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  • Charles T Campbell Microbiology Laboratory
  • Infectious Eye Diseases: Zoster Laboratory
  • Ocular Biomechanics Laboratory
  • Ocular Surface Development Laboratory
  • Retinal Development Laboratory
  • Trabecular Meshwork Cell Biology Laboratory
  • Viral Immunology Laboratory
  • Visual Neuroscience Laboratory
  • Corneal Cell Biology Laboratory
  • Outflow Tract Engineering Laboratory
  • Biomedical Visualization Laboratory
  • Ocular Surface Regenerative Therapy Laboratory
  • Optic Nerve Regeneration Laboratory
  • Charles & Louella Snyder Ocular Development, Disease and Regeneration Laboratory
  • Ophthalmic Biomaterials Lab
  •  
    bullet point  Charles T Campbell Microbiology Laboratory
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    Regis P. Kowalski, MS, M(ASCP)
    Executive Director of The Charles T. Campbell Ophthalmic Microbiology Lab

    Eric Romanowski, MS
    Research Director

    Robert M.Q. Shanks, PhD
    Director of Basic Research

    Lab Personnel
    Lisa M Karenchak (Specialty Laboratory Technologist in Ophthalmic Microbiology)
    Kathleen Yates (Sr. Research Specialist)

    Lab Personnel for Dr. Shanks
    Kim Brothers, PhD (Postdoctoral Associate)
    Jake Callaghan (Research Technician)
    Nick Stella(Lab Manager and Sr. Research Technician)

    Research Interests
    The Charles T. Campbell Ophthalmic Microbiology Laboratory is unique because of its two separate yet integrated components. The laboratory consists of a fully certified clinical diagnostic ophthalmic microbiology laboratory and a research laboratory that focuses on infectious diseases (adenovirus, HSV-1, bacteria) of the anterior segment of the eye and their treatment.

    The clinical laboratory has developed its own website to serve as a resource to all interested in ocular microbiology (http://visualeyes.upmc.edu/eyemicrobiologylab/index.html). The website also serves as the homepage for the Ocular Immunology and Microbiology Group (OMIG).

    For more information, please follow these links:
    Charles T Campbell Microbiology Laboratory Website
     
    Contact Information
    Regis Kowalski
    MS M(ASCP)
    412-647-7211
    kowalskirp@upmc.edu
    EEINS-1020, 203 Lothrop Street, Pittsburgh PA 15213
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    bullet point  Infectious Eye Diseases: Zoster Laboratory
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    Paul (Kip) R. Kinchington, PhD
    Associate Professor of Ophthalmology, Molecular Genetics and Biochemistry
    The Campbell Laboratory for Infectious Eye Diseases
    University of Pittsburgh School of Medicine

    Lab Personnel
    Michael Yee (Lab Manager and Sr. Research Technician)
    Benjamin Treat (MVM Graduate student)


    Research Interests
    Paul (Kip) Kinchington, Ph. D. heads the Molecular Herpesvirus unit of the Campbell Laboratory of Infectious Diseases in The Department of Ophthalmology. His research addresses viruses that cause ocular complications and potential blindness, particularly Varicella Zoster Virus, the cause of Herpes Zoster (“Shingles”).

    Herpes zoster (also known as “shingles”) is a debilitating and crippling disease seen mostly in the elderly and in patients whose immunity is weakened by disease, cancer or treatment. Zoster is not “caught” from someone else, but rather arises from within us when the Varicella Zoster Virus (VZV) awakens from a quiet “latent” state that was established in a person’s sensory nerves during the childhood disease chickenpox. Most adults over 30 have VZV within us and a third will get zoster in our lifetimes. Zoster can have devastating effects on vision. It may induce a cloudy cornea that reduces vision: it can destroy the retina and the means to see light at the back of the eye; It may make the cornea totally numb (atrophic cornea), resulting in blinding eye wounds and damage from simple tasks such as applying eye drops: And it can cause a host of drastic neurological problems that affect the eye and means to see. These include tics, palsies, uncontrollable eye movements and most important, an intractable, debilitating and difficult-to-treat pain that may last for months to years..

    Our group is one of only a few in the world that study VZV and its biology. Our research is geared to understanding how VZV remains quiet in a person’s nerves for so long (decades), what makes it awaken, and why the virus causes so much pain when it causes zoster. First, we have developed a tissue culture model of human neurons that is allowing us an unprecedented look at what happens to the virus at the dormant ‘latency’ phase in nerves and the factors are that awaken the virus from this state. We have also been able to use this same system to visualize the virus moving along the nerves and understand how it reaches the skin and eye (and can be blocked). Secondly, we have developed a model that is allowing us to address why VZV causes so much pain. This model is not only enabling us to address the mechanisms by which pain is induced, but is also allowing us to test and develop better strategies to treat or even prevent pain associated with zoster. These lines of research could well establish a highly novel approach to treatment that could give long lasting relief to patients with zoster and chronic pain. Given that zoster and the associated pain are important diseases of the elderly, and that pain is more likely to be more severe as one ages, our work could improve the quality of life of many patients that reach their twilight years.

    Dr. Kinchington is Director of Molecular Biology facilities in the Department of Ophthalmology, which is an NEI funded and sponsored core facility to aid the programs of all vision researchers in Pittsburgh in cloning, DNA and RNA manipulation, development of vectors to express proteins, and bioinformatics analyses of large datasets assessing gene expression.

    For more information, please follow these links:
    Molecular Virology and Microbiology Program

    Select Recent Publications
    1. Guedon JG , Zhang M, Glorioso JC, Goins WF and Kinchington PR. Relief of Pain Induced by Varicella Zoster Virus (VZV) in a Rat Model of Post-Herpetic Neuralgia using a Herpes Simplex Virus (HSV) Vector Expressing Enkephalin Gene Therapy In press

    2. Sloutskin A, Yee MB, Kinchington PR, Goldstein RS. Var4icella zoster virus and herpes simplex virus 1 can infect and replicate in the same neurons whether co-or superinfected. J Virology, 2014 In Press

    3. D'Aiuto L, Prasad KM, Upton CH, Viggiano L, Milosevic J, Raimondi G, McClain L, Chowdari K, Tischfield J, Sheldon M, Moore JC, Yolken RH, Kinchington PR, Nimgaonkar VL. Persistent Infection by HSV-1 Is Associated With Changes in Functional Architecture of iPSC-Derived Neurons and Brain Activation Patterns Underlying Working Memory Performance. Schizophr Bull. 2014 Mar 12. [Epub ahead of print] PubMed PMID: 24622295.

    4. Sloutskin A, Yee MB, Kinchington PR, Goldstein RS. Varicella zoster virus and herpes simplex virus type 1 can infect and replicate in the same neurons whether co- or superinfected. J Virol. 2014 Feb 26. [Epub ahead of print] PubMed PMID:24574392.

    5. Jones M, Dry IR, Frampton D, Singh M, Kanda RK, Yee MB, Kellam P, Hollinshead M, Kinchington PR, O'Toole EA, Breuer J. RNA-seq analysis of host and viral gene expression highlights interaction between varicella zoster virus and keratinocyte differentiation. PLoS Pathog. 2014 Jan 30;10(1):e1003896. doi: 10.1371/journal.ppat.1003896. eCollection 2014 Jan. PubMed PMID: 24497829; PubMed Central PMCID: PMC3907375.

    6. Kinchington PR. Targeting Host Pathways to Block HSV-1 at the Cornea. Invest Ophthalmol Vis Sci. 2014 Feb 3;55(2). pii: 716. doi: 10.1167/iovs.14-13879. PubMed PMID: 24492207.

    7. Depledge DP, Kundu S, Jensen NJ, Gray ER, Jones M, Steinberg S, Gershon A, Kinchington PR, Schmid DS, Balloux F, Nichols RA, Breuer J. Deep sequencing of viral genomes provides insight into the evolution and pathogenesis of varicella zoster virus and its vaccine in humans. Mol Biol Evol. 2014 Feb;31(2):397-409. doi: 10.1093/molbev/mst210. Epub 2013 Oct 25. PubMed PMID: 24162921; PubMed Central PMCID: PMC3907055.

    9. Sloutskin A, Kinchington PR, Goldstein RS. Productive vs non-productive infection by cell-free varicella zoster virus of human neurons derived from embryonic stem cells is dependent upon infectious viral dose. Virology. 2013 Sep 1;443(2):285-93. doi: 10.1016/j.virol.2013.05.021. Epub 2013 Jun 12. PubMed PMID: 23769240; PubMed Central PMCID: PMC3733239.

