Current Trainees

Photo Name Project Mentor Email
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
Butler, Mitchel "Mitch" Subarachnoid hemorrhage (SAH) is a debilitating injury most commonly caused by ruptured cerebral aneurysm; the disease leads to significant functional neurologic disabilities, including epilepsy. Prior preclinical and clinical studies have revealed associations between SAH-induced vascular damage and altered inflammatory as well as electrical signaling mechanisms in the brain. Our lab combines the endovascular perforation rat model of SAH with long-term video-EEG monitoring together with downstream measurements of vascular changes and neuroinflammation, specifically increases in microglia. In parallel, we leverage longitudinal clinical, EEG, and computed tomography (CT) brain imaging data to investigate how SAH injury impacts electrical activity and epileptic outcomes in the human. In this combined preclinical and clinical project, I am developing imaging-based methods to (1) quantify changes in the extent and location of bleeding in the brain and (2) relate them to metrics of electrical and neuroinflammatory activity. Jeffrey Loeb, MD, PhD and Jan Kitajewski, PhD mbutle28@uic.edu
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
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
McCann, Maximilian A, PhD The integrity of the endothelial barrier in the retina is critical, as disruption of this barrier leads to vessel leakage, macular swelling, and visual impairments in patients with diabetic retinopathy. Vascular endothelial growth factor (VEGF) is a key inducer of endothelial barrier permeability and is chronically elevated in many patients with diabetes. It acts in two phases. In the initial phase, VEGF induces signaling events that physically open the barrier, allowing vessel leakage. The second phase is less defined and brings about a prolonged effect that has a slower onset, which suggests transcriptional changes are at play. Neutralization of VEGF with anti-VEGF therapies has proven to be a vital treatment that lowers VEGF levels, and leads to reclosure of breached endothelial barriers, resolves macular edema, and restores vision. However, not all patients benefit from anti-VEGF, and even those who initially respond well can become unresponsive. Therefore, alternative therapies to anti-VEGF are needed. My research focuses on laying the groundwork for these therapies by developing a better understanding of the processes that govern pathological vessel opening and reclosure. Jan Kitajewski, PhD mccann7@uic.edu

Previous Trainees

Photo Name Project Mentor Email
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
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
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
Sargis, Timothy When activated by its ligand Dll4, Notch1 signaling acts as a negative regulator of angiogenic sprout initiation. Conversely, the Notch ligand Jagged1 has been discovered to be pro-angiogenic. Endothelial-specific Jagged1 loss leads to reduced angiogenesis during retinal development, wound healing, and tumor angiogenesis. How Jagged1 mediates its pro-angiogenic function is currently not well understood. Several models for Jagged1 function have been proposed: Jagged1 may be a competitor of Dll4, or a unique Notch signal activator. We hypothesize that Jagged1 interacts with another Notch protein, Notch4, to promote angiogenesis and that this signaling is distinct from the role of Dll4/Notch1 signaling. This project aims to describe a new signaling pair (Jagged1-Notch4) and to develop new approaches to promote wound healing through regulation of Jagged1 or Notch4 activities. Jan Kitajewski, Ph.D. and Luisa DiPietro, DDS, Ph.D. tsargi2@uic.edu

The VBST-TP is funded by training grant (T32 HL144459) from the National, Heart, Lung, and Blood Institute (NHLBI).