Research Areas Defined
|The Washington University Neurofibromatosis (NF) Center uses a team approach to understand the roles of the NF genes in health and disease. This team is composed of clinicians and laboratory scientists focused on accelerating the pace of scientific discovery and its application to the care of individuals with NF. Their mission is to galvanize and promote research on NF, achieving significant breakthroughs in the diagnosis and treatment of nervous system tumors and establishing Washington University as an international beacon for NF research. A cross-disciplinary endeavor, the Washington University NF Center eliminates obstacles to research and establishes a framework for innovative scientific collaboration among investigators using cutting-edge research and medical technologies. The Washington University NF Center also provides advanced care for people with NF. Areas of intense focus include the following four aspects of our team’s neurofibromatosis research efforts.|
Visual loss in children with neurofibromatosis type 1 (NF1)-associated optic glioma
While 15-20% of children with NF1 will develop a low-grade brain tumor involving the optic nerve called an optic pathway glioma, it is not known whether the patient age, gender or tumor location can be used to predict who will require treatment. Moreover, it is not clear whether some groups of children with NF1-associated optic gliomas are at higher risk for vision loss or treatment failure. As part of an international consortium, Dr. Gutmann and his colleagues are studying the impact of chemotherapy on vision in children with NF1. In addition, these investigations are aimed at identifying risk factors for poor outcome in children with optic pathway gliomas.
Ji J, Shimony J, Gao F, McKinstry RC, Gutmann DH. Optic nerve tortuosity in children with neurofibromatosis type 1. Pediatr Radiol. (in press)
Gutmann DH, Avery R. Ferner RE, Listernick R. Visual function and optic pathway glioma: A critical response. JAMA Opthalmol. 131: 120-1, 2013.
Avery RA, Ferner RE, Listernick R, Fisher MJ, Gutmann DH, Liu GT. Visual acuity of children with low grade gliomas of the visual pathway: Implications for patient care and clinical research. J Neurooncol. 110: 1-7, 2012.
Fisher MJ, Loguidice M, Gutmann DH, Listernick R, Ferner RE, Ullrich NJ, Packer RJ, Tabori U, Hoffman RO, Ardern-Holmes SL, Hummel TR, Hargrave DR, Boufet E, Charrow J, Bilaniuk LT, Balcer LJ, Liu GT. Visual outcomes in children with neurofibromatosis type 1 associated optic pathway glioma following chemotherapy: A mulit-center retrospective analysis. Neuro-Oncology. 14: 790-7, 2012.
Gutmann DH, Listernick R, Ferner RE. Screening for symptomatic optic pathway glioma in children with neurofibromatosis type 1. Eye. 25: 818, 2011.
Listernick R, Ferner RE, Liu GT, Gutmann DH. Optic pathway gliomas in neurofibromatosis-1: Controversies and recommendations. Ann Neurol. 61: 189-98, 2007.
Preclinical evaluation of new brain tumor therapies in Nf1 genetically-engineered mice
After the identification of the Nf1 gene and its protein (neurofibromin), it became possible to envision a time when new drug therapies for NF1-associated tumors might replace the missing function of neurofibromin. Over the past decade, several promising candidate compounds have been identified, which need to be evaluated in model organisms prior to the application to children and adults with NF1. To this end, Dr. David Gutmann and his colleagues in the Washington University NF Center have an active research program to evaluate new drugs for the treatment of optic glioma using Nf1 genetically-engineered mice. These studies are designed to rapidly test the most promising candidate drugs prior to their evaluation in children and adults with NF1. One such drug, rapamycin, is now in clinical trials for children with NF1-assocaited glioma. Additional compounds are currently being evaluated in several Nf1 genetically-engineered mice with optic glioma.
Banerjee S, Gianino SM, Gao F, Christians U, Gutmann DH. Interpreting mammalian target of rapamycin and cell growth inhibition in a genetically-engineered mouse model of Nf1-deficient astrocytes. Mol Cancer Ther. 10: 279-91, 2011.
Hegedus B, Banerjee D, Yeh T-H, Rothermich S, Perry A, Rubin JB, Garbow JR, Gutmann DH. Preclinical cancer therapy in a mouse model of neurofibromatosis-1 optic glioma. Cancer Res. 68: 1520-8, 2008.
