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INDIVIDUAL RESEARCHER

Susan E. LaFlamme , Ph.D.
Professor
e-mail: laflams@mail.amc.edu


Education

1984 - Ph.D. from Columbia University


Current Research

The LaFlamme lab’s expertise is cell biology with a specific interest in the functional significance of the interaction of cells with their extracellular environment, specifically components of the extracellular matrix (ECM) through integrin receptors. Cytokinesis ensures the proper segregation of genetic and cytoplasmic material between daughter cells in the final step of cell division, and thus is essential for normal development and tissue homeostasis. A major focus of the lab is to understand the mechanisms by which integrins regulate cytokinesis and to determine whether these mechanisms are conserved in increasing complex physiological contexts. Results from the LaFlamme lab indicate that integrins regulate abscission, the last step in cytokinesis, and point to a component of the abscission machinery as a target of integrin regulation. To study integrin-regulated cytokinesis, the lab employs multiple models including a classic CHO cell model, in which integrin activity and signaling can be easily manipulated and specific mechanisms can be easily analyzed, and then the contribution of these mechanisms are examined in progressively more complex physiological contexts. These include the examination of integrin-regulated cytokinesis during the formation of acini in 3D cell culture and during morphogenesis of the murine salivary gland in organ culture, as well as during development using mouse genetic models. A second interest of the lab is to understand the contribution of the interaction of integrins with specific basement membrane components in regulating of the formation and maturation of the neovasculature associated with cutaneous wound repair. Both developmental and cutaneous wound healing studies demonstrated that the endothelial expression of integrin a6b4 is down regulated during early stages of angiogenesis ad up regulated during vessel maturation. The LaFlamme lab is interested in identifying the mechanisms that regulate the endothelial expression of a6b4 and to determine whether this regulation is required for angiogenesis, vessel maturation and/or function. The information gained from these studies will likely have important implications for wound healing and tumor angiogenesis.The LaFlamme lab’s expertise is cell biology with a specific interest in the functional significance of the interaction of cells with their extracellular environment, specifically components of the extracellular matrix (ECM) through integrin receptors. Cytokinesis ensures the proper segregation of genetic and cytoplasmic material between daughter cells in the final step of cell division, and thus is essential for normal development and tissue homeostasis. A major focus of the lab is to understand the mechanisms by which integrins regulate cytokinesis and to determine whether these mechanisms are conserved in increasing complex physiological contexts. Results from the LaFlamme lab indicate that integrins regulate abscission, the last step in cytokinesis, and point to a component of the abscission machinery as a target of integrin regulation. To study integrin-regulated cytokinesis, the lab employs multiple models including a classic CHO cell model, in which integrin activity and signaling can be easily manipulated and specific mechanisms can be easily analyzed, and then the contribution of these mechanisms are examined in progressively more complex physiological contexts. These include the examination of integrin-regulated cytokinesis during the formation of acini in 3D cell culture and during morphogenesis of the murine salivary gland in organ culture, as well as during development using mouse genetic models. A second interest of the lab is to understand the contribution of the interaction of integrins with specific basement membrane components in regulating of the formation and maturation of the neovasculature associated with cutaneous wound repair. Both developmental and cutaneous wound healing studies demonstrated that the endothelial expression of integrin a6b4 is down regulated during early stages of angiogenesis ad up regulated during vessel maturation. The LaFlamme lab is interested in identifying the mechanisms that regulate the endothelial expression of a6b4 and to determine whether this regulation is required for angiogenesis, vessel maturation and/or function. The information gained from these studies will likely have important implications for wound healing and tumor angiogenesis.



PubMed Publications

  1. Berrier AL, Martinez R, Bokoch GM, LaFlamme SE: The integrin ? tail is required and sufficient to regulate adhesion signaling to Rac1. J Cell Sci 115:4285-4291, 2002.


  2. Hiran TS, Mazurkiewicz JE, Kreienberg P, Rice FL, LaFlamme SE: Endothelial expression of the ?6?4 integrin is negatively regulated during angiogenesis. J Cell Sci 116:3771-3781, 2003.


  3. Reverte CG, Benware A, Jones CW, LaFlamme SE: Perturbing integrin function inhibits microtubule growth from centrosomes, spindle assembly, and cytokinesis. J Cell Biol 174(4): 491-497, 2006.


  4. LaFlamme SE, Nieves B, Colello D, Reverte CG: Integrins as regulators of the mitotic machinery. Curr Opin Cell Biol 20:576-582, 2008.


  5. Nieves B, Jones CW, Ward R, Ohta Y, Reverte CG, LaFlamme SE: The NPIY motif in the integrin ?1 tail dictates the requirement for talin1 in outside-in signaling. J Cell Sci 123:1216-1226, 2010.


  6. Colello D, Reverte CG, Ward R, Jones CW, Magidson V, Khodjakov A, LaFlamme SE: Androgen and Src signaling regulate centrosome activity. J Cell Sci 123:2094-2102, 2010.


  7. Colello D, Mathew S, Ward R, Pumiglia K, and LaFlamme SE: Integrins regulate microtubule nucleating activity of the centrosome through MEK/ERK signaling. J. Biol. Chem. 287:2520-2530, 2012.


  8. Desai D, Singh P, Van De Water L, and LaFlamme SE: Dynamic regulation of integrin ?6?4 during angiogenesis: Potential implications for pathogenic wound healing. Adv. Wound Care 2:401-409, 2013.


  9. Matthew, S.S., Nieves, B., Sequeira, S., Sambandamoorthy, S., Pumiglia, K., Larsen, M., and LaFlamme, S.E.: Integrins promote cytokinesis through the RSK signaling axis. J. Cell Sci. 127:534-545, 2014.