Lawrence E. Goldfinger, PhD
Associate Professor, Department of Anatomy and Cell Biology
Associate Professor, Sol Sherry Thrombosis Research Center
- Contact Information
- About Me
Overall research in my lab explores the molecular mechanisms of cellular signal transduction, with several related foci: 1) intercellular signaling in platelet-tumor interactions, including the contributions of Ras family small G proteins; 2) the contributions of protein trafficking to the signaling and oncogenic functions of Ras proteins; 3) Ras signaling in platelets, regulating thrombosis and hemostasis. My long term goal is to reach a new understanding of cellular information processing and its contributions to signal responses and to translate these findings into pre-clinical approaches.
1. Intercellular signaling in platelet-tumor interactions.
We recently discovered that platelet microparticles – small extracellular vesicles released by blood platelets into plasma - infiltrate solid tumors by means of the unusual permeability of tumor vasculature, whereupon the platelet microparticles anchor to tumor cells and transfer genetic information in the form of platelet-derived microRNAs (miRNAs), which downregulate gene expression through sequence-specific binding to cognate RNA targets. We have identified platelet-derived miRNAs and several of the tumor cell target genes involved in this transfer, and found that this intercellular genetic transfer has profound effects on tumor growth in vivo. We are continuing to characterize the interaction of platelet microparticles with tumor cells and effects on tumor progression, tumor angiogenesis, and metastasis.
2. The contributions of protein trafficking to the signaling and oncogenic functions of Ras proteins.
We have recently shown that oncogenic H-Ras engages in distinct anterograde vesicular transport from the non-oncogenic paralogue, R-Ras. Using molecular genetics, pharmacology, live cell microscopy, protein biochemistry, and in vivo tumor models, we are exploring the roles of plasma membrane microdomain targeting and sequestration in Ras mitogenic and oncogenic signaling and functions, effects on tumor progression, and translational studies to develop inhibitors for Ras mutant cancers.
3. Ras signaling in platelets, regulating thrombosis and hemostasis.
We have been studying the contributions of the Ras family of small G proteins – typically associated with mitogenic signaling, in cytosolic signaling and agonist responses in anucleate (amitotic) platelets. We have found that several of these proteins, RhoG and the Ras paralogue TC21/R-Ras2, mediate platelet activation states and hemostatic responses. We are currently investigating the molecular mechanisms and functional outcomes of these effects.
- Education, Training & Credentials
- PhD, Cell Biology, Northwestern University Medical School, 1999
- BS, Biology, Carnegie Mellon University, 1995
- American Society for Cell Biology
- North American Vascular Biology Organization
- American Association for the Advancement of Science