Gutmann DH, Hunter-Schaedle K, Shannon KM. Harnessing preclinical mouse models to inform human clinical cancer trials. J Clin Invest. 116: 847-52, 2006
Understanding the role of the tumor microenvironment in brain tumor formation and growth
Brain tumors are composed of both cancerous and non-cancerous cells. Previous studies in Dr. David Gutmann’s laboratory revealed that the non-cancerous cells may play a critical role in the development and growth of optic gliomas in Nf1 genetically-engineered mice. To further define the contribution of these non-cancerous cells to glioma growth, investigators at the Washington University NF Center are working together to combine their individual expertise. Dr. Gutmann and his colleagues showed that immune system-like cells, called microglia, are abundant in both human and mouse optic gliomas and that these cells are critical for optic glioma growth in Nf1 genetically-engineered mice. These exciting findings suggest that new targets for therapeutic drug design might result from the identification of the factors made by glioma-associated microglia. Teaming with Drs. Elaine Mardis, Joshua Rubin, Jeffrey Leonard and David Piwnica-Worms, Dr. Gutmann is directing studies aimed at discovering these critical microglia growth factors using advanced RNA sequencing methods developed at the Genome Institute at Washington University. The results from these studies may one day lead to treatments that target these non-cancerous cells in the tumor microenvironment.
Pong WW, Higer SB, Gianino SM, Emnett RJ, Gutmann DH. Reduced microglial CX3CR1 expression delays neurofibromatosis-1 glioma formation. Ann Neurol. 73: 303-8, 2013.
Simmons GW, Pong WW, Emnett RJ, White CR, Gianino SM, Rodriguez FJ, Gutmann DH. Neurofibromatosis-1 heterozygosity increases microglia in a spatially-and temporally-restricted pattern relevant to mouse optic glioma formation and growth. J Neuropathol Exp Neurol. 70: 51-62, 2011.
Daginakatte GC, Gianino SM, Zhao NW, Parsadanian AS, Gutmann DH. Increase JNK signaling in Neurofibromatosis-1 (Nf1) heterozygous microglia activation and promotes optic glioma proliferation. Cancer Res. 68: 10358-66, 2008.
Daginakatte GC, Gutmann DH. Neurofibromatosis-1 (Nf1) heterozygous brain microglia elaborate paracrine factors that promote Nf1-deficient astrocyte and glioma growth. Hum Mol Genet. 16: 1098-112, 2007.
Defining the role of the neurofibromatosis type 1 (NF1) gene in normal brain development
The observation that children with NF1 have learning, memory and behavioral problems suggests that the Nf1 gene neurofibromin is important in brain development and function. To better understand the role of neurofibromin in normal brain development, Dr. Gutmann and his colleagues are using novel strains of genetically-engineered mice. These studies are aimed at determining the mechanism by which neurofibromin regulates the growth of progenitor cells (neural stem cells) and their differentiation into neurons, astrocytes and oligodendrocytes. The goal of these studies is to determine exactly how neurofibromin regulates normal brain development and function with an eye towards future treatments that leverage these new insights.
Hegedus B, Yeh T-H, Lee DY, Emnett RJ, Li J, Gutmann DH. Neurofibromin regulates somatic growth through the hypothalamic-pituitary axis. Hum Mol Genet. 17: 2955-66, 2008.
Hegedus B, Dasgupta B, Shin JE, Emnett RJ, Hart-Mahon EK, Elghazi L, Bernal-Mizrachi E, Gutmann DH. Neurofibromatosis-1 regulates neuronal and glial cell differentiation from neuroglial progenitors in vivo by both cAMP and Ras-dependent mechanisms. Cell Stem Cell. 1: 443-57, 2007.
Dasgupta B, Gutmann DH. Neurofibromin regulates neural stem cell proliferation, survival and astroglial differentiation in vitro and in vivo. J Neurosci. 25: 5584-94, 2005.
Understanding the cellular origins of brain tumors
Research over the past decade has shown that brain tumors can arise from a number of different types of cells in the brain. Determining where these come from in children with NF1 may yield new insights into how best to prevent their formation. To understand the origins of optic pathway gliomas in NF1, Dr. Gutmann and his colleagues are using novel strains of genetically-engineered mice. These studies are focused on finding which cells in the developing brain give rise to optic pathway gliomas in children. In addition, similar studies are underway to identify the cells in the developing brain responsible for childhood brain tumors in people without NF1.
Solga AC, Gianino SM, Gutmann DH. NG2-cells are not the cell of origin for murine neurofibromatosis-1 (Nf1) optic glioma. Oncogene. (in press)
Lee DY, Gianino SM, Gutmann DH. Innate neural stem cell heterogeneity determines the patterning of glioma formation in children. Cancer Cell. 22: 131-8, 2012.