    10. Swamynathan S, Buela KA, Kinchington P, Lathrop KL, Misawa H, Hendricks RL, Swamynathan SK. Klf4 regulates the expression of Slurp1, which functions as an immunomodulatory peptide in the mouse cornea. Invest Ophthalmol Vis Sci. 2012 Dec 19;53(13):8433-46. doi: 10.1167/iovs.12-10759. PubMed PMID: 23139280.

    11. Grigoryan S, Kinchington PR, Yang IH, Selariu A, Zhu H, Yee M, Goldstein RS. Retrograde axonal transport of VZV: kinetic studies in hESC-derived neurons. J Neurovirol. 2012 Dec;18(6):462-70. doi: 10.1007/s13365-012-0124-z. Epub 2012 Aug 24. PubMed PMID: 22918852; PubMed Central PMCID: PMC3556991.

    12. Kinchington PR, Leger AJ, Guedon JM, Hendricks RL. Herpes simplex virus and varicella zoster virus, the house guests who never leave. Herpesviridae. 2012 Jun 12;3(1):5. doi: 10.1186/2042-4280-3-5. PubMed PMID: 22691604; PubMed Central PMCID: PMC3541251.

    13. Dukhovny A, Sloutskin A, Markus A, Yee MB, Kinchington PR, Goldstein RS. Varicella-zoster virus infects human embryonic stem cell-derived neurons and neurospheres but not pluripotent embryonic stem cells or early progenitors. J Virol. 2012 Mar;86(6):3211-8. doi: 10.1128/JVI.06810-11. Epub 2012 Jan 11. PubMed PMID: 22238301; PubMed Central PMCID: PMC3302301.

    14. Kinchington PR, Goins WF. Varicella zoster virus-induced pain and post-herpetic neuralgia in the human host and in rodent animal models. J Neurovirol. 2011 Dec;17(6):590-9. doi: 10.1007/s13365-011-0069-7. Epub 2011 Dec 28. PubMed PMID: 22205584; PubMed Central PMCID: PMC3946975.

    15. Markus A, Grigoryan S, Sloutskin A, Yee MB, Zhu H, Yang IH, Thakor NV, Sarid R, Kinchington PR, Goldstein RS. Varicella-zoster virus (VZV) infection of neurons derived from human embryonic stem cells: direct demonstration of axonal infection, transport of VZV, and productive neuronal infection. J Virol. 2011 Jul;85(13):6220-33. doi: 10.1128/JVI.02396-10. Epub 2011 Apr 27. PubMed PMID: 21525353; PubMed Central PMCID: PMC3126485.

    16. Erazo A, Yee MB, Banfield BW, Kinchington PR. The alphaherpesvirus US3/ORF66 protein kinases direct phosphorylation of the nuclear matrix protein matrin 3. J Virol. 2011 Jan;85(1):568-81. doi: 10.1128/JVI.01611-10. Epub 2010 Oct 20. PubMed PMID: 20962082; PubMed Central PMCID: PMC3014177.

    17. Ramachandran S, Davoli KA, Yee MB, Hendricks RL, Kinchington PR. Delaying the expression of herpes simplex virus type 1 glycoprotein B (gB) to a true late gene alters neurovirulence and inhibits the gB-CD8+ T-cell response in the trigeminal ganglion. J Virol. 2010 Sep;84(17):8811-20. doi: 10.1128/JVI.00496-10. Epub 2010 Jun 23. PubMed PMID: 20573821; PubMed Central PMCID: PMC2919033.

    18. Erazo A, Kinchington PR. Varicella-zoster virus open reading frame 66 protein kinase and its relationship to alphaherpesvirus US3 kinases. Curr Top Microbiol Immunol. 2010;342:79-98. doi: 10.1007/82_2009_7. Review. PubMed PMID: 20186610; PubMed Central PMCID: PMC3936600.

     
    Contact Information
    Paul Kinchington
    Ph.D.
    412-647-6319
    kinchingtonp@msx.upmc.edu
    EEINS-1016, 203 Lothrop Street, Pittsburgh PA 15213
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    bullet point  Ocular Biomechanics Laboratory
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    Ian A. Sigal, PhD
    Assistant Professor of Ophthalmology
    Laboratory of Ocular Biomechanics
    University of Pittsburgh School of Medicine

    Lab Personnel
    Danielle Hu (Research Assistant)
    Ning-Jiun Jan (Graduate Student)
    Alexandra Judisch (Systems Analyst)
    Huong Tran (Graduate Student)
    Andrew Voorhees, PhD ( Postdoctoral Research Associate)

    Research Interests
    The objective of the Laboratory of Ocular Biomechanics is to study the eye as a biomechanical structure. More specifically our work is aimed at identifying the causes of glaucoma, with the ultimate intention of finding a way to prevent vision loss.

    In our daily lives we rarely think of the eye as a biomechanical structure. The eye, however, is a remarkably complex structure with biomechanics involved in many of its functions. For our eyes to be able to track moving objects, for example, requires a delicate balance of the forces exerted by several muscles. Forces are also responsible for deforming the lens and allow focusing. A slight imbalance between the forces and tissue properties may be enough to alter or even preclude vision. These effects may take place quickly or over long periods, even years. Understanding ocular biomechanics is therefore important for preventing and treating vision loss.

    For more information, please follow these links:
    Ocular Biomechanics Laboratory website

    Select Recent Publications
    1.H. Yang, G. Williams, J.C. Downs, I.A. Sigal, M.D. Roberts, H. Thompson and C. F. Burgoyne. “Outward migration of the anterior and posterior lamina cribrosa insertions and early cupping in non-human primate experimental glaucoma”. Accepted by Invest Ophthalmol Vis Sci on 31 May 2011.

    2.I.A. Sigal, “An applet to estimate the IOP-induced stress and strain within the optic nerve head”. Invest Ophthalmol Vis Sci, Epub 28 Apr 2011, PMID: 21527378.

    3. L. Kagemann, G. Wollstein, H. Ishikawa, I.A. Sigal, L.S. Folio, J. Xu, H. Gong and J.S. Schuman, “3D Visualization of Aqueous Outflow Structures In-Situ in Humans”. Experimental Eye Research, Epub 15 Apr 2011 (Camras Special Issue). PMID: 21514296.

    4. R. Norman, J.G. Flanagan, I.A. Sigal, S. Rausch, I. Tertinegg and C.R. Ethier. “Finite element modeling of the human sclera: influence on optic nerve head biomechanics and connections with glaucoma”. Experimental Eye Research, Epub 29 Sep 2010. PMID 20883693.

    5.J.C. Downs, M.D. Roberts and I.A. Sigal, “Glaucomatous cupping of the lamina cribrosa: a review of the evidence for active progressive remodeling as a mechanism”, Experimental Eye Research, Epub 11 Aug 2010, PMID 20708001.

    6.I.A. Sigal, H. Yang, M.D. Roberts, C.F. Burgoyne and J.C. Downs, “IOP-induced lamina cribrosa displacement and scleral canal expansion: an analysis of factor interactions using parameterized eye-specific models”, Invest Ophthalmol Vis Sci. 52(3):1896-1907, Mar 2011.

    7. N.G. Strouthidis, B. Fortune, H. Yang, I.A. Sigal and C.F. Burgoyne, “Longitudinal change detected by spectral domain optical coherence tomography in the glaucomatous optic nerve head and peripapillary retina”, Invest Ophthalmol Vis Sci. 52(3):1206-19, Mar 2011.

    8.H. Yang, H. Thompson, M.D. Roberts, I.A. Sigal, J.C. Downs and C. F. Burgoyne. “Deformation of the early glaucomatous monkey optic nerve head connective tissue following acute IOP elevation within 3-D histomorphometric reconstructions”, Invest Ophthalmol Vis Sci, 52(1):345-63, Jan 2011.

    9.M.D. Roberts, I.A. Sigal, Y. Liang, C.F. Burgoyne and J. C. Downs. “Changes in the biomechanical response of the optic nerve head in early experimental glaucoma”, Invest Ophthalmol Vis Sci. 51(11):5675-5684, Nov 2010.

    10. P.G. Sanfilippo, A. Cardini, I.A. Sigal, J. Ruddle, B.E. Chua, A.W. Hewitt, and D.A. Mackey. “A geometric morphometric assessment of the optic cup in glaucoma”, Experimental Eye Research, 91(3): 405-414, Sep 2010.
     
