About
38
Publications
4,634
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
1,423
Citations
Citations since 2017
Additional affiliations
October 2012 - present
February 2008 - October 2012
January 2006 - December 2007
Publications
Publications (38)
Purpose:
Recently, several new therapies have emerged to address locally advanced cutaneous basal cell and squamous cell carcinomas. Given the constraints of the ocular adnexa and orbit, this review was designed to discuss the role of these modalities in this region.
Methods:
A PubMed search was carried out to analyze the utility of United State...
Purpose:
To compare the expression of CD73 in indolent nodular basal cell carcinomas and cutaneous lesions that invade the orbit.
Methods:
Immunohistochemical staining for CD73 was performed on nodular basal cell carcinomas and invasive basal cell carcinomas. The numbers of positively staining cells were counted across 5 consecutive ×40 microsco...
Purpose:
To determine if calcitonin gene-related peptide (CGRP) is overexpressed in blind, painful eyes.
Methods:
This was a retrospective cross-sectional randomized control study conducted at a tertiary level hospital. Eight specimens of eyes enucleated by a single surgeon were included in the study. The control group patients underwent exenter...
Purpose:
To assess the role of nuclear factor kappa-B (NFKB) in cutaneous specimens of rosacea and unaffected tissue.
Methods:
Immunohistochemical staining was performed for the activated, phosphorylated variant of NFKB (pNFKB) in eyelid specimens of rosacea (n = 12) and normal, healthy tissue (n = 12). The numbers of positively staining cells/4...
Transforming growth factor β (TGFβ) signaling plays crucial roles in maintaining vascular integrity and homeostasis, and is established as a strong activator of vascular smooth muscle cell (VSMC) differentiation. Chronic inflammation is a hallmark of various vascular diseases. Although TGFβ signaling has been suggested to be protective against infl...
Introduction—Rosacea is a prevalent, chronic skin disease that is characterized by transient or persistent erythema, telangiectasia, papules, and pustules. Although it is primarily referred to as a cutaneous condition, rosacea can affect the periorbital skin and eye, manifesting itself in a variety of ways. Currently, preventative treatments that i...
Vascular leakage is a hallmark of the inflammatory response. Acute changes in endothelial permeability are due to post-translational changes in intercellular adhesion and cytoskeleton proteins. However, little is known about the mechanisms leading to long-term changes in vascular permeability. Here, we show that Interleukin-6 (IL-6) promotes an inc...
While rosacea is a common entity with significant cosmetic, socioeconomic, and vision-threatening impacts, this disorder remains incurable. Furthermore, until quite recently, many of the therapeutic options for rosacea had not been assessed through rigorous clinical testing with meaningful outcome measures. Nonetheless, new medical and surgical int...
Objective:
Laminar flow activates myocyte enhancer factor 2 (MEF2) transcription factors in vitro to induce expression of atheroprotective genes in the endothelium. Here we sought to establish the role of Mef2c in the vascular endothelium in vivo.
Approach and results:
To study endothelial Mef2c, we generated endothelial-specific deletion of Mef...
Purpose:
The programmed death-1 pathway negatively regulates the immune system. Previous reports have indicated worse tumor-related outcomes with increased expression of the ligand for this pathway. This study was undertaken to assess the role of the PD pathway in cutaneous malignancies that invade the orbit.
Methods:
Immunohistochemical stainin...
Purpose:
Rosacea-related cutaneous inflammation is a common cause of ocular surface disease. Currently, there are no specific pharmacologic therapies to treat ocular rosacea. Here, we aimed at determining the differences in intracellular signaling activity in eyelid skin from patients with and without ocular rosacea.
Methods:
This was an observa...
Endothelial p120-catenin (p120) maintains the level of vascular endothelial cadherin (VE-Cad) by inhibiting VE-cad endocytosis. Loss of p120 results in a decrease in VE-Cad levels leading to the formation of monolayers with decreased barrier function (as assessed by transendothelial electrical resistance [TEER]), while overexpression of p120 increa...
Activation of Src Family Kinase (SFK) signaling is required for the increase in endothelial permeability induced by a variety of cytokines and growth factors. However, we previously demonstrated that activation of endogenous SFKs by expression of dominant negative C-terminal Src Kinase (DN-Csk) is not sufficient to decrease endothelial adherens jun...
FLAG-tagged MKK6E expression in Dox-treated iMKK6E cells.
A, Pre-confluent monolayers of HDMEC were infected with lentivirus containing active FLAG-tagged MKK6 construct (iMKK6E) under the control of an inducible promoter. These cells were reseeded and allowed to become confluent for 3 days. Then, confluent iMKK6E-HDMEC monolayers were treated with...
DN-Csk does not increase the sensitivity of HLMEC or HUVEC to low dose TNF-?.
