Our epithelial surfaces are normally resistant to infection. Therefore, researchers who study infectious disease commonly use of models that deliberately compromise the target tissue (or otherwise bypass barriers) so that disease can be enabled and studied. These infection models have led to a plethora of important information about factors involved in pathology and/or its resolution when disease is initiated. However, other models are needed to study barriers to infection, or early events that occur prior to disease initiation when it occurs in the absence of overt injury.

In our laboratory, we have developed novel in vivo and in vitro methods for studying defenses during health using the eye and the opportunistic bacterium Pseudomonas aeruginosa as models. We have also advanced imaging technologies that enable us to see into the living epithelium to observe what bacteria do and how the tissue responds in either resistant or susceptible states. Using these methods, and employing array/knockout/knockdown technologies, we have identified specific factors that modulate the ability of bacteria to penetrate the ocular surface epithelium. The data show that pathogen recognition systems are involved in resistance, and suggest that bacterial adaptation in vivo contributes to pathogenesis. Studies aimed at understanding early interactions between microbes and the ocular surface prior to disease initiation have potential for development of novel methods to prevent (rather than simply treat) infection of the eye or other sites.

UC Berkeley Vision Science, Molecular and Cell Biology: Why study the eye?

The lab is working on two inter-related goals.

1. To determine how the healthy corneal surface resists infection and how contact lens wear then compromises those defenses.

a) The laboratory’s long standing NIH (NEI) grant is aimed at understanding the molecular factors that prevent bacterial penetration of the corneal epithelium when the eye is healthy, how the functionality of that defense system is modulated, and the bacterial factors that enable penetration when the system is compromised. Barriers to our understanding in this area have included the lack of available in vivo models for studying these processes. Traditionally researchers have used “infection models” to study tissue interactions with bacteria. These involve deliberately compromising the tissue to induce enable susceptibility to infection, adding the microbe and then studying what happens next. Those who study corneal infection extensively use a scratch injury model that enables susceptibility by physically removing the epithelial barrier to expose the vulnerable stroma. Disease follows because direct placement of the microbe into the stroma stimulates a damaging inflammatory response.

This scratch injury model is problematic for the Fleiszig laboratory’s research goals for two reasons. Firstly, it bypasses the need for bacteria to penetrate the epithelium, which is the event the laboratory seeks to understand. Secondly, the lab is interested in understanding the events that determine health when the cornea is resistant to infection, not events that occur when there is disease. Due to the lack of suitable model systems, most of our knowledge about epithelial interactions with bacteria and the potential role of the epithelia in defense have necessarily come from cell culture studies.

Wild Type P. aeruginosa thrives in membrane blebs; type three secretion system mutants do not.
A. Angus, IAI, 2008

In the past 2 years, the laboratory has succeeded in developing multiple models (in vivo and in vitro) that enable epithelial cell penetration by bacteria to be studied. Together, these models provide the opportunity to do experiments either in the context of, or without, potentially confounding factors present in vivo, as is needed to test hypotheses. In the past year, the laboratory has also developed new imaging technologies that enable bacterial interactions with the epithelium to be imaged in living intact eyes without the need for any tissue dissection, staining, or other types of sample preparation/processing.

myd88
MyD88 is involved in corneal epithelium barrier function. C. Tam et al, PLoS ONE, 2011

b) A separate investigation to determine how the ocular surface retains its sterility was funded by a Grand Challenges Explorations Grant from the Gates Foundation. The long-term goal of this project is bold: To develop therapies to prevent any type of infection of any body site based on eye derived molecules.

2. Fundamental studies of bacterial/epithelial cell interactions using P. aeruginosa as a model organism.

The goal of this project is to determine how P. aeruginosa survive inside corneal epithelial cells, and the necessity for that strategy in the disease process. The data to date show that corneal epithelial cells normally traffic bacteria to intracellular vesicles where they are killed, but P. aeruginosa possesses virulence factors that enable it to bypass this innate defense. Experimental approaches involving biochemical and genetic methods, combined with various images techniques, are being used to describe the details of the intimate interactions between P. aeruginosa and eukaryotic cells. The results will enlighten us about how bacteria cause disease and should also contribute to our understanding of epithelial cell biology.

P. aeruginosa causes sight threatening pathology in the eye and life threatening infections at other sites. These include serious lung disease in children with cystic fibrosis and in AIDS patients, and life theatening skin infections in burns victims. Thus, this line of research could ultimately lead to new means for treating multiple diseases.