    Contact Information
    Ian Sigal
    PhD
    412-802-8872
    sigalia@upmc.edu
    EEINS-930, 203 Lothrop Street, Pittsburgh PA 15213
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    bullet point  Ocular Surface Development Laboratory
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    Shivalingappa (Shiva) Swamynathan, PhD
    Assistant Professor of Ophthalmology
    Laboratory of Ocular Surface Development
    University of Pittsburgh School of Medicine

    Lab Personnel
    Sudha Swamynathan (Research Technician)

    Research Interests

    In the mouse, following eye opening around 2 weeks after birth, cells in the 1-2 cell layered epithelium proliferate and differentiate to form a 4-5 cell layered stratified squamous epithelium by 20 days after birth. The mature corneal epithelium containing 5-8 cell layers is present by 6 to 8 weeks after birth. Krüppel-like transcription factors KLF4 and KLF5 are among the most abundant transcription factors in the mouse cornea. KLF4 and KLF5 share an identical DNA-binding domain and regulate a diverse array of critical cellular functions. Considering that Klf4-null and Klf5-null mice die before mature cornea is formed, we have resorted to conditional deletion of Klf4 and Klf5 gene in the surface ectoderm- derived tissues of the eye (lens, cornea, conjunctiva and eyelids) by mating Klf4-loxP or Klf5-loxP mice with Le-Cre mice. Klf4 conditional null (Klf4CN) and Klf5CN mice display normal viability and fertility, and a defective ocular surface. Detailed analysis of their ocular surface phenotype along with identification of the corneal and conjunctival KLF4-target genes as well as corneal KLF5-target genes provided new insights into the non-redundant roles of KLF4 and KLF5 in post-natal maturation of the ocular surface. We plan to pursue this line of work further to understand the molecular basis for diverse functions of KLF4 and KLF5 in maturation and maintenance of the ocular surface.

    In a second line of research, we are investigating the functions of the secreted Ly6/urokinase plasminogen activator receptor-related protein-1 (Slurp1), associated with the hyperkeratotic disorder Mal-de-Meleda. Slurp1 is one of the most abundantly expressed peptides in the mouse cornea and is secreted into the tear film. Our recent work demonstrated that Slurp1 expression is (i) increased upon mouse eyelid opening when the cornea is first exposed to the environment, (ii) critically dependent on the transcription factor KLF4, (iii) abrogated within 24 h of bacterial lipopolysaccharide injection or Herpes-Simplex-Virus Type-1 (HSV-1) infection concurrent with neutrophil infiltration, (iv) decreased in inflamed Klf4CN corneas, and (v) suppressed by pro-inflammatory cytokines IL-4, IL-13 and TNF-. More importantly, Slurp1 expression was significantly reduced in adenoviral keratitis model of corneal inflammation, restoration of which restricted the neutrophilic infiltrate, providing convincing evidence in favor of an immunomodulatory role for Slurp1. We are pursuing this line of work further to determine the value of Slurp1 as a target for developing novel therapeutic approaches for managing inflammatory disorders of the ocular surface.

    We are interested in grooming scientists with a serious commitment to basic research in ocular surface development. Graduate student or Postdoctoral research fellow positions are available to study the molecular mechanisms of regulation of gene expression during ocular surface development. If interested, please contact the PI by email (Swamynathansk@upmc.edu) with your CV and a short summary of your research experience and goals.

    Select Recent Publications
    1.Swamynathan, S.K.* (2013). Ocular surface development and gene expression. J Ophthalmol. 2013: 103947. doi: 10.1155/2013/103947. PMID: 23533700

    2.Swamynathan, S., Buela, K.A, Kinchington, P., Misawa, H., Lathrop, K.L., Hendricks, R.L. and Swamynathan, S.K.* (2012). Klf4 regulates the expression of Slurp1, which functions as an immunomodulatory peptide in the mouse cornea. Invest. Ophthalmol. Vis. Sci. 53:8433-8446. PMID: 23139280

    3.Kenchegowda, D., Harvey, S.A.K., Swamynathan, S., Lathrop, K.L. and Swamynathan, S.K.* (2012) Critical Role of Klf5 in Regulating Gene Expression during Post-Eyelid Opening Maturation of Mouse Corneas. PLoS ONE 7(9): e44771. doi:10.1371/journal.pone.0044771. PMID: 23024760

    4.Kenchegowda, D, Swamynathan, S, Gupta, D, Wan, H, Whitsett, J, and Swamynathan S.K*. 2011. Conditional disruption of mouse Klf5 results in defective eyelids with malformed meibomian glands, abnormal cornea and loss of conjunctival goblet cells. Dev. Biol. 356:5-18. PMID: 21600198

    5.Gupta, D., Harvey, S.A., Kaminski, N. and Swamynathan, S.K*. 2011. Mouse conjunctival forniceal gene expression during postnatal development and its regulation by Krüppel-like factor 4. Invest. Ophthalmol. Vis. Sci. 52:4951-4962. PMID: 21398290

    6.Swamynathan, S., Kenchegowda, D., Piatigorsky, J. and Swamynathan, S.K*. 2011. Regulation of the corneal epithelial barrier function by Krüppel-like transcription factor 4. Invest. Ophthalmol. Vis. Sci. 52:1762-1769. PMID: 21051695

    7.Swamynathan, S.K.* (2010). Kruppel-Like Factors: Three fingers in control. Human Genomics. 4(4): 1-8. PMID: 20511139

    8.Young, R.D., Swamynathan, S.K.*, Boote, C., Mann, M., Quantock, A.J., Piatigorsky, J., Funderburgh, J.L., and Meek, K.M. 2009. Stromal edema in Klf4 conditional null mouse cornea is associated with altered collagen fibril organization and reduced proteoglycans. Invest. Ophthalmol. Vis. Sci. 50:4155-4161. PMID: 19387067

    9.Swamynathan, S.K*., Davis, J. and Piatigorsky, J. (2008). Identification of candidate KLF4 target genes reveals the molecular basis of the diverse regulatory roles of KLF4 in the mouse cornea. Invest. Ophthalmol. Vis. Sci. 49: 3360-3370. PMID: 18469187

    10.Kozmik, Z., Swamynathan, S.K., Ruzickova, J., Jonasova, K., Paces, C., Vlcek, C., and Piatigorsky, J. (2008). Cubozoan crystallins: Evidence for convergent evolution of Pax regulatory sequences. Evol. Dev. 10: 52-61. PMID: 18184357

    11.Swamynathan, S.K. and Piatigorsky, J. (2007) Regulation of the mouse B-Crystallin and MKBP/HspB2 Promoter activities by shared and gene specific intergenic elements: The importance of context dependency. Int. J. Dev. Biol. 51: 689-700. PMID: 17939115

    12.Swamynathan, S.K*., Katz, J.P., Kaestner, K.H., Ashery-Padan, R., Crawford, M.A. and Piatigorsky, J. (2007) Conditional deletion of the mouse Klf4 gene results in corneal epithelial fragility, stromal edema, and loss of conjunctival goblet cells. Mol. Cell. Biol. 27: 182-194. PMID: 17060454

    13.Kanungo, J., Swamynathan, S.K., and Piatigorsky, J. (2004) Abundant corneal gelsolin in Zebrafish and the ‘Four-Eyed’ fish, Anableps anableps: Possible analogy with multifunctional lens crystallins. Experimental Eye Res. 79: 949-956. PMID: 15642334

    14.Swamynathan, S.K., Crawford, M.A., Robison Jr, W.G., Kanungo, J and Piatigorsky, J. (2003). Adaptive differences in the structure and macromolecular compositions of the air and water corneas of the four-eyed fish (Anableps anableps). FASEB Journal 17: 1996-2005. PMID: 14597669

    15.Kanungo, J., Kozmik, Z, Swamynathan, S.K., and Piatigorsky, J. (2003) Gelsolin is a dorsalizing factor in zebrafish. Proc. Natl. Acad. Sci. USA. 100: 3287-3292. PMID: 12629212

    16.Swamynathan, S.K. and Piatigorsky, J. (2002) Orientation-dependent influence of an intergenic enhancer on the regulation of transcription of the divergently transcribed mouse shsp/B-crystallin and MKBP/HSPB2 genes. J. Biol. Chem. 277: 49700-49706. PMID: 12403771
     
    Contact Information
    Shiva Swamynathan
    PhD
    412-802-6437
    Swamynathansk@upmc.edu
    EEINS-1025, 203 Lothrop St., Pittsburgh, PA 15213
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    bullet point  Retinal Development Laboratory
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    Xiangyun Wei, PhD
    Associate Professor of Ophthalmology,
    Microbiology and Molecular Genetics, and Developmental Biology Retinal Development Laboratory
    University of Pittsburgh School of Medicine

    Lab Personnel
    Chuanyu Guo, PhD (Postdoctoral Research Associate)


    Research Interests
    Multicellular organisms arrange cells in special patterns to form distinct structures through a set of developmental instructions that we do not fully understand. In my laboratory, we use the zebrafish retina as a model system to study the molecular mechanisms underlying cellular pattern formation in the central nervous system.

