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Center for Human Nutrition

 
Tomas Guilarte
Professor
Academic Degrees
PhD, Johns Hopkins University, 1980; MS, University of Florida, 1976; BS, University of Florida, 1974.
Departmental Affiliation
Environmental Health Sciences
Joint Departmental Affiliations
International Health
Departmental Address
615 North Wolfe Street, Room E6622
Baltimore, MD 21205
Phone: (410) 955-2485
Fax: (410) 502-2470
Research and Professional Experience

The research interests of my laboratory are in the areas of neurotoxicology and neuroscience. We are elucidating the central nervous system (CNS) effects produced by exposure to low levels of lead (Pb) during development, and the role of the NMDA subtype of ionotropic glutamate receptors. We study the molecular mechanisms by which Pb produces impairments in cognitive function and those processes that are NMDA receptor-dependent. We use molecular, cellular and behavioral approaches to address specific questions. We are also interested in assessing intervention strategies that can ameliorate or modify the effects of developmental Pb exposure on cognitive function. In this regard, we have recently shown that environmental enrichment reverses the cognitive and molecular deficits induced by Pb. This work is funded by NIEHS grant #ES06189.

A second major focus of our research is to validate and apply an in vivo biomarker of brain injury that is applicable to assess the effects of environmental chemicals on the CNS as well as to assess the onset and progression of neurodegenerative diseases. We are interested in understanding and measuring the response of a biomarker protein, the peripheral benzodiazepine receptor (PBR). The PBR is located exclusively in glial cells, not in neurons, making it a biomarker of gliosis and brain injury. We have demonstrated that following neurotoxicant-exposure this protein is selectively increased in brain regions that are damaged. Our goal is to use this biomarker in humans since the PBR response to brain injury can be monitored using non-invasive brain imaging techniques, such as Positron Emission Tomography. This work is funded by NIEHS grant #ES07062.

We are also studying the molecular and behavioral effects of chronic low-level manganese exposure. Manganese in the form of Methylcyclopentadienyl manganese tricarbonyl (MMT) is approved as a fuel additive. The widespread use of Mn-containing gasoline may increase human exposures as a result of environmental contamination. Exposure to high levels of manganese results in a Parkinsonian-like syndrome. However, the CNS effects of chronic low-level manganese exposures is not currently known. This project involves scientists from the Department of Pathology, Anatomy & Cell Biology at the Thomas Jefferson University School of Medicine, the Department of Radiology at the Johns Hopkins Hospital and the Department of Environmental Health Sciences at the Bloomberg School of Public Health. This work is funded by NIEHS grant #ES10975.

Another project involves the development and validation of an early biomarker of Parkinson's disease using non-invasive brain imaging techniques such as Positron Emission Tomography (PET). This work was funded by a grant from the Michael J. Fox Foundation for Parkinson's Disease Research.

Our most recent projects involve studies on the potential deleterious effects of nanoparticles on the central nervous system. This effort is funded by a pilot project from the Institute for NanoBiotechnology at Johns Hopkins University. We are also examining the effects of welding fumes on learning and memory function in mice and this effort is funded by a grant from the Manganese Health Research Program.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Keywords

Environmental Health Sciences; Neurotoxicology; lead neurotoxicity/NMDA receptor/learning and memory; manganese neurotoxicity; biomarkers of brain injury/Parkinson's disease; brain imaging/positron emission tomography/magnetic resonance imaging and spectroscopy; neurotoxic effects of nanomaterials.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Honors and Awards

2008 - Member, Institute for NanoBioTechnology at Johns Hopkins University.

2006-present - Member, Steering Committee, Manganese Health Research Program, Washington DC.

2000 - President Elect, Neurotoxicology Specialty Section of the Society of Toxicology

1999 - Vice-President Elect, Neurotoxicology Specialty Section of the Society of Toxicology

1999-2003 - Member, Environmental Health Review Committee, NIEHS

Associate Editor, Neurotoxicology (1999-2006)

Editorial Board, Neurotoxicology (2006-present)

Editorial Board, Toxicology and Applied Pharmacology (2002-present)

National and International Society Memberships:

-Delta Omega National Public Health Honorary Society -American Association for the Advancement of Science -Society for Neuroscience -Society of Toxicology & Neurotoxicology Specialty Section -International Behavioral Neuroscience Society -International Neurotoxicology Association -Society for Molecular Imaging

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Selected Publications

Guilarte TR: Manganese and Parkinson's disease: A critical review and new findings. Environmental Health Perspectives, accepted, 2010.

