Gwen Lagoda

Johns Hopkins Medicine, Baltimore, Maryland, United States

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Publications (53)121.98 Total impact


  • No preview · Article · May 2015 · Journal of Sexual Medicine

  • No preview · Article · May 2015 · Journal of Sexual Medicine
  • G. Lagoda · U. Anele · T. Goetz · A. L. Burnett

    No preview · Article · May 2015 · Journal of Sexual Medicine
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    ABSTRACT: IntroductionErectile dysfunction is a major complication of radical prostatectomy, commonly associated with penile neuropathy. In animal models of peripheral nerve injury, glial growth factor-2 (GGF2), a member of the neuregulin family of growth factors, has neuroprotective and neurorestorative properties, but this potential has not been established after cavernous nerve (CN) injury.AimsThe effectiveness of GGF2 in preserving axonal integrity and recovering erectile function in a rat model of radical prostatectomy-associated CN injury.Methods Adult male Sprague-Dawley rats underwent bilateral CN crush injury (BCNI) or sham surgery. Rats were administered GGF2 (0.5, 5, or 15 mg/kg) or vehicle subcutaneously 24 hour pre and 24-hour post-BCNI, and once weekly for 5 weeks. Erectile function was assessed in response to electrical stimulation of the CN. CN survival was assessed by fluorogold retrograde axonal tracing in major pelvic ganglia (MPG). Unmyelinated axons in the CNs were quantitated by electron microscopy.Main Outcome MeasuresErectile function recovery, CN survival, and unmyelinated CN axon preservation in response to GGF2 treatment following BCNI.ResultsErectile function was decreased (P < 0.05) after BCNI, and it was improved (P < 0.05) by all doses of GGF2. The number of fluorogold-labeled cells in the MPG was reduced (P < 0.05) by BCNI and was increased (P < 0.05) by GGF2 (0.5 and 5 mg/kg). The percentage of denervated Schwann cells in the BCNI group was higher (P < 0.05) than that in the sham-treated group and was decreased (P < 0.05) in the GGF2-treated (5 mg/kg) BCNI group. In the BCNI + GGF2 (5 mg/kg) group, the unmyelinated fiber histogram demonstrated a rightward shift, indicating an increased number of unmyelinated axons per Schwann cell compared with the BCNI group.ConclusionsGGF2 promotes erectile function recovery following CN injury in conjunction with preserving unmyelinated CN fibers. Our findings suggest the clinical opportunity to develop GGF2 as a neuroprotective therapy for radical prostatectomy. Burnett AL, Sezen SF, Hoke A, Caggiano AO, Iaci J, Lagoda G, Musicki B, and Bella AJ. GGF2 is neuroprotective in a rat model of cavernous nerve injury-induced erectile dysfunction. J Sex Med **;**:**–**.
    No preview · Article · Feb 2015 · Journal of Sexual Medicine
  • W.C. Perkins · G.A. Lagoda · A. Burnett · N.M. Fried
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    ABSTRACT: Identification and preservation of the cavernous nerves (CNs) during prostate cancer surgery is critical for post-operative sexual function. Electrical nerve stimulation (ENS) mapping has previously been tested as an intraoperative tool for CN identification, but was found to be unreliable. ENS is limited by the need for electrode-tissue contact, poor spatial precision from electrical current spreading, and stimulation artifacts interfering with detection. Alternatively, optical nerve stimulation (ONS) provides noncontact stimulation, improved spatial selectivity, and elimination of stimulation artifacts. This study compares ENS to pulsed/CW ONS to explore the ONS mechanism. A total of eighty stimulations were performed in 5 rats, in vivo. ENS (4 V, 5 ms, 10 Hz) was compared to ONS using a pulsed diode laser nerve stimulator (1873 nm, 5 ms, 10 Hz) or CW diode laser nerve stimulator (1455 nm). Intracavernous pressure (ICP) response and nerve compound action potentials (nCAPs) were measured. All three stimulation modes (ENS, ONS-CW, ONS-P) produced comparable ICP magnitudes. However, ENS demonstrated more rapid ICP response times and well defined nCAPs compared to unmeasurable nCAPs for ONS. Further experiments measuring single action potentials during ENS and ONS are warranted to further understand differences in the ENS and ONS mechanisms.