    The vertebrate retina develops from a single sheet of neuroepithelial cells, which later differentiate and reorganize into layered structures during retinal neurogenesis. Each retinal layer is composed of specific neuronal classes and executes distinct functions. The molecular mechanisms that control retinal pattern formation remain largely unknown.

    To understand how retinal cells organize, my lab uses a variety of experimental approaches that involve Genetics, Molecular Biology, Cell Biology, Biochemistry, and Developmental Biology. Our research is currently focused on the following areas: epithelial polarity in retinal morphogenesis; cell-cell adhesion in balancing tissue cohesion and cellular mobility; and cell nuclear structure in regulating retinal gene expression.

    Postdoctoral positions are available to study the molecular mechanisms of cellular pattern formation in the zebrafish retina

    Select Recent Publications

    1. J. Zou, X. Wang, and X. Wei (2012) Crb apical polarity proteins maintain zebrafish retinal cone mosaics via intercellular binding of their extracellular domains. Developmental Cell. May 9. [Epub ahead of print]

    2.J. Zou, X. Yang, and X. Wei (2010) Restricted Localization of Ponli, a Novel Zebrafish MAGUK-Family Protein, to the Inner Segment Interface Areas between Green, Red, and Blue Cones. Investigative Ophthalmology & Visual Science. 51 (3): 1738-1746.

    3.X. Yang, J. Zou, D. Hyde, L. Davidson, and X. Wei (2009) Stepwise maturation of apicobasal polarity of the neuroepithelium is essential for vertebrate neurulation. Journal of Neuroscience. 29:11426-11440.

    4.J. Zou, K. Lathrop, M. Sun, X. Wei (2008) Intact RPE maintained by Nok is essential for retinal epithelial polarity and cellular patterning in zebrafish. Journal of Neuroscience. 28(50):13684 –13695.

    5.X. Wei, C. Yan, Y. Luo, X. Shi, S. Nelson, and D. Hyde. (2004). The zebrafish Par-3 homolog is required for separation of the eye fields and retinal lamination, but not neuronal specification. Developmental Biology. 269:286-301.

    6.X. Wei and J. Malicki. (2002). nagie oko, encoding a MAGUK-family protein, is essential for cellular patterning of the retina. Nature Genetics. 31, 150-157.

    7.X. Wei, S. Somanathan, J. Samarabandu and R. Berezney. (1999). Three-dimensional visualization of transcription sites and their association with splicing factor-rich nuclear speckles. Journal of Cell Biology 146: 543-558.

    8.X. Wei, J. Samarabandu, R.S. Devdhar, A. Siegel. R. Acharya, R. Berezney. (1998) Segregation of transcription and replication sites into higher order domains. Science. 281: 1502-1505.
     
    Contact Information
    Xiangyun Wei
    PhD
    412-383-5845
    weix@upmc.edu
    BST 3 -5060,  3501 Fifth Ave., Pittsburgh, PA 15213 , 
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    bullet point  Trabecular Meshwork Cell Biology Laboratory
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    Yiqin Du, MD, PhD
    Assistant Professor of Ophthalmology
    University of Pittsburgh School of Medicine

    Lab Personnel
    Andrew E. Yang (Research Technician)
    Zoey Yi Zhou (Graduate Student)

    Research Interests
    Glaucoma is the leading cause of irreversible blindness throughout the world and the second leading cause of blindness overall in the USA. Increased resistance to aqueous humor outflow through the trabecular meshwork (TM) results in elevated intraocular pressure (IOP), the most important risk factor for glaucoma. Reduced TM cellularity is observed with age and correlates with increased outflow resistance and elevated IOP. Current therapies for control of IOP involve pharmacological reduction of aqueous production and surgical enhancement of outflow. But lowering of intraocular pressure by biological modification of TM function has remained elusive. Our research is currently focused on: identifying characteristics of trabecular meshwork stem cells in vitro and in vivo; investigating how the stem cells function in animal models of glaucoma; studying stem cell-based therapy for glaucoma using TM stem cells or other types of stem cells for autologous transplantation.

    Select Recent Publications

    1.Yiqin Du*, Danny Roh, Mary Mann, Martha Funderburgh, James Funderburgh, Joel Schuman. Multiple stem cells from trabecular meshwork become phagocytic TM cells. (*Corresponding author) Invest. Ophthalmol. Vis. Sci. 2012; 53: 1566-1575.

    2.Craig Boote*, Yiqin Du*, Sian R. Morgan , Jonathan Harris , Christina S. Kamma-Lorger , Sally Hayes , Kira L. Lathrop, Danny S. Roh, Michael K. Burrow, Jennifer Hiller , Nicholas J. Terrill , James L. Funderburgh, Keith M. Meek. Quantitative Assessment of Ultrastructure and Light Scatter in Mouse Corneal Debridement Wounds. (*contributed equally to this work). Invest. Ophthalmol. Vis. Sci. 2012; 53: 2786-2795.

    3.Jian Wu, Yiqin Du, James L Funderburgh, William R Wagner. The engineering of organized human corneal tissue through the spatial guidance of corneal stromal stem cells. Biomaterials 2012, 33: 1343-1352.

    4.Yiqin Du, Danny Roh, Martha Funderburgh, Mary Mann, Kacey Marra, Peter Rubin, Xuan Li, James Funderburgh. Adipose-Derived Stem Cells Differentiate to Keratocytes in vitro. Mol. Vis. 2010;

    5.Yiqin Du, Eric Carlson, Martha L. Funderburgh, Naxin Guo, David E. Birk, Winston W. Kao, James L. Funderburgh. Stem Cell Therapy Restores Transparency to Defective Murine Corneas. Stem Cells. 2009, 27 (7): 1635-1642.

    6.Yiqin Du, Nirmala Sundarraj, Martha L. Funderburgh, Stephen A. Harvey, David E. Birk, James L. Funderburgh. Secretion and Organization of a Cornea-like Tissue in vitro by Stem Cells from Human Corneal Stroma. Invest. Ophthalmol. Vis. Sci. 2007; 48: 5038-5045. PMCID: PMC2874676.

    7.Yanling Ma, Yongsheng Xu, Zhifeng Xiao, Wei Yang, Chun Zhang, E Song, Yiqin Du, Lingsong Li. Reconstruction of chemically burned rat corneal surface by bone marrow-derived human mesenchymal stem cells. Stem Cells. 2006; 24: 315 - 321.

    8.Yiqin Du, Martha L Funderburgh, Mary M Mann, Nirmala SundarRaj, James L Funderburgh. Multipotent Stem Cells in Human Corneal Stroma. Stem Cells. 2005; 23: 1266-1275.

    9.Martha L. Funderburgh, Yiqin Du, Mary M. Mann, Nirmala SundarRaj, James L Funderburgh. PAX6 Expression Identifies Progenitor Cells for Corneal Keratocytes. FASEB J. 2005; 19: 1371-1373.

    10.Yiqin Du, Jing Chen, James L Funderburgh, Xiuan Zhu, Lingsong Li. Functional reconstruction of rabbit corneal epithelium by human limbal cells cultured on amniotic membrane. Mol Vis. 2003; 9:635-643
     
    Contact Information
    Yiqin Du
    MD, PhD
    412-648-9826
    duy@upmc.edu
    S750 BST South, 3500 Terrace Street, Pittsburgh, PA 15261, 
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    bullet point  Viral Immunology Laboratory
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    Robert L. Hendricks, PhD
    Joseph F. Novak Endowed Chair
    Professor and Vice-Chair for Research
    Director, Ophthalmology & Visual Sciences Research Center
    Departments of Ophthalmology, Immunology, Microbiology and Molecular Genetics and Biochemistry
    University of Pittsburgh School of Medicine

    Lab Personnel
    Kate Carroll (Graduate Student)
    Moira Geary (Research Technician)
    Jared E. Knickelbein, MD/ PhD (Resident/ Fellow)
    Alexander Rowe, PhD (Postdoctoral Research Associate)
    Hongmin Yun MD, PhD (Research Associate)

    Research Interests
    Dr. Hendricks’ research focuses on three important aspects of the immune response to herpes simplex virus type 1 (HSV-1):

    HSV-1 induces immunopathology in the cornea of the eye that can lead to scarring and blindness. CD4 T cells through Th1 and Th17 cytokines mediate the inflammation in HSV-1 infected mouse corneas, providing an interesting and clinically important model for studying mechanisms of T cell-mediated inflammation and tissue destruction. The clarity of the corneal tissue permits direct observation of the developing inflammation, and the cornea facilitates manipulation of the T cell-antigen presenting cell interaction and local cytokine and chemokine functions, the focus of current studies.

