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Fall 2011
Newsletter

STUDENT RESEARCH

Click the following links for information on current research opportunities.
 


Jacque Duncan, M.D. - Retinitis Pigmentosa and Age-related Macular Degeneration
Jennifer La Vail, Ph.D. - The Intracellular Transport of Neurotropic Viruses
Todd Margolis, M.D., Ph.D. - Neuronal Regulation of Herpes Simplex Virus Infection
David Sretavan, M.D., Ph.D. - Retinal Axons in Growth and Disease

(more opportunities to come soon!)


Jacque L. Duncan, MD
Email: duncanj@vision.ucsf.edu
Phone : 415-514-4241

Our research is focused on patients with inherited retinal degenerations, like retinitis pigmentosa, Stargardt disease, and age-related macular degeneration. Patients with all these diseases eventually lose their photoreceptors and ultimately, their vision. We use novel, high-resolution imaging devices to look at the central cone photoreceptors in patients with inherited retinal degenerations with the following goals:

1. To understand how different genetic mutations affect photoreceptor structure and survival.

2. To develop a new way of monitoring photoreceptor loss during disease progression over time.

3. To study the effects of new treatments for inherited retinal degenerations by direct visualization of the affected cone photoreceptors in patients participating in clinical trials.

We welcome UCSF and visiting medical students, graduate students and post-doctoral fellows interested in joining our group for summer, 3 month and year-long projects to contact Dr. Duncan directly at duncanj@vision.ucsf.edu.

Recent Publications:

Talcott,K.E., Ratnam,K., Sundquist,S.M., Lucero,A.S., Lujan,B.J., Tao,W., Porco,T.C., Roorda,A., & Duncan,J.L. "Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic factor treatment" Invest. Ophthalmol. Vis. Sci. published 18 November 2010, 10.1167/iovs.10-6479 [publish ahead of print]

Duncan,J.L., Talcott,K.E., Ratnam,K., Sundquist,S.M., Lucero,A.S., Day,S., Zhang,Y., Roorda,A. Cone structure in retinal degeneration caused by mutations in the peripherin/RDS gene. Invest. Ophthalmol. Vis. Sci. doi: 10.1167/iovs.10-6549 (2010) [publish ahead of print]

Godara P, Dubis A, Roorda A, Duncan JL, Carroll J. Adaptive optics retinal imaging: emerging clinical applications. Optometry and Vision Science, [publish ahead of print]

Yoon MK, Roorda A, Zhang Y, Nakanishi C, Wong L-JC, Zhang Q, Gillum L, Green A, Duncan JL. Adaptive optics scanning laser ophthalmoscopy images demonstrate abnormal cone structure in a family with the mitochondrial DNA T8993C mutation. Investigative Ophthalmology and Visual Science, 2009;50(4):1838-1847.

Roorda A, Zhang Y, Duncan J. High-resolution in vivo imaging of the RPE mosaic in eyes with retinal disease. Investigative Ophthalmology and Visual Science, 2007; 48(5):2297-2303.

Duncan JL, Zhang Y, Gandhi J, Nakanishi C, Othman M, Branham KEH, Swaroop A, Roorda A. High resolution imaging of cones in patients with inherited retinal degenerations using adaptive optics. Investigative Ophthalmology and Visual Science, 2007; 48(7):3283-3291.

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David W. Sretavan M.D., Ph.D.

email: SretavanD@vision.ucsf.edu

  

Our laboratory is interested how retinal ganglion cells and their axons interact with the cellular and molecular environment of the optic nerve in the settings of trauma and disease. Specific research areas include:

1) Retinal axon responses and survival in the optic nerve following acute trauma and chronic progressive injury.

2) Novel methods for axon repair utilizing micro and nanotechnology platforms.

Research studies are conducted using various mouse models of traumatic CNS, PNS injury and glaucomatous optic neuropathy. Methodologies include microscale cell culture, time-lapse microscopy, in vivo manipulations, thin film neuronal micropatterning, microfabricated surgical devices, and microfluidics. Research opportunities are available to UCSF and visiting students usually as 12 month projects, although 3 month or summer research projects will also be considered.

Selected publications

Liu, X., Hawkes, E., Ishimaru, T., Tran, T., Sretavan, D. EphB3 : An Endogenous Mediator of Adult Axon Plasticity After CNS Injury. J. Neurosci. 26: 3087-3101, 2006. PMID: 16554460.

