Reaching Others University at Buffalo - The State University of New York
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Sarah                          Zhang

Sarah X. Zhang MD

Department of Ophthalmology

Associate Professor

Specialty/Research Focus

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

 
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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:
  • Postdoctoral Fellow, Cell biology/Medicine, University of Oklahoma Health Sciences Center (2005)
  • Postdoctoral Fellow, Ophthalmology/Biochemistry, Medicial University of South Carolina (2002)
  • PhD, Ophthalmology/Ocular pharmacology, Sun Yat-sen University (2001)
  • 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, Summa Cum Laude (1990)
Employment:
  • Associate Professor, University at Buffalo (2012-present)
  • Associate Professor, Medicine, University of Oklahoma Health Sciences Center (2012)
  • Adjunct Associate Professor, Physiology, University of Oklahoma Health Sciences Center (2012)
  • Adjunct Associate Professor, Ophthalmology, University of Oklahoma Health Sciences Center (2012)
  • Full member and GPiBS student Mentor, Neuroscience and Physiology, University of Oklahoma Health Sciences Center, Graduate College (2010–2012)
  • Member, University of Oklahoma, Oklahoma Center for Neuroscience (2010–2012)
  • 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:
  • 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–August 2015
    ER stress and diabetic retinopathy
    NIH, NEI
    Role: Principal Investigator
    $1,790,000
  • July 2011–June 2014
    Molecular mechanism for diabetic retinopathy
    American Diabetes Association
    Role: Principal Investigator
    $345,000
  • November 2010–October 2013
    Targeting Histone Deacetylase in Diabetic Retinopathy
    OCAST
    Role: Principal Investigator
    $135,000
  • September 2011–August 2013
    ER stress and diabetic retinopathy
    NIH, NEI
    Role: Principal Investigator
    $53,684
  • April 2010–July 2012
    Translational regulation of anti-oxidant genes in the RPE
    American Health Assistance Foundation
    Role: Principal Investigator
    $100,000
  • July 2009–June 2012
    Lipoproteins and PEDF in the Vascular Complications of Diabetes
    NIH, NIDDK
    Role: Co-Investigator
    $1,378,367
  • September 2009–August 2010
    A novel regulator of pro-inflammatory genes in diabetic retinopathy
    Role: Principal Investigator
    $110,000
  • September 2007–June 2010
    Mentoring Diabetes Research in Oklahoma
    Role: Principal Investigator
    $666,000
See All (8 Total) >

