Lucia Wille

Education

MASSACHUSETTS INSTITUTE OF TECHNOLOGY, Cambridge, MA Ph. D. in Biology, 2000-present

COLLEGE OF WILLIAM AND MARY, Williamsburg, VA Bachelor of Science in Biology, 1996-2000

GRADUATE STUDENT Cambridge, MA Thesis Advisor: Dr. Douglas Lauffenburger, Massachusetts Institute of Technology

UNDERGRADUATE RESEARCHER Williamsburg, VA
Research Advisor: Dr. Diane Shakes, College of William and Mary

Publications

Nencioni A, Wille L, Dal Bello G, Boy D, Cirmena G, Wesselborg S, Belka C, Brossart P, Patrone F, Ballestrero A. Cooperative cytotoxicity of proteasome inhibitors and tumor necrosis factor-related apoptosis-inducing ligand in chemoresistant Bcl-2-overexpressing cells. Clin Cancer Res. 2005 Jun 1;11(11):4259-65.

Davis*, E. S., L. Wille*, B. A. Chestnut, P. L. Sadler, D. C. Shakes, and A. Golden. Multiple Subunits of the C. elegans Anaphase-Promoting-Complex are required for the metaphase-to-anaphase transition during meiosis I. Genetics. 2002 Feb;160(2):805-13. (* Co-first authors)

Recent Abstract

T lymphocyte response to antigen is determined, at least in part, by the affinity of the T cell receptor (TCR) for the MHC/antigen ligand. We propose that qualitatively and quantitatively different signals are triggered by low and high affinity TCR ligands, for these signals induce distinct cell fates including the production of IL-2 and other cytokines. The capacity of a TCR to respond to a set of altered peptide ligands (APLs) -- ligands with amino-acid substitutions within the antigenic peptide -- provides an opportunity for examining how ligand changes can lead to different cellular responses. Our hypothesis is that multiple signaling pathways dynamically encode information in a combinatorial network state which can translate small changes in TCR ligation events into predictable differences in cellular outcomes. To test this hypothesis we are defining a quantitative, multidimensional map of TCR avidity, signaling events, and cytokine production/apoptosis. A mouse T cell hybridoma 1B6 is activated with three APLs and examined for changes in signaling pathways’ activation that lead to quantitative differences in activation-induced cell death and cytokine production. Cellular outputs as measured via ELISA and FACS demonstrate large changes in IL-2 and apoptosis between the different APLs. Intracellular signaling events for the same APL conditions are measured using semi-quantitative phosphoprotein western blots and high-throughput kinase activity assays. Our studies focus on the signaling dynamics of Erk, p38, Akt, JNK, MK2, NFAT, and IKK. To date, our methodology has provided unique signatures in the ERK, JNK, Akt, and p38/MK2 pathways associated with weak and strong APL avidity. Partial least squares regression is applied to extract statistical relationships between TCR ligation, signaling events, and cytokine production/apoptosis. The statistical model generated from these relationships can successfully predict a priori IL-2 for a new experimental peptide stimulus not included in the training set.