Lee DY, Yeh T-H, Emnett RJ, White CR, Gutmann DH. Neurofibromatosis-1 regulates neuroglial progenitor proliferation and glial differentiation in a brain region-specific manner. Genes & Development. 24: 2317-29, 2010.
Yeh T-H, Lee DY, Giannino SM, Gutmann DH. Microarray analyses reveal regional astrocyte heterogeneity with implications for neurofibromatosis type 1 regulated glial proliferation. GLIA. 57: 1239-49, 2009.
Developing new treatments for attention deficits and learning disabilities in children with neurofibromatosis type 1
Nearly two-thirds of all children with NF1 exhibit problems with attention and impulsivity. In an effort to develop new treatments for these common problems, cross-disciplinary studies in the Washington University NF Center are leveraging Nf1 genetically-engineered mice. These investigations are designed to understand the molecular and cellular basis for attention deficits in NF1. Spearheaded by Dr. David Wozniak in the Department of Psychiatry, these experiments have already led to the development of behavioral tests in mice suitable for preclinical drug evaluation. Working with Dr. Robert Mach in the Department of Radiology, Drs. Gutmann and Wozniak have recently applied positron emission tomography (PET) imaging to the preclinical evaluation of promising drugs for attention deficit. Future studies will combine imaging and behavior assessments to identify and test new candidate treatments for NF1-associated attention deficit.
Diggs-Andrew KA, Tokuda K, Izumi Y, Zorumski CF, Wozniak DF, Gutmann DH. Dopamine deficiency underlies learning deficits in neurofibromatosis-1 mice. Ann Neurol. 73: 309-15, 2013.
Diggs-Andrews KA, Gutmann DH. Modeling cognitive dysfunction in neurofibromatosis-1. Trends Neurosci. 36: 237-47, 2013.
Brown JA, Xu J, Diggs-Andrews KA, Wozniak DF, Mach RH, Gutmann DH. PET imaging for attention deficit preclinical drug testing in neurofibromatosis-1 mice. Exp Neurol. 232: 333-8, 2011.
Brown JA, Emnett RJ, White C, Yuede C, Conyers S, O’Malley K, Wozniak DF, Gutmann DH. Reduced striatal dopamine underlies the attention system dysfunction in neurofibromatosis-1 mutant mice. Human Mol Genet. 19: 4515-28, 2010.
Identifying new treatments for neurofibromatosis type 1 (NF1) associated tumors
With the identification of the Nf1 gene in 1990, it became possible to define the mechanism by which the Nf1 protein (neurofibromin) controls cell growth. Over the past decade, Dr. Gutmann and his colleagues have focused on determining the precise way neurofibromin regulates the growth of brain cells. Using a team effort involving numerous investigators at the Washington University NF Center, we aim to discover new drugs for the treatment of tumors arising in children and adults with NF1. Drs. David Piwnica-Worms, Joshua Rubin, Jason Weber and David Gutmann have been working together for the past seven years to identify such promising compounds and determine how they block NF1-associated tumor growth. These studies have already led to the identification of rapamycin drugs now in clinical trial for plexiform neurofibromas and brain tumors as well as compounds that restore normal cyclic AMP signaling in NF1-associated tumors in mice. We continue to refine these targeted treatments to optimally inhibit tumor growth with minimal effects on the normal brain.
Banerjee S, Crouse NR, Emnett RJ, Gianino SM, Gutmann DH. Neurofibromatosis-1 regulates mTOR-mediated astrocyte growth and glioma formation in a TSC/Rheb-independent manner. Proc Natl Sci USA. 108: 15996-6001, 2011.
Warrington NM, Gianino SM, Jackson E, Goldhoff P, Garbow JR, Piwnica-Worms D, Gutmann DH, Rubin JB. Cyclica AMP suppression is sufficient to induce gliomagenesis in a mouse model of neurofibromatosis-1. Cancer Res. 70: 5717-27, 2010.
Sun T, Gianino SM, Jackson E, Piwnica-Worms D, Gutmann DH, Rubin JB. CXCL12 alone is insufficient for gliomagenesis in Nf1 mutant mice. J Neuroimmunol. 224: 108-13, 2010.
Banerjee S, Byrd JN, Gianino SM, Harpstrite SE, Rodriguez FJ, Tuskan RG, Reilly KM, Piwnica-Worms D, Gutmann DH. Neurofibromin controls cell growth by regulating STAT3 activity in vitro and in vivo. Cancer Res. 70: 1356-66, 2010.