Journal Articles:
See All (33 Total) >

Presentations:
  • "Adaptive unfolded protein response in retinal endothelial cells and diabetic retinopathy." XX Biennial Meeting of the International Society for Eye Research, International Society for Eye Research, Diabetic retinopathy (2012)
  • "Macrophage-derived elastinolytic protease is essential for ischemia-induced macrophage acitvation and aberrant retinal vascular remodeling" XX Biennial Meeting of the International Society for Eye Research, International Society for Eye Research, Angiogenesis (2012)
  • "Activating transcription factor 4 regulates immune response in endothelial cells and mediates vascular inflammation in diabetic retinopathy" American Diabetes Association 72nd Scientific Sessions, American Diabetes Association (2012)
  • "Associations of Serum Pigment Epithelium Derived Factor Levels With Renal Dysfunction, Body Habitus and Dyslipidemia in Type 2 Diabetes Patients" American Diabetes Association 72nd Scientific Sessions, American Diabetes Association (2012)
  • "Deficient XBP1 signaling in endothelial cells exacerbates leukostasis and tight junction damage in diabetic retinopathy" American Diabetes Association 72nd Scientific Sessions, American Diabetes Association (2012)
  • "PEDF Response to Exercise in Normal Weight and Overweight Adolescents" American Diabetes Association 72nd Scientific Sessions, American Diabetes Association (2012)
  • "Dysregulated unfolded protein response: a novel mechanism for cigarette smoke-induced RPE cell injury" Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), ARVO (2012)
  • "Integrating Inflammatory Signaling and Cellular Stress Response by Activating Transcription Factor 4 in Vascular Endothelial Cells and Retinal Diseases." Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), Association for Research in Vision and Ophthalmology (ARVO) (2012)
  • "X-box Binding Protein 1 Regulates Endothelial Inflammation and Blood-retinal Barrier Homeostasis in Diabetic retinopathy." Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), Association for Research in Vision and Ophthalmology (ARVO) (2012)
  • "ER stress, angiogenesis and inflammation in diabetic retinopathy" Keystone Symposium on Complications of Diabetes, Keystone (2012)
  • "Unfolded Protein Response in Retinal Diseases: Understanding the Signaling from the Endoplasmic Reticulum" LSU Health Sciences Center (2011)
  • "X box-binding protein 1 is a key regulator of JNK activation and inflammatory factor production in retinal Müller cells. ." Harold Hamm Diabetes Center Diabetes Symposium (2011)
  • "Endoplasmic Reticulum Protein 29 (ERp29) and Age-Related Macular Degeneration" OCNS 20th Anniversary Symposium, OCNS (2011)
  • "ER stress, inflammation and diabetic retinopathy" The 47th European Association for the Study of Diabetes (EASD) Annual Meeting, European Association for the Study of Diabetes (EASD), ER stress in Diabetes and Diabetic Complications (2011)
  • "The unfolded protein response: from the endoplasmic reticulum to diabetic retinopathy" OCNS Seminar Series, OCNS (2011)
  • "X-box binding protein 1: a critical regulator of autophagy and cell survival in the RPE." Dean McGee Eye Institute Symposium, Dean McGee Eye Institute (2011)
  • "Regulation of retinal inflammation by the unfolded protein response: a new mechanism for diabetic macular edema." University at Buffalo/SUNY (2011)
  • "Activating Transcription Factor 4 is A Novel Pathogenic Gene in Retinal Inflammation and Endothelial Cell Death in Diabetic Retinopathy" Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), Association for Research in Vision and Ophthalmology (ARVO) (2011)
  • "Endoplasmic Reticulum Stress is implicated in Cigarette Smoking-induced Apoptosis of RPE Cells" Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), Association for Research in Vision and Ophthalmology (ARVO) (2011)
  • "Loss of XBP1 in the Aging RRE Reduces Autophagy and Exacerbates RPE Cell Death: A Novel Mechanism for Age-related Macular Degeneration" Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), Association for Research in Vision and Ophthalmology (ARVO) (2011)
  • "Endoplasmic reticulum stress and retinal diseases" Zhongshan Ophthalmic Center, Sun Yat-sen University (2010)
  • "Pathogenic role of activating transcription factor 4 in Müller cell-derived inflammatory cytokine production in diabetic retinopathy" The International Symposium on Ocular Pharmacology and Therapeutics (2010)
  • "Pigment Epithelium-derived Factor (PEDF) in Diabetes and Diabetic Complications" The Third Affiliated Hospital of Sun Yat-sen University (2010)
  • "Comparison of Pigment Epithelium-derived Factor (PEDF) in Normal Weight and Obese Boys and Girls" HHDC Diabetes Symposium. (2010)
  • "Activation of Endoplasmic Reticulum Stress by Hyperglycemia is Essential for Inflammatory Cytokine Production in Müller cells in Diabetes" XIX Biennial Meeting of the International Society for Eye Research, International Society for Eye Research (2010)
  • "Transcriptional Regulation of Anti-oxidant Genes in the RPE" XIVth International Symposium on Retinal Degeneration (2010)
  • "Apob Leakage in Two Diabetic Retinopathy Related Animal Models" Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO),, Association for Research in Vision and Ophthalmology (ARVO) (2010)
  • "Preconditioning with Endoplasmic Reticulum Stress Mitigates Retinal Inflammation and Vascular Leakage through Activation of X-box Binding Protein 1" Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) (2010)
  • "X-box Binding Protein 1 is A Novel Regulator of Anti-oxidant Genes in the RPE." Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), Association for Research in Vision and Ophthalmology (ARVO) (2010)
  • "XBP1 Suppresses Pathological Retinal Neovascularization via inhibition of Integrin β3 and VEGF Pathways." Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), Association for Research in Vision and Ophthalmology (ARVO) (2010)
See All (30 Total) >
Service Activities:
  • NIH, Special Emphasis Panel/Scientific Review Group ZRG1 MDCN-A; Member; Grant Reviewer (2013)
  • ISRN Ophthalmology; Editorial Board Member (2012–2017)
  • Journal of Diabetes Research and Clinical Metabolism; Editorial Board Member (2012–2017)
  • Member, Publications Committee (PUBS), Association for Research in Vision and Ophthalmology (ARVO); Committee Member (2012–2015)
  • Australia Macular Degeneration Foundation Grant Review Panel; Member; Grant Reviewer (2012)
  • NIH, Special Emphasis Panel/Scientific Review Group ZRG1 BDCN-H; Member; Grant Reviewer (2012)
  • International Journal of Biochemistry and Molecular Biology; Editorial Board Member (2011–2016)
  • World Journal of Ophthalmology; Editorial Board Member (2011–2015)
  • Diabetes UK Research Grant Review Panel; Member; Grant Reviewer (2011–2012)
  • NIH, NIDDK, Special Emphasis Panel/Scientific Review Group ZDK1 GRB - J(O1); Member; Grant Reviewer (2011)
  • Journal of Diabetes and Metabolism; Editorial Board Member (2010–2015)
  • World Journal of Diabetes; Editorial Board Member (2010–2015)

Clinical Specialties:
Clinical Offices:
Insurance Accepted:

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Contact Information

Department of Ophthalmology
Ross Eye Institute
308 Farber Hall, 3435 Main Street
Buffalo, NY 14215
Phone: 716-645-1808
Fax: 716-862-6526
Email: xzhang38@buffalo.edu


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