Philadelphia University + Thomas Jefferson University
Sidney Kimmel Medical College
Department of Medicine

Research Activity

The Cardeza Center pursues a broad range of basic research that can be divided into three focus areas: basic research, clinical/translational and core laboratories.  We also host a seminar series during the academic year.

Leonard Edelstein, PhD

Dr. Edelstein’s laboratory studies gene expression in megakaryocytes and platelets and their role in cardiovascular disease and thrombopoiesis. Current research includes:

  • Activated platelets release microparticles (MPs) which contain RNA and protein. These MPs have been shown to deliver miRNAs to endothelial cells in culture and alter the level of RNAs in these cells. We are studying this effect in a flow chamber in which the endothelial cells are cultured under shear stress and then analyzing the effect on genes regulated by inflammation or shear stress, two processes important to atherosclerotic plaque formation.

  • Genome wide association studies have identified ~50 loci in the human genome associated with heart attacks. However, neither the genetic variant responsible for the increased risk nor the cell type in which it functions has been identified. We are developing methods to identify which locus-linked genes are functional in platelets and the effect the common variants have on their expression and function.

  • Arterial hypertension is associated with thrombotic events due to platelet activation. The exact mechanism by which hypertensive platelets become more sensitive to agonist stimulation is unknown. We have collected platelet miRNA from healthy and pre-hypertensive subjects and found association between miRNA level and blood pressure.  We will use this data to identify differentially expressed genes responsible for the increased function in platelets.


Platelet microparticles infiltrating solid tumors transfer miRNAs that suppress tumor growth

The role of platelet microvesicles in intercellular communication

Identification of a functional genetic variant driving racially dimorphic platelet gene expression of the thrombin receptor regulator, PCTP

TULA-2 (T-Cell Ubiquitin Ligand-2) Inhibits the Platelet Fc Receptor for IgG IIA (FcγRIIA) Signaling Pathway and Heparin-Induced Thrombocytopenia in Mice

Integrative Multi-omic Analysis of Human Platelet eQTLs Reveals Alternative Start Site in Mitofusin 2

MicroRNAs in platelet physiology and function

Anti-miR-148a regulates platelet FcγRIIA signaling and decreases thrombosis in vivo in mice

Common variants in the human platelet PAR4 thrombin receptor alter platelet function and differ by race

MicroRNA expression differences in human hematopoietic cell lineages enable regulated transgene expression

Human platelet microRNA-mRNA networks associated with age and gender revealed by integrated plateletomics

The human platelet: Strong transcriptome correlations among individuals associate weakly with the platelet proteome

Mechanism of race-dependent platelet activation through the protease-activated receptor-4 and Gq signaling axis

Racial differences in human platelet PAR4 reactivity reflect expression of PCTP and miR-376c

MicroRNAs in Platelet Production and Activation

The complex transcriptional landscape of the anucleate human platelet.

MicroRNAs in platelet production and activation

Small RNAs as potential platelet therapeutics

Human genome-wide association and mouse knockout approaches identify platelet supervillin as an inhibitor of thrombus formation under shear stress

High-throughput screening uncovers a compound that activates latent HIV-1 and acts cooperatively with a histone deacetylase (HDAC) inhibitor

MicroRNAs in platelet production and activation


Leonard Edelstein, PhD

Leonard Edelstein, PhD
Research Assistant Professor

Xiango Kong, MD

Xiango Kong, MD
Research Associate

Namrata Madan, PhD

Namrata Madan, PhD
Postdoctoral Fellow

Michael Whitley

Michael Whitley
Graduate Student

Lin Ma

Joanne Vesci 
Research Technician

Lin Ma

Lin Ma
Research Technician

Arie Horowitz, DSc

My laboratory conducts basic research in vascular biology. Our objective is to understand how blood vessels regulate the permeability of their walls. Specifically, we study how the junctions between adjacent endothelial cells on the lumen of vessels are maintained, and how they respond to external stimuli, such as vascular endothelial growth factor. We pursue these questions by probing intracellular signaling pathways and protein complexes that determine the behavior of the junctions. We use cell culture and genetically modified mouse models in combination with advanced optical imaging techniques.

In addition to my membership in the Cardeza Center, I am an adjunct faculty in Cancer Biology, and a member of the Genetics, Genomics and Cancer Biology graduate program, and of the Sidney Kimmel Cancer Center in the Extracellular Matrix and Metastasis program.

