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Aguilar, Victor |
Atherosclerotic plaque growth is subject to factors beyond an individual’s diet. Growth is subject to factors such as blood flow hemodynamics, inflammation signals, and cell-cell interactions. My objective is to understand how these factors affect vascularization. Prior research has shown that vascular growth is enhanced by the presence of oxidized lipids, a phenomenon that was shown to be dependent on lipid uptake protein CD36. I am interested in utilizing CD36 expression to analyze changes in angiogenic gene expression and cell signaling in endothelium exposed to pro-atherogenic conditions in vitro. This work will incorporate in vivo work on transgenic endothelial-specific CD36-null mice to assess impact on long-term progression of induced atherosclerosis. |
Irena Levitan, Ph.D. and Richard Minshall, Ph.D. |
vaguil8@uic.edu |
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Axen, Cassondra |
Women usually live longer than men and this longevity in women is likely due to the ability of women to conceive child. Pregnancy is not merely a childbearing experience, as it promotes a wonderful physiological alteration in the pregnant mother. In this regard, during pregnancy the fetal cells (FCs) have been shown to migrate from developing fetus, into the maternal circulation, and these FCs are known to remain for decades in maternal circulation. However, the exact role of these FCs are not completely understood. Therefore, my research project will be to characterize the phenotype of these FCs at the cellular and molecular level using lineage tracing genetic technology in the mice. Thereafter, I will address the ability of these FCs to repair tissue damage and restore organ function in the aftermath of experimental tissue injury such as ARDS, acute myocardial infarction (AMI), and peripheral arterial disease (PAD). |
Kishore Wary, PhD and Richard Minshall, PhD |
caxen2@uic.edu |
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Ewenighi-Amankwah, Chinwe, PhD |
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer characterized by lack of expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) overexpression. TNBC is known for its aggressiveness, organ metastases, and poor prognosis than other types of breast cancer. TNBCs are more common among African-ancestry populations. TNBC accounts for 39% of breast cancers in African American women under the age of 50, but only 16% in Caucasian women of the same age group. Because TNBC lacks receptors for estrogen, progesterone, and HER2 overexpression, there are no targeted therapies, and affected patients rely only on chemotherapy. Notch4 from a family of the Notch signaling pathway plays crucial roles in cellular developmental pathways, including proliferation, differentiation, and apoptosis. Of all four Notch receptors, Notch4 is more attractive in TNBC. A positive correlation exists between TNBCs and high expression of Notch4. There is a need for targeted therapy for TNBC, and notch4 seems promising. My study investigates the role of Notch4 in tumor endothelium, growth, vascularization, metastasis, and therapeutic targeting. |
Jan Kitajewski, PhD and Kishore Wary, PhD |
chinwe2@uic.edu |
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Gordon, Ben |
Triple negative breast cancer (TNBC) makes up to 20% of breast cancer diagnoses, with a 5-year survival as low as 11% for late stage metastatic disease. Unfortunately, while surgery and adjuvant chemotherapy are effective treatment option for early stage disease, there are very few therapeutic options for advanced metastatic TNBC spread. Importantly, TNBC is unresponsive to hormonal and targeted therapies of other types of breast cancer. In the complex metastatic cascade, Circulating Tumor Cells (CTCs) cross the endothelial barrier twice: first to enter systemic circulation (intravasation) and then to exit circulation (extravasation). My proposal aims to study Jag1-mediated Notch signaling as a potential target to limit TNBC metastatic spread by focusing on tumor-endothelial interactions during tumor cell extravasation from circulation into secondary organs. Our previous work targeting Jag1- mediated Notch signaling with Notch1 decoys attenuated TNBC endothelial binding and transendothelial migration (TEM). We therefore hypothesize that Jag1 is a novel mediator of TNBC extravasation. Theoretically, Jag1 could activate endothelial or tumor Notch, as the receptor is expressed on both cell types. To address both of these possibilities, I have generated CRISPR/Cas9 treated TNBC clonal cell lines targeting Jag1. To address intrinsic tumor Notch signaling, I will engineer TNBC cell lines with a dominant-negative inhibitor of intrinsic Notch signaling. Using these tools, extravasation will be modelled in vitro, in a cutting-edge microfluidics system that recapitulates the capillary microenvironment, and in vivo via intravenous injection of TNBC cells followed by tracking of lung capillary extravasation. The goal of my research proposal is to interrogate a Notch-based mechanism of TNBC extravasation during metastasis. |
Jan Kitajewski, PhD and Jalees Rehman, PhD |
bgordo6@uic.edu |
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Phillips, Evan, PhD |
The objective of my project is to define and analyze cardiac lymphatic networks and the process of endogenous and growth factor-stimulated lymphangiogenesis in the context of cardiac hypertrophy. I am investigating the potential for cardiac lymphatic vessel generation, remodeling of the cardiac microenvironment, and immune cell trafficking via cardiac lymphatics. This project therefore requires an in situ morphological and molecular analysis method such as 3D multiplex microscopy. I will adapt tissue clearing appropriate for high-resolution 3D localization of multiple vascular, stromal, and inflammatory markers in cardiac tissue. This whole tissue imaging approach will help us understand the relevance of cardiac lymphatics in a new disease context and whether stimulated lymphangiogenesis hold therapeutic promise here. |
Steve Seung-Young Lee, PhD and Jan Kitajewski, PhD |
phillipe@uic.edu |
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Tevino, Troy |
Healthy blood-brain barrier endothelial cells restrict entry of pathogenic T cells into the brain. In neuroinflammation, blood-brain barrier damage permits migration of T cells into the brain via Caveolin-1 endothelial vesicles. However, the molecular signals targeting T cells to caveolar vesicles remain unclear. In this work, I will test the hypothesis that T cell CXCR3 inside out integrin signaling directs and enforces phospho-Caveolin-1 dependent migration across blood-brain barrier endothelial cells. My goal is to address this mechanism to restrict entry of neurodegenerative T cells and promote delivery of neuroprotective T cell subsets. |
Dan Shaye, PhD and Sarah Lutz, PhD |
ttrevi2@uic.edu |
