Goldfinger Research

Contact

Name: Lawrence Goldfinger, PhD

1020 Locust Street
JAH, 394
Philadelphia, PA 19107

Contact Number(s):

Highlighted Publications

Lazar, S, Wurtzel, JGT, Chen, X, Ma, P, Goldfinger, LE. 2021. High efficiency transfection of platelets with naked double-stranded miRNAs modulates signal-activated translation and platelet function. Platelets 32(6):794-806. PMID: 32838617.

We demonstrate the ability of ex vivo platelets to internalize ectopic miRNAs by unassisted transfection, and to utilize them to modulate signal-activated translation and platelet function, including modulation of extracellular vesicle generation.

Michael, JV, Wurtzel, JGT, Mao, GF, Rao, AK, Kolpakov, MA, Sabri, A, Hoffman, NE, Rajan, S, Tomar, D, Madesh, M, Nieman, MT, Yu, J, Edelstein, LC, Rowley, JW, Weyrich, AS, and Goldfinger, LE. 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 microvesicles (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, JGT, Dangelmaier, C, Manne, BK, Bhavanasi, D, Kostyak, JC, Kim, S, Holinstat, M, Kunapuli, SP, Goldfinger, LE. 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.

Chen, X, Gupta, S, Cooper, M, DeHelian, DJ, Zhao, X, Naik, M, Wurtzel, JGT, Stalker, TJ, Goldfinger, LE, McKenzie, SE, Benovic, J, Brass, LF, Naik, UP, 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 across multiple labs in the Cardeza Foundation, demonstrating novel negative regulatory signaling pathways of platelet function and hemostasis.

Recent Publications

Altered platelet-megakaryocyte endocytosis and trafficking of albumin and fibrinogen in RUNX1 haplodeficiency

Plasma growth factors maintain constitutive translation in platelets to regulate reactivity and thrombotic potential

Phosphatidylserine-blocking nanoparticles inhibit thrombosis without increased bleeding in mice

Defective RAB31-mediated megakaryocytic early endosomal trafficking of VWF, EGFR, and M6PR in RUNX1 deficiency

Platelet microRNAs inhibit primary tumor growth via broad modulation of tumor cell mRNA expression in ectopic pancreatic cancer in mice

Signals | Integrin signaling

Platelets and extracellular vesicles and their cross talk with cancer

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

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

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

Regulation of H-Ras-driven MAPK signaling, transformation and tumorigenesis, but not PI3K signaling and tumor progression, by plasma membrane microdomains

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