    No preview · Article · Jan 2015
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    ABSTRACT: Optical nerve stimulation (ONS) is being explored as an alternative to electrical nerve stimulation (ENS) for use as an intra-operative diagnostic method for identification and preservation of prostate cavernous nerves (CNs) during radical prostatectomy. Nerve priming and fatigue studies were performed to further characterize CNs and provide insight into the different ONS and ENS mechanisms. ONS studies were conducted using a 1455-nm diode laser, coupled to fiber optic probe, and delivering a collimated, 1-mm-diameter laser spot on CNs. For nerve priming studies, laser power was escalated in 5 mW increments (15 - 60 mW) with each stimulation lasting 15 s, until a strong ICP response was observed, and then power was similarly de-escalated. For ONS fatigue studies, a constant laser power was delivered for a period of 10 min. ENS studies were conducted for comparison, with standard parameters (4 V, 5 ms, 16 Hz) for fatigue studies (10 min. duration), but incrementally increasing/decreasing voltage (0.1 - 4.0 V) for priming studies with 15 s stimulations. ONS threshold was approximately 20% higher during initial escalating laser power steps (6.4 W/cm2) than in subsequently de-escalating laser power steps (5.1 W/cm2), demonstrating a nerve priming effect. Evidence of nerve priming during ENS was not observed. For nerve fatigue studies, ONS of CNs showed a peak ICP response at about 60 s, followed by a gradual decay in ICP, while ENS maintained a strong, but cyclical ICP. Nerve priming may allow repetitive ONS of CNs at lower and hence safer laser power settings. Both nerve priming and fatigue studies revealed different mechanisms for ONS and ENS.
    No preview · Article · Jan 2015
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    ABSTRACT: Introduction: The pathogenesis of diabetic erectile dysfunction (ED) includes neuropathy, but the molecular basis for neurogenic ED is incompletely understood. The RhoA/ROCK pathway has been implicated in diabetic neuropathy and in ED, but its role in diabetic neurogenic ED is not known. Aims: The aim of this study was to determine whether hydroxyl fasudil, a ROCK inhibitor, affects diabetic neuropathy-related ED. Methods: Type 1 diabetes mellitus was induced in male rats by streptozotocin (75mg/kg, intraperitoneally). After 8 weeks, diabetic rats were administered hydroxyl fasudil, a selective ROCK inhibitor (10mg/kg/day, intraperitoneally) or vehicle, for 4 weeks. Age-matched control, nondiabetic, rats were treated intraperitoneally for 4 weeks with saline. At week 12, after a 2 day washout, neuro-stimulated erectile function was evaluated. Major pelvic ganglia (MPG) were collected for Western blot analysis of RhoA, ROCK-1, ROCK-2, phospho (P)-AKT (Ser473), and P-phosphatase and tensin homolog (P-PTEN) (Ser380/Thr382/383). Main Outcome Measures: Effect of ROCK inhibitor hydroxyl fasudil on erectile function and ROCK/P-AKT/P-PTEN pathway in the MPG of diabetic rats. Results: Erectile response was significantly (P<0.05) reduced in diabetic rats compared with nondiabetic rats and was preserved (P<0.05) in diabetic rats treated with hydroxyl fasudil. In diabetic rats, RhoA and ROCK-2 protein expressions in MPG were increased (P<0.05) and remained increased in hydroxyl fasudil-treated rats. P-AKT (Ser473) expression was decreased (P<0.05), whereas P-PTEN (Ser380/Thr382/383) expression was increased (P<0.05) in MPG of diabetic rats compared with nondiabetic rats, and both were reversed (P<0.05) in diabetic rats treated with hydroxyl fasudil. Conclusion: Improved erectile function and restored P-AKT and P-PTEN in the MPG with hydroxyl fasudil treatment suggest the role of Rho signaling via PTEN/AKT pathway in neurogenic diabetic ED.
    No preview · Article · Jun 2014 · Journal of Sexual Medicine
  • Gwen Lagoda · Tabitha Goetz · Arthur L. Burnett