Inside Science Feature, Killer Eyes: Stopping Infections

Suzi Suzanne Fleiszig, OD, PhD
Principal Investigator
fleiszig(at)berkeley.edu
Linked In
Honors and Awards
  • Harold A. Stein Lecturer 2016, Contact Lens Association of Ophthalmologists
  • Consultant to the FDA, 2014-present
  • The Rubin Medal, International Society for Contact Lens Research, 2013
  • Legend Award, American Optometric Association, 2012
  • Councilor, American Society for Microbiology, 2012-present
  • Editorial Board Member for Infection & Immunity (2012-present), Investigative Ophthalmology & Vision Science (2012-2014), PLoS One (2012-present), and Frontiers in Cellular & Infection Microbiology (2011-present)
  • Chair, 2012 Gordon Research Conference (GRC): Biology and Pathobiology of the Cornea
  • Ad hoc reviewer, various NIH special emphasis panels (2001-present), Bacterial Pathogenesis (BACP) Study Section (2015-present).
  • Thygusen Lecturer, Ocular Microbiology and Immunology Group (OMIG) American Academy of Ophthalmology 2011
  • Donald Korb Award for Excellence, American Optometric Association 2010
  • Hyndiuk Lecturer, Medical College of Wisconsin 2010
  • Silver Fellow, Association for Research in Vision and Ophthalmology 2010
  • Vice President, Tear Film & Ocular Surface Society 2009-2013
  • Chair, Division D: Bacteria of Medical Importance, American Society for Microbiology 2007-2010
  • President, International Society for Contact Lens Research 2007-2009
  • Program Committee (IM), Association for Research in Vision and Ophthalmology, 2006-2009
  • National Plan Planning Committee for the NIH National Eye Institute 2004-2009
  • NIH service: Permanent Member, Anterior Eye Disease (AED) Study Section, 2005-2009
  • Governing Board, Tear Film and Ocular Surface Society 2005-2009
  • Glenn A. Fry Award, American Academy of Optometry 2005
  • Heinz Lecturer, Proctor Foundation UCSF 2004
  • Morton D. Sarver Chair, UC Berkeley 1997-2001
  • Borish Award, American Academy of Optometry 1997
  • “David” David Evans, PhD
    Co-Principal Investigator
    djevans(at)berkeley.edu
    Linked In
    David’s Touro University faculty page
    “Matteo” Matteo Metruccio, PhD
    Assistant Researcher
    Postdoc, 2013-2015
    metruccio(at)berkeley.edu
    Linked In
  • EIMID-IAPP fellow (Marie Curie Fellowship) (European Initiative for basic research in Microbiology and Infectious Diseases-Industry-Academia Partnerships and Pathways) From 2010 to 2012, Max Plank Institute for Infection Biology, Germany-Novartis Vaccines and Diagnostics, Italy.
  • PhD in Functional Biology of Cellular and Molecular Systems, University of Bologna, 2010
  • Master of Science (M.Sc.) in Biotechnology, University of Bologna, 2005
  • Research interests: Host-Pathogen interactions, Infectious disease, Innate immunity
  • Hart Horneman
    Staff Research Associate
    Lab Manager
    hhorneman(at)berkeley.edu
    Abby Abby Kroken, PhD
    Postdoctoral Fellow
    arkroken(at)berkeley.edu
    Linked In
    Google Scholar
  • NRSA Fellow, 2015-present
  • ISCLR Travel Grant Award, 2015
  • PhD in Microbiology and Molecular Genetics, Medical College of Wisconsin, 2013
  • Research Interests: Bacterial toxins, host-pathogen interactions, microscopy
  • Jianfang Jianfang Li, PhD
    Postdoctoral Fellow
    lijianfang(at)berkeley.edu
    Linked In
  • The International Postdoctoral Exchange Fellowship from China Postdoctoral Council, 2014-present
  • PhD, Shandong University, 2013
  • Master's Degree, Shenyang Pharmaceutical University, 2006
  • Vince Vincent Nieto, PhD
    Postdoc
    vnieto(at)berkeley.edu
    Linked In
  • PhD, The University of Texas at Austin, 2013
  • Research Interests: Microbiology, Bacterial Pathogenesis
  • Melinda Grosser, PhD
    Postdoc
    mgrosser(at)berkeley.edu
  • PhD in Microbiology and Immunology, University of North Carolina, Chapel Hill
  • Steph Stephanie Wan
    Graduate Student
    stephanie.wan(at)berkeley.edu
    Linked In
  • TFOS Travel Grant Award, 2016
  • ISCLR Travel Grant Award, 2015
  • Bachelor of Science in Biology, Tufts University, 2014
  • Virginia Ling
    Lab Assistant
    URAP student
    weichen.v.ling060242(at)berkeley.edu
  • B.A., Integrative Biology, Class of 2018
  • Research Interests: Infectious disease, bacterial secretion systems
  • Sarah Alsamman
    URAP Student

  • SURF L&S Fellow, 2016
  • B.A., Public Health and Molecular and Cell Biology, Class of 2017
  • Camille Chen
    URAP Student
    Patrick Hagan
    URAP Student
    Si Jie Ma
    URAP Student

    Professor Suzanne Fleiszig

    University of California, Berkeley
    School of Optometry
    688 Minor Hall
    Office: (510) 643-0990
    Lab: (510) 642-0511
    Fax: (510) 643-5109
    Email: fleiszig(at)berkeley.edu

    Prospective Graduate Students

    Undergraduate Research

    Undergraduates should apply for research experience through URAP. Generally we cannot accept volunteers.

