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University of California - Davis Center for the Study of Environmental Factors in the Etiology of Autism
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Principal Investigator: Isaac Pessah, PhD
| Overview | Selected Results |
| Exposures and Outcomes | Community Partners |
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The UC Davis Center for Children’s Environmental Health (CCEH) was established in 2001 with the objective of understanding genetic and environmental risk factors contributing to the incidence and severity of childhood autism. The ultimate goal of the Center is to understand common patterns of dysfunction in autism and elucidate mechanisms by which chemicals known to be toxic to the developing nervous and immune systems (neuroimmunotoxicants) contribute to abnormal development of social behavior in children, leading to strategies for prevention and intervention. The CCEH brings together a truly multidisciplinary team of research scientists whose main research interest is the understanding of complex etiologies that contribute to autism risk.
Autism is a neurodevelopmental disorder defined by deficiencies of social reciprocity and communication, and by repetitive (stereotypic) behavior. The majority of autism cases seem likely to arise from a multiplicity of genetic and environmental factors, including susceptibility genes. Models using family and twin data suggest that between two and ten loci may be implicated.
Surveys in California indicate an apparent 210% increase in the number of cases of profound autism in children diagnosed over the past 10 years. There is growing concern from parents and health professionals that prenatal and postnatal exposure to xenobiotics (such as mercurials, halogenated aromatics and pesticides) and biotic factors (such as vaccine antigens) could act synergistically to alter the expression of as-yet unidentified susceptibility and genetic factors to result in autism spectrum disorders.
The UC Davis Center is designed on several levels to investigate how the interaction of susceptibility genes with exposure to environmental chemicals may increase the risk and severity of autism and to identify which combination of chemical exposures may confer the greatest threat.
2001-2006
Project 1, The CHARGE Study (Childhood Autism Risks from Genetics and Environment) began in 2001 as the first case-control epidemiological study of environmental factors in the etiology of autism. The main focus was to understand if autism is an immunological disorder, a neurological disorder, or both. Project 2, Animal Models of Autism, proposed to identify for the first time how known neurotoxicants of concern to children’s health influence the development of social behavior and mediating brain regions such as the amygdala. The importance of signaling activity from the immune system during critical periods of neurodevelopment has been documented. Project 3, Cellular and Molecular Mechanisms of Autism, integrated elements of Projects 1 and 2 to examine molecular mechanisms underlying neurodevelopmental disorders associated with human autism and animal models of autism.
The Center developed possible diagnostic markers of autism (based on transcriptional analysis and immune markers). Results from the CHARGE and animal studies could have an impact on public perception and policy regarding risk assessment and define limits for children with ASD as a particularly susceptible population.
The research projects have been integrated within a Center framework providing extensive facility core capabilities in xenobiotic/lipid analysis, cell activation biomarkers and molecular biomarkers. The Center consists of an Administrative Core, three Facility Cores, and the three Research projects, designed to integrate three different levels of scientific inquiry to understand how genetic and environmental factors can combine to alter critical signaling activities of immune and nervous systems and to gain insight into how these changes relate to higher-order CNS function.
2006-2011
Project 1: The CHARGE, CHARGE-BACK, and MARBLES Studies. These studies build upon the discovery of immunologic and molecular biomarkers specific to children with autism found in 2-5 year olds enrolled in the CHARGE Study by extending the investigation of post-diagnosis differences to the pre-diagnostic period. The hypothesis being tested is that children with autism can be distinguished from those without autism by markers of immune dysregulation (at birth, as well as post-diagnosis) and by prenatal, immunologically relevant events and exposures. Investigators will also determine if children with and without autism differ with regard to exposures, body burdens, and excretion of xenobiotics, including metals, pesticides and PBDEs. Researchers will collect a second set of blood samples from 375 children who enrolled in the CHARGE study in the first project period and this study (CHARGE-BACK) will examine stability over time in the immune cell markers that were determined when these children were 2-5 years old. This project also includes the launch of a new cohort study that tracks 200 women at high risk of giving birth to a child who develops autism, starting from early pregnancy and following the pregnancies and the babies to the age of three years. This new cohort study is called Markers of Autism Risk in Babies – Learning Early Signs (MARBLES).
Project 2: Immunological Susceptibility
to Autism
While studies in the first project period were aimed at a broad
analysis of immune function in patients with autism, the current
project addresses the mechanisms responsible for the numerous
alterations in immune homeostasis uncovered in the earlier
studies. The primary focus is on the mechanisms responsible
for such anomalies in immune function through an in-depth analysis
of cellular immune function. The overall hypothesis is that
patients with autism have a fundamental defect at the cellular
level that ultimately leads to abnormalities in immune function
and heightened susceptibility to environmental triggers.
Project 3: Models of Neurodevelopmental
Susceptibility
The long range goal of this project is to determine if exposure
to environmental toxicants early in development contributes to
the etiology of neurodevelopmental disorders such as autism,
using animal (mouse) models. A
related goal is to determine whether susceptibility to autoimmune
disease increases the neurotoxicity of environmental contaminants
and increases the risk for developing disorders such as autism.
Primary Exposures: Neuroimmunotoxicants, including mercury and halogenated organics (PCBs and PBDEs).
Primary Outcomes: Autism and related neurodevelopmental disorders.
2001-2006
The Childhood Autism Risk from Genetics and the Environment (CHARGE) Study began as the first large-scale epidemiologic investigation of underlying causes for autism and triggers of regression.
The first phase of this case-control study integrated information about environmental exposure and tissue samples from 2000 California children, 2-5 years of age – 700 autistic, 700 children with developmental delay or mentally retarded but nonautistic controls (MR/DD) and 600 normally developing controls from the general population (GP) and their immediate families.
