Sarah X. Zhang M.D.

Sarah Zhang

Sarah X. Zhang


Department of Ophthalmology

Jacobs School of Medicine & Biomedical Sciences

Specialty/Research Focus

Apoptosis and cell death; Gene Expression; Gene Therapy; Metabolism; Molecular and Cellular Biology; Molecular Basis of Disease; Neurobiology; Ophthalmology; Protein Folding; Retina; Signal Transduction; Vision science

Contact Information
Department of Ophthalmology
Ross Eye Institute
JSMBS, Rm 4116
Buffalo, New York 14203
Phone: 716-645-1808

Professional Summary:

The research in my lab has focused on two main areas: 1). molecular mechanisms of inflammation, angiogenesis, vascular and neuronal degeneration in retinal diseases; 2). potential roles of angiogenic inhibitors in obesity, insulin resistance and diabetes. The first line of research centers on gene regulation and signal transduction pathways underlying the neurovascular injury in diabetic retinopathy, retinopathy of prematurity and age-related macular degeneration. In recent years, we are focusing our efforts on the function and mechanism of the UPR signaling in normal and diseased retinal cells. The latter one combines basic and clinical research to study biomarkers and mechanism of type 2 diabetes.

1. ER stress and the UPR signaling in retinal neurovascular injury and diabetic retinopathy. The endoplasmic reticulum (ER) is the primary site for protein synthesis and folding. Failure of this machinery to fold newly synthesized proteins presents unique dangers to the cell and is termed “ER stress.” In response to the stress, cells have evolved an intricate set of signaling pathways named the unfolded protein response (UPR) to restore the ER homeostasis. In addition, the UPR is known to regulates many genes involved in important physiological processes to modulate cell activity and cell fate. The project in my laboratory is aimed to understand the role of ER stress and the UPR in retinal vascular endothelial cell dysfunction and neuronal degeneration in diabetic retinopathy. Our previous work has implicated several key UPR branches such as IRE-XBP1 and ATF4-CHOP in retinal inflammation and vasculopathy in diabetes. Currently, we are employing integrated genetic tools and animal models to study the function of UPR genes in the retina and to dicepher the molecular links between the UPR signaling and inflammatory pathways in retinal cells. Findings from these studies are anticipated to identify novel therapeutic targets and develop new treatments for diabetic retinopathy.
2. Mechanisms and potential therapies for RPE death in age-related macular degeneration. The retinal pigment epithelium (RPE) plays an essential role in maintaining the normal structure and function of photoreceptors. RPE dysfunction and cell death is a hallmark pathological characteristic of age-related macular degeneration (AMD), a disease that accounts for the majority of vision impairment in the elderly. Using transgenic mouse models, we discovered that the transcription factor XBP1 is a critical regulator of oxidative stress and cell survival in RPE cells. Genetic depletion or inhibition of XBP1 sensitizes the RPE to stress resulting in cell death. Our ongoing studies focus on identifying the target genes of XBP1 in RPE cells through which the protein regulates cell survival. We are also investigating if these proteins could offer potential salutary effects to protect RPE cells from oxidative injury and degeneration in disease conditions such as AMD.
3. Roles and mechanisms of angiogenic/anti-angiogenic factors in obesity, insulin resistance and diabetes. Obesity, insulin resistance and Type 2 diabetes are clustered as the most important metabolic disorders, substantially increasing morbidity and impairing quality of life. Excess body fat mass, particularly visceral fat, leads to dysregulation of adipokines (proteins secreted from fat cells), resulting in higher risk of cardiovascular diseases. Our recent findings indicate that angiogenic/anti-angiogenic factors are associated with obesity, diabetes and diabetic complications. For example, pigment epithelium-derived factor (PEDF), a major angiogenic inhibitor, is an active player in adipose tissue formation, insulin resistance and vascular function. In the future, we hope to futher understand the functions and mechanisms of these proteins in lipid metabolism and adiposity. In collaboration with a number of clinical investigators, we are exploring the physiological application of these factors as novel biomarkers and therapeutic targets in the diagnosis and treatment of diabetes, metabolic disorders and peripheral vascular diseases.

