Jan Kitajewski, PhD, Sweeney Basic Science Professor - Program Director and Mentor
Dr. Kitajewski is the Head of the Department of Physiology and Biophysics. His research interests are in dissecting mechanisms of physiological and tumor angiogenesis, focusing on cell fate determination (Notch), GPCR signaling (CLIC), and ECM remodeling (MT-MMP/ANTXR). This research studies the impact of angiogenic pathways on development, physiological processes, ocular disease and cancer progression. He has several awarded patents that involve entities designed to disrupt pathological angiogenesis, notably the “Notch decoys”. Dr. Kitajewski’s vascular biology research focuses on angiogenic mechanisms and incorporates translational and drug discovery efforts. His lab developed Notch decoys which target Notch angiogenic function in tumor vasculature. Current work on these patent-protected entities is focusing on purifying and assessing clinically relevant Jagged inhibitors to test their efficacy against tumor angiogenesis in mouse models. The Kitajewski lab has research support from the pharmaceutical company Eisai to evaluate a novel antibody-based inhibitor to tumor angiogenesis and tumor stem cell function.
Kishore K. Wary, PhD, Associate Professor - Co-Director and Mentor
Dr. Wary is a cardiovascular and regenerative biologist, with research studies on small molecules-mediated re-vascularization, vascular regeneration and angiogenesis. His multidisciplinary research is funded by American Heart Association (AHA) and National Institutes of Health (NIH). In collaboration with Drs. Malik and Rehman, he published on the regulation of endothelial differentiation from human and mouse stem and iPS cells. Dr. Wary has tuned his lab to produce high-quality iPS cells and test their efficacy in genetically engineered mouse models. He has also integrated his long-standing expertise in integrin signaling into ongoing projects studying vascular differentiation. Dr. Wary has served as a member of study sections including the NIH, AHA, NYSTEM Cell, Lupus, NASA, Fulbright and NSF. He chaired and co-chaired stem cell mini-symposia, and moderated poster and abstract sessions at EB and AHA meetings. Dr. Wary co-organized the Vasculata 2017 at UIC, sponsored by NHLBI/NIH grant (1R13 HL137360) and NAVBO . Vasculata 2017 was widely recognized as one of the most successful; the attendance was among the best achieved.
Theme 1: Vascular Signaling
Asrar Malik, PhD, Schweppe Professor - Theme Leader
Dr. Malik is the Head of the Department of Pharmacology at UIC and his laboratory is recognized for the study of signaling pathways that regulate the endothelial barrier function. Malik lab studies thrombin activation of its proteolytically cleaved receptor, mechanisms of regeneration of injured vessels through lineage tracing of endothelial cells, transcriptional and signaling mechanisms of differentiation of embryonic stem cells to endothelial cells, and strategies of using reprogrammed endothelial cells to repair vascular injury. Dr. Malik is UIC’s most preeminent vascular biologist, having authored over 550+ articles, many describing VE-cadherin adherens junctions (AJ) function in regulating endothelial barrier in relation to lung vascular inflammation and acute lung injury. He directs a T32 in lung biology which has been ongoing for over two decades (T32 HL007829-22), attesting to his superb experience in training.
Andrei Karginov, PhD, Assistant Professor - Mentor
Dr. Karginov studies how endothelial barrier is regulated at the level of adherens junctions (AJs). He developed optogenetic and molecular tools to activate tyrosine kinases (e.g., Src) or phosphatases (PTPs and SHIP-1) at the single cell level, either promoting or disrupt VE-cadherin-mediated endothelial barrier function. Dr. Karginov expertise include developing biosensors, photo-activatable probes, and high-resolution imaging techniques.
Dolly Mehta, PhD, Professor - Mentor
Dr. Mehta laboratory investigates signaling mechanisms by which dysregulation of Ca2+-permeable TRP channels such TRPC6 and TRPC1 compromise endothelial barrier function in lungs and investigates how kinases, focal adhesion kinase and sphingosine kinase 1, stimulate endothelial barrier formation and restoration of lung fluid balance in models of inflammatory lung injury.