    No preview · Article · Apr 2014 · Journal of Sexual Medicine

  • No preview · Article · Apr 2014 · Journal of Sexual Medicine
  • Serhat Tozburun · G.A. Lagoda · A.L. Burnett · N.M. Fried
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    ABSTRACT: The cavernous nerves, which course along the surface of the prostate gland, are responsible for erectile function. Urologic surgeons are challenged in preserving these nerves during prostate cancer surgery, due to their microscopic nature and variable location among patients. Current intra-operative diagnostic methods for identifying, imaging, and preserving these delicate nerves during removal of a cancerous prostate gland remain sub-optimal. Our laboratory is focused on developing optical-based methods for detecting these nerves. This manuscript reviews progress in pre-clinical development of infrared optical nerve stimulation as a potential technique for identifying the cavernous nerves. Critical laser parameters for safe and reliable stimulation of the cavernous nerves, development of laser and fiber optic probe instrumentation, and novel approaches are presented.
    No preview · Article · Mar 2014 · IEEE Journal of Selected Topics in Quantum Electronics
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    ABSTRACT: Optical nerve stimulation (ONS) has been commonly performed in the laboratory using high-power, pulsed, infrared (IR) lasers including Holmium:YAG, diode, and Thulium fiber lasers. However, the relatively high cost of these lasers in comparison with conventional electrical nerve stimulation (ENS) equipment may represent a significant barrier to widespread adoption of ONS. Optical stimulation of the prostate cavernous nerves (CN's) has recently been reported using lower cost, continuous-wave (CW), all-fiber-based diode lasers. This preliminary study describes further miniaturization and cost reduction of the ONS system in the form of a compact, lightweight, cordless, and inexpensive IR laser. A 140-mW, 1560-nm diode laser was integrated with a green aiming beam and delivery optics into a compact ONS system. Surface and subsurface ONS was performed in a total of 5 rats, in vivo, with measurement of an intracavernous pressure (ICP) response during CW laser irradiation for 30 s with a spot diameter of 0.7 mm. Short-term, CW ONS of the prostate CN's is feasible using a compact, inexpensive, batterypowered IR laser diode system. This ONS system may represent an alternative to ENS for laboratory studies, and with further development, a handheld option for ONS in the clinic to identify and preserve the CN's during prostate cancer surgery.
    No preview · Article · Feb 2014 · Proceedings of SPIE - The International Society for Optical Engineering
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    ABSTRACT: To characterize transforming growth factor beta 1 (TGFβ1) and related signaling pathway proteins in a large cohort of human penile tissue (HPT) samples. HPT was collected from patients undergoing penile prosthesis implantation for erectile dysfunction (ED) and divided into the following 2 groups: postradical prostatectomy ED (RP-ED; n = 57) and organic ED (O-ED; n = 30). HPT from patients undergoing partial penectomy without ED was used as controls (CON; n = 6). Western blot analysis was performed to investigate the protein expressions of TGFβ1, thrombospondin 1 (TSP1; an activator of TGFβ1), fibronectin (an extracellular matrix glycoprotein induced by TGFβ1), and a family of transcriptional factors activated by TGFβ1 (Smad2, phospho-Smad2-serine-465/467 [pSmad2], Smad3, phospho-Smad3-serine-423/425 [pSmad3]). Expressions of TGFβ1 and TSP1 were significantly higher in RP-ED (P <.05) and O-ED (P <.05) groups compared with that of the CON group and were not different between either ED groups. Expressions of Smad2, pSmad2, Smad3, pSmad3, and fibronectin were similar among all groups. Within the RP-ED group, a subgroup analysis showed that time from RP to penile prosthesis implantation was related to increased expression of pSmad2 (P <.05), and previous history of intracavernosal injection was related to increased expression of TGFβ1 (P <.05). Our results demonstrate that TSP1- and TGFβ1-dependent fibrotic changes occur in penile tissue in patients with ED regardless of etiology. The unchanged expression of the Smad transcriptional factors may be reconciled by a Smad-independent downstream signaling pathway transmitting TGFβ1 signals.