Education and Training:

  • Fellowship, Cell biology/Medicine, University of Oklahoma Health Sciences Center (2005)
  • Fellowship, Ophthalmology/Biochemistry, Medicial University of South Carolina (2002)
  • MS, Ophthalmology, Sun Yat-sen University (2000)
  • Fellowship, Retina, Zhongshan Ophthalmic Center, Sun Yat-sen University (1997)
  • Residency, Zhongshan Ophthalmic Center, Sun Yat-sen University (1995)
  • MD, Medicine, Sun Yat-sen University of Medical Science (1990)


  • Professor, Ophthalmology, University at Buffalo Jacobs School of Medicine and Biomedical Sciences (2018-present)
  • Associate Professor, Ophthalmology, University at Buffalo Jacobs School of Medicine & Biomedical Sciences (2012–2018)
  • Adjunct Associate Professor, Ophthalmology, University of Oklahoma Health Sciences Center (2012)
  • Adjunct Associate Professor, Physiology, University of Oklahoma Health Sciences Center (2012)
  • Associate Professor, Medicine, University of Oklahoma Health Sciences Center (2012)
  • Adjunct Assistant Professor, Physiology, University of Oklahoma Health Sciences Center (2010–2012)
  • Assistant Professor, Medicine, University of Oklahoma Health Sciences Center (2006–2012)

Awards and Honors:

  • SUNY Chancellor's Award for Excellence in Scholarship and Creative Activities (2023)
  • ARVO Gold Fellow (2022)
  • Exceptional Investigative Ophthalmology & Visual Science Review (2022)
  • ARVO Silver fellow (2021)
  • UB Exceptional Scholars – Sustained Achievement (2021)
  • Women's leadership program mentor (2021)
  • Buffalo Blue Sky coins (2021)
  • Young Investigator Travel Award, American Diabetes Association (2011)
  • Young Investigator Award, the XIV International Symposium on Retinal Degene (2010)
  • Dr. William Talley Diabetes Research Award (2010)
  • Provost’s Research Award (2009)
  • Travel Fellowship award, International society of eye research (ISER) (2008)
  • COMAA Research Scholar (2007)
  • ARVO Travel Fellowship Award (2005)
  • New Investigator Award (2001)

Research Expertise:

  • Angiogenesis and vascular pathophysiology: Regulation of angiogenesis and retinal vasculature, role of angiogenic inhibitors, VEGF signaling,vascular permeability, endothelial dysfunction, tight junction and adhesion juntion, mechanisms of retinopathy of prematurity.
  • Biomarkers and mechanisms of diabetic complications: Role of angiogenic inhibitors as biomarkers in diabetes, diabetic complications and metabolic disorders, role of angiogenic inhibitors in obesity, insulin resistance and type 2 diabetes.
  • Endoplasmic reticulum stress, protein folding and unfolded protein response: Role of ER stress in retinal diseases and signaling pathways of unfolded protein response in retinal angiogenesis, inflammation and neurodegeneration
  • Molecular mechanisms of diabetic retinopathy: Regulation of blood-retinal barrier, mechanisms of vascular degeneration, retinal ischemia and retinal neovascularization; signaling pathways of inflammatory response in retinal cells and mechanisms and role of inflammation in diabetic retinopathy.
  • Retinal neurodegeneration: Molecular mechanisms of age-related macular degeneration, RPE cell death and dysfunction, autophagy and new drug target for neuroprotection.