- This project integrated units on environmental epidemiology, clinical assessment and statistical/data management. Tissue samples including blood, urine, hair and a buccal swipe were collected from children in two distinct geographic areas: the Sacramento Valley and the Los Angeles basin. A community advisory committee met regularly with Center investigators to help define interactions with the communities being studied.
- The aims of the first phase of the study (from 2001 to 2006) included assessing the influence of environmental exposures, the role of susceptibility factors and the interplay between these in the etiology of autism and its phenotypic variation. Chemicals with known or suspected neurodevelopmental toxicity, such as PCBs, certain pesticides, and metals were investigated. This study has also pursued hypotheses including mercury (thimerosal) present in vaccines given during infancy and early childhood, and biochemical susceptibility with respect to metabolic, immunologic, and neuronal gene expression profiles and genetic polymorphisms.
- A fingerprint derived from the blood of autistic children indicates that nutritive and micronutritive metals are very closely clustered, whereas xenobiotic metals, such as mercury, are largely distributed with a large variance. The Center has been studying how this variance correlates to the definable factors (such as regressive autism) seen in the medical histories of the children in the study.
For detailed information on this study, see:
Review Article – Hertz-Picciotto I, Croen LA, Hansen R, Jones CR, van de Water J, Pessah IN 2006. The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism. Environ Health Perspect. 2006 Jul;114(7):1119-25.
Project 2: Animal Models of Autism (2001-2006)
These studies were designed to determine how early prenatal and/or postnatal exposure to known immunotoxicants and neurotoxicants (such as mercury and PCBs) in the presence and absence of immune challenge influences normal development of social behavior. Two animal models were utilized:
- The first model examined outcomes of social behavior in primates in response to neonatal exposure to thimerosal (ethylmercury) and a defined mixture of PCBs of concern to human exposure. This permits detailed analysis of social behaviors that are most closely related to those observed in developing children.
- The second model utilized mice in a broader study of the mechanisms of action of suspected immunotoxicants and neurotoxicants on social behavior. The specific aims of the mouse studies were to: (1) develop a battery of behavioral probes to assess social behavior in mice; (2) to evaluate the effects of prenatal and early postnatal exposure to thimerosal, methyl mercury and PCBs on the emergence and quality of social behavior in mice; (3) to determine whether the expected toxicity of chemicals in the environment is altered in mice whose immune systems have been activated early in postnatal development by administration of bacterial endotoxin lipopolysaccaride (LPS); and (4) to examine selected brain regions in xenobiotics-treated mice for structural alterations that may be similar to those observed in autism.
- Once animals were tested for social function, tissue samples were examined to determine the distribution and levels of xenobiotics in defined regions of the CNS, cytokine and autoantigen profiling of the nervous system, gene array profiling and functional analysis using cellular imaging and electrophysiological and biochemical techniques.
- Mouse models also permit genetic manipulation of expression. For example, researchers studied the consequence of deleting the Homer 1 gene, an adapter protein critically important for regulating active synapses, on a variety of social and cognitive behaviors. Methods include using detailed CNS stereology to correlate with changes in social behavior.
Project 3: Molecular and Cellular Mechanisms of Autism (2001-2006)
A working hypothesis of the first phase of the Center was that there is a specific type of cellular dysfunction within the immune system of autistic children, and the Center examined the dendritic cell (DC), an antigen-presenting cell in the immune system. It is possible that the DCs are presenting wound antigens, vaccine antigens, or xenobiotics, and the immune system responds by activating hundreds of T cells.
The goal of this project was to understand the molecular and cellular mechanism by which low levels of ethylmercury (thimerosal), PCBs, and polybrominated diphenylethers (PBDEs) can dysregulate dendritic cell (DC) and neuronal signaling. This project also assessed the influence of these chemicals on the growth and development of glial/hippocampal neurons and was designed to understand genetic factors that impart susceptibility to immunotoxicants and developmental neurotoxicants. The long-term goal is to define common mechanisms in immune and neural cells responsible for developmental toxicity of these environmental agents.
Researchers at the UC Davis Children’s Center examined the actions of mercurials (PBDEs and PCBs) since they represent a high-priority concern. Cytokine secretion profiles were determined for peripheral blood mononuclear cells (PBMCs) cultured from autistic and matched control children from the CHARGE study.
Researchers studied three hypotheses related to the underlying mechanisms of susceptibility to immunotoxic and neurotoxic agents.
- Hypothesis 1: PBMCs from autistic children exhibit significant differences in their sensitivity and/or pattern of cell activation and cytokine secretion when challenged in vitro with MMR vaccine antigens. Researchers looked into the underlying signaling mechanisms which may contribute to abnormal immune cell responses, and are proceeding to identify the underlying genetic susceptibility genes and see if tyrosine kinase receptors are involved. Among the motivations for this research were observations that certain xenobiotics, such as non-coplanar PCBs, synergize cellular responses to antigen stimulation to a greater degree in autistic children when compared to non-autistic PBMCs.
- Hypothesis 2: Mercurials and halogenated organics (such as PCBs, PBBs and PBDEs) influence glial and neural cell interactions with effects on growth, dendritic branching and synaptogenesis. An extension of this hypothesis is to utilize the products of antigen-stimulated and control PBMC from both autistic and non-autistic children to address differential effects on neuronal cell growth rate and pattern, dendritic spine elongation and apoptosis.
- Hypothesis 3: Functional and biochemical changes may be associated with mice tested for social behavioral deficits after in vivo exposure to antigen/xenobiotic combinations from Project 2.
2006-2011
Project 1:The CHARGE, CHARGE-BACK, and MARBLES Studies
The Epidemiology Project of the UC Davis