Xingjun Fan, PhD

Xingjun Fan, Ph.D.

Professor
Department of Cellular Biology and Anatomy
James and Jean Culver Vision Discovery Institute
Carl T. Sanders Research & Education Building, CB2707
Office: 706-721-2019
Laboratory: 706-721-4979
envelope-o icon xfan@augusta.edu


Laboratory members:

Zongbo Wei, PhD, Assistant Research Scientist
Kailin Li, PhD, Postdoctoral Fellow
Kazi Rafsan Radeen, Graduate Student

We are recruiting talented postdoctoral fellows. Please send your CV to xfan@augusta.edu

Research Interests

We are a research group specializing in aging and age-related diseases. Our work focuses on the role of reactive oxygen species (ROS) in aging, particularly in relation to glutathione homeostasis. We investigate how ROS contributes to age-related conditions, including age-related nuclear cataract (ARNC) and Alzheimer’s disease (AD). Additionally, we use in vitro and in vivo model systems to study posterior capsule opacification (PCO), a common complication following cataract surgery.

Current Research

  • Mechanisms and consequences of impaired glutathione homeostasis in the aging lens.

Age-related cataracts (ARC) are the leading cause of blindness worldwide, with oxidation identified as a major risk factor in their formation. Glutathione (GSH), the most abundant antioxidant in the lens, decreases progressively with age, especially in the lens nucleus. Typically found at millimolar concentrations in most cell types, GSH is the primary non-enzymatic antioxidant in tissues, cells, and cellular compartments. Beyond serving as an intracellular redox regulator, GSH also influences gene expression, epigenetics, and amino acid checkpoints. Our lab focuses on understanding how GSH levels decline during lens aging and exploring its roles in lens biology, biochemistry, and transparency.

  • Lens epithelial cell fibrosis and posterior capsule opacification (PCO)

Cataract surgery is currently the only treatment for cataract-related vision impairment, with approximately 4 million procedures performed annually in the U.S. and 26 million worldwide. Posterior capsule opacification (PCO), often referred to as secondary cataract, is the most common complication following cataract surgery. PCO incidence rates vary depending on intraocular lens (IOL) quality and surgeon experience, typically ranging from 4-45% within 5 years for adults, and reaching nearly 100% in children within 2 years post-surgery. While the mechanisms behind PCO formation are largely unknown, it is believed that PCO initiation and progression share a similar pathogenesis with tissue fibrosis. Our research aims to investigate the mechanisms and pathogenesis of LEC fibrotic responses after cataract surgery to better understand the initiation and progression of PCO.

  • The pathogenic role of disrupted glutathione homeostasis in amyloid beta pathology

Alzheimer’s disease (AD) is marked by extracellular beta-amyloid (Aβ) deposition in senile plaques and intracellular neurofibrillary tangles. Aβ peptides (both 40- and 42-mer) are produced from the amyloid precursor protein (APP) via the amyloidogenic pathway. Strong evidence suggests that reactive oxygen species (ROS) play a pivotal role in the onset and progression of AD, aligning with aging as the primary risk factor for AD pathogenesis, given that ROS are a key hallmark of aging. Our research is focused on testing the hypothesis that disrupted brain GSH homeostasis in aging promotes the amyloidogenic pathway and neurodegeneration.

Recent Publications:

  1. Zongbo Wei, Caili Hao, Kazi Radeen, Zheng Hao, Kavitha Kettimuthu, Kristal Maner-Smith, Shinya Toyokuni, Xingjun Fan. Proceedings of the National Academy of Sciences (PNAS), 2024, 121 (48): e2407842121
  2. Zongbo Wei, Caili Hao, Kazi Radeen, Ramkumar Srinivasagan, Jian-kang Chen, Shruti Sharma. Meghan McGee-Lawrence, Mark Hamrick, Vincent Monnier, Xingjun Fan. Prevention of Age-related truncation of gamma glutamylcysteine ligase catalytic subunit (GCLC) delays cataract formation. Science Advances. 2024, 10(17):eadl1088.
  3. Sidra Islam, Michael Do, Brett S Frank, Grant L Hom, Samuel Wheeler, Hisashi Fujioka, Benlian Wang, Geeta Minocha, David R Sell, Xingjun Fan, Kirsten J Lampi, Vincent M Monnier, α-Crystallin chaperone mimetic drugs inhibit lens γ-crystallin aggregation: potential role for cataract prevention. J Biol Chem. 2022 Aug 26; 102417.
  4. Wei Z, Hao C, Srinivasagan R, Wu H, Chen JK, Fan X. Mitotic Activation Around Wound Edges and Epithelialization Repair in UVB-Induced Capsular Cataracts. Invest Ophthalmol Vis Sci. 2021 Dec 1;62(15):29. 
  5. Wei Z, Hao C, Huangfu J, Srinivasagan R, Zhang X, Fan X. Aging lens epithelium is susceptible to ferroptosis. Free Rad Bio Med. 2021, May 1; 167:94-108.
  6. Huangfu J, Hao C, Wei Z, Wormstone IM, Yan H, Fan X. Cellular FLICE-like inhibitory protein (cFLIP) critically maintains apoptotic resistance in human lens epithelial cells. Cell Death and Disease, 2021, Apr 9; 12(4):386.
  7. Fan X*, Sell DR, Hao C, Liu S, Wang B, Wesson DW, Siedlak S, Zhu X, Kavanagh TJ, Harrison FE, Monnier VM*. Vitamin C is a source of oxaldehyde and glycative stress in age-related cataract and neurodegenerative diseases. Aging Cell. 2020 Jul; 19(7): e13176.
  8. Whitson JA, Wilmarth PA, Klimek J, Monnier VM, David L, Fan X. Proteomic analysis of the glutathione-deficient LEGSKO mouse lens reveals activation of EMT signaling, loss of lens specific markers, and changes in stress response proteins.Free Rad Biol Med. 2017 Dec;113:84-96. doi: 10.1016/j.freeradbiomed.2017.09.019. Epub 2017 Sep 22. PubMed PMID: 28951044; PubMed Central PMCID: PMC5699945.
  9. Wei Z, Caty J, Whitson J, Zhang AD, Srinivasagan R, Kavanagh TJ, Yan H, Fan X. Reduced Glutathione Level Promotes Epithelial-Mesenchymal Transition in Lens Epithelial Cells via a Wnt/β-Catenin-Mediated Pathway: Relevance for Cataract Therapy.Am J Pathol. 2017 Nov;187(11):2399-2412. doi: 10.1016/j.ajpath.2017.07.018. Epub 2017 Aug 19. PubMed PMID: 28827139.
  10. Whitson JA, Zhang X, Medvedovic M, Chen J, Wei Z, Monnier VM, Fan X. Transcriptome of the GSH-Depleted Lens Reveals Changes in Detoxification and EMT Signaling Genes, Transport Systems, and Lipid Homeostasis.Invest Ophthalmol Vis Sci. 2017 May 1;58(5):2666-2684. doi: 10.1167/iovs.16-21398. PubMed PMID: 28525556; PubMed Central PMCID: PMC5444549.

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