Our three major ongoing projects are:

1.    Regulation of cell junction dynamics by membrane traffic. We found that the GTPase Rab13, which recycles tight junction proteins, facilitates the translocation of RhoA and its guanine exchange factor PLEKHG5/Syx from cell junctions to the cell leading edge (Wu et al., 2011). This implicates Rab13 in cell migration, a previously unknown function of this protein. We are investigating the in vivo function of Rab13 using a new mouse model with an endothelial cell-specific deletion of rab13. We previously found that global deletion of rab13 is embryonic lethal. In collaboration with the synthetic chemistry lab of Dr. Katarzyna Błażewska at Lodz University of Technology, we are screening small molecule inhibitors of vascular development in the zebrafish, in order to identify compounds that may inhibit angiogenesis.


2.    Large-scale identification of genes involved in mediating the effects of VEGF on endothelial cell junctions. We are leveraging CRISPR-dCas9 gRNA inhibitory and activating libraries in order to either silence or activate genes that code for proteins that are components of specific pathways. Our current focus is on VEGF, but we will pursue additional cell-junction modifying pathways, e.g. angiopoietin. In order to generate sufficient coverage of the gRNA libraries, which code for all the annotated human genes, we miniaturized the permeability assay to 100-200 mm microcarrier beads. The beads are permeable and take up fluorescent probes once the confluent cell monolayer that covers them is exposed to VEGF. The resulting light signal facilitates the sorting of the beads to separate those where junction response to VEGF was inhibited. In collaboration with Dr. Eric Londin from the Computational Medicine Center of Thomas Jefferson University, we will identify genes that are required for the effect of VEGF on cell junctions.


3.    The basis of signal specificity in endothelial cell junctions. VEGF and angiopoietin-1 are essential for blood vessel viability and integrity, but they have opposite effects on endothelial cell junctions. While the former triggers junction disassembly, the latter stabilizes them. Our previous study (Ngok et al., 2012) indicated that the localization of the RhoA guanine exchange factor Syx can explain in part the opposite effects of VEGF and Ang1 on cell junctions. Syx is displaced from cell junctions by VEGF, whereas Ang1 retains Syx at the junctions. Numerous junction transmembrane and cytoplasmic proteins are scaffolded by the large adaptor protein MPDZ. Therefore, we employ MPDZ as a convenient tool for determining how different agonists generate different. We identified new binding partners of MPDZ that may link its function to membrane trafficking, and are currently analyzing the molecular basis of MPDZ’s function. In parallel, we are phenotyping a new mpdz loss-of-function mouse model, to test the in vivo function of MPDZ. The preliminary phenotyping data suggest that mpdz-/- mice suffer from several major anatomic and functional effects, including loss of hearing and heart hypertrophy.


Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease

Analysis of retinoic acid-induced neural differentiation of mouse embryonic stem cells in two and three-dimensional embryoid bodies

Letter by Horowitz Regarding Article, "protein Interactions at Endothelial Junctions and Signaling Mechanisms Regulating Endothelial Permeability"

The versatility of RhoA activities in neural differentiation

RhoA inhibits neural differentiation in murine stem cells through multiple mechanisms

The cytoplasmic domain of neuropilin-1 regulates focal adhesion turnover

VEGF and angiopoietin-1 exert opposing effects on cell junctions by regulating the Rho GEF Syx

Stimulus-dependent phosphorylation of profilin-1 in angiogenesis

Regulation of VEGF signaling by membrane traffic

Rab13-dependent trafficking of RhoA is required for directional migration and angiogenesis

Erratum: Vascular endothelial growth factor and semaphorin induce neuropilin-1 endocytosis via separate pathways (Circulation Research (2008) 103 (e71-e79))

Imaging of growth factor-augmented angiogenesis after myocardial infarction: glimmers of a spatiotemporal pattern?