Chang, W., Hawkes, E., Kliot, M., Sretavan, D. In Vivo Use Of A Nanoknife For Axon Microsurgery. Neurosurgery 61: 683-692, 2007. PMID: 17986929

Chang, W., Sretavan, D. Novel High-Resolution Micropatterning for Neuron Culture Using Poly-lysine Adsorption On A Cell Repellant, Plasma Polymerized Background. Langmuir 24: 13048-13057, 2008. PMID: 18925765

Fu, C., Tran, T., Sretavan, D. Axonal/Glial Upregulation of EphB/ephrin-B Signaling in CD-1 Mouse Experimental Ocular Hypertension. Invest. Ophthal. Vis. Sci. Epub 2009 Oct 8. PMID: 19815726

Chang, W.C., Hawkes, E., Keller, C. and Sretavan, D.W. Axon Repair: Surgical Applications At A Subcellular Scale. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010 Jan 25. [Epub ahead of print]. PMID: 20101712

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Jennifer LaVail, Ph.D

phone: (415) 476-1694
email: jhl@itsa.ucsf.edu

  

Understanding the mechanisms of intraaxonal transport of neurotropic viruses is the key to understanding and controlling their spread between the epithelial surface and the nervous system. A second focus of the lab is to understand the mechanisms by which Herpes virus spreads within and between corneal cells.  Specific research areas include:

1) Mechanism that control the assembly and transport of Herpes simplex virus in neurons.

2) Real-time imaging of the movement of GFP-labeled viral protein in axons.

3) Host cell and viral glycoproteins that direct the spread of virus in corneal epithelium.

4) Factors that affect viral patterns of encephalitis.

To carry out these studies, we have identified two viral mutant strains that will facilitate our research into these transport mechanisms. We analyze their behaviors using cell culture, immunohistochemistry, electron microscopy and protein chemistry. We are looking for UCSF and visiting medical and graduate students to join our group for long-term projects as well as for 3 month projects.

Selected publications

Ohara, P.T., Chin, M.S. and J.H. LaVail. The spread of Herpes Simplex Virus type 1 from trigeminal neurons to cornea: an immunoelectron microscopy study. J.Virol. 74:4776-4786, 2000.

Bearer, E.L., X.O. Breakefield, D. Schuback, T.S. Reese and J.H. LaVail. Retrograde axonal transport of herpes simplex virus: evidence for a single mechanism and a role for tegument. P.N.A.S. (USA), 97 (14): 8146-8150, 2000

Ohara, P.T., Tauscher, A.N. and J.H. LaVail. Two paths for dissemination of Herpes simplex virus from infected trigeminal ganglion to murine cornea. Brain Res. 899: 260-263, 2001.

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Todd P. Margolis M.D., Ph.D.

email: tpms@itsa.ucsf.edu

Our laboratory is primarily interested in neuronal regulation of latent infection with Herpes Simplex Virus.

Specific research areas include:

1) Identifying and characterizing neuronal gene products that
repress productive HSV infection.

2) Differences in the regulation of latent infection of HSV-1 and
HSV-2.

3) The development of a novel model for studying spontaneous
reactivation of HSV-1 from latent infection.

Research studies are conducted using techniques ranging from basic molecular methods, to cell culture systems to mouse models of HSV ocular disease. We also make extensive use of fluorescence and confocal microscopy and in situ hybridization. Research opportunities are available to UCSF and visiting students usually as 12 month projects, although 3 month or summer research projects will also be considered.

We have recently expanded our research interests to include the study of the molecular genetics of corneal dystrophies.

Selected publications

Yang L, CC Voytek and TP Margolis. Immunohistochemical Analysis of Primary
Sensory Neurons Latently Infected with Herpes Simplex Virus. J. Virol 74:209-217,
2000.

Ellison A, L Yang and TP Margolis: Establishment of Latent Herpes SimplexVirus type 1 Infection in Resistant, Sensitive and Immunodeficient Mouse Strains. Virology 268:17-28, 2000.

Summers BC, TP Margolis and DA Leib: HSV-1 Corneal Infection Results in Periocular Disease by Zosteriform Spread. J. Virol. 75:5069-5075, 2001.

Feldman LT, AR Ellison, CC Voytek, L Yang, P Krause and TP Margolis. Molecular Reactivation of HSV-1 Latency in Mouse Trigeminal Ganglia. Proc. Natl. Acad. Sci. 99:978-83, 2002.

Ellison AR, L Yang, AV Cevallos and TP Margolis: Analysis of the HSV UL6 Coding Region in Patients with HSV Necrotizing Stromal Keratitis. Virology 310: 24-26, 2003.

Warren JF, Aldave AJ, Srinivasan M, Thonar EJ, Kumar AB, Cevallos V, Whitcher JP,
Margolis TP. Novel mutations in the CHST6 gene associated with macular corneal
dystrophy in southern India. Arch Ophthalmol. 2003 Nov; 121(11): 1608-12.

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