Richard Minshall, PhD, Professor - Mentor
Dr. Minshall’s research program focuses on how structural and scaffolding functions of the endothelial protein caveolin-1 regulate trafficking dynamics of caveolae, PMN adhesion and transmigration, and endothelial proliferation and differentiation during injury and tissue repair. He investigates GPCR mechanisms in endothelial cells that regulate von Willbrand Factor (vWF) secretion during microvascular thrombosis and multi-organ system failure in sepsis. Dr. Minshall has shown that a 6-amino acid sequence of G12 interacts with SNAP to promote vWF secretion from endothelial cell Weibel Palade bodies. The focus now is to test whether a cell-permeable peptide mimetic can effectively block mortality in rodent models of sepsis.
Shane Phillips, PhD, Professor - Mentor
Dr. Phillips has clinical expertise in kinesiology and cardiovascular rehabilitation. His laboratory explores relationships among dietary habits, obesity, and exercise in African American and Latinos. He directs the Vascular Biology Laboratory in the College of Applied Health Sciences where he studies obesity, hypertension, and the control of blood flow and responses of the microcirculation to surgery, diet and exercise interventions.
Chinnaswamy Tiruppathi, PhD, Professor - Mentor
Dr. Tiruppathi is known for seminal work on endothelial barrier integrity/function in collaboration with Dr. Malik. He pioneered quantitative approaches to measure transendothelial electrical resistance (TER) across an endothelial monolayer (marketed by Applied Biosystems) and his lab studies the mechanisms of Ca2+ regulated signaling pathways in vascular inflammation.
Theme 2: Angiogenesis & Regeneration
Kishore Wary, PhD, Associate Professor - Theme Leader
(See description under Program Co-Directors)
Luisa DiPietro, DDS/PhD, Professor - Mentor
Dr. DiPietro explores the mechanisms of angiogenesis in relation to skin/dermal wound healing. A major focus in her laboratory is to address the question why some blood vessels regress. In this regard, DiPietro lab is exploring the mechanism by which apoptotic endothelial cells might influence fibroblast function, thereby connecting vascular overgrowth, vascular regression, EC apoptotic load, and fibrosis/scar formation.
Irena Levitan, PhD, Professor - Mentor
Dr. Levitan studies mechanisms that underlie endothelial dysfunction with focus on biophysical properties of endothelial membranes and sub-membrane cytoskeleton and shear stress mechano-transduction mechanisms. She is defining how lipids in plasma membranes, such as cholesterol and phosphoinositides, regulate ion channels. She addresses the role of membrane lipids in the generation of sphingosine-1-phosphate.
Usha Raj, PhD, Professor - Mentor
Dr. Raj is a physician scientist studying the regulation of vasomotor tone in the pulmonary circulation of the fetus and newborn and the pathogenesis of pulmonary vascular remodeling in pulmonary hypertension (PH). She has trained numerous students, pre- and post-doctoral fellows, and visiting professors. Dr. Raj served as a faculty mentor on several NIH-T32 training grants, as an external advisor to a Pulmonary training grant at Columbia University , and is a faculty mentor on two other training programs at UIC.
Jalees Rehman, PhD, Associate Professor - Mentor
Dr. Rehman is a physician scientist, his lab investigates the biology of angiogenesis and regeneration using human endothelial progenitor cells (EPCs). He also studies the role of mitochondria in human embryonic stem cells (hESCs) with the goal of enhancing their differentiation potential. He is identifying distinct subsets of EPCs, using computational approaches for transplantation and regeneration of ischemic/injured blood vessels.
Owen Tamplin, PhD, Assistant Professor - Mentor
Using zebrafish and mouse models, Dr. Tamplin studies the hematopoietic stem cell (HSC), where HSCs interact and are instructed by endothelium, focusing on dynamic interactions between HSCs, endothelial, and stromal cells. He received a K01 NIDDK Career Development Award and an American Society of Hematology Junior Faculty Scholar Award. He recently secured an NIH-RO1 from the NHLBI and is training one postdoctoral fellow and two graduate students, thus he recently became a full mentor in VBST.