    No preview · Article · Oct 2013 · Urology
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    ABSTRACT: We evaluated the therapeutic potential of a sustained nitric oxide (NO)-releasing compound to correct the molecular hallmarks and pathophysiology of priapism, an important but poorly characterized erectile disorder. 1,5-Bis-(dihexyl-N-nitrosoamino)-2,4-dinitrobenzene (C6') and an inactive form of the compound [1,5-bis-(dihexylamino)-2,4-dinitrobenzene (C6)] were tested in neuronal cell cultures and penile lysates for NO release (Griess assay) and biological activity (cGMP production). The effect of local depot C6' or C6 was evaluated in mice with a priapic phenotype due to double neuronal and endothelial NO synthase deletion (dNOS(-/-)) or human sickle hemoglobin transgenic expression (Sickle). Changes in NO signaling molecules and reactive oxygen species (ROS) surrogates were assessed by Western blot. The physiological response after C6' treatment was assessed using an established model of electrically stimulated penile erection. C6' generated NO, increased cGMP, and dose dependently increased NO metabolites. C6' treatment reversed abnormalities in key penile erection signaling molecules, including phosphodiesterase type 5, phosphorylated endothelial nitric oxide synthase, and phosphorylated vasodilator-stimulated phosphoprotein. In Sickle mice, C6' also attenuated the increased ROS markers gp91(phox), 4-hydroxynonenal, and 3-nitrotyrosine. Finally, C6' corrected the excessive priapic erection response of dNOS(-/-) mice. Exogenous sustained NO release from C6' corrects pathological erectile signaling in mouse models of priapism and suggests novel approaches to human therapy.-Lagoda, G., Sezen, S. F., Hurt, K. J., Cabrini, M. R., Mohanty, D. K., Burnett, A. L. Sustained nitric oxide (NO)-releasing compound reverses dysregulated NO signal transduction in priapism.
    No preview · Article · Sep 2013 · The FASEB Journal
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    ABSTRACT: To optimize the infrared laser wavelength and optical nerve stimulation (ONS) parameters for both deep and rapid subsurface cavernous nerve (CN) stimulation in a rat model, in vivo. A 150-mW, 1490-nm diode laser providing an optical penetration depth (OPD) of 518 μm in water was operated in continuous-wave mode during stimulation of the CNs in 8 rats for 15 seconds irradiation time through a custom-built, single-mode fiber optic probe capable of producing a collimated, 1-mm diameter laser beam. Successful ONS was judged by an intracavernous pressure response in the rat penis. Subsurface ONS at 1490 nm was also compared with previous studies using 1455 nm and 1550 nm near-infrared diode laser wavelengths. Subsurface ONS of the rat CN was successful through fascia layers with a thickness up to 380 μm using an incident laser power of ∼50 mW. Intracavernous pressure response times as short as 4.6 ± 0.2 seconds were recorded using higher laser powers below the nerve damage threshold. The 1490-nm diode laser represents a compact, low cost, high power, and high quality infrared light source for use in ONS. This wavelength provides deeper penetration than 1455-nm diode laser and more rapid and efficient nerve stimulation than 1550-nm diode laser.
    No preview · Article · Aug 2013 · Urology
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    ABSTRACT: Optical nerve stimulation (ONS) may be useful as a diagnostic tool for intraoperative identification and preservation of the prostate cavernous nerves (CN), responsible for erectile function, during prostate cancer surgery. Successful ONS requires elevating the nerve temperature to within a narrow range (∼42 to 47°C) for nerve activation without thermal damage to the nerve. This preliminary study explores a prototype temperature-controlled optical nerve stimulation (TC-ONS) system for maintaining a constant (±1°C) nerve temperature during short-term ONS of the rat prostate CNs. A 150-mW, 1455-nm diode laser was operated in continuous-wave mode, with and without temperature control, during stimulation of the rat CNs for 15 to 30 s through a fiber optic probe with a 1-mm-diameter spot. A microcontroller opened and closed an in-line mechanical shutter in response to an infrared sensor, with a predetermined temperature set point. With TC-ONS, higher laser power settings were used to rapidly and safely elevate the CNs to a temperature necessary for a fast intracavernous pressure response, while also preventing excessive temperatures that would otherwise cause thermal damage to the nerve. With further development, TC-ONS may provide a rapid, stable, and safe method for intraoperative identification and preservation of the prostate CNs.