Cleavage of syndecan-4 by ADAMTS1 provokes defects in adhesion

Branching morphogenesis

The Amot/Patj/Syx signaling complex spatially controls RhoA GTPase activity in migrating endothelial cells

Branching morphogenesis

Syx, a rhoA guanine exchange factor, is essential for angiogenesis in vivo

Vascular endothelial growth factor and semaphorin induce neuropilin-1 endocytosis via separate pathways

Directional cues in angiogenesis

Erratum: Binding of internalized receptors to the PDZ domain of GIPC/synectin recruits myosin VI to endocytic vesicles (Proceedings of the National Academy of Sciences of the United States of America (August 22, 2006) 103, 34 (12735-12740) DOI: 10.1073/pnas.0605317103)


Arie Horowitz, D.Sc

Arie Horowitz, DSc
Associate Professor

Junning Yang, PhD

Junning Yang, PhD
Research Associate

Junning Yang, PhD

Claire Simonneau, PhD
Postdoctoral Fellow

Junning Yang, PhD

Ioana Stefanescu, B.Sc.
Research Technician

Steven McKenzie, MD PhD


Dr. McKenzie is a Hematology physician-scientist with clinical expertise in adult and pediatric non-malignant hematologic disorders and a scientific expertise in translational research. He works in the Cardeza Hemophilia and Thrombosis Center and also in the Hereditary Anemias Center. He is a member of the Sidney Kimmel Cancer Center (SKCC), in the Molecular Biology and Genetics Program. He is a member of two Graduate Programs:

  • Genetics, Genomics and Cancer Biology

  • Immunology and Microbial Pathogenesis

He is a physician mentor for Thomas Jefferson University MD/PhD program.  

Dr. McKenzie directs two major laboratory research projects. The first project has a focus on immune-mediated thrombocytopenia and thrombosis syndromes (see McKenzie and Sachais, Current Opinion in Hematology, September 2014). This work led to the first and only mouse model of heparin-induced thrombocytopenia and thrombosis (HIT). The current work explores Novel Therapeutics in HIT, in an NIH-supported Program Project grant with Drs. Poncz and Rauova at Children’s Hospital of Philadelphia, Drs. Cines, Sachais and Cuker at University of Pennsylvania, and Dr. Arepally at Duke. In another subproject, Dr. McKenzie is co-funded on an NIH R01 with Dr. Bergmeier at UNC Chapel Hill and Dr. Woulfe at University of Delaware to explore platelet signaling mechanisms.

The second major McKenzie lab project focuses on the Genomics and Molecular Genetics of inter-individual variation in human platelet activation via FcgammaRIIa. This molecule has dual functions, as a receptor for IgG immune complexes and as a transmembrane adapter in integrin “outside-in” signaling. In collaboration with Dr. Paul Bray, who led the PRAX1 study, our team has identified differentially expressed mRNAs and miRNAs as well as genomic variants that regulate platelet reactivity. Team members of our longstanding Platelet Interest Group are Drs. Bray, McKenzie, Holinstat, Edelstein and Naik at Thomas Jefferson University, Drs. Rigoutsos and Londin at Thomas Jefferson University Computational Medicine Center, Dr. Fortina of SKCC Genomics, Drs. Shaw and Simon at Baylor, and Dr. Kunapuli at Temple. Dr. McKenzie is also co-funded, with Dr. Holinstat as PI, on work that involves 12-LOX and diabetes vascular biology.  Our foci in the McKenzie lab moving forward are novel molecular genetic pathways for determination of receptor levels, protein tyrosine phosphatase activity and oligo-ubiquitylation in platelet FcgammaRIIa  functions.


Platelets release pathogenic serotonin and return to circulation after immune complex-mediated sequestration

5B9, a monoclonal antiplatelet factor 4/heparin IgG with a human Fc fragment that mimics heparin-induced thrombocytopenia antibodies

Erratum: TULA-2 protein phosphatase suppresses activation of Syk through the GPVI platelet receptor for collagen by dephosphorylating Tyr(P)346, a regulatory site of Syk (The Journal of Biological Chemistry (2016) 291 (22427-22441) DOI: 10.1074/jbc.M116.743732)

Endothelial antigen assembly leads to thrombotic complications in heparin-induced thrombocytopenia

TULA-2 (T-Cell Ubiquitin Ligand-2) Inhibits the Platelet Fc Receptor for IgG IIA (FcγRIIA) Signaling Pathway and Heparin-Induced Thrombocytopenia in Mice

TULA-2 protein phosphatase suppresses activation of syk through the GPVI platelet receptor for collagen by dephosphorylating Tyr(P)346a regulatory site of syk

