Ongoing Research in the Kazlauskas Lab
After a multi-decade period in academia, Dr. Kazlauskas closed his research lab at the Schepens Eye Research Institute/Harvard Medical School to transition to F. Hofmann-La Roche in Basel, Switzerland, where he joined the Department of Ophthalmology and contributed to the drug development process. In 2017 Dr. Kazlauskas re-started academic research focused on preventing patients with diabetes from developing diabetic retinopathy, and improving current approaches to treat this condition.
Pharmacosignaling in PDR
The goal of this project is to elucidate the molecular basis of anti-VEGF’s benefit in patients with proliferative diabetic retinopathy (PDR). The clinical observation that neutralizing VEGF reduces retinal edema and improves visual acuity in most patients, motivates us to investigate the underlying mechanism of this phenomenon. To this end we are first identifying changes in gene expression and signaling events that are associated with anti-VEGF treatment in patients. The next step is to determine which of these changes are responsible for the therapeutic benefit. These discoveries will guide the design of alternative therapies for patients that do not fully benefit from existing anti-VEGFs. Furthermore, we will develop biomarkers that will improve our ability to diagnose susceptibility, monitor both disease progression, and the efficacy of intervention.
Preventing diabetic retinopathy
The delay in development of diabetic retinopathy (DR) in most patients with diabetes (DM) indicates the existence of an endogenous system that protects the retina from DM-induced damage (Fig 1). We posit that failure of this system is a prerequisite for DR, and its persistence underlies the extended delay (> 50 years) of DR in medalists, which is unrelated to glycemic control. The nature of the system that protects from DR has not been investigated at least in part due to the paucity of experimental systems that model it. Identifying the molecular mediators of this endogenous system along with their mechanism of action will enable development of novel approaches to prevent DR, which would be of substantial benefit in light of the ineffectiveness of currently available prophylactic options.
We developed novel in vitro and ex vivo assays to model the endogenous system that protects the retinal vasculature from DM-driven damage. Using these assays we discovered that prolonged exposure of primary human retinal endothelial cells (HRECs) to hyperglycemia (HG) triggers adaptation, which results in resistance to the damaging effects of HG. Furthermore, the underlying mechanism of adaption involves a shift in metabolism and improved mitochondrial functionality. Importantly, key features of this in vitro phenomenon appear to occur in the retinal vessels of mice. We are continuing to investigate the endogenous system that protects the retinal vasculature from DM-driven damage.
Our lab consists of a principal investigator and a highly motivated and enthusiastic research team: three postdoctoral fellows, a graduate student, a research technician, a clinical research coordinator, an intern, and four medical students.
ANDRIUS KAZLAUSKAS, PHD
Andrius Kazlauskas, PhD is a vascular biologist seeking to understand the pathogenesis of blinding eye diseases. He received his PhD in Chemistry from Cleveland State University, and was a postdoc at the Fred Hutchinson Cancer Research Center in Seattle, where he investigated signaling pathways by which receptor tyrosine kinase initiated cell proliferation in the context of cancer. As a faculty member at the University of Colorado and then Harvard Medical School, Dr. Kazlauskas interrogated signaling events underlying pathogenesis of cancer and retinal disorders such as proliferative diabetic retinopathy (PDR), age-related macular degeneration and proliferative vitreoretinopathy. Dr. Kazlauskas obtained first-hand experience and insight in translational research while working in the Ophthalmology Department of F. Hoffman-La Roche in Basel, Switzerland. He returned to academia to elucidate signaling networks responsible for pathogenesis, and how therapeutic intervention rewires them.
Lina Lietuvninkas, BS
Lina completed her BS degree in Biology from the University of Oklahoma. She is currently assisting in research on the effects of Activin on VEGF-induced permeability in hyperglycemic endothelial cells. In the future she would like to attend graduate school and continue work in research.
Basma Baccouche, PHD
Basma completed her PhD at Carthage University, Tunisia. She is evaluating changes in gene expression and their contribution to VEGF and anti-VEGF control of permeability in high glucose cultured human retinal endothelial cells.
Maximilian McCann, PHD
Max completed his PhD at the University of Illinois at Chicago. His research focuses on the processes involved in the pathological opening of blood vessels in the retina and how anti-VEGF therapy reverses this in patients.
Janani Rajasekar, PhD
Janani Rajasekar completed her PhD in Biological Sciences from CSIR-CFTRI, India. She is currently working on identifying the gene expression patterns in retina to understand the role of cellular adaption involved in delayed onset of diabetic retinopathy.
Yanliang Li, MD, PHD
Yanliang earned her PhD degree in a joint program between UIC and Fudan Uvinersity, China in 2021. She is investigating the mechanism that delays the onset of retinopathy in diabetic mice.
Helena Chang Zin Ying
Helena obtained her bachelor’s degree in Microbiology at UC Davis and is currently a Ph.D. student in the GEMS program at UIC. After earning her BS, Helena worked as a research assistant in Dr. Sungjin Kim’s lab on adaptive NK cells for three years. Due to the COVID-19 pandemic, she had the opportunity to work part-time at the COVID lab, processing saliva samples with RT-PCR. Helena’s research focus in the Kazlauskas lab is to understand the mechanism used by HRECs to resist oxidative stress in high glucose.
Norma Del Risco
Norma completed her BA in Biochemistry at Judson University. She is currently working towards understanding the oxidative stress induced by proliferative diabetic retinopathy.
Amy Song, BA
Amy completed her BA in neuroscience and global health at Northwestern University. Prior to medical school, she worked as a technician at an ophthalmology clinic. She is currently investigating the role of hyperglycemia-induced mitochondrial adaptation in the delayed onset of diabetic retinopathy, specifically, differentiating between endothelial cell and pericyte responses.
Brandon Cho, BA
University of Illinois at Chicago
Lions Illinois Eye Research Institute
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