    No preview · Article · Jun 2013 · Journal of Biomedical Optics
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    ABSTRACT: Optical nerve stimulation (ONS) is being explored for identification and preservation of the cavernous nerves (CN), responsible for erectile function, during prostate cancer surgery. This study compares three pulsed infrared lasers to determine whether differences in spectral linewidth and/or temporal pulse profile influence successful ONS of CN. Infrared laser radiation from the Capella diode laser (1873 nm, 5 ms, 10 Hz), Thulium fiber laser (TFL) (1873 nm, 5 ms, 10 Hz), and solid-state Holmium:YAG laser (2120 nm, 200 μs, 5 Hz) were transmitted through 400-μm-corediameter optical fibers, producing a 1-mm-diameter-spot on the nerve surface. Successful ONS was judged by an intracavernous pressure (ICP) response in the penis (n =10 rats) during a total stimulation time of 30 s. The narrow linewidth TFL (Δλ ~ 0.5 nm) and broad linewidth Capella laser (Δλ ~ 12 nm) performed similarly, producing ICP responses with a threshold radiant exposure of ~ 0.45 J/cm2, and ICP response times of 12-17 s, while the Holmium laser stimulated at ~ 0.59 J/cm2, and ICP response times of about 14-28 s. All three lasers demonstrated successful ONS of CN. ICP response time was dependent on the rate of energy deposition into the CN, rather than linewidth or temporal pulse profile.
    No preview · Conference Paper · Mar 2013
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    ABSTRACT: Successful identification of the cavernous nerves (CN’s) during radical prostatectomy requires detection of the CN’s through a thin layer of overlying fascia. This study explores the 1490 nm infrared (IR) diode laser wavelength for rapid and deep subsurface CN stimulation in a rat model, in vivo. A 150-mW, 1490-nm diode laser providing an optical penetration depth of ~ 520 μm was used to stimulate the CN’s in 8 rats through a single mode fiber optic probe with 1-mm-diameter spot and 15 s irradiation time. Successful ONS was judged by an intracavernous pressure response (ICP) in the rat penis. Subsurface ONS at 1490 nm was also compared with previous studies using 1455 and 1550 nm IR diode laser wavelengths. ONS was observed through fascia layers up to 380 μm thick using an incident laser power of ~ 50 mW. ICP response times as short as 4.6 ± 0.2 s were recorded using higher laser powers bust still below the nerve damage threshold. The 1490-nm diode laser represents a compact, low cost, high power, and high quality infrared light source for use in ONS. This wavelength provides deeper optical penetration than 1455 nm and more rapid and efficient nerve stimulation than 1550 nm.
    No preview · Conference Paper · Mar 2013
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    ABSTRACT: Successful identification and preservation of the cavernous nerves (CN), which are responsible for sexual function and vulnerable to damage during prostate cancer surgery, will require subsurface detection of the CN's beneath a thin fascia layer. This study explores the feasibility of optical nerve stimulation (ONS) in the rat with a fascia layer placed over the CN. Two near-infrared diode lasers with wavelengths of 1455 and 1550 nm were operated in continuous-wave mode for stimulation of the CN in 8 rats, in vivo. Successful ONS was confirmed by an intracavernous pressure (ICP) response in the rat penis at 1455 nm through fascia with a thickness up to 110 μm and at 1550 nm through fascia with a thickness up to 450 μm. Higher incident laser power was required to produce an ICP response as fascia thickness was increased. Also, weaker and slower ICP responses were observed as fascia thickness was increased. Subsurface ONS of the rat CN at a depth of 450 μm using a 1550 nm laser is feasible as an intermediate step towards developing ONS as an intra-operative diagnostic tool for identification and preservation of the cavernous nerves during prostate cancer surgery. (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).
