- Campbell Family Assistant Professor of Cancer Research, University of Notre Dame
- Associate Specialist, University of California, San Francisco
- Postdoctoral Fellow, University of California, San Francisco
- Ph.D. in Cell and Developmental Biology, Harvard University
- B.S. in Biochemistry, B.S. in Molecular Biology, University of Texas, Austin
- American Cancer Society Postdoctoral Fellowship
- Ruth L. Kirschstein National Research Service Award, NIH
- NSF Predoctoral Fellowship
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.
Frietze, S.; O'Geen, H.; Littlepage, L.E.; Simion, C.; Sweeney, C.A.; Farnham, P.J.; Krig, S.R. "Global analysis of ZNF217 chromatin occupancy in the breast cancer cell genome reveals an association with ERalpha." BMC Genomics 2014, 15, 520.
Kessenbrock, K.; Dijkgraaf, G.J.P.; Lawson, D.A.; Littlepage, L.E.; Shahi, P.; Pieper, U.; Werb, Z. "A Role for Matrix Metalloproteinases in Regulating Mammary Stem Cell Function via the Wnt Signaling Pathway." Cell Stem Cell 2013, 13 (3), 300-313.
Littlepage, L.E.; Adler, A.S.; Kouros-Mehr, H.; Huang, G.; Chou, J.; Krig, S.R.; Griffith, O.L.; Korkola, J.E.; Qu, K.; Lawson, D.A.; Xue, Q.; Sternlicht, M.D.; Dijkgraaf, G.J.; Yaswen, P.; Rugo, H.S.; Sweeney, C.A.; Collins, C.C.; Gray, J.W.; Chang, H.Y.; Werb, Z. "The Transcription Factor ZNF217 is a Prognostic Biomarker and Therapeutic Target during Breast Cancer Progression." Cancer Discov. 2012, 2(7), 638-651. Link
Littlepage, L.E.; Sternlicht, M.D.; Rougier, N.; Phillips, J.; Gallo, E.; Yu, Y.; Williams, K.; Brenot, A.; Gordon, J.; Werb, Z. "Matrix Metalloproteinases Contribute Distinct Roles in Neuroendocrine Prostate Carcinogenesis, Metastasis, and Angiogenesis Progression." Cancer Res. 2010, 70(6), 2224-2234. Link
Kouros-Mehr, H.; Bechis, S.K.; Slorach, E.M.; Littlepage, L.E.; Egeblad, M.; Ewald, A.J.; Pai, S.Y.; Ho, I.C.; Werb, Z. "GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model." Cancer Cell 2008, 13(2), 141-152. Link
Adler, A.S.; Littlepage, L.E.; Lin, M.; Kawahara, T.L.A.; Wong, D.J.; Liu, H.; Werb, Z.; Chang , H.Y. "CSN5 isopeptidase activity links COP9 signalosome activation to breast cancer progression." Cancer Res. 2008, 68(2), 506-515. Link