Neal AP, Stansfield KH, Worley PF, Thompson RE, Guilarte TR: Lead exposure during synaptogenesis alters vesicular proteins and impairs vesicular release: Potential role of NMDA receptor-dependent BDNF signaling. Toxicological Sciences 116: 249-263, 2010.

Guilarte TR: APLP1, Alzheimer's-like pathology and neurodegeneration in the frontal cortex of manganese-exposed non-human primates. Neurotoxicology, in press, 2010.

Choi J, Zheng Q, Katz HE, Guilarte TR: Silica-based nanoparticle uptake and cellular response by primary microglia. Environmental Health Perspectives, in press, 2010.

Wang H, Pullambhatla M, Guilarte TR, Mease RC, Pomper MG: Synthesis of [125I]-IodoDPA-713, a new probe for imaging inflammation. Biochemical Biophysical Research Communications 389: 80-83, 2009.

Burton NC, Schneider JS, Syversen T, Guilarte TR: Effects of chronic manganese exposure on glutamatergic and GABAergic markers in the non-human primate brain. Toxicological Sciences 111: 131-139, 2009.

Guilarte TR: Prenatal lead exposure and schizophrenia: further evidence and more neurobiological connections. Environmental Health Perspectives 112: A724, 2009.

Schneider JS, Decamp E, Clark K, Bouquio C, Syversen T, Guilarte TR: Effects of chronic manganese exposure on working memory in non-human primates. Brain Research 1258: 86-95, 2009.

Burton NC, Guilarte TR: Manganese neurotoxicity: Lessons learned from longitudinal studies in non-human primates. Environmental Health Perspectives 117: 325-332, 2009.

Guilarte TR, Burton NC, McGlothan JL, Verina T, Zhou Y, Alexander M, Pham L, Griswold M, Wong DF, Syversen T, Schneider JS: Impairment of nigrostriatal dopamine neurotransmission by manganese is mediated by pre-synaptic mechanism(s): Implications to manganese-induced parkinsonism. Journal of Neurochemistry 107: 1236-1247, 2008.

McGlothan JL, Karcz-Kubicha M, Guilarte TR: Developmental lead exposure impairs extinction of conditioned fear in young adult rats. Neurotoxicology 29: 1127-1130, 2008.

Guilarte TR, Burton NC, Verina T, Prabhu VV, Becker KG, Syversen T, Schneider JS: Increased APLP1 expression and neurodegeneration in the frontal cortex of manganese-exposed non-human primates. Journal of Neurochemistry 105: 1948-1959, 2008. [Selected by NIEHS-ENVIRONMENTAL FACTOR in their extramural papers of the month for the May 2008 issue]

Chen M-K, Guilarte TR: Translocator protein 18kDa: molecular sensor of brain injury and repair. Pharmacology & Therapeutics (invited review) 118: 1-17, 2008.

Guilarte TR, Hammoud DA, McGlothan JL, Caffo BS, Foss CA, Kozikowski AP, Pomper MG: Dysregulation of Glutamate Carboxypeptidase II in Psychiatric Disease. Schizophrenia Research 99:324-332, 2008.

Chen M-K, Kuwabara H, Zhou Y, Adams RJ, Brasic JR, McGlothan JL, Verina T, Burton NC, Alexander M, Kumar A, Wong DF, Guilarte TR: VMAT2 and dopamine neuron loss in a primate model of Parkinson's disease. Journal of Neurochemistry 105: 78-90, 2008.

Guilarte TR, Chen M-K: Manganese inhibits NMDA receptor channel function: Implications to psychiatric and cognitive effects. Neurotoxicology 28: 1147-1152, 2007. [Science Direct TOP25 Hottest Articles. Subject Area: Neuroscience, Journal: Neurotoxicology, July-September, 2007; Rank #25].

Aschner M, Guilarte TR, Schneider JS, Zheng W. Manganese: Recent Advances in Understanding its Transport and Neurotoxicity. Toxicology & Applied Pharmacology, 221: 131-147, 2007.

Verina T, Rohde CA, Guilarte TR. Environmental lead exposure in early life alters granule cell neurogenesis and morphology in the hippocampus of young adult rats. Neuroscience, 145: 1037-1047, 2007.