Warrington NM, Woener BM, Daginakatte GC, Dasgupta B, Perry A, Gutmann DH, Rubin JB. Spatiotemporal differences in CXCL12 expression and cyclic AMP underlie the unique pattern of optic pathway glioma growth in neurofibromatosis type 1. Cancer Res. 67: 8588-95, 2007.
Sandsmark DK, Zhang H, Hegedus B, Pelletier CL, Weber JD, Gutmann DH. Nucleophosmin mediates mammalian target of rapamycin-dependent actin cytoskeleton dynamics and proliferation in neurofibromin-deficient astrocytes. Cancer Res. 67: 4790-9, 2007.
Dasgupta B, Yi Y, Chen DY, Weber JD, Gutmann DH. Proteomic analysis reveals hyperactivation of the mTOR pathway in NF1-associated human and mouse brain tumors. Cancer Res. 65: 2755-60, 2005.
Improved therapies for NF1 Malignant Peripheral Nerve Sheath Tumors (MPNSTs)
One area of study is focused on identifying the genetic changes that predict malignant transformation and spread (metastasis) using advanced genomic sequencing strategies. A second area of investigation aims to develop better small-animal models of MPNST development and metastasis to provide a platform to find better treatment strategies for these deadly cancers.
Yu J, Deshmukh H, Payton JE, Durham C, Scheithauer BW, Tihan T, Prayson RA, Guha A, Bridge JA, Ferner RE, Lindberg GM, Gutmann RJ, Emnett RJ, Salavaggione L, Gutmann DH, Nagarajan R, Watson MA, Perry A. Array-based comparative genomic hybridization identifies CDK4 and FOXM1 alterations as independent predictors of survival in malignant peripheral nerve sheath tumor. Clin Cancer Res. 17: 1924-34, 2011.
Bhola P, Banerjee S, Mukherjee J, Balasubramanium A, Arun V, Karim Z, Burrell K, Croul S, Gutmann DH, Guha A. Preclinical in vivo evaluation of rapamycin in human malignant peripheral nerve sheath explant xenograft. Int. J Cancer. 126: 563-71, 2010.
Miller SJ, Rangwala F, Williams J, Ackerman P, Kong S, Jegga AG, Kaiser S, Aronow BJ, Frahm S, Luwe L, Mautner V, Updahyaya M, Muir D, Wallace M, Hagen J, Quelle DE, Watson MA, Perry A, Gutmann DH, Ratner N. Large-scale molecular comparison of human schwann cells to malignant nerve sheath tumor cell lines and tissues. Cancer Res. 66: 2584-91, 2006.
Develop small-animal models to promote personalized medicine
A new initiative is focused on developing mouse models of brain tumors and attention deficits that incorporate the specific NF1 genetic mutations observed in people with NF1. These unique strains will be employed to develop more individualized treatments for children and adults with NF1-associated clinical problems.
Function of the neurofibromatosis type 1 (NF1) gene in brain nerve cells
Individuals with NF1 are prone to learning disabilities, behavioral problems, seizures and motor delays–all indicative of impairments in normal nerve cell (neuron) function. Dr. Gutmann and his colleagues are leading studies to understand how the Nf1 protein (neurofibromin) controls the function of neurons in the brain. These investigations have revealed that reduced neurofibromin function in the brain leads to impaired neuron lengths and survival, which reflects the role of neurofibromin in controlling cyclic AMP levels. Current efforts are directed at defining the mechanism underlying neurofibromin cyclic AMP regulation in neurons and identifying drugs capable of restoring normal neuron function.
Brown JA, Diggs-Andrews KA, Gianino SM, Gutmann DH. Neurofibromatosis-1 heterozygosity impairs CNS neuronal morphology in a cAMP/PKA/ROCK-dependent manner. Molecular and Cellular Neuroscience. 49: 13-22, 2012.
Brown JA, Gianino SM, Gutmann DH. Defective cAMP generation underlies the sensitivity of central nervous system neurons to neurofibromatosis-1 heterozygosity. J Neurosci. 30: 5579-89, 2010.
Hegedus B, Hughes WF, Garbow JR, Gianino SM, Banerjee D, Kim K, Ellisman MH, Brantley MA, Gutmann DH. Optic nerve dysfunction in a mouse model of neurofibromatosis-1 optic glioma. J Neuropathol Exp Neurol. 68: 542-51, 2009.