Theme 3: Vascular Therapeutics
Jan Kitajewski, PhD, Sweeney Basic Science Professor - Theme Leader
(See description under Program Co-Directors)
Dawood Darbar, MD, Professor and Chief of Cardiology - Mentor
Dr. Darbar is a clinician-scientist and member of the CCVR. He has extensive experience in training postdoctoral researchers, residents, fellows, and doctoral students, having mentored 29 trainees as either primary (21) or co-mentor (8), including 12 fellows, 5 of whom have secured extramural funding including AHA and K23 awards. His training experience is exceptional. Dr. Darbar’s research is directed to translation of cardiovascular pathophysiology, with a focus on atrial fibrillation (AF), a major public health problem. After arriving at UIC, he established the University of Illinois at Chicago (UIC) AF Registry and used these resources to identify clinical, genetic and molecular subtypes of AF, laying the groundwork for a long-term vision of replacing empiric treatment for AF with mechanism-based therapy. These advances enable Dr. Darbar’s group to identify common variants that modulate responses to antiarrhythmic drugs, ablation and AV nodal drug therapies in AF.
Xiaoping Du, PhD, Professor - Mentor
The Du lab studies thrombosis, hemostasis, and vascular biology, including the study cell adhesion and signaling, including: 1) signaling mechanisms of platelet adhesion receptor, glycoprotein Ib-IX. 2) signaling mechanisms of integrins, particularly β3 integrins. 3) role of GTP binding proteins in platelet activation, and 4) role of nitric oxide-cGMP-dependent signaling pathway in regulating platelet function. Dr. Du collaborates with Dupage Medical Technology, Inc. in developing a novel anti-platelet drug that does not cause bleeding, reported in “A directional switch of integrin signaling and a new anti-thrombotic strategy (Shen et al, Nature 2013). This work is supported by NHLBI vascular Innovation/Therapeutic Advancement (VITA) contract.
Yulia Komarova, PhD, Associate Professor - Mentor
Dr. Komarova’s research focusses on the cross-talk between microtubule cytoskeleton and VE-cadherin-mediated adhesions in microvascular endothelial cells, critical for maintenance of basal endothelial barrier permeability. Using the knowledge of microtubule-mediated lung vascular permeability allowed her lab to develop novel therapeutic targets to treat inflammatory diseases. Dr. Komarova has support from the Vascular Interventions/Innovations and Therapeutic Advances (VITA) to identify promising drug candidates that have the highest potential in combating acute respiratory distress syndrome (ARDS) and to promote translational studies and clinical validation. This grant is entitled “Novel Drug-Based Therapy for Treatment of Vascular Leakage.
R. John Solaro, PhD, Professor - Mentor
Dr. Solaro’s research is on regulation of cardiac contractility by signaling to and from the sarcomere/cytoskeletal network. Acquired heart failure linked to sarcomeric proteins forms the basis of studies in the lab. Seminal studies conducted by Dr. Solaro with Merck Darmstadt demonstrated the feasibility of modifying sarcomeric function by pharmacological agents useful in acute and chronic heart failure. Collaborative interactions with pharmaceutical companies include Novartis, Merck, Sandoz, Boheringer Nippon, and Abbott, led to clinical development of sarcomere activators that are now in clinical use. Working with Cytokinetics and Trevina, Inc. his lab helped develop sarcomere activators, one of which, Omecamtiv Mecarbil, is in phase 3 clinical trials.
Beata Wolska, PhD, Professor - Mentor
Dr. Wolska’s laboratory is interested in mechanisms regulating cardiac function both in physiological and pathological conditions, focusing on the role of Ca2+ delivery to and from myofilaments, and the myofilament response to Ca2 in genetically linked cardiomyopathies (CM). Her work provided evidence indicating the hypertrophic CM (HCM) phenotype can be rescued through modifications at the level of the myofilaments or through alterations promoting Ca2+ homeostasis. The current focus of the lab is the study of Pak1 (a pleiotropic kinase) and the sphingosine-1-phosphate receptor agonist, FTY720/fingolimod, as potential anti-hypertrophic and -arrhythmic targets for HCM, and small-molecular inhibitor of myofilaments activity, developed by MyoKardia, as a target for HCM.
Terry Vanden Hoek, MD, Professor - Mentor
Dr. Vanden Hoek is the Head of Emergency Medicine and an NIH funded researcher focused on improving survival after cardiac arrest, who has a strong record of training physician scientists. He is an expert in the biology of the heart and in preventing and treating heart attack. His current NIH funded research investigates a novel therapeutic, a cell permeable PTEN inhibitory peptide (TAT-PTEN9c), and exploring whether rapid and transient PTEN inhibition with onset of action within minutes of CPR is highly protective of cardiac arrest survival. He is also a strong advocate of public health education activities and leads the Illinois Heart Rescue program, which teaches cardiopulmonary resuscitation in the community, and he helped develop CPR guidelines for the AHA.