    When corneas become scarred by recurrent bouts of HSV-1 induced inflammation the only recourse is corneal transplantation. Unfortunately patients with recurrent HSV-1 corneal disease reject transplanted corneas at a very high rate. Our laboratory is employing a model of corneal transplantation in mice to study the mechanisms of accelerated corneal graft rejection in mice with previous HSV-1 corneal disease.

    During primary infection at mucosal surfaces, HSV-1 invades sensory neurons, is transported to neuronal cell bodies in the sensory ganglia, and there establishes a latent (quiescent) infection. Reactivation from latency results in recurrent disease in innervated tissues including the cornea. Our laboratory first demonstrated that CD8 T cells provide active immunesurveillance of latently infected neurons, preventing reactivation from the latent state. We are currently characterizing T cell receptor specificity and function of CD8 T cells in latently infected sensory ganglia with the goal of developing vaccines or other means of augmenting their protective function.

    Select Recent Publications
    1.St. Leger, A.J., Peters, B., Sidney, J., Sette, A., and Hendricks, R.L.:Defining the herpes simplex virus-specific CD8+ T cell repertoire in C57BL/6 mice. J. Immunol. 186: 3927-3933, 2011

    2.Frank, G. M., A. J. Lepisto, M. L. Freeman, B. S. Sheridan, T. L. Cherpes, and R. L. Hendricks. 2010. Early CD4(+) T cell help prevents partial CD8(+) T cell exhaustion and promotes maintenance of Herpes Simplex Virus 1 latency. J.Immunol. 184:277-286.

    3. Sheridan, B. S., T. L. Cherpes, J. Urban, P. Kalinski, and R. L. Hendricks. 2009. Reevaluating the CD8 T-cell response to herpes simplex virus type 1: involvement of CD8 T cells reactive to subdominant epitopes. J.Virol. 83:2237-2245. PMC 2643732

    4. Knickelbein, J. E., K. M. Khanna, M. B. Yee, C. J. Baty, P. R. Kinchington, and R. L. Hendricks. 2008. Noncytotoxic lytic granule-mediated CD8+ T cell inhibition of HSV-1 reactivation from neuronal latency. Science 322:268-271. PMC 2680315

    5. Cherpes, T. L., J. L. Busch, B. S. Sheridan, S. A. Harvey, and R. L. Hendricks. 2008. Medroxyprogesterone acetate inhibits CD8+ T cell viral-specific effector function and induces herpes simplex virus type 1 reactivation. J.Immunol. 181:969-975. PMC 2553693

    6. Freeman, M. L., B. S. Sheridan, R. H. Bonneau, and R. L. Hendricks. 2007. Psychological stress compromises CD8+ T cell control of latent herpes simplex virus type 1 infections. J.Immunol. 179:322-328. PMC 2367250

    7. Sheridan, B. S., K. M. Khanna, G. M. Frank, and R. L. Hendricks. 2006. Latent virus influences the generation and maintenance of CD8+ T cell memory. J.Immunol. 177:8356-8364. PMC 2366996

    8. Decman, V., P. R. Kinchington, S. A. Harvey, and R. L. Hendricks. 2005. Gamma interferon can block herpes simplex virus type 1 reactivation from latency, even in the presence of late gene expression. J.Virol. 79:10339-10347. PMC 1182646

    9. Xu, M., A. J. Lepisto, and R. L. Hendricks. 2004. CD154 signaling regulates the Th1 response to herpes simplex virus-1 and inflammation in infected corneas. J.Immunol. 173:1232-1239.

    10. Khanna, K. M., R. H. Bonneau, P. R. Kinchington, and R. L. Hendricks. 2003. Herpes simplex virus-specific memory CD8+ T cells are selectively activated and retained in latently infected sensory ganglia. Immunity 18:593-603.
     
    Contact Information
    Robert L. Hendricks
    PhD
    412-647-5754
    hendricksrr@upmc.edu
    EEI-919, 203 Lothrop St., Pittsburgh, PA 15213
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    bullet point  Visual Neuroscience Laboratory
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    Matthew A. Smith, PhD
    Assistant Professor of Ophthalmology
    Visual Neuroscience Laboratory
    University of Pittsburgh School of Medicine

    Lab Personnel
    Sanjeev Khanna (Graduate Student)
    Roma O. Konecky, PhD ( Postdoctoral Research Associate)
    Robert Morrison (Graduate Student)
    Samantha Nelson (Research Technician)
    Adam C. Snyder, PhD (Postdoctoral Research Associate)

    Research Interests
    Our research employs neurophysiological and computational approaches to study the primate visual system. Specifically, we are interested in the dynamics of visual processing at the level of individual neurons and populations. We study how the temporal structure of neuronal responses can teach us about cortical circuits, how form processing is accomplished by a distributed network of neurons, and how populations of neurons integrate information provided by inputs within and between cortical regions.

    For more information, please follow these links:
    Visual Neuroscience Laboratory Website

    Select Recent Publications
    1. Snyder AC, Morais MJ, Smith MA (2013) Variance in population firing rate as a measure of slow time-scale correlation. Front Comput Neurosci, 7: 176

    2. Smith MA, Sommer MA (2013) Spatial and temporal scales of correlation in macaque V4. J Neurosci, 33: 5422–5432

    3. Smith MA, Jia X, Zandvakili A, Kohn A (2013) Laminar dependence of neuronal correlations in visual cortex. Journal of Neurophysiology, 109: 940–947

    4. Jia X, Smith MA, Kohn A (2011) Stimulus selectivity and spatial coherence of gamma components of the local field potential. J Neurosci, 31: 9390–9403

    5. Kelly RC, Smith MA, Kass RE, Lee TS (2010) Local field potentials indicate network state and account for neuronal response variability. J Comp Neurosci, 29: 567–579

    6.Smith MA, Kohn A (2008) Spatial and temporal scales of neuronal correlation in primary visual cortex. J Neurosci, 28: 12591–12603
     
    Contact Information
    Matthew A. Smith
    PhD
    412-647-2313
    smithma@pitt.edu
    EEINS-914, 203 Lothrop St., Pittsburgh, PA 15213
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    bullet point  Corneal Cell Biology Laboratory
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    James L. Funderburgh, PhD
    Professor of Ophthalmology
    Professor, Cell Biology & Physiology
    University of Pittsburgh School of Medicine

    Lab Personnel
    Martha Funderburgh (Lab Manager and Sr. Research Technician)
    Moira Geary (Research Technician)
    Mary Mann (Research Technician)

    Research Interests
    The Funderburgh lab focuses on the cornea, an organ that provides a visual portal to the world. The connective tissue of the cornea is extremely tough, and transparent to light. It also presents a significant biological barrier to infection. In millions of individuals, worldwide, however the cornea has lost its transparency due to disease or trauma. Corneal scarring can disrupt vision permanently. Our work focuses on the biological processes that produce and maintain the unique connective tissue of the cornea as well as the pathological changes that occur during scarring. These involve studies of extracellular matrix molecules and how they influence cell behavior.

    Our work extends to studies designed to reverse the scarring process or replace scarred cornea with bioengineered cornea tissue. Over the past few years we have explored the use of stem cells to restore corneal transparency. Using nanofiber scaffolding we found that stem cells produce a tissue identical to that of the transparent tissue of the cornea. We are developing this material to serve as replacement of corneal tissue in scarred eyes. I addition we have found that adult stem cells induce regeneration of corneal tissue, removing pathological tissue and replacing it with organized transparent new tissue. These adult cells can be obtained autologously, allowing individuals to treated with their own cells. Our lab is actively investigating the mechanism by which adult stem cells induce tissue regeneration and is developing an approach to clinical trials for using corneal stem cells to treat blindness.

    Select Recent Publications
    1.Wu J, Du Y, Watkins SC, Funderburgh JL, Wagner WR. The engineering of organized human corneal tissue through the spatial guidance of corneal stromal stem cells. Biomaterials 2011 November 10.

    2.Roh DS, Funderburgh JL. Rapid changes in connexin-43 in response to genotoxic stress stabilize cell-cell communication in corneal endothelium. Invest Ophthalmol Vis Sci 2011 July;52(8):5174-5182.

    3.Hara H, Koike N, Long C, Piluek J, Roh DS, SundarRaj N, Funderburgh JL, Mizuguchi Y, Isse K, Phelps CJ, Ball SF, Ayares DL, Cooper DK. Initial in vitro investigation of the human immune response to corneal cells from genetically engineered pigs. Invest Ophthalmol Vis Sci 2011 July;52(8):5278-5286.

