Titles and Education

1. B.S., University of Wisconsin
2. Ph.D., University of Pennsylvania
3. V.M.D., University of Pennsylvania

Research

Breast Cancer

Patients with aggressive, therapy resistant estrogen receptor positive (ER+) breast cancers comprise the majority of breast cancer mortality. Yet the factors which lead to the development of this disease, drive metastasis, and reduce treatment sensitivity are poorly understood. Hormones dictate the cycles of proliferation, differentiation and apoptosis that mammary function in reproduction, and anti-estrogens have been the main adjuvant therapy. The Schuler laboratory uses preclinical in vitro and in vivo models to investigate how hormones and their interactions with other oncogenic factors fuel the development and progression of these tumors, and the mechanisms by which the microenvironment modulates hormone actions and treatment responses.

We team with clinical oncologists and pathologists, as well as experts in immunology, genomics and steroid hormone signaling, the extracellular matrix, motility/ invasion and stem cell biology, with the long term goal of identifying novel preventative and treatment approaches.     

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Responsibilities

Professor
 

Graduate Training

• Cellular and Molecular Biology
• Molecular and Environmental Toxicology
• Endocrinology/ Reproductive Physiology
• Comparative Biomedical Sciences Graduate Program
• MD/ PhD
• Biotechnology
• Cancer Biology 
• Molecular and Cellular Pharmacology

• Department of Medicine, affiliate faculty
• Center of Women's Health and Women's Health Research
• Comprehensive Cancer Center

Recent Publications

1. O’Leary, K.A., A.M. Bates, W.J. Jin, B.M. Burkel, R.N. Sriramaneni, S.E. Emma, E.J. Nystuen, E.G. Sumiec, S.M. Ponik, Z.S. Morris and L.A. Schuler. Estrogen receptor blockade and radiation therapy cooperate to enhance the response of immunologically cold ER+ breast cancer to immunotherapy. Breast Cancer Research 25:68, doi: 10.1186/s13058-023-01671-y, 2023.
2. Schuler, L.A.; Murdoch, F.E. Endogenous and Therapeutic Estrogens: Maestro Conductors of the Microenvironment of ER+ Breast Cancers. Cancers 13: 3725, 2021. https://doi.org/10.3390/cancers13153725
3. Schuler, L.A. and K.A. O’Leary. Prolactin:  the third hormone in breast cancer. (invited review) Front Endocrinol 13:910978 DOI: 10.3389/fendo.2022.910978, 2022. 
4. Morgan M.M., B.P. Johnson, L.A. Schuler, E.T. Alarid, and D.J. Beebe. Modeling chemicals effects of on breast cancer: the importance of the microenvironment in vitro, Integrative Biology 12:21-33, 2020.
5. O’Leary, K.A., D.E. Rugowski, M.P. Shea, R. Sullivan, A.R. Moser and L.A. Schuler. Prolactin synergizes with canonical Wnt signals to drive development of ER+ cancers via activation of the Notch pathway. Cancer Lett 503:231-239, 2021.
6. Jallow, F., K.A. O’Leary, D.E. Rugowski, J.E. Guerrero, S.M. Ponik, and L.A. Schuler. Bidirectional interactions between the extracellular matrix and estrogen and antagonists, driving breast cancer progression, Oncogene 38: 6913-6915, 2019. Recognized by Extracellular Matrix News and Mammary Cell News; featured as Matrix Biology Highlight.  PMCID: 6814534
7. Campbell, K.M., K.A. O’Leary, D.E. Rugowski, W.A. Mulligan, E.K. Barnell, Z.L. Skidmore, K. Krysiak, M. Griffith, L.A. Schuler, O.L. Griffith. Spontaneous aggressive ERα+ mammary tumor model is driven by Kras activation. Cell Reports 28:1526-1537, 2019. Recognized by Mammary Cell News. PMCID:6713291.
8. Shea, M.P., K.A. O’Leary, S.A. Fakhraldeen, V. Goffin, A. Friedl, K.B. Wisinski, C.M. Alexander and L.A. Schuler.  Anti-estrogen therapy increases plasticity and cancer stemness of prolactin-induced ERα+ mammary carcinomas. Cancer Res 78:1672-1684, 2018. PMCID: 5882549
9. O’Leary, K.A., M.P. Shea, Stephanie Salituro, Courtney E. Blohm and L.A. Schuler.  Prolactin alters the mammary epithelial hierarchy, increasing progenitors and facilitating ovarian steroid action.  Stem Cell Reports 9:1167-1179, 2017.  PMCID: 5639259
10. Barcus C.E., K.A. O’Leary, J.L. Brockman, D.E. Rugowski, Y. Liu, N. Garcia, M. Yu, P.J. Keely, K.W. Eliceiri, L.A. Schuler.  Elevated collagen-I augments tumor progressive signals, intravasation and metastasis of prolactin-induced estrogen receptor alpha positive mammary tumor cells.  Breast Cancer Res 19:1-13, 2017.  PMCID: 5244528
11. O'Leary, K.A., M.P. Shea, L.A. Schuler.  Modeling prolactin actions in breast cancer in vivo:  insights from the NRL-PRL mouse.  Adv. Exp. Biol. Med.  846:201-220, 2015.  PMCID:   4770878
12. Barcus, C.E., E.C. Holt, P.J. Keely, K.W. Eliceiri, and L.A. Schuler.  Dense collagen-I matrices enhance pro-tumorigenic estrogen-prolactin crosstalk in MCF-7 and T47D breast cancer cells.  PLoS One. 2015 Jan 21;10(1):e0116891.  PMCID:  4301649
13. O’Leary, K.A., F. Jallow, D.E. Rugowski, R. Sullivan, K.W. Sinkevicius, G.L. Greene and L.A. Schuler.  Prolactin activates ERα in the absence of ligand in female mammary development and carcinogenesis in vivo, Endocrinology 154:4883-4892, 2013.   PMCID:  3836081