Understanding the genetics of neurofibromatosis type 1 (NF1) associated brain tumors
The development of new drugs for NF1-associated brain tumors requires a comprehensive analysis of these tumors in both mice and humans. To accomplish this goal, Dr. Gutmann and his colleagues are preforming detailed studies to identify types of cells present in mouse optic gliomas and the interactions between these various cells in controlling brain tumor growth. In addition, Dr. Elaine Mardis and her team at the Genome Institute at Washington University are applying advanced whole genome sequencing methods to NF1-associated human tumors to comprehensively define the genetic changes present in these complex tumors.
Gutmann DH, McLellan MD, Hussain I, Wallis JW, Fulton LL, Fulton RS, Magrini V, Demeter R, Wylie T, Kandoth C, Leonard JR, Guha A, Miller CA, Ding L, Mardis ER. Somatic neurofibromatosis type 1 (NF1) inactivation characterizes NF1-associated pilocytic astrocytoma. Genome Res. 23: 431-9, 2013.
Ho CY, Bar E, Giannini C, Marchionni L, Karajannis MA, Zagzag D, Gutmann DH, Eberhart CG, Rodriguez FJ. MicroRNA profiling in pediatric pilocytic astrocytoma reveals biologically relevant targets, including PBX3, NFIB, and METAP2. Neuro Oncol. 15: 69-82, 2013.
Kim K-Y, Ju WK, Hegedus B, Gutmann DH, Ellisman ME. Ultrastructural characterization of the optic pathway in a mouse model of neurofibromatosis-1 optic glioma. Neuroscience. 170: 178-88, 2010.
Tibbetts KM, Emnett RJ, Gao F, Perry A, Gutmann DH, Leonard J. Histopathologic predictors of pilocytic astrocytoma event-free survival. Acta Neuropathologica. 117: 657-65, 2009.
Rodriguez FJ, Giannini C, Asmann YW, Sharma MK, Perry A, Tibbetts KM, Jenkins RB, Sheithauer BW, Anant S, Jenkins S, Eberhart EG, Sarkaria JN, Gutmann DH. Gene expression profiling of NF1-associated and sporadic pilocytic astrocytomas identifies ALDH1L1 as an underexpressed candidate biomarker in aggressive astrocytoma subtypes. J Neuropath Exp Neurol. 67: 1194-204, 2008.
Rodriguez FJ, Perry A, Gutmann DH, O’Neill BP, Leonard J, Bryant S, Giannini C. Gliomas in neurofibromatosis type 1: A clinical study of 100 patients. J Neuropath Exp Neurol. 67: 240-9, 2008.
Determining the role of the neurofibromatosis type 2 (NF2) gene in ependymoma formation
Individuals with NF2 are prone to the development of spinal cord tumors, called ependymomas. These glial cell tumors arise from progenitor cells in the spinal cord. In order to develop more targeted treatments for these tumors, Dr. Gutmann and his colleagues have employed Nf2 genetically-engineered mice to define the mechanism underlying Nf2 protein (merlin) regulation of spinal cord glial cells and progenitor cell growth. These studies have revealed new ways the merlin controls cell growth in the nervous system. Current investigations are focused on merlin function in spinal cord progenitor cells in an effort to identify new therapies for NF2-associated ependymoma.
Houshmandi SS, Emnett RJ, Giovannini M, Gutmann DH. The neurofibromatosis-2 protein, merlin, regulates glial cell growth in an ErbB2 and Src dependent manner. Mol Cell Biol. 29: 1472-86, 2009.
Lau Y-KI, Murray L, Houshmandi SS, Xu Y, Gutmann DH, Yu Q. Merlin is a potent inhibitor of glioma growth. Cancer Res. 68: 5733-42, 2008.
Defining the spectrum of clinical problems in children with neurofibromatosis type 1 (NF1)
While much clinical research has focused on tumors, children with NF1 can have a variety of problems with behavior, motor coordination and attention. To better understand the impact of these issues on the lives of children with NF1, several investigators at the Washington University NF Center have initiated clinical studies to define the spectrum of attention deficits, developmental delays, short stature and sleep problems in children with NF1. These initial studies will provide researchers with a more in-depth understanding of these clinical features and will lead to future investigations aimed at developing more personalized treatments for children with NF1 who have these specific problems.
