Lauffenburger:Cell Signaling and Regulatory Networks

Lauffenburger Lab

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Cell Signaling and Regulatory Networks In this area we are attempting to understand, in terms of quantitative systems dynamics, regulation and dysregulation of cell phenotypic behavioral responses (e.g., death, proliferation, differentiation, migration) as governed by signaling networks activated by growth factors, cytokines, and extracellular matrix. We have a major focus on the EGF receptor family, which is strongly implicated in cancer progression, and on the TNF receptor family, which is involved in cell death/survival decisions in response to tissue. Our goal is to develop predictive computational models for cell phenotypic decisions in terms of underlying signaling network properties, with application to drug discovery and development. Ben Cosgrove (BE Doctoral), in collaboration with Prof. Linda Griffith (BE/ME, MIT) Quantitative analysis of cell signaling activities and phenotypic cellular outcomes (proliferation, apoptosis, survival) in primary hepatocytes induced by the cytokine TNFα and physiologically relevant pro-growth (e.g. EGF, HGF) or pro-apoptotic (e.g. viral infection) co-stimuli administered in standard two-dimensional and novel three-dimensional culture systems. Multivariate signaling activity and proliferation/apoptosis outcome data are analyzed using data-driven methods to explore intracellular and extracellular cross-talk and feedback mechanisms regulating hepatocyte decision-making processes. Ericka Noonan (BE doctoral), in collaboration with Prof. Leona Samson (BE, MIT) Analysis of the signaling events downstream of DNA damage, specifically damage produced by alkylating agents, and how these signals control the cellular response of death/survival. Megan Palmer (BE doctoral) Quantitative experimental and computational modeling analysis of the mechanisms of signaling network cross-talk downstream of the T cell receptor and interleukin (IL)-2 family cytokines in naïve CD8 T cells. Robin Prince (BE doctoral), in collaboration with Prof. Roger Kamm (ME/BE, MIT) and Prof. Richard Lee (Brigham & Women's Hospital, Harvard) Experimental and computational modeling studies of HB-EGF ligand/receptor signaling in cardiac myocytes as related to cardiac hypertrophy and the expression of the gap junctional protein, Connexin43. Nancy Guillen (BE doctoral) Understanding the role of microRNAs in intracellular signaling networks regulating hepatocellular carcinoma (HCC) cell behavior. Quantitative and time resolved studies of IFNgamma and TRAIL-induced microRNA expression in a HCC cell line are analyzed using a multivariate modeling approach.