Hinck, Lindsay - University of California, Santa Cruz - Molecular, Cell & Developmental Biology Faculty

个人简介

B.S., Western Washington University M.S., UC Davis Ph.D., Stanford University Postdoctorate, UC San Francisco

研究领域

Cellular Interactions During Organogenesis and Tumorigenesis My colleagues and I are interested in how epithelial cells assemble into organs during development, and how the reverse process occurs during cancer when cells disassemble and metastasize to inappropriate locations. We study two families of positional cues, called Slits and Netrins that were originally identified in the nervous system where they direct the construction of elaborate networks of neuronal connections. We focus on how these cues control the development of the mammary gland, and how loss of these cues during tumor progression contributes to breast cancer. Currently, the laboratory has projects in three areas. Building an organ: The mammary gland is an elaborate tree-like epithelial structure, comprising an outer layer of myoepithelial cells and an inner layer of secretory luminal epithelial cells. We discovered new roles for Slit2 and Netrin1 in mediating the interactions between these two epithelial cell layers. Now we are investigating how these cues signal through their respective receptors to generate cell contact that is at once flexible and strong. Stem cells and self renewal: The mammary gland is remarkable in its capacity to self renew since every pregnancy results in prodigious cell growth to prepare for milk production. Stem cells required to maintain this process reside in specialized environments (niches) squeezed between the luminal and myoepithelial cells layers. We are exploring how loss of Slits and Netrins disrupts these niches, and the biological consequences of this disruption. Loss of growth control and cancer: One in eight women in the United States will develop breast cancer in her lifetime. Only about 15% of these cancers have been linked to specific gene mutations; therefore a major challenge in breast cancer research is to identify the causes of the disease. We have identified Slits as breast tumor suppressors that regulate several critical pathways controlling cell proliferation and migration. Current research focuses on developing therapeutic strategies to target these pathways.

近期论文

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Making Connections: Guidance Cues and Receptors at Nonneural Cell-Cell Junctions. Beamish IV, Hinck L, Kennedy TE. Cold Spring Harb Perspect Biol. 2018 Nov 1;10(11). pii: a029165. doi: 10.1101/cshperspect.a029165. Review. Extracellular Regulation of the Mitotic Spindle and Fate Determinants Driving Asymmetric Cell Division. Smith P, Azzam M, Hinck L. Results Probl Cell Differ. 2017;61:351-373. doi: 10.1007/978-3-319-53150-2_16. Review. Diverse regulation of mammary epithelial growth and branching morphogenesis through noncanonical Wnt signaling. Kessenbrock K, Smith P, Steenbeek SC, Pervolarakis N, Kumar R, Minami Y, Goga A, Hinck L, Werb Z. Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3121-3126. doi: 10.1073/pnas.1701464114. Epub 2017 Mar 7. IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC. Ennajdaoui H, Howard JM, Sterne-Weiler T, Jahanbani F, Coyne DJ, Uren PJ, Dargyte M, Katzman S, Draper JM, Wallace A, Cazarez O, Burns SC, Qiao M, Hinck L, Smith AD, Toloue MM, Blencowe BJ, Penalva LO, Sanford JR. Cell Rep. 2016 May 31;15(9):1876-83. doi: 10.1016/j.celrep.2016.04.083. Epub 2016 May 19. Loss of miR-203 regulates cell shape and matrix adhesion through ROBO1/Rac/FAK in response to stiffness. Le LT, Cazares O, Mouw JK, Chatterjee S, Macias H, Moran A, Ramos J, Keely PJ, Weaver VM, Hinck L. J Cell Biol. 2016 Mar 14;212(6):707-19. doi: 10.1083/jcb.201507054. Mammary Stem Cell Self-Renewal Is Regulated by Slit2/Robo1 Signaling through SNAI1 and mINSC. Ballard MS, Zhu A, Iwai N, Stensrud M, Mapps A, Postiglione MP, Knoblich JA, Hinck L. Cell Rep. 2015 Oct 13;13(2):290-301. doi: 10.1016/j.celrep.2015.09.006. Epub 2015 Oct 1. SLIT/ROBO2 signaling promotes mammary stem cell senescence by inhibiting Wnt signaling. Harburg G, Compton J, Liu W, Iwai N, Zada S, Marlow R, Strickland P, Zeng YA, Hinck L. Stem Cell Reports. 2014 Sep 9;3(3):385-93. doi: 10.1016/j.stemcr.2014.07.007. Epub 2014 Aug 28. Changes in cell and tissue organization in cancer of the breast and colon. Hinck L, Näthke I. Curr Opin Cell Biol. 2014 Feb;26:87-95. doi: 10.1016/j.ceb.2013.11.003. Epub 2013 Dec 5. Review.