Templer AK, Titus JB, Gutmann DH. A neuropsychological perspective on attention problems in neurofibromatosis type 1. J. Atten Disord. (in press)
Wessel LE, Gao F, Gutmann DH, Dunn CM. Longitudinal analysis of developmental delays in children with neurofibromatosis type 1. J Child Neurol. (in press)
Wessel LE, Albers AC, Gutmann DH, Dunn CM. The association between hypotonia and brain tumors in children with neurofibromatosis type 1. J Child Neurol. (in press)
Soucy EA, van Oppen D, Nejedly NL, Gao F, Gutmann DH, Hollander AS. Height assessments in children with neurofibromatosis type 1. J Child Neurol. 28: 303-7, 2013.
Isenberg JC, Templer A, Gao F, Titus JB, Gutmann DH. Attention skills in children with neurofibromatosis type 1. J Child Neurol. 28: 45-9, 2013.
Johnson KJ, Hussain I, Williams K, Santens R, Mueller NL, Gutmann DH. Development of an international internet-based neurofibromatosis type 1 patient registry. Contemp Clin Trials. 34:305-11, 2013.
Soucy EA, Gao F, Gutmann DH, Dunn CM. Developmental delays in children with neurofibromatosis type 1. J Child Neurol. 27: 641-4, 2012.
Predictive value of café-au-lait macules for the diagnosis of neurofibromatosis type 1 (NF1)
Children with NF1 often come to medical attention when birthmarks called café-au-lait macules are found on their skin; however, it is not known whether the presence of these birthmarks can accurately predict who will develop NF1 or what features of NF1 they will have. Studies are ongoing with Dr. Susan Mallory and her colleagues in Dermatology to define the utility of café-au-lait macule shape and number in determining who will eventually be diagnosed with NF1. These investigations are designed to better characterize the dermatologic (skin) features associated with NF1 and understand their clinical importance in the management of children suspected of having this condition.
Nunley KS, Gao F, Albers AC, Bayliss SJ, Gutmann DH. Predictive value of café-au-lait macules at initial consultation in the diagnosis of neurofibromatosis type 1. Arch. Dermat. 145: 883-7, 2009.
Genetic predictors of brain tumor formation in children with neurofibromatosis type 1 (NF1)
While current genetic testing can determine with great accuracy whether a child has NF1, it cannot provide prognostic information regarding the development of specific features of the condition. In this regard, we are unable to identify children with NF1 at highest risk for the development of brain tumors (optic pathway gliomas). Dr. Joshua Rubin in the Department of Pediatrics is spearheading an international study using advanced genomic methods to identify subtle DNA changes that predict the development of brain tumors in children with NF1. His pioneering efforts have begun to reveal genomic regions associated with NF1 glioma formation. Future studies may lead to the development of DNA markers for predictive genetic testing in children with NF1.
Johnson KJ, Fisher MJ, Listernick RL, North KN, Schorry EK, Viskochil D, Weinstein M, Rubin JB, Gutmann DH. Parent-of-origin in individuals with familial neurofibromatosis type 1 and optic pathway glioma. Fam Cancer. 11: 653-6, 2012.
Advanced imaging of optic gliomas in mice and children with neurofibromatosis type 1 (NF1)
While current brain imaging can clearly identify brain tumors in children with NF1, they do not provide predictive information about the clinical behavior of the tumor. Over the past several years, new imaging modalities have been developed which offer the potential to identify brain tumors with more aggressive clinical behavior. Dr. Joshua Shimony in the Department of Radiology is currently employing one of these novel imaging methods, called functional connectivity MRI, to determine whether this advanced imaging technique can predict optic glioma growth and vision decline in children with NF1. Dr. Shimony and his colleagues are currently enrolling new patients in this exciting study. In addition, Dr. Joel Garbow in the Department of Chemistry is working with investigators in the Washington University NF Center to discover more refined imaging modalities using Nf1, mouse strains which one day might be evaluated in children with NF1.
Dorward IG, Luo J, Perry A, Gutmann DH, Mansur DB, Rubin JB, Leonard JR. Post-operative imaging surveillance in pediatric pilocytic astrocytomas. J. Neurosurg. Ped. 6: 346-52, 2010.
Jost SC, Ackerman JW, Garbow JR, Manwaring LP, Gutmann DH, McKinstry RC. Diffusion-weighted and dynamic contrast-enhanced imaging as markers of clinical behavior in children with optic pathway glioma. Pediatric Radiology. 38: 1293-9, 2008.
Banerjee D, Hegedus B, Gutmann DH, Garbow JR. Detection and measurement of neurofibromatosis-1 mouse optic glioma in vivo. Neuroimage. 35: 1434-7, 2007.