Grants and Sponsored Research:

  • September 2010–February 2025
    ER stress and diabetic retinopathy
    NIH, NEI
    Role: Principal Investigator
  • February 2020–January 2025
    Molecular Mechanisms of Severe Diabetic Retinopathy
    Role: Principal Investigator
  • July 2019–June 2022
    Targeting Neuroinflammation for RGC Protection in Glaucoma
    BrightFocus Foundation
    Role: Principal Investigator
  • September 2018–August 2020
    ER stress and diabetic retinopathy (Admin Supplements)
    NIH, NEI
    Role: Principal Investigator
  • December 2014–December 2016
    Study of the ER-mitochondria interface as a new target in diabetic retinopathy
    NIH, NEI
    Role: Principal Investigator
  • September 2015–August 2016
    ER stress and diabetic retinopathy (Admin Supplements)
    Role: Principal Investigator
  • July 2011–June 2014
    Molecular mechanism for diabetic retinopathy
    American Diabetes Association
    Role: Principal Investigator
  • November 2010–October 2013
    Targeting Histone Deacetylase in Diabetic Retinopathy
    Role: Principal Investigator
  • April 2010–July 2012
    Translational regulation of anti-oxidant genes in the RPE
    American Health Assistance Foundation
    Role: Principal Investigator
  • July 2009–June 2012
    Lipoproteins and PEDF in the Vascular Complications of Diabetes
    Role: Co-Investigator
  • September 2009–August 2010
    A novel regulator of pro-inflammatory genes in diabetic retinopathy
    Role: Principal Investigator
  • September 2007–June 2010
    Mentoring Diabetes Research in Oklahoma
    Role: Principal Investigator
See all (2 more)

Journal Articles:

See all (63 more)


  • "“Endoplasmic Reticulum Stress: the Good, the Bad, and the Ugly”" Cornerstone Seminar Series, School of Optometry, University of Alabama at Birmingham (2023)
  • "Development of Novel Therapeutics for Age-related Macular Degeneration" Owen Locke Foundation (2023)
  • "“Transcriptional Regulation of Stress Response in Retinal Neurons”" Annual Ophthalmology Symposium (2023)
  • "“OPG-RANKL-RANK Pathway in Diabetic Retinopathy”" Ophthalmology Grand Rounds (2023)
  • "“ER Stress Signaling in Retinal Aging and Disease”" Oral Biology Seminar, School of Dental Medicine, University at Buffalo, Buffalo (2023)
  • "“Endothelial NADPH Oxidase 4 and Redox Signaling in Angiogenesis and Diabetic Retinopathy”" The Medical Scientist Training Program Seminar (2023)
  • "“ER-associated Stress Signaling Pathway in Diabetic Retinopathy”" XXVth Biennial Meeting of the International Society of Eye Research (2023)
  • "Overexpression of NADPH Oxidase 4 Induces Endothelial Senescence by Impairing Mitochondrial Biogenesis and ATF4 Activation" ARVO 2022 (2022)
  • "Redox regulation of endothelial function in retinal disease" Joint Vision Research Lab Group Meetings (2021)
  • "Activation of NADPH oxidase 4 Promotes Angiogenic Progenitor Dysfunction in Diabetic Retinopathy" ARVO annual meeting 2021 (2021)
  • "Impaired UPRER is Associated with Chronic Endoplasmic Reticulum Stress in Aging Endothelial Cells" ARVO annual meeting 2021 (2021)
  • "Redox Regulation of Endothelial Progenitor Function and Senescence in the Aging Retina" ARVO annual meeting 2021 (2021)
  • "The Neuroprotective Action of p58IPK Does not Involve Macrophages in Retinal Disease Models" ARVO annual meeting 2021 (2021)
  • "Measurement of energy metabolism in dissociated mouse retinal rod photoreceptors" ARVO 2022
See all (4 more)

Service Activities:

