Pengfei Paul Lu    Associate Professor, PI
InstituteSchool of Life Science and Technology
Research AreaMammalian Developmental Biology; Cancer Biology

Dr. Lu received his Bachelor’s degree from Wuhan University in 1993 and his Ph.D. degree from the University of Texas at Austin in 2001. Starting from 2002, Dr. Lu was a postdoctoral fellow in the University of California at San Francisco, where he also served as an associate specialist from 2006. In 2010, Dr. Lu joined the faculty of the University of Manchester in the United Kingdom, where he was a senior research fellow (assistant professor) in the Paterson Institute for Cancer Research and the Wellcome Trust Centre of Cell-Matrix Research. Dr. Lu came back to the States in 2014 and was a visiting assistant professor in the Department of Anatomy at UCSF. In July 2015, he joined the faculty of the School of Life Sciences and Technology at ShanghaiTech University.

Research Interests
A central theme in developmental and cancer biology is to understand the mechanisms by which the local microenvironment, or niche, influences fundamental aspects of a cell’s behavior. Although it is widely recognized that embryonic mesenchyme is essential for organ specification and differentiation during development, how the postnatal stroma maintains cell fate and differentiation during organ homeostasis and function, and how it may deteriorate during aging and other pathologies such as cancers have remained largely unknown. Using genetic mouse models, 3D in vitro cultures, and patient-derived xenografts, we focus on the cellular and molecular mechanisms by which the local stromal microenvironment regulates mammary gland development and breast cancer. We recently showed that mammary stroma promotes epithelial morphogenesis by modulating FGF signaling and extracellular matrix remodeling and that this process is regulated by EGF signaling. This FGF-EGF signaling loop is essential for epithelial-stromal crosstalk in the postnatal stroma and its activities are regulated by genes of the Sprouty family. Our current efforts are focused on understanding the role of mammary stroma, and ECM remodeling in particular, in adult stem cell biology and epithelial morphogenesis. In addition, we strive to elucidate how abnormal stroma, for example due to deregulated FGF or EGF signaling activities, may contribute to tumor onset and progression.

Selected Publications

1. Koledova, Z. and Lu, P.*, 2017. A 3D fibroblast-epithelium co-culture model for understanding microenvironmental role in the mammary gland. Methods Mol Biol.1501:217-231.

2. Yao, L., Lu, P., Ling, E. A. 2016. Melatonin suppresses Toll like receptor 4-dependent caspase-3 signaling activation coupled with reduced production of proinflammatory mediators in hypoxic microglia. PLOS One. 3;11(11):e0166010.

3. Koledova, Z., Zhang, X., Streuli C., Clarke, R., Klein, O., Werb, Z., Lu, P.*, 2016.  SPRY1 regulates mammary epithelial morphogenesis by modulating EGFR-dependent stromal paracrine signaling and ECM remodeling. Proc Natl Acad Sci U S A. 113(39):E5731-40.

4. Werb, Z. and Lu, P., 2015. The role of stroma in tumor development. Cancer J. 21(4):250-3.

5. Zhang, X., Trevino, D., Koledova, Z., Qiao, G., Streuli, C.H., Lu, P.*, 2014. FGF ligands of the postnatal mammary stroma regulate distinct aspects of epithelial morphogenesis. Development.141(17):3352.

6.  Zhang, X., Qiao, G., Lu, P.*, 2014. Epithelial branching morphogenesis in the mammary gland is directed by modulating levels of Fibroblast Growth Factor signaling. PLOS One. 9;9(4):e92735.

7.    Howard, B.A. and Lu, P., 2014. Stromal regulation of embryonic and postnatal mammary epithelial development and differentiation. Semin Cell Dev Biol. 25-26:43-51.

8.   Kim, E.J., Jung, H.S., Lu, P.*, 2013. FGF signaling in embryonic mammary gland development. J Mammary Gland Biol Neoplasia. 11(3-4):213-28.

9.    Lu, P., Weaver, VM., Werb, Z. 2012. Extracellular matrix: a dynamic niche component during cancer progression.J Cell Biol. 196(4):395-406.

10.  Lu, P., Takai, K., Weaver, VM., Werb, Z. 2011. Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb Perspect Biol. 3(12).

11. Lu, P. and Werb, Z. 2008. Patterning mechanisms of branched organs. Science. 322, 1506-9.

12. Lu, P., Ewald, A.J., Martin, G.R., Werb, Z. 2008. Genetic mosaic analysis reveals FGF receptor 2 function in terminal end buds during mammary gland branching morphogenesis. Developmental Biology. 321 (1), 77-87.

13.  Lu, P.*, Yu, Y., Perdue, Y., Werb, Z*. 2008. The apical ectodermal ridge is a timer for generating distal limb progenitors. Development.135, 1395-405.

14.  Lu, P., Sternlicht M.D., Werb, Z. 2006. Comparative mechanisms of branching morphogenesis in diverse systems. J Mammary Gland Biol Neoplasia. 11(3-4):213-28.

15.  Sternlicht M.D., Kouros-Mehr H., Lu, P., Werb, Z. (2006). Hormonal and local control of mammary branching morphogenesis. Differentiation. 74(7):365-81.

16. Lu, P., Minowada, G., Martin GR. 2006. Increasing Fgf4 expression in the mouse limb bud causes polysyndactyly and rescues the skeletal defects that result from loss of Fgf8 function. Development. 133, 33-42.