    4.Du Y, Danny S. Roh, Martha L. Funderburgh, Mary M. Mann, Kacey G. Marra, J. Peter Rubin, Xuan Li, James L. Funderburgh. (2010) Adipose-derived stem cells differentiate to keratocytes in vitro Molecular Vision 2010; 16:2680-2689

    5.Guo N, Li X, Mann MM, Funderburgh ML, Du Y, Funderburgh JL. (2010) Hyaluronan synthesis mediates the fibrotic response of keratocytes to transforming growth factor beta. J Biol Chem. 2010 Aug 4. PMID: 20685654

    6.Y. Hayashi, MK. Call, T-I Chikama, H Liu, EC. Carlson, Y Sun, E. Pearlman, JL Funderburgh, G Baccock, C-Y Liu, Y O, and Winston Kao (2010) Requirement of Lumican for Neutrophil Extravasation Following Corneal Injury and Wound Healing. Journal of Cell Science, May 2010

    7.Impact on the corneal endothelium of mitomycin C during photorefractive keratectomy. Danny S. Roh and JL Funderburgh. Journal of Refractive Surgery 2009 Oct;25(10):894-7. PMID: 19835330

    8.Robert D. Young, Shivalingappa K. Swamynathan, Craig Boote, Mary Mann, Andrew J. Quantock, Joram Piatigorsky, James L. Funderburgh and Keith M. Meek. Stromal Edema in Klf4 Conditional Null Mouse Cornea is Associated with Altered Collagen Fibril Organization and Reduced Proteoglycans. Invest Ophthalmol Vis Sci. 2009 Sep;50(9):4155-61. PMID: 19387067

    9.Yiqin Du, Eric C Carlson, Martha L Funderburgh, David E Birk, Eric Pearlman, Naxin Guo, Winston W-Y Kao, James L Funderburgh. Stem Cell Therapy Restores Transparency To Defective Murine Corneas Stem Cells, 2009 Jul;27(7):1635-42.PMID: 19544455

    10.Danny S. Roh, Amanda L. Cook, Steven S. Rhee, Amar Joshi, Regis Kowalski, Deepinder K. Dhaliwal, James L. Funderburgh. DNA Cross-linking, Double-strand Breaks and Apoptosis in Corneal Endothelial Cells After a Single Exposure to Mitomycin-C. Invest Ophthalmol Vis Sci 2008; 49 (11) 4837-43. PMID 18658901
     
    Contact Information
    James L. Funderburgh
    Ph.D.
    412-647-3853
    jlfunder@pitt.edu
    EEINS-1011, 203 Lothrop Street, Pittsburgh PA 15213
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    bullet point  Outflow Tract Engineering Laboratory
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    Nils Loewen, MD, PhD
    Assistant Professor of Ophthalmology
    University of Pittsburgh School of Medicine

    Lab Personnel
    Ralitsa Loewen, MD ( Postdoctoral Research Associate)
    Pritha Roy Sangupta, MD ( Postdoctoral Research Associate)


    We are actively recruiting postdocs, technicians and students.

    Research Interests
    Novel glaucoma outflow treatments; Gene therapy; Lentiviral vectors
    Low pressure glaucoma; Suprachoroidal shunts

    In his basic research, Dr. Loewen’s lab is focused on bioengineering of the ocular outflow system to lower eye pressure. He spearheaded gene therapy for glaucoma with lentiviral vectors. He developed a technique to permanently genetically modify the outflow tract of the eye, the site of the primary pathology in glaucoma. His present research is focused on using these tools to reverse engineer a working outflow tract with stem cells as a novel treatment of glaucoma.

    Current Projects
    Clinical Research

    • Comparison of Two Micro-Incisional Glaucoma Surgeries
      We are comparing two safer and faster glaucoma surgeries in early to advanced glaucoma.

    • Change of Aqueous Outflow Patterns Following Trabecular Meshwork Ablation
      We are measuring live how outflow changes in patients who underwent trabectome surgery.


    Basic Research

    • Ocular outflow tract engineering using vector ablation and stem cells
      We are using gene therapy and stem cells to improve outflow and lower eye pressure in preclinical model systems.

    • In vivo mobilization of outflow tract stem cells
      We mobilize meshwork stem cells to regenerate the normal aqueous outflow

    For more information, please follow these links:
    Outflow Tract Engineering
     
    Contact Information
    Nils Loewen
    MD, PhD
    412-647-2152
    loewenna@upmc.edu
    EEINS-8th Floor, 203 Lothrop Street, PIttsburgh PA, 15213
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    bullet point  Biomedical Visualization Laboratory
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    Kira L. Lathrop, MAMS
    Assistant Professor of Ophthalmology
    Co-director, Imaging Module
    University of Pittsburgh School of Medicine
    Swanson School of Engineering/ Bioengineering

    Lab Personnel
    Jessica Steele (Lab Technician)


    Research Interests
    Imaging, microscopy, image analysis and quantitation, the Palisades of Vogt, optical coherence tomography, imaging ethics

    For more information, please follow these links:

    Select Recent Publicaitons
    1. Yun H, Lathrop KL, Yang E, Sun M, Kagemann l, Fu V, Stolz DB, Schuman JS, Du Y. A Laser-Induced Mouse Model with Long-Term Intraocular Pressure Elevation. PloS One 2014 Sep 12;999):e107446. DOI: 10.1371/journal pone.0107446. ecollection 2014.

    2. Sanfilippo PG, Grimm JL, Flanagan JG, Lathrop KL, Sigal IA. Application of Elliptic Fourier Analysis to Describe the Lamina Cribrosa Shape with Age and Intraocular Pressure. Exp. Eye Res. 2014 Sep 2; 128C:1-7. DOI: 10.1016/jexer.2014.08.013 [Epub ahead of print]

    3. Ksander BR, Paraskevi EK, Wilson BJ, Saab KR, Guo Q, Ma J, McGuire SP, Gregory MS, Vincent WJB, Perez VL, Cruz-Guilloty F, Kao WWY, Call MK, Tucker BA, Zhan Q, Murphy GF, Lathrop KL, Alt C, Mortensen LJ, Lin CP, Zieske JD, Frank MH, Frank NY. ABCB5 is a Limbal Stem Cell Gene Required for Corneal Development and Repair. Nature 02 July 2014 DOI 10.1038/nature13426

    4. Syed-Picard FN, Du Y, Lathrop KL, Mann M, Funderburgh ML, Funderburgh JL. Dental Pulp Stem Cells: a New Cellular Resource for Corneal Stromal Regeneration. Stem Cells Trans Med 03Jun14 in press

    5. Yun H, Rowe AM, Lathrop KL, Harvey SA, Hendricks RL. Reversible nerve damage and cornea pathology in murine herpes simplex stromal keratitis J Virol. 2014 Jul 15;88(14):7870-80. DOI 10.1128/JVI.01146-14. Epub 2014 Apr 30.

    6. Lathrop KL, Steketee MB. Mitochondrial Dynamics in Retinal Ganglion Cell Axon Regeneration and Growth Cone Guidance. J Ocul Biol. 2013 Sep 21;1(2):9.

    7. Medina CA, Rowe AM, Yun H, Knickelbein JE, Lathrop KL, Hendricks RL. Azithromycin Treatment Increases Survival of High-Risk Corneal Allotransplants. Cornea 2013 May;32(5):658-66. PMID:23407315

    8. Fu J, Fang W, Zou J, Sun M, Lathrop K, Su G, Wei X. A Robust Procedure for Distinctively Visualizing Zebrafish Retinal Cell Nuclei Under Bright Field Light Microscopy. J Histochem Cytochem 2013 March;61(3);248-56. PMID:23204114

    9. Swamynathan S, Buela KA, Kinchington P, Lathrop KL, Misawa H, Hendricks RL, Swamynathan SK. Klf4 regulates the expression of Slurp1, which functions as an immunomodulatory peptide in the mouse cornea. Invest Ophthalmol Vis Sci. 2012 Nov 8. doi:pii: iovs.12-10759v1. 10.1167/iovs.12-10759. (Epub ahead of print) Pubmed pmid: 23139280

    10. Thomas SM, Sahu B, Rapireddy S, Bahal R, Wheeler SE, Procopio EM, Kim J, Joyce SC, Contrucci S, Wany Y, Chiosea SI, Lathrop KL, Watkins S, Grandis JR, Armitage BA, Ly DH. Antitumor Effects of EGFR Antisense Guanidine-based Pep-tide Nucleic Acids in Cancer Models. ACS Biological Chemistry 2013 Feb15;8(2):345-352. PMID: 23113581