    No preview · Article · Oct 2012 · Journal of Biophotonics
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    ABSTRACT: Purpose: Priapism is a vasculopathy that occurs in approximately 40% of patients with sickle cell disease. Mouse models suggest that dysregulated nitric oxide synthase and RhoA/ROCK signaling as well as increased oxidative stress may contribute to the mechanisms of sickle cell disease associated priapism. We examined changes in the protein expression of nitric oxide synthase and ROCK signaling pathways, and a source of oxidative stress, NADPH oxidase, in penile erectile tissue from patients with a priapism history etiologically related and unrelated to sickle cell disease. Materials and methods: Human penile erectile tissue was obtained from 5 patients with sickle cell disease associated priapism and from 6 with priapism of other etiologies during nonemergent penile prosthesis surgery for erectile dysfunction or priapism management and urethroplasty. Tissue was also obtained from 5 control patients without a priapism history during penectomy for penile cancer. Samples were collected, immediately placed in cold buffer and then frozen in liquid nitrogen. The expression of phosphodiesterase 5, endothelial nitric oxide synthase, neuronal nitric oxide synthase, inducible nitric oxide synthase, RhoA, ROCK1, ROCK2, p47(phox), p67(phox), gp91(phox) and β-actin were determined by Western blot analysis. Nitric oxide was measured using the Griess reaction. Results: In the sickle cell disease group phosphodiesterase 5 (p <0.05), endothelial nitric oxide synthase (p <0.01) and RhoA (p <0.01) expression was significantly decreased, while gp91(phox) expression (p <0.05) was significantly increased compared to control values. In the nonsickle cell disease group endothelial nitric oxide synthase, ROCK1 and p47(phox) expression (each p <0.05) was significantly decreased compared to control values. Total nitric oxide levels were not significantly different between the study groups. Conclusions: Mechanisms of sickle cell disease associated priapism in the human penis may involve dysfunctional nitric oxide synthase and ROCK signaling, and increased oxidative stress associated with NADPH oxidase mediated signaling.
    No preview · Article · Sep 2012 · The Journal of urology
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    ABSTRACT: Successful identification and preservation of the cavernous nerves (CN), which are responsible for sexual function, during prostate cancer surgery, will require subsurface detection of the CN beneath a thin fascia layer. This study explores optical nerve stimulation (ONS) in the rat with a fascia layer placed over the CN. Two near-IR diode lasers (1455 nm and 1550 nm lasers) were used to stimulate the CN in CW mode with a 1-mm-diameter spot in 8 rats. The 1455 nm wavelength provides an optical penetration depth (OPD) of ~350 μm, while 1550 nm provides an OPD of ~1000 μm (~3 times deeper than 1455 nm and 1870 nm wavelengths previously tested). Fascia layers with thicknesses of 85 - 600 μm were placed over the CN. Successful ONS was confirmed by an intracavernous pressure (ICP) response in the rat penis at 1455 nm through fascia 110 μm thick and at 1550 nm through fascia 450 μm thick. Higher incident laser power was necessary and weaker and slower ICP responses were observed as fascia thickness was increased. Subsurface ONS of the rat CN at a depth of 450 μm using a 1550 nm laser is feasible.
    No preview · Article · Feb 2012 · Proceedings of SPIE - The International Society for Optical Engineering

Publication Stats

686 Citations
121.98 Total Impact Points

Institutions

  • 2007-2015
    • Johns Hopkins Medicine
      • Department of Urology
      Baltimore, Maryland, United States
  • 2013
    • Universidade Federal de São Paulo
      San Paulo, São Paulo, Brazil
  • 2006-2013
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 2008
    • University of North Carolina at Charlotte
      • Department of Physics & Optical Science
      Charlotte, North Carolina, United States