Publications

Lawrence Goldfinger

Contact

Name: Lawrence Goldfinger, PhD

1020 Locust Street
JAH, 394
Philadelphia, PA 19107

Telephone: 215-955-5324

Highlighted Publications

Michael, J.V., Wurtzel, J.G.T., Mao, G.F., Rao, A.K., Kolpakov, M.A., Sabri, A., Hoffman, N.E., Rajan, S.,Tomar, D., Madesh, M., Nieman, M.T., Yu, J., Edelstein, L.C., Rowley, J.W., Weyrich, A.S., and Goldfinger, L.E. 2017. Platelet microparticles infiltrating solid tumors transfer miRNAs that suppress tumor growth. Blood 130(5):567-580. PMID: 28500171. PMCID: PMC5542851.

We demonstrate, for the first time, in vivo association of platelet-derived microparticles with cancer cells in solid tumors, transfer of platelet-derived microRNAs to the tumor cells, and anti-tumor effects via microRNA-mediated gene regulation in the target cells.

Janapati, S., Wurtzel, J.G.T., Dangelmaier, C., Manne, B.K., Bhavanasi, D., Kostyak, J.C., Kim, S., Holinstat, M., Kunapuli, S.P., Goldfinger, L.E. 2018. TC21/RRas2 regulates glycoprotein VI-FcRg-mediated platelet activation and thrombus stability. Journal of Thrombosis and Haemostasis. 16:1632-1645. PMID: 29883056. PMCID: PMC6286703.

We show regulatory roles for small GTPases not previously characterized in platelets, in receptor-proximal platelet signaling, platelet function, and in vivo thrombosis. 

Rowley, J.W., Chappaz, S., Corduan, A., Chong, M.M.W., Campbell, R., Khoury, A., Manne, B-K., Wurtzel, J.G.T., Michael, J.V., Goldfinger, L.E., Murnaw, M.M., Nieman, M.T., Kile, B.T., Provost, P., and Weyrich, A.S. 2016. Dicer1 mediated miRNA processing shapes the mRNA profile and function of murine platelets. Blood 127(14):1743-1751. PMID: 26773046. PMCID: PMC4825412.

In this collaborative study, we show for the first time that platelet microRNAs are essential mediators of platelet gene expression, cellular function, and of hemostasis and thrombosis.

Chen, X., Gupta, S., Copper, M., DeHelian, D.J., Zhao, X., Naik, M., Wurtzel, J.G.T., Stalker, T.J., Goldfinger, L.E., McKenzie, S.E., Benovic, J., Brass, L.F., Naik, U.P., Ma, P. 2020. GRK6 regulates the hemostatic response to injury through its rate-limiting effects on GPCR signaling in platelets. Blood Advances 4(1):76-86. PMID: 31899801.

A recent study representing ongoing collaboration with Peisong Ma’s lab in the Cardeza Foundation, demonstrating novel negative regulatory signaling pathways of platelet function and hemostasis.

Recent Publications

GRK6 regulates the hemostatic response to injury through its rate-limiting effects on GPCR signaling in platelets

High-efficiency unassisted transfection of platelets with naked double-stranded miRNAs modulates signal-activated translation and platelet function

Horizontal RNA transfer goes deep: platelet consumption and microRNA utilization by vascular smooth muscle cells

ELMO1 deficiency enhances platelet function

Concepts and advances in cancer therapeutic vulnerabilities in RAS membrane targeting

GPVI inhibitor as antitumor gateway drug

TC21/RRas2 regulates glycoprotein VI–FcRγ-mediated platelet activation and thrombus stability

Defective RAB1B-related megakaryocytic ER-to-Golgi transport in RUNX1 haplodeficiency: Impact on von Willebrand factor

Platelet Microparticles and miRNA Transfer in Cancer Progression: Many Targets, Modes of Action, and Effects Across Cancer Stages

Transcription factor RUNX1 regulates platelet PCTP (phosphatidylcholine transfer protein): Implications for cardiovascular events differential effects of RUNX1 variants

Platelet microparticles infiltrating solid tumors transfer miRNAs that suppress tumor growth

Dysregulation of PLDN (pallidin) is a mechanism for platelet dense granule deficiency in RUNX1 haplodeficiency

Regulation of Ras signaling and function by plasma membrane microdomains

Inhibition of galectin-1 sensitizes hras-driven tumor growth to rapamycin treatment

Dicer1-mediated miRNA processing shapes the mRNA profile and function of murine platelets

The RLIP76 N-terminus binds ARNO to regulate PI 3-kinase, Arf6 and Rac signaling, cell spreading and migration

RLIP76 regulates Arf6-dependent cell spreading and migration by linking ARNO with activated R-Ras at recycling endosomes

RLIP76 regulates HIF-1 activity, VEGF expression and secretion in tumor cells, and secretome transactivation of endothelial cells

Three-dimensional reconstruction of neovasculature in solid tumors and basement membrane matrix using ex Vivo X-ray microcomputed tomography

Activation of PI3K and R-ras signaling promotes the extension of sensory axons on inhibitory chondroitin sulfate proteoglycans

RhoG protein regulates glycoprotein VI-Fc receptor γ-chain complex-mediated platelet activation and thrombus formation

Integrin Signaling

Emerging treatments in lung cancer - targeting the RLIP76 molecular transporter

RALBP1/RLIP76 depletion in mice suppresses tumor growth by inhibiting tumor neovascularization

Palmitoylation regulates vesicular trafficking of R-Ras to membrane ruffles and effects on ruffling and cell spreading