng - Postdoctoral Fellow
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