Theme 4: Neurovascular Biology
Orly Lazarov, PhD, Professor - Theme Leader
Dr. Lazarov investigates molecular and cellular mechanisms underlying cognitive decline during aging and disease, with an emphasis on neurogenesis and hippocampal plasticity in learning and memory, and its dysfunction in Alzheimer’s disease. She studies the process of learning and memory, neurogenesis, the roles of familial Alzheimer’s disease-linked proteins, and cognitive failure and memory loss. The Lazarov lab collaborates with Dr. Rich Minshalll to examine type-2-diabetes associated damage to brain vasculature and cerebrovascular dysfunction as a contributor to cognitive decline, in collaboration with Dr. Kitajewski.
James Lee, PhD, Associate Professor - Mentor
James Lee uses biophysical engineering principles and techniques to investigate the roles of membrane and cell mechanics on oxidative stress, inflammation, amyloid-β clearance, amyloidogenesis, and alterations in blood brain barrier. Various nano-mechanical characterizations, microscopic and spectroscopic, photonic, cell manipulation techniques, including atomic force microscopy, micropipette cell manipulation and aspiration, beam splitter, and laser are employed in both his basic biomedical and clinical research projects.
Ali Djalilian, MD, Associate Professor - Mentor
Dr. Ali Djalilian is a physician scientist and ophthalmologist with an NIH/NEI funded program investigating the mechanism by which Notch1 regulates corneal epithelial barrier repair. He is also an expert on treatment of corneal neovascularization (CVN), including novel and experimental therapeutics targeting VEGF, and has studied the role of macrophages and mesenchymal stromal cells in cornea-specific angiogenesis. Thus, he has extensive experience conducting research on corneal disease prevention and treatment.
Michael Grassi, PhD, Associate Professor - Mentor
Dr. Grassi is a physician-scientist with clinical expertise in genetic aspects of diabetic retinopathy. In his research he uses cell-based models of retinal disease in genomic and chemical high throughput studies to identify key pathways and novel therapeutic targets for vascular retinopathies. Thus, Dr. Grassi’s clinical background in treating patients with ocular vascular disease, his translational research focus, and a demonstrated ability in participating on interdisciplinary scientific teams attest to his strength as a VBST member.
Jeffrey A. Loeb MD/PhD, Professor - Mentor
Dr. Loeb is the Head of the Department of Neurology & Rehabilitation. Dr. Loeb has been the recipient of research and teaching awards, including one of the Best Doctors in America 2007-2013. He is a member of the American Academy of Neurology, American Epilepsy Society, Society for Neuroscience, and American Neurological Association. Dr. Loeb’s research focuses on neuregulins in development and has been actively translating these basic discoveries into novel therapeutics for neurological disorders ranging from multiple sclerosis, ALS, epilepsy, and brain vascular malformations. He is the recipient of NIH, NSF, and many private foundations grants and continues to excel in the arena of translational medicine.
Mark Rosenblatt, MD, Professor - Mentor
Dr. Rosenblatt, Head of the Department of Ophthalmology & Visual Sciences, is a clinician scientist with interest in corneal regenerative medicine who is developing novel regenerative treatments for ocular surface and corneal disease, including programs in ocular surface tissue engineering, corneal epithelial stem cells, and the repair of corneal nerves and sensation after injury. Dr. Rosenblatt has embarked upon an ocular surface tissue engineering project which uses surface modified silk films to optimize outcomes of ocular surface reconstruction. He translates these findings to clinically relevant models of corneal disease as a prelude to treating patients with potentially blinding corneal disease.
Leon Tai, PhD, Assistant Professor - Mentor
Dr. Tai’s research examines the blood-nerve, blood-spinal cord and blood-brain barrier. These barrier interfaces function in homeostasis and neuronal activity, through preventing the uptake of unwanted molecules, removing waste products, supplying essential nutrients and signaling molecules, and modulating inflammation. His goal is to identify and therapeutically target mechanistic pathways that underlie barrier and neuronal dysfunction in aging and neurodegenerative disorders, particularly Alzheimer's disease, chronic pain, ALS and metabolic dysfunction.
The VBST-TP is funded by training grant (T32 HL144459) from the National, Heart, Lung, and Blood Institute (NHLBI).