     
    Contact Information
    Kira L. Lathrop
    Assistant Professor
    412-647-3492
    lathropkl@upmc.edu
    EEINS-1032, 203 Lothrop Street, Pittsburgh PA 15213
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    bullet point  Ocular Surface Regenerative Therapy Laboratory
    a dividing bar
     
     
    Ladan Espandar, MD, MS
    Assistant Professor of Ophthalmology
    University of Pittsburgh School of Medicine

    Lab Personnel
    Jacqueline Vasseur (Research Technician)

    Research Interests
    Corneal clarity is critical to maintain accurate vision. The corneal epithelium on the surface of the eye is subject to constant erosion from the external environment, and it is replaced by a persistent self-renewal process of corneal epithelial stem cells, that are located in the outer corneal area known as the limbus. Potential blinding injuries such as chemical burn can cause limbal stem cell deficiency (LSCD), in which there are persistent epithelial defects, corneal vascularization and lack of epithelial cell renewal. Despite advances in surgical techniques, LSCD remains one of the most difficult and challenging conditions for clinicians to manage. Our lab focus is to evaluate a basis of new treatment strategies for eyes of those inflicted with LSCD, in which the healthy limbal microenvironment is re-established using stem cells from the same person adipose tissue. Our work emphases on adult stem cell biology specifically anti-inflammatory property of adipose derived stem cells in re-establishment of limbal niche and the molecular mechanism(s) of adipose derived stem cells and limbal epithelial stem cell interactions in limbal stem cell microenvironment restoration. Our long-term goal is to find potential points of intervention for therapeutic benefit in future fundamental and clinical studies to develop more effective stem cell therapies for the patients suffering from LSCD induced corneal blindness.

    For more information, please follow these links:
    Ocular Surface Regenerative Therapy Laboratory Website


    Select Recent Publications

    1. Blanco-Mezquita T, Espandar L, Torres R, Alvarez-Barcia A, Cantalapiedra-Rodriguez R, Martinez-Garcia C, Merayo-Lloves J. Does mitomycin C cause toxicity in the cornea after photorefractive keratectomy? A comparative wound-healing study in a refractive surgery animal model. Cornea. 2014 Nov;33(11):1225-31. PubMed PMID: 25170578.

    2. Espandar L, Caldwell D, Watson R, Blanco-Mezquita T, Zhang S, Bunnell B. Application of adipose-derived stem cells on scleral contact lens carrier in an animal model of severe acute alkaline burn. Eye Contact Lens. 2014 Jul;40(4):243-7. PubMed PMID: 24901976.

    3. Espandar L, Boehlke CS, Kelly MP. First report of keratitis in familial cold autoinflammatory syndrome. Can J Ophthalmol. 2014 Jun;49(3):304-6. PubMed PMID: 24862780.

    4. Espandar L, Cummings TJ, Boehlke CS. Unilateral microsporidia keratitis in a healthy non-contact lens wearer. JAMA Ophthalmol. 2014 Jul;132(7):822. PubMed PMID: 24830662.

    5. Espandar L, Allingham RR, Afshari NA. Stromal duplication of the iris. JAMA Ophthalmol. 2013 Nov;131(11):1442. PubMed PMID: 24232083.

    6. Espandar L, Carlson AN. Lamellar keratoplasty: a literature review. J Ophthalmol. 2013;2013:894319. Epub 2013 Oct 7. Review. PubMed PMID: 24223301; PubMed Central PMCID: PMC3816057.

    7. Zhang S, Espandar L, Imhof KM, Bunnell BA. Differentiation of Human Adipose-derived Stem Cells along the Keratocyte Lineage In vitro. J Clin Exp Ophthalmol. 2013 Feb 27;4(270). pii: 11435. PubMed PMID: 23936748; PubMed Central PMCID: PMC3737075.

    8. Tandon A, Espandar L, Cupp D, Ho S, Johnson V, Ayyala RS. Surgical management or postkeratoplasty glaucoma: a meta-analysis. J Glaucoma. 2014 Sep;23(7):424-9. PubMed PMID: 23221909.

    9. Espandar L, Bunnell B, Wang GY, Gregory P, McBride C, Moshirfar M. Adipose-derived stem cells on hyaluronic acid-derived scaffold: a new horizon in bioengineered cornea. Arch Ophthalmol. 2012 Feb;130(2):202-8. PubMed PMID: 22332213.

    10. Moshirfar M, Khalifa YM, Davis D, Fenzl CR, Espandar L, Chang JC, Mamalis N, Mifflin MD. Descemet stripping automated endothelial keratoplasty using donor corneas with previous laser in situ keratomileusis or photorefractive keratectomy: a case series and donor cap histopathology. Cornea. 2012 May;31(5):533-7. PubMed PMID: 21993455.

     
    Contact Information
    Ladan Espandar
    MD, MS
    espandarl@upmc.edu
    EEINS- 1029 Floor, 203 Lothrop Street, Pittsburgh PA 15213
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    bullet point   Optic Nerve Regeneration Laboratory
    a dividing bar
     
     
    Mike Steketee, PhD
    Assistant Professor of Ophthalmology
    Louis J. Fox Center for Vision Restoration
    McGowan Institute for Regenerative Medicine
    University of Pittsburgh School of Medicine

    Lab Personnel
    Anne Faust
    Asma Naqvi
    Yolandi van der Merwe
    Tanchen Ren

    Research Interests

    Translational nanotechnology
    Delivering therapeutics specifically to injured central nervous system axons is a persistent clinical and biological problem. To address this problem, I am developing nanoparticle-based platforms to deliver molecular and genetic therapeutics to injured axons in vivo.

    Targeting and manipulating Trk signaling endosomes with magnetic nanoparticles. Successfully targeted functionalized magnetic nanoparticles (fMNPs) to active TrkB signaling endosomes in retinal ganglion cells (RGCs) in vitro and in vivo, indicating fMNPs may provide a viable platform for delivering therapeutics to inaccessible regions of the injured central nervous system. I am currently expanding this work in collaboration with Shanta Dhar, Ph.D. at the University of Georgia to target therapeutics specifically to mitochondria in retinal ganglion cell axons to modulate mitochondrial activity after injury with the goal of reducing reactive oxygen species production and associated neurodegenerative damage.

    Extracellular Matrix technology
    Reconstructive tissue repair in the retina and optic nerve remains a persistent clinical problem. Extracellular matrix technology (ECM) has been successfully applied to promote regeneration in most organs and tissues throughout the body, including lung, heart, muscle, and skin. However, the application of ECM technology to the central nervous system has been limited. In collaboration with Dr. Stephen Badylak’s laboratory, we are applying extracellular matrix technology to the injured retina and optic nerve to prevent neurodegeneration and to reduce destructive immune system inflammation while promoting constructive immune system repair.

    Mitochondrial biology in CNS axons
    Mitochondria are ubiquitously located in the axonal growth cone during development and regeneration. However, their role in axon growth is largely unstudied. We recently showed that mitochondrial dynamics are developmentally regulated in RGC axons, mitochondrial dynamics regulate both intrinsic axon growth and guidance responses to extrinsic cues, and increasing mitochondrial fusion but not fission, permits retinal ganglion cells to cross inhibitory CSPG borders in culture without reducing neurite growth, suggesting that altering mitochondrial dynamics after injury may provide a novel strategy to improve CNS axon regeneration. I am expanding this work to identify how mitochondria regulate signaling in the growth cone during axon regeneration to determine how mitochondrial dynamics and function can be manipulated to promote axon regeneration through non-permissive tissues in the injured CNS.

    Nuclear-encoded mitochondrial genes are regulated in CNS by activity. Showed that light induced activity increases the local translation of nuclear encoded mRNAs that localize to the outer mitochondrial membrane in RGC axons in vivo. Developed a novel method to isolate mitochondria directly from pre- and post injured RGC axons in vivo for transcript- and proteomic analyses before and after traumatic optic neuropathies. I am expanding this work to identify the molecular mechanisms regulating the activity-dependent localization of nuclear-encoded electron transport chain mRNAs to mitochondria in the retinal ganglion cell axons.

    Growth cone biology
    Growth cone dynamics regulate intrinsic neurite growth rate in RGCs. We recently showed that decreased intrinsic axon growth ability in RGC neurons is mediated by distinct changes in growth cone motility, not a general failure in axon growth ability. I am expanding this work to determine how increasing intrinsic axon growth potential in retinal ganglion cells influences growth cone guidance decisions during regeneration with the long term goal of promoting axon target reinnervation with temporal and spatial specificity.