Yates MS, Tauchi M, Katsuoka F, Flanders KC, Liby KT, Honda T, Gribble GW, Johnson DA, Johnson JA, Burton NC, Guilarte TR, Yamamoto M, Sporn MB, Kensler TW. Pharmacodynamic characterization of chemoprotective triterpenoids as exceptionally potent inducers of Nrf2-regulated genes. Molecular Cancer Therapeutics, 6: 154-162, 2007.

Guilarte TR, McGlothan JL, Degaonkar M, Chen M-K, Barker PR, Syversen T, Schneider, JS. Evidence for cortical dysfunction and widespread manganese accumulation in the non-human primate brain following chronic manganese exposure: A 1H-MRS and MRI study. Toxicological Sciences, 94: 351-358, 2006.

Schneider JS, Decamp E, Koser AJ, Fritz S, Emberger H, Syversen T, Guilarte TR. Effects of chronic manganese exposure on cognitive amd motor functioning in non-human primates. Brain Research, 1118: 222-231, 2006.

Burton NC, Kensler TW, Guilarte TR. In vivo modulation of the parkinsonian phenotype by Nrf2. Neurotoxicology, 27: 1094-1100, 2006. [Science Direct TOP25 Hottest Articles. Subject Area: Neuroscience, Journal: Neurotoxicology, July-September, 2006; Rank #18]-[Science Direct TOP25 Hottest Articles. Subject Area: Neuroscience, Journal: Neurotoxicology, October-December, 2006; Rank #4]-[Science Direct TOP25 Hottest Articles. Subject Area: Neuroscience, Journal: Neurotoxicology, January-March, 2007; Rank #13]-]-[Science Direct TOP25 Hottest Articles. Subject Area: Neuroscience, Journal: Neurotoxicology, April-June, 2007; Rank #25].

Papadopoulos V, Baraldi M, Guilarte TR, Knudsen TB, Lacapere J-J, Lindemann P, Norenberg MD, Nutt D, Weizman A, Zhang M-R, Gavish M. Translocator protein (18 kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends in Pharmacological Sciences, 27: 402-409, 2006. [Science Direct TOP25 Hottest Articles. Subject Area: Pharmacology, Toxicology and Pharmaceutical Science; Journal: Trends in Pharmacological Sciences; July to September, 2006; Rank # 11].

Guilarte TR, Chen M-K, McGlothan JL, Verina T, Wong DF, Zhou Y, Alexander M, Rohde CA, Syversen T, Decamp E, Koser AJ, Fritz S, Gonczi H, Anderson DW, Schneider JS. Nigrostriatal dopamine system dysfunction and subtle motor deficits in Mn-exposed non-human primates. Experimental Neurology, 202: 381-390, 2006.

Zhou Y, Chen M-K, Endres CJ, Ye W, Brasic JR, Alexander M, Crabb AH, Guilarte TR, Wong DF. Extended simplified reference tissue model for quantification of single dynamic PET studies with amphetamine challenge. NeuroImage, 33: 550-563, 2006.

Chen M-K, Guilarte TR: Imaging the peripheral benzodiazepine receptor response in CNS demyelination and remyelination, Toxicological Sciences 91: 532-539, 2006.

Toscano CD, McGlothan JL, Guilarte TR: Experience dependent regulation of zif268 gene expression and spatial learning, Experimental Neurology. 200: 209-215, 2006.

Chen M-K, Lee J-S, McGlothan JL, Furukawa R, Adams RJ, Alexander M, Wong DF, Guilarte TR: Acute manganese administration alters dopamine transporter levels in the non-human primate striatum, NeuroToxicology 27: 229-236, 2006. [Science Direct TOP25 Hottest Articles. Subject Area: Neuroscience, Journal: Neurotoxicology, January-March, 2006; Rank #25].

Guilarte TR, McGlothan JL, Foss CA, Zhou J, Heston WD, Kozikowski AP, Pomper MG: Glutamate carboxypeptidase II levels in rodent brain using [125I]-DCIT quantitative autoradiography. Neuroscience Letters 387: 141-144, 2005.

Hardwick MJ, Chen M-K, Baidoo K, Pomper MG, Guilarte TR: In vivo Imaging of Peripheral Benzodiazepine Receptors in Mouse Lungs: A Biomarker of Inflammation. Molecular Imaging, 4: 432-438, 2005.