Mice expressing low levels of CalDAG-GEFI exhibit markedly impaired platelet activation with minor impact on hemostasis

Identification of novel Syk-independent functional roles of FcγRIIa in platelet outside-in signaling using transgenic mice expressing human FcγRIIa

Syk inhibition in ischemic stroke

Platelet transactivation by monocytes promotes thrombosis in heparin-induced thrombocytopenia

The antigenic complex in HIT binds to B cells via complement and complement receptor 2 (CD21)

Anti-miR-148a regulates platelet FcγRIIA signaling and decreases thrombosis in vivo in mice

Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- And tissue-specific microRNAs

Platelet 12-LOX is essential for FcγRIIa-mediated platelet activation

MicroRNA expression differences in human hematopoietic cell lineages enable regulated transgene expression

Human platelet microRNA-mRNA networks associated with age and gender revealed by integrated plateletomics

The human platelet: Strong transcriptome correlations among individuals associate weakly with the platelet proteome

Identification of a developmental gene expression signature, including hox genes, for the normal human colonic crypt stem cell niche: Overexpression of the signature parallels stem cell overpopulation during colon tumorigenesis

Advances in the pathophysiology and treatment of heparin-induced thrombocytopenia

Protein kinase C δ deficiency enhances megakaryopoiesis and recovery from thrombocytopenia


Steven E. McKenzie, MD PhD

Steven E. McKenzie, MD PhD

Shaji Abraham, PhD

Shaji Abraham, PhD

Yuhang Zhou

Yuhang Zhou

Past Members

Pierette Andre

Pierette Andre

Ulhas P. Naik, PhD

The Naik laboratory is focused on developing therapeutic strategies to interrupt the progress of cardiovascular disease and cancer. In this regard, the team has identified several novel gene products that play key regulatory roles in the progression of these diseases. Using cell and molecular biological approaches, the team has characterized the potential role of calcium- and integrin-binding protein family and junctional adhesion molecule family members in physiological and pathological settings. Cutting edge technologies, such as the yeast two-hybrid system, siRNA, transgenic mouse models, systems biology, nanotechnology and fluid dynamics modeling are routinely employed in the laboratory.

Some specific projects involve:

  • Positive and negative regulatory mechanisms of platelet activation during thrombosis

  • Mechanism of new blood vessel formation (angiogenesis) during ischemia and cancer

  • Mechanism of breast and prostate cancer cell metastasis

  • Use of nanotechnology to deliver drugs to specifically targeted sites

Current Projects

  • 2P20 RR015588-10

  • 1R01 HL113118-02

  • 1R01 HL119374-01

  • AHA Grant-in-Aid

  • Fraunhofer-UD Research Grant


CIB1 protects against MPTP-induced neurotoxicity through inhibiting ASK1

Obesity-induced endoplasmic reticulum stress causes lung endothelial dysfunction and promotes acute lung injury

Binding of CIB1 to the aIIb tail of aIIbβ3 is required for FAK recruitment and activation in platelets

Ask1 regulates murine platelet granule secretion, thromboxane A2generation, and thrombus formation

Effect of Vorapaxar Alone and in Combination with Aspirin on Bleeding Time and Platelet Aggregation in Healthy Adult Subjects

Bacteria exploit platelets

Junctional adhesion molecule-A suppresses platelet integrin αIIbβ3signaling by recruiting Csk to the integrin-c-Src complex

Manipulating integrin signaling for anti-thrombotic benefits

High-throughput flow cytometry screening reveals a role for junctional adhesion molecule a as a cancer stem cell maintenance factor

Junctional Adhesion Molecule-A Regulates Vascular Endothelial Growth Factor Receptor-2 Signaling-Dependent Mouse Corneal Wound Healing

Fucoidan is a novel platelet agonist for the C-type lectin-like receptor 2 (CLEC-2)

Effects of JAM-A deficiency or blocking antibodies on neutrophil migration and lung injury in a murine model of ALI

A spatial model for integrin clustering as a result of feedback between integrin activation and integrin binding

CASK interacts with PMCA4b and JAM-A on the mouse sperm flagellum to regulate Ca2+homeostasis and motility

JAM-A protects from thrombosis by suppressing integrin α IIbβ 3-dependent outside-in signaling in platelets

Calcium- and integrin-binding protein 1 regulates megakaryocyte ploidy, adhesion, and migration