    Our records are incomplete! If you're not listed, or would like to provide a website or Linked In profile, please email arkroken(at)berkeley.edu and we will update this page!

    Name Role Contact
    Aaron Sullivan, MS, PhD Graduate Student, 2011-2015, Postdoc 2015-2016 Linked In
    Anna Xie Optometry Student Researcher, 2015-2016 Linked In
    Julio Martinez Pre-doctoral Scholar, Sally Casanova Scholarship 2015-2016
    Angeline Truong High School Student Volunteer, 2015-2016
    Tyler Kim
    URAP Student, 2016
    Joyce Fong
    Administrative Staff, 2013-2015 Linked In
    Alyssa Louie
    Administrative Staff, 2013-2015 Linked In
    Anthony Del Cid
    Undergraduate researcher (UC Santa Cruz), 2015
    Megan Lopez
    Optometry Student Researcher, 2015 Linked In
    Amber Jolly, PhD Postdoc (T32 Fellow), 2012-2015 Linked In
    An Nguyen
    Lab Assistant
    Stephanie Chang
    URAP Student, 2014-2015, Rose Hills Fellow, 2015
    Emily Wen
    URAP Student, 2014-2015
    Kevin Quach
    URAP Student, 2014-2015
    TY Yvonne Wu, OD MPH PhD
    Postdoc Fellow, 2012-2014 Linked In
    Kailyn Kim
    URAP Student, 2012-2014 Linked In
    KP Connie Tam, PhD
    Postdoc, Assistant Researcher
    Victoria Hritonenko, PhD
    Postdoc (NRSA fellow) Linked In
    Susan Heimer, PhD
    Visiting Scholar, 2009-2013 Linked In
    Desire Takawira, PhD
    Postdoc Linked In
    James Mun, PhD
    Graduate Student, 2005-2011
    Victoria Tran, PhD
    Graduate Student, 2007-2011
    Danielle Augustin, PhD
    Graduate Student, 2007-2011 (NRSA fellow 2009-2011) Linked In
    Julio Ramirez, PhD
    Staff Research Associate, 2009-2010
    Annette A Angus, PhD
    Graduate Student, 2004-2009 Linked In
    Sarah Lewis, OD
    Staff Research Associate, 2005-2009
    Amanda Ackerman Lee, MA, MPH
    Graduate Student, 2004-2008
    Irania Alaracon, MS, PhD
    Graduate Student, 2003-2007
    Inna Maltseva, OD, PhD
    Graduate Student, 2000-2005, Optometry Student, 1996-1999 Linked In
    Minjian Ni, Ph.D
    Postdoc, 2002-2006
    Carol Lakkis, BScOptom, PhD, Visiting Scholar, 1996-1997, Assistant Researcher, 2001-2002 Linked In

    Research in the Fleiszig Lab is funded by the following foundations:

    Ongoing:

  • NIH/NEI: R01 EY024060 (Fleiszig): Corneal infection: The role of bacterial adaptation. 8/1/2014-7-31-2019
  • NIH/NEI: R01 EY011221 (Fleiszig): Significance of Corneal Cell Invasion By Bacteria. 7/1/1995 – 8/31/2019
  • NIH/NEI: F32 EY025969 (Kroken): Corneal infection: Bacterial localization versus virulence

    Past Support:

  • NIH/NIAID: R01 AI 079192 (Fleiszig): Intracellular lifestyle of Pseudomonas aeruginosa. 12/5/2008 – 11/30/2014
  • Industry (Fleiszig): Pathogenesis of P. aeruginosa corneal infection. 3/1/2013 – 2/28/2014
  • Allergan Inc. (Fleiszig): Role of dry eye in susceptibility to Pseudomonas aeruginosa infection. 01/1/2009 – 12/31/2013
  • Bill and Melinda Gates Foundation (Grand Challenges Exploration): The Eye as a Source of Novel Broad-Spectrum Anti-Infectives.10/1/2008 – 4/30/2010
  • Alcon Research, Inc.: Penetration of the corneal epithelium by cytotoxic strains of P. aeruginosa. 03/1/09 – 09/30/10