    For more information, please follow these links:
    Louis J. Fox Center for Vision Restoration

    Select Recent Publications

    1. Pita-Thomas, W., Steketee, M.B., Moysidis, S.N., Thakor, K., Hampton, B., Goldberg, J.L. (2014) Promoting filopodial elongation in neurons by membrane-bound magnetic nanoparticles. Nanomedicine: Nanotechnology, Biology, and Medicine. In Press.

    2. Steketee, M.B., Daneman, R., Lamoureax, P., Wang, J.T., Heideman, S., Barres, B., Goldberg, J.L. (2014) Decreased axon growth ability is regulated developmentally at the growth cone in retinal ganglion cells. IOVS.

    3. Lathrop, K. and Steketee, M.B. (2013) Mitochondrial dynamics in retinal ganglion cell axon regeneration and growth cone guidance. Peer Reviewed Review, Journal of Ocular Biology. (2013).

    4. Steketee M.B. and Goldberg, J.L. (2012) Signaling endosomes and growth cone motility in axon regeneration. Axon Growth and Regeneration. International review of Neurobiology.

    5. Steketee, M.B., Moysidis, S., Kreymerman, A., Silva, J., Weinstein, J.E., Iqbal S., Goldberg, J.L. (2012) Mitochondrial dynamics regulate growth cone motility, guidance, and neurite growth rate in retinal ganglion cells. IOVS 12:10298

    6. Steketee, M.B., Moysidis, S.N., Weinstein, J.W., Pita-Thomas, W, Xiao-Lu Jin, Raju, H.B., Iqbal, S., Goldberg, J.L. (2011) Signaling endosome localization regulates growth cone dynamics and neurite growth, PNAS 2011 108 (47) 19042-19047

    7. Steketee, M., and K.W. Tosney (2002) Three Functionally Distinct Adhesions in filopodia: shaft adhesions control lamellar extension, J. Neurosci. 22: 8071-8083

    8. Steketee, M., K. Balazovich, and K.W. Tosney (2001) Filopodial initiation and a novel filament-organizing center, the focal ring. Mol. Biol. Cell 2001 12: 2378-2395

    9. Steketee, M. and K.W. Tosney (1999). Contact with isolated sclerotome cells steers sensory growth cones by altering distinct elements of extension. J. Neurosci. 19: 3495-3506.

    10. Steketee, M. (2000). Sensory growth cone guidance by filopodial contact, filopodial initiation, and a novel actin filament organizing center, the focal ring. Dissertation. Neuroscience Program, University of Michigan Medical School.

     
    Contact Information
    Mike Steketee, PhD
    412-624-9936
    stekem@pitt.edu
    McGowan Institute, 450 Technology Drive, Suite 300, Pittsburgh, PA, 15219
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    bullet point  Charles & Louella Snyder Ocular Development, Disease and Regeneration Laboratory
    a dividing bar
     
     
    Jeffrey M. Gross, PhD
    Professor of Ophthalmology
    E. Ronald Salvitti Chair in Ophthalmology Research
    Director, Louis J. Fox Center for Vision Restoration
    University of Pittsburgh School of Medicine

    Lab Personnel
    Krista Angileri (Graduate Student)
    Natalie Gath (Graduate Student)
    Nick Hanovice (Graduate Student)
    Andrea Hartsock, PhD (Postdoctoral Research Associate)
    Jiwoon Lee, PhD (Postdoctoral Research Associate)
    Pawat Seritrakul (Graduate Student)

    Research Interests
    Our research focuses on vertebrate eye development, disease and regeneration utilizing the zebrafish as a model system. Combining forward genetic screens with reverse genetic and embryological manipulations we hope to understand the molecular, cellular and developmental events that regulate eye formation and visual function. Current areas of interest in the lab include studies focusing on the development and maintenance of the lens, retina, hyaloid vasculature and retinal pigmented epithelium of the eye, and elucidation of the molecular and cellular mechanisms that regulate ocular morphogenesis and regeneration Our research combines molecular, cellular, biochemical, transgenic and in vivo imaging techniques to address these questions. It is our hope that these studies will ultimately lead to a better understanding of visual system disorders such as macular degeneration, retinal degenerations, cataracts and ocular colobomata that often result in blindness in afflicted patients.

    For more information, please follow these links:
    Ocular Development, Disease and Regeneration Laboratory
    Louis J. Fox Center for Vision Restoration

    Select Recent Publications

    1. Hartsock A, Arnold V, Lee C and JM Gross “In Vivo Analysis of Hyaloid Vasculature Morphogenesis in Zebrafish: A role for the lens in maturation and maintenance of the hyaloid” – Developmental Biology – 394(2):327-39 (2014)

    2. Lee C, JB Wallingford and JM Gross – “Mutation in cluap1/qilin results in photoreceptor degeneration in zebrafish” – Investigative Ophthalmology and Visual Science – 55(7):4585-4592 (2014)

    3. Seritrakul P and JM Gross “Expression of the de novo DNA Methyltransferases (dnmt3-dnmt8) during zebrafish lens development” - Developmental Dynamics - Feb;243(2):350-6 (2014)

    4. Shine L, Kilty C, Gross JM, and B Kennedy “Vacuolar ATPases and their role in vision” in Retinal Degeneration 2013 (2014)

    5. Daly CMS, Willer J, Gregg RG and JM Gross “snow white, a zebrafish model of Hermansky-Pudlak Syndrome Type 5” Genetics Oct;195(2):481-94. (2013)

    6. Lee J, Lee BK and JM Gross “Bcl6a function is required during optic cup formation to prevent p53-dependent apoptosis and colobomata” Human Molecular Genetics Sep 1;22(17):3568-82 (2013)

    7. Lee J, Cox BD, Daly C, Lee C, Nuckels RJ, Tittle RK, Uribe RA and JM Gross “An ENU mutagenesis screen in zebrafish for visual system mutants identifies a novel splice-acceptor site mutation in patched2 that results in colobomas” Investigative Ophthalmology and Visual Science – 53(13):8214-21 (2012)

    8. Hayes J, Hartsock A, Napier H, Link BA and JM Gross “Integrin alpha5/Fibronectin and Focal adhesion kinase are required for normal lens development in zebrafish” – Molecular Biology of the Cell – 23(24) 4725-38 (2012)

    9. Luo J, Uribe RA, Hayton S, Calinescu A, Gross JM, PF Hitchcock “Midkine-A functions upstream of Id2a to regulate cell cycle kinetics in the developing vertebrate retina” Neural Development - 7(1):33 (2012)

    10. Uribe RA, Kwon T, Marcotte EM, JM Gross "Id2a functions to limit Notch pathway activity and thereby influence the transition from proliferation to differentiation of retinoblasts during zebrafish retinogenesis"– Developmental Biology, 371, 280-292 (2012)
     
    Contact Information
    Jeff Gross
    PhD
    412-383-7325
    grossjm@pitt.edu
    BST-3 2028, 3501 Fifth Avenue, Pittsburgh, PA 15213
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    bullet point  Ophthalmic Biomaterials Lab
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    Morgan Fedorchak, PhD
    Assistant Professor of Ophthalmology

    Lab Personnel
    Liza Bruk, BS—PhD Student, Bioengineering

    Research Interests
    Drug delivery, biomaterials, regenerative medicine, tissue engineering, glaucoma

    The Ophthalmic Biomaterials Lab focuses on the engineering of novel materials to address critical issues in ophthalmology. This includes the development of a completely unique, semi-permanent eye drop platform for delivering ophthalmic drugs. Controlled release systems are of particular interest in the eye, where patients stand to benefit greatly from significantly decreased dosing frequency and risk of side effects. Our lab is currently testing a number of these systems for a variety of diseases, including glaucoma and ocular infection. Another aim of the lab is regeneration and/or protection of ocular tissues using readily-translatable biomimetic materials.

    For more information, please follow these links:
    The Fedorchak Lab
    McGowan Institute for Regenerative Medicine
    Louis J. Fox Center for Vision Restoration
    Swanson School of Engineering

    Select Recent Publications
    Dr. Fedorchak's Publications

    Funding Support
    Wallace H. Coulter Foundation
    Research to Prevent Blindness
    National Eye Institute
    Commonwealth of Pennsylvania

    Announcements
    The Ophthalmic Biomaterials Lab is currently seeking highly qualified applicants for an open postdoctoral research position in the field of drug delivery. If interested, please contact Dr. Fedorchak (fedorchak@pitt.edu) and include a copy of your CV.


     
    Contact Information
    Morgan Fedorchak, PhD
    412-624-8625
    fedorchak@pitt.edu
    EEINS- 930 Floor, 203 Lothrop Street, Pittsburgh PA 15213
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