  • Frontiers in Cell and Developmental Biology; Review Editor (2023–present)
  • NEI Special Emphasis Panel ZEY1-VSN(03) (2023)
  • Research Grants Council (RGC), Hong Kong (2023–present)
  • Fighting Blindness Ireland; Reviewer (2023–present)
  • Award Committee, Association for Research in Vision and Ophthalmology (ARVO); Member (2023–2027)
  • Modulator, Session “Diabetic Retinopathy (clinical studies)”, ARVO meeting; Modulator (2023)
  • Member, Associate Professor/Professor Search Committee (2023)
  • Chair, Assistant Professor Search Committee (2023)
  • Member, MD/PhD Admission Committee (2022–present)
  • Judge, Annual CSTEP research symposium (2022–present)
  • Frontiers in Genetics (section of Genetics of Aging); Associate Editor (2022–present)
  • NIH ZRG1 EMNR-B (02) Special Emphasis Panel; Member (2021)
  • NIH ZRG1 ETTN-M (12) Special Emphasis Panel; Member (2021)
  • ; Member, 2021 Peer Reviewed Medical Research Program (PRMRP) (2021)
  • Special Issue "Molecular Mechanisms of Angiogenesis and Inflammation in Retinal Diseases” in the journal Cells; Guest Editor (2021–present)
  • ; Participant, Ride for Roswell (2021–present)
  • ; Mentor, Women’s Leadership Program, ARVO (2021–2022)
  • VA ZRD1 ENDA-L 01 Endocrinology-A (ENDA); Member (2021)
  • NEI Individual Mentored Career Awards study section ZEY1 VSN 03; Member (2021)
  • Mentor, Collegiate Science & Technology Entry Program (CSTEP) Program (2021–present)
  • Cells; Editorial Board Member (2021–present)
  • ; Member, Women Professors of Ophthalmology, AUPO (2021–present)
  • ; Chair, Continuing Medical Education Committee (CME), ARVO (2020–2022)
  • Member and Chair (2022-2023), Promotion and Tenure Committee, JSMBS (2020–2023)
  • Departmental Alternative Representative, Faculty council (2019–present)
  • Organizer/Moderator, Joint Vision Research Lab Group meetings series (2019–present)
  • Organizer, Distinguished lectures in Vision Science series (2019–present)
  • Member, IRB Review Committee, Department of Ophthalmology/Ross eye Institute (2019–present)
  • Neuroscience Graduate Program, Admissions Committee; Member (2019–present)
  • NEI; NIH DPVS;; Panel Member (2016–2020)
  • Institutional Biosafety Committee; Member (2016–2020)
  • ; Judge, Neuroscience Day (2016–present)
  • Scientific Review Committee, Department of Ophthalmology/Ross eye Institute; Member (2016–present)
  • Faculty Council; Member (2016–present)
  • Facilities Planning & Budget; Member (2016–present)
  • Member, Promotions and Tenure Committee, Department of Ophthalmology; Ophthalmology/Ross eye Institute (2016–present)
  • Journal of Eye Disease; Editorial Board member (2015–present)
  • Fight For Sight;; Grant Reviewer (2014–present)
  • Diabetes UK; Diabetes UK Research Grant;; Grant Reviewer (2014–present)
  • Mentor; CLIMB PRO and SURF program, SUNY (2014–present)
  • Resident Interview, participated 2014, 2015, 2016, 2017, 2018, and 2021 (2013–present)
  • Mentor; Center for Undergraduate Research & Creative Activities (CURCA) (2013–present)
  • American Diabetes Association; American Diabetes Association Grant Review Panel;; Panel Member (2013–present)
  • Publications Committee (PUBS), Association for Research in Vision and Ophthalmology (ARVO); Member (2012–2015)
  • Journal of Diabetes Research and Clinical Metabolism; Editorial Board member (2012–present)
  • Medical Research Council (UK); Reviewer (2012–present)
  • International Journal of Biochemistry and Molecular Biology; Editorial Board member (2011–present)
  • Journal of Diabetes and Metabolism; Editorial Board member (2010–present)
  • Cell Diff Death, Communcations Biology, Exp Eye Res, IOVS, EMBO-EMM, EMBO, Pharmacological Research, Diabetes, Diabetologia, Sci Rep, Nat Commun, Prog Retina Eye Res, FASEB J, etc; Review for multiple journals (2003–present)

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Contact Information

Department of Ophthalmology
Ross Eye Institute
JSMBS, Rm 4116
Buffalo, New York 14203
Phone: 716-645-1808