Thomas Jefferson University
Sidney Kimmel Medical College
Department of Medicine

Goldfinger, Lawrence

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Lawrence Goldfinger, PhD

Contact Dr. Goldfinger

1020 Locust Street
Suite 394
Philadelphia, PA 19107


(215) 955-9170 fax

Medical School

Carnegie Mellon University
Northwestern University Medical School

Research Interests

We are seeking to understand the molecular cell biology regulating how circulating blood platelets contribute to hemostasis and thrombosis, and to apply this understanding to modulate platelet function in various contexts.  Our research program spans molecular studies of control of platelet gene expression, the cell biological outcomes of this regulation, physiological studies of platelet function, and development of tools for pre-clinical applications in health and disease.

Platelet microRNAs as modulators of hemostasis and thrombosis

Hemostasis (prevention of blood leak after vascular injury by formation of a clot) and thrombosis (clot formation generally not in response to injury, which can cause pathological complications) are considered the primary functions of platelets, and platelets require many genes to carry out these functions.  In additon to those genes, platelets are enriched in small non-coding RNAs known as microRNAs (miRNAs) that are genrally understood to function to dampen the expression levels of protein-coding genes, and therby suppress gene activity.  We have found that miRNAs are important regulators of platelet function.  We are seeking to understand how miRNAs regulate platelet function in hemostasis and thrombosis, to identify the specific miRNAs and gene targets involved, and to develop strategies to manipulate miRNA function and modulate platelet reactivity to support hemostais or supress thrombotic potential.

Molecular control of mRNA translation in platelets

Platelets are anucleate cell fragments that circulate in blood for 7-10 days.  Hence, platelets lack genomic DNA but they do contain protein-coding message RNAs (mRNAs), un-spliced pre-mRNAs and mRNA splicing machinery, as well as all the necessary molecular and cellular componets to support translation of mRNA into protein, and to degrade exisiting proteins.  Platelet reactivity, hemostatic capacity and thrombotic potential vary widely in humans and we are investigating how control of protein translation contributes to this variation.  Although mRNA translation in platelets (despite an inability to generate new mRNAs) was recognized many years ago, very little remains known about how platelets translate new protein necessary for their ongoing metabolism and reactivity while in circulation.  We are exploring the molecular signaling controlling mRNA translation in circulating platelets, including the roles of platelet miRNAs, and the cellular and physiological outcomes and effects.  Based on these mechanistic studies, we are developing translational approaches to control platelet reactivity via miRNA manipulation and other approaches in multiple contexts.

Publications

Most Recent Peer-Reviewed Publications

  1. GRK6 regulates the hemostatic response to injury through its rate-limiting effects on GPCR signaling in platelets
  2. High-efficiency unassisted transfection of platelets with naked double-stranded miRNAs modulates signal-activated translation and platelet function
  3. Horizontal RNA transfer goes deep: platelet consumption and microRNA utilization by vascular smooth muscle cells
  4. ELMO1 deficiency enhances platelet function
  5. Concepts and advances in cancer therapeutic vulnerabilities in RAS membrane targeting
  6. GPVI inhibitor as antitumor gateway drug
  7. TC21/RRas2 regulates glycoprotein VI–FcRγ-mediated platelet activation and thrombus stability
  8. Defective RAB1B-related megakaryocytic ER-to-Golgi transport in RUNX1 haplodeficiency: Impact on von Willebrand factor
  9. Platelet Microparticles and miRNA Transfer in Cancer Progression: Many Targets, Modes of Action, and Effects Across Cancer Stages
  10. Transcription factor RUNX1 regulates platelet PCTP (phosphatidylcholine transfer protein): Implications for cardiovascular events differential effects of RUNX1 variants
  11. Platelet microparticles infiltrating solid tumors transfer miRNAs that suppress tumor growth
  12. Dysregulation of PLDN (pallidin) is a mechanism for platelet dense granule deficiency in RUNX1 haplodeficiency
  13. Regulation of Ras signaling and function by plasma membrane microdomains
  14. Inhibition of galectin-1 sensitizes hras-driven tumor growth to rapamycin treatment
  15. Dicer1-mediated miRNA processing shapes the mRNA profile and function of murine platelets
  16. The RLIP76 N-terminus binds ARNO to regulate PI 3-kinase, Arf6 and Rac signaling, cell spreading and migration
  17. RLIP76 regulates Arf6-dependent cell spreading and migration by linking ARNO with activated R-Ras at recycling endosomes
  18. RLIP76 regulates HIF-1 activity, VEGF expression and secretion in tumor cells, and secretome transactivation of endothelial cells
  19. Three-dimensional reconstruction of neovasculature in solid tumors and basement membrane matrix using ex Vivo X-ray microcomputed tomography
  20. Activation of PI3K and R-ras signaling promotes the extension of sensory axons on inhibitory chondroitin sulfate proteoglycans
  21. RhoG protein regulates glycoprotein VI-Fc receptor γ-chain complex-mediated platelet activation and thrombus formation
  22. Integrin Signaling
  23. Emerging treatments in lung cancer - targeting the RLIP76 molecular transporter
  24. RALBP1/RLIP76 depletion in mice suppresses tumor growth by inhibiting tumor neovascularization
  25. Palmitoylation regulates vesicular trafficking of R-Ras to membrane ruffles and effects on ruffling and cell spreading