Pericyte-endothelial cell interaction: A survival mechanism for the tumor vasculature

Contra-regulation of calcium- and integrin-binding protein 1-induced cell migration on fibronectin by PAK1 and MAP kinase signaling

Efficient implementation of the proper outlet flow conditions in blood flow simulations through asymmetric arterial bifurcations

Probabilistic modeling and analysis of the effects of extra-cellular matrix density on the sizes, shapes, and locations of integrin clusters in adherent cells


Ulhas P. Naik, PhD

Ulhas P. Naik, PhD

Randall Derstine, MS

Randall Derstine, MS

Kalyan Golla, PhD

Kalyan Golla, PhD

Meghna U. Naik, MSc

Meghna U. Naik, MSc

Picture Not Available

Pravin Patel, BS

Cardeza Seminars


September 7 – Peisong Ma, PhD, (Penn), Curtis 218
September 21 – Ramani Ramchandran, PhD, (Medical College of Wisconsin), Curtis 218
September 28 – Rosario Scalia, MD, PhD, (Temple), Curtis 218
October 12 – Satoru Eguchi, MD, PhD, (Temple) Curtis 218
October 26 – Kellie Machalus, PhD, (Harvard), Curtis 218
November 2 – Martha Sola-Visner, MD, (Harvard), Curtis 218
November 16 – Alexander M. Mazo, PhD, (Jefferson), Curtis 218
November 30 – Stephen Vatner, MD, (Rutgers), Curtis 218
December 21 – Colin Greineder, MD, PhD, (Penn), Curtis 218
January 4 – Yi Fan (Penn)
January 25 – Adam Cuker, MD, (Penn), Hamilton 505
February 1 – Bruno Calabretta, MD, PhD, (Jefferson), Hamilton 505
February 22 – Jianxin Sun, PhD, (Jefferson), Hamilton 505
March 1 – James Keen, PhD, (Jefferson), Hamilton 505
March 22 – Jason M. Butler, PhD, (Cornell), Hamilton 505
April 12 – Peter Newman, PhD, (Wisconsin Blood Center), Hamilton 505
April 26 – Suresh Joseph, PhD, (Jefferson), Hamilton 505
May 10 – Jean Baum, PhD, (Rutgers) - Hamilton 505
May 24 – TBD


All Seminars in Jefferson Alumni Hall 307 at 12:00 pm unless otherwise noted.

September 9 - Gerd A. Blobel, MD, PhD (CHOP)

October 14- Vinod Vijayan, Ph.D. (Baylor College of Medicine)

November 11 - Fabio Recchia, MD, PhD (Temple)

December 2 - Bing-Hua Jiang, PhD (Jefferson)

December 16 - Andrew E. Aplin, PhD (Jefferson)

January 6 - Daniel J. Rader, MD (UPenn)

January 20 – Gyorgy Hajnoczky, MD, PhD (Jefferson)

February 10 - Lawrence E. Goldfinger, PhD (Temple)

February 24 - Khadija Rafiq, PhD (Jefferson)

March 2 - Paul J Gadue, PhD (CHOP)

March 16 - Ross S. Summer, MD (Jefferson)

April 13 - Wei Tong, PhD (CHOP)

April 27 - Philip B.Wedegaertner, PhD (Jefferson)

May 11 - Patrick Provost (Centre Hospitalier de l'Université Laval (CHUL))

2014 - 2015

September 3 – Caleb Kallen (Thomas Jefferson University)

September 17 – Shey-Shing Sheu (Thomas Jefferson University)

October 1 – Deepak Deshpande (Thomas Jefferson University)

October 15 – Domenico Pratico (Temple University)

October 29 – John Semple (University of Toronto; St. Michael’s Hospital)

November 12 – John Weisel (University of Pennsylvania)

January 28 – Athan Kuliopulos (Tufts University)

February 11 – Rajanikanth Vadigepalli (Thomas Jefferson University)

February 25 – Khadija Rafiq (Thomas Jefferson University)

March 11 – Robert Flaumenhaft (Harvard University)

March 25 – Jean Pierre Issa (Temple University)

April 8 – Shawn Jobe (Milwaukee Blood Research Institute)

April 22 – Jerry Nadler (EVMS, Chair of Medicine)

May 13 – Ian Blair (University of Pennsylvania)

May 27 – TBA