Hammoud DA, Enders CJ, Chander AR, Guilarte TR, Wong DF, Sacktor NC, McArthur JC, Pomper MG: Positron Emission Tomography with [11C]-R-PK11195 in HIV-associated Dementia. Journal of NeuroVirology 11: 346-355, 2005.

Toscano CD, O'Callaghan JP, Guilarte TR: Calcium/Calmodulin-dependent Protein Kinase II activity and expression are altered in the hippocampus of Pb-exposed rats. Brain Research 1044: 51-58, 2005.

Toscano CD, Guilarte TR: Lead neurotoxicity: From exposure to molecular effects. Brain Research Reviews 49: 529-554, 2005. [Science Direct TOP25 Hottest Articles. Subject Area: Neuroscience, Journal: Brain Research Review, January-March, 2006; Rank #17].

Guilarte TR: Prenatal lead exposure and schizophrenia: A plausible neurobiologic connection. Environmental Health Perspectives 112: A724, 2004.

Guilarte TR: Peripheral Benzodiazepine Receptor Imaging in Glial Cells: Molecular Sensors of Brain Pathology. In: The Role of Glia in Neurotoxicity (second edition) Aschner M and Costa L., eds. chapter 12, pp 207-219, 2004.

Chen MK, Baidoo K, Verina T, Guilarte TR: Peripheral Benzodiazepine Receptor imaging in CNS demyelination: Functional implications of anatomical and cellular localization. Brain 127: 1379-1392, 2004.

Guilarte TR: Functional implications of neuronal NMDA receptor subunit expression in the rat brain following developmental lead exposure. In: Molecular Neurotoxicology: Transcriptional Targets., edited by Nasser H. Zawia. Taylor and Francis, Chapter 5, pp87-105, 2004.

Toscano CD, McGlothan JL, Guilarte TR: Lead exposure alters cyclic-AMP response element binding protein (CREB) phosphorylation and binding activity in the developing rat brain. Developmental Brain Research 145: 219-228, 2003.

Guilarte TR, Nihei MK, McGlothan JL, Howard AS: Methamphetamine-induced deficits of brain monoaminergic neuronal markers: distal axotomy or neuronal plasticity. Neuroscience 122: 499-513, 2003.

Guilarte TR, McGlothan JL: Selective decrease in NR1 subunit splice variant mRNA in the hippocampus of Pb2+- exposed rats: Implications for synaptic targeting and cell surface expression of NMDAR complexes. Molecular Brain Research 113: 37-43, 2003.

Mankowski JL, Queen SE, Tarwater PJ, Adams RJ, Guilarte TR: Elevated peripheral benzodiazepine receptor expression in simian immunodeficiency virus encephalitis. Journal of NeuroVirology 9: 1-7, 2003.

Guilarte TR, Toscano CD, McGlothan JL, Weaver SA: Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure. Annals of Neurology 53: 50-56, 2003.

Toscano CD, Hashemzadeh-Gargari H, McGlothan JL, Guilarte TR: Developmental Pb(2+) exposure alters NMDAR subtypes and reduces CREB phosphorylation in the rat brain. Developmental Brain Research 139: 217-226, 2002.

Nihei MK, Guilarte TR: Molecular changes in glutamatergic synapses induced by Pb2+: Associations with deficits in LTP and spatial learning. Neurotoxicology 22: 635-643, 2001.

Nihei MK, McGlothan JL, Toscano CD, Guilarte TR: Low level Pb2+ exposure affects hippocampal PKC-gamma gene and protein expression. Neuroscience Letters 298: 212-216, 2001.

Kuhlmann AC, Guilarte TR: Cellular and subcellular localization of peripheral benzodiazepine receptors after trimethyltin neurotoxicity. Journal of Neurochemistry 74: 1694-1704, 2000.

Guilarte TR, McGlothan JL, Nihei MK: Hippocampal expression of N-Methyl-D-Aspartate Receptor (NMDAR-1) splice variant mRNA is altered by developmental exposure to Pb2+. Molecular Brain Research 76:299-305, 2000.

Nihei MK, Desmond NL, McGlothan JL, Kuhlmann AC, Guilarte TR: NMDA receptor subunit changes are associated with Pb2+-induced deficits of LTP and spatial learning. Neuroscience 99: 233-242, 2000.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Tomas Guilarte Photo