Laurie Littlepage

Research Interests

Littlepage's research program is focused on the contributions of the epithelium and surrounding stroma/microenvironment to both cancer progression and normal tissue development in the mammary gland and prostate.

She has focused on three major projects:

• The transcription factor/oncogene Znf217 that promotes a progenitor cell phenotype, metastasis and chemoresistance during breast cancer progression
• MMP3/Stromelysin-1 promotion of progenitor expansion, genomic instability, DNA damage, and centrosome amplification during mammary tumor progression
• Matrix metalloproteinases that contribute distinct roles in neuroendocrine prostate carcinogenesis, metastasis, and angiogenesis progression.

Overall, her research is grounded in understanding the mechanisms of cancer progression and in identifying therapies that prevent or reverse cancer in patients. She develops and uses integrated mouse models and genome-wide association studies to understand the contributions of specific genes in vivo at multiple points in cancer progression, spanning from normal mammary development to tumor progression and metastasis and chemotherapy resistance.

She uses a combination of mouse and human xenograft in vivo models, cell culture and organotypic cultures, and systems biology approaches to study biomarkers of epithelial plasticity and to determine how these genes drive aberrations in fundamental biological processes, e.g., differentiation state, progenitor cell maintenance, metabolism, and genomic integrity.

She also is identifying targeted therapies appropriate for personalized treatment of cancer patients based on these biomarkers.

Selected Publications

• Khan, S.; Mejia, F.; Shin, J.; Hwang, G.; Omstead, D. T.; Wu, J. M.; Cole, S. L.; Littlepage, L. E. and Bilgicer, B. "Disease-Driven Engineering of Peptide-Targeted DM1 Loaded Liposomal Nanoparticles for Enhanced Efficacy in Treating Multiple Myeloma by Exploring DM1 Prodrug Chemistry" 2023 Biomaterials, 292, 121913. DOI: 10.1016/j.biomaterials.2022.121913.
• Charlestin, V.; Fulkerson, D.; Matus, C.; Walker, Z. T.; Carthy, K. and Littlepage, L. E. "Aquaporins: New Players in Breast Cancer Progression and Treatment Response" 2022 Frontiers in Oncology, 12, 988119. DOI: 10.3389/fonc.2022.988119.
• Liu, Y. H.; Bhagwate, A.; Winham, S. J.; Stephens, M. T.; Harker, B. W.; McDonough, S. J.; Stallings-Mann, M. L.; Heinzen, E. P.; Vierkant, R. A.; Hoskin, T. L.; Frost, M. H.; Carter, J. M.; Pfrender, M. E.; Littlepage, L.; Radisky, D. C.; Cunningham, J. M.; Degnim, A. C. and Wang, C. "Quality Control Recommendations for RNASeq using FFPE Samples Based on Pre-Sequencing Lab Metrics and Post-Sequencing Bioinformatics Metrics" 2022 BMC Medical Genomics, 15 (1), 195. DOI: 10.1186/s12920-022-01355-0.
• Curtis, K. J.; Mai, C.; Martin, H.; Oberman, A. G.; Alderfer, L.; Romero-Moreno, R.; Walsh, M.; Mitros, S. F.; Thomas, S. G.; Dynako, J. A.; Zimmer, D. I.; McNamara, L. M.; Littlepage, L. E. and Niebur, G. L. "The Effect of Marrow Secretome and Culture Environment on the Rate of Metastatic Breast Cancer Cell Migration in Two and Three Dimensions" 2021 Molecular Biology of the Cell, 32 (10), pp.1009-1019. DOI: 10.1091/mbc.E19-12-0682.
• Northey, J. J.; Barrett, A. S.; Acerbi, I.; Hayward, M. K.; Talamantes, S.; Dean, I. S.; Mouw, J. K.; Ponik, S. M.; Lakins, J. N.; Huang, P. J.; Wu, J. M.; Shi, Q. M.; Samson, S.; Keely, P. J.; Mukhtar, R. A.; Liphardt, J. T.; Shepherd, J. A.; Hwang, E. S.; Chen, Y. Y.; Hansen, K. C.; Littlepage, L. E. and Weaver, V. M. "Stiff Stroma Increases Breast Cancer Risk by Inducing the Oncogene ZNF217" 2020 Journal of Clinical Investigation, 130 (11), pp.5721-5737. DOI: 10.1172/JCI129249.
• Omstead, D. T.; Mejia, F.; Sjoerdsma, J.; Kim, B.; Shin, J.; Khan, S.; Wu, J. M.; Kiziltepe, T.; Littlepage, L. E. and Bilgicer, B. "In Vivo Evaluation of CD38 and CD138 as Targets for Nanoparticle-Based Drug Delivery in Multiple Myeloma" 2020 Journal of Hematology & Oncology, 13 (1), 145. DOI: 10.1186/s13045-020-00965-4.