A, HLMEC were seeded at confluence and incubated for 72 hours. Then, growth media was replaced by low serum media and cells were infected with adenovirus to express either LacZ (control) or DN-Csk. After another 16 h, cells were treated with low-dose TNF-?. TEER was measu...
Endothelial cells form a semipermeable, regulated barrier that limits the passage of fluid, small molecules, and leukocytes between the bloodstream and the surrounding tissues. The adherens junction, a major mechanism of intercellular adhesion, is comprised of transmembrane cadherins forming homotypic interactions between adjacent cells and associa...
To delineate signals by which the vascular abnormalities inherent to ocular rosacea arise and to correlate these signals with elements of the innate immune system.
Experimental study. Immunohistochemical staining was performed for a variety of vascular markers and for toll-like receptor-4 on eyelid biopsies taken from patients with ocular rosacea a...
Endothelial barrier function is critical for tissue fluid homeostasis, and its disruption contributes to various pathologies, including inflammation and sepsis. Thrombin is an endogenous agonist that impairs endothelial barrier function. We showed that the thrombin-induced decrease in transendothelial electric resistance of cultured human endotheli...
Ocular rosacea is an incurable disease that affects millions of Americans annually. While multiple therapeutic strategies have been devised to address this disorder (including topical and oral medications, laser and light-based treatments, and surgical interventions), our current interventions are largely nonspecific and often ineffective. Nonethel...
A prior investigation has demonstrated that innate immune-specific cytokines are enriched in idiopathic orbital inflammation (IOI). To further document the role of innate immunity in IOI, the authors sought to determine whether toll-like receptors (TLRs) are present in biopsy specimens of this disorder.
Immunohistochemical staining for TLR2, TLR3,...
Leukocyte transendothelial migration (TEM) is regulated by several signaling pathways including Src family kinases (SFK) and the small RhoGTPases. Previous studies have shown that vascular endothelial-cadherin (VE-cad) forms a complex with β-,γ-, and p120-catenins and this complex disassociates to form a transient gap during leukocyte TEM. Addition...
To characterize the molecular biologic environment of pathological skin in ocular rosacea and to differentiate the levels of inflammatory molecules in ocular rosacea from those of normal skin.
The concentrations of 48 molecules were assayed in cutaneous biopsies taken from patients with ocular rosacea and from normal controls.
There were very few m...
Angiogenesis is crucial for embryogenesis, reproduction, and wound healing and is a critical determinant of tumor growth and metastasis. The multifunctional signal transducer Ras is a proto-oncogene and frequently becomes mutated in a variety of human cancers, including angiosarcomas. Regulation of Ras is important for endothelial cell function and...
Activation of Src family kinases (SFK) and the subsequent phosphorylation of VE-cadherin have been proposed as major regulatory steps leading to increases in vascular permeability in response to inflammatory mediators and growth factors. To investigate Src signaling in the absence of parallel signaling pathways initiated by growth factors or inflam...
The stress-activated kinase p38 plays key roles in tumor suppression and induction of tumor cell dormancy. However, the mechanisms behind these functions remain poorly understood. Using computational tools, we identified a transcription factor (TF) network regulated by p38alpha/beta and required for human squamous carcinoma cell quiescence in vivo....
Endoplasmic reticulum (ER) stress signaling can be mediated by the ER kinase PERK, which phosphorylates its substrate eIF2alpha. This in turn, results in translational repression and the activation of downstream programs that can limit cell growth through cell cycle arrest and/or apoptosis. These responses can also be initiated by perturbations in...
Cancer dormancy is a poorly understood stage of cancer progression. However, the ability to control this step of the disease offers novel therapeutic opportunities. Here we summarize recent findings that implicate the extracellular matrix and adhesion receptor signaling in the escape or induction of tumor dormancy. We further review evidence sugges...
The mechanisms that determine whether a tumor cell that has disseminated to a secondary site will resume growth immediately, die or enter a state of dormancy are poorly understood. Although tumor dormancy represents a common clinical finding, studying the mechanisms behind this stage of tumor progression has been challenging. Furthermore, it is tho...
It has been proposed that occult, disseminated metastatic cells are refractory to chemotherapy due to lack of proliferation. We have shown that p38 activation induces dormancy of squamous carcinoma cells. We now show that p38 signaling in these cells activates a prosurvival mechanism via the up-regulation of the endoplasmic reticulum (ER) chaperone...
We have investigated the role of a classical isoform of protein kinase C (PKCgamma) in promoting immortalized mammary cell tumorigenesis in vivo and the contribution of proteases and adhesion molecules to this process. We hypothesized that overexpression of PKCgamma in immortalized mammary epithelial cells may initiate, by activating the mitogenic...
Target organ of metastasis determines the fate of metastasis. The soluble factors released from one or more cell types in the new stroma may influence growth and survival of metastatic cells. In the present study, we used conditioned media from the kidney, liver and lung, the latter being the target organ of metastasis of murine mammary adenocarcin...
