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Photo of Kazlauskas, Andrius

Andrius Kazlauskas, PhD

Professor

Department of Physiology and Biophysics

Department of Ophthalmology and Visual Science

Contact

Building & Room:

LIERI L221

Office Phone:

312-996-6707

Lab

Building & Room:

LIERI L245

Email:

ak20@uic.edu

Related Sites:

About Heading link

Andrius Kazlauskas 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 how receptor tyrosine kinase signaling governs 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. Hoffmann-La Roche in Basel, Switzerland. He joined the faculty in both the Department of Physiology and Biophysics, and Ophthalmology and Visual Sciences in 2017.

Research/Teaching Heading link

The overall goal of the Kazlauskas Lab is to elucidate the effect of diabetes (DM) on the retinal vasculature.  The resulting conceptual advances will guide development of new therapeutic approaches to prevent patients with DM from developing diabetic retinopathy (DR), and improve current options to treat patients who have already developed DR.  Several areas of research in the Kazlauskas Lab are summarized below.

Resilience to diabetic retinopathy (RDR)

Diabetic retinopathy (DR), the most common microvascular complication of diabetes (DM), is the leading cause of blindness in working-age individuals. Fortunately, manifestation of DR is not coincident with the onset of DM.  It takes over two decades for patients to develop sight-threatening DR.  While the mechanism of resilience to diabetic retinopathy (RDR) is unknown, it is likely to involve suppression of DM-driven events that damage the retina.  For instance, DM damages the retina and causes DR by accelerating senescence of the retinal vasculature.  Since mitochondrial dysfunction drives senescence, we posit that RDR involves enforcing mitochondrial functionality in the face of DM.  Our recent discoveries support this hypothesis.  In an in vitro model, increased clearance of dysfunctional mitochondria (mitophagy) is associated with acquisition of RDR and required for cells to retain key features of RDR.  Furthermore, mitophagy increases in the retinal vessels of mice that have acquired RDR.  As mice lose RDR mitophagy declines.  These in vitro and in vivo data support our working hypothesis that RDR protects from DM-driven senescence by increasing mitophagy.  Ongoing studies are designed to further test this hypothesis and develop approaches to prevent the loss of RDR, which will indefinitely delay the onset of DR.

A bioinformatics-based approach to identify new therapeutic approaches and targets for PDR

The therapeutic efficacy of anti-VEGF (vascular endothelial growth factor) in patients with diabetic retinopathy (DR) demonstrates the central role of VEGF in the pathogenesis of this vascular disease.  Not all patients experience adequate benefit from anti-VEGF, and even those who do can suffer detrimental side effects of this therapeutic option.  The overall goal of this project is to identify new therapeutic approaches and targets for patients who have developed vision threatening forms of diabetic retinopathy such as proliferative diabetic retinopathy (PDR) diabetic macular edema (DME).

The standard of care for patients that have advanced to end-stage PDR is surgery to remove pathological blood vessels.  The availability of such clinical specimens constitutes an opportunity to investigate the transcriptional profile within pathological blood vessels in patients.  We embraced this opportunity by assembling a team to consent patients, collect surgical specimens, isolate the CD31+ cells from the pathological vessels, and determine their gene expression profile using RNA sequencing.  To date, we generated high-quality PDR patient endothelial transcriptomes from the CD31+ cells from ten end-stage PDR patients.  This project involves mining these transcriptomes to define the molecular signature of PDR within the endothelium. The molecular signature will then be used to establish novel classes of therapeutic targets, identify alternative targets for anti-VEGF therapy, and generate pre-clinical data for the best targets.

Selected Publications

Li Y, Yan Z, Chaudhry K, Kazlauskas A. Renin-Angiotensin-Aldosterone System (RAAS) Is One of the Effectors by Which Vascular Endothelial Growth Factor (VEGF)/anti-VEGF Controls the Endothelial Cell Barrier. Am J Pathol. 2020 Sep;190(9):1971-1981.

Serikbaeva A, Li Y, Ganesh B, Zelkha R, Kazlauskas A. Hyperglycemia Promotes Mitophagy and Thereby Mitigates Hyperglycemia-Induced Damage. Am J Pathol. 2022 Dec;192(12):1779-1794. doi: 10.1016/j.ajpath.2022.08.004.

McCann M, Li Y, Baccouche B, Kazlauskas A. VEGF Induces Expression of Genes That Either Promote or Limit Relaxation of the Retinal Endothelial Barrier.  Int J Mol Sci 2023 Mar 29;24(7):6402. doi: 10.3390/ijms24076402

Li Y, Baccouche B, Del-Risco N, Park J, Song A, McAnany J, Kazlauskas A. The slow progression of diabetic retinopathy is associated with transient protection of retinal vessels from death.  Int J Mol Sci. 2023 June 29;24(10):10869.

Serikbaeva A, Li Y, Ma S, Yi D, Kazlauskas A. Resilience to diabetic retinopathy. Prog Retin Eye Res. 2024 May 11;101:101271. doi: 10.1016/j.preteyeres.2024.101271.