The main interest in my laboratory revolves around the elucidation principles of eye physiology at the molecular level, discerning mechanisms of their regulation, and pathophysiological consequences of their malfunction for ocular health. Based on this knowledge, our goal is to design, test, and validate, new therapeutic strategies against prevalent eye disorders, including age-related retinal degeneration or dry eye syndrome.
Over the last several years, we have performed productive research focused on understanding biochemical principles governing lipid metabolism in the eye. We have contributed substantially to understanding the mechanistic principles of ocular retinoid metabolism, regeneration of the visual chromophore, and the production of unique lipids involved in forming the protective tear film. Based on our education and training, we have successfully combined methods of organic and protein chemistry, structural biology, and modern instrumental analytical techniques with in vivo studies to elucidate fundamental processes responsible for maintaining eye health as well as predicted pathophysiological consequences of their malfunction. Building upon these basic discoveries, we developed and tested novel pharmacological strategies for the treatment of progressive retinal diseases and dry eye syndrome. This experience encouraged us to look for new promising pharmacological targets and spearhead innovative projects that aim at developing methods of preventing and preserving ocular health.
I research the physiology of vision at the molecular level and lipid metabolism and homeostasis in the eye. I also design therapeutic strategies against age-related retinal degeneration and dry eye syndrome.
Discovery of Nonretinoid Inhibitors of CRBP1: Structural and Dynamic Insights for Ligand-Binding Mechanisms. Plau J, Morgan CE, Fedorov Y, Banerjee S, Adams DJ, Blaner WS, Yu EW, Golczak M. ACS Chem Biol. 2023 Oct 20;18(10):2309-2323. doi: 10.1021/acschembio.3c00402. Epub 2023 Sep 15. PMCID: PMC10591915.
Molecular basis for the interaction of cellular retinol binding protein 2 (CRBP2) with nonretinoid ligands. Silvaroli JA, Plau J, Adams CH, Banerjee S, Widjaja-Adhi MAK, Blaner WS, Golczak M. J Lipid Res. 2021;62:100054. doi: 10.1016/j.jlr.2021.100054. Epub 2021 Feb 23. PMID:33631211. PMCID: PMC8010219.
Deficiency in Acyl-CoA:Wax Alcohol Acyltransferase 2 causes evaporative dry eye disease by abolishing biosynthesis of wax esters. Widjaja-Adhi MAK, Silvaroli JA, Chelstowska S, Trischman T, Bederman I, Sayegh R, Golczak M. FASEB J. 2020 Oct;34(10):13792-13808. doi: 10.1096/fj.202001191R. Epub 2020 Aug 26. PMID: 32851726. PMCID: PMC7722226.
Abnormal Cannabidiol Modulates Vitamin A Metabolism by Acting as a Competitive Inhibitor of CRBP1. Silvaroli JA, Widjaja-Adhi MAK, Trischman T, Chelstowska S, Horwitz S, Banerjee S, Kiser PD, Blaner WS, Golczak M. ACS Chem Biol. 2019 Mar 15;14(3):434-448. doi: 10.1021/acschembio.8b01070. Epub 2019 Feb 18. PMID: 30721022. PMCID: PMC6420351.
LRAT-specific domain facilitates vitamin A metabolism by domain swapping in HRASLS3. Golczak M, Sears AE, Kiser PD, Palczewski K. Nat Chem Biol. 2015 Jan;11(1):26-32. doi: 10.1038/nchembio.1687. Epub 2014 Nov 10. PMID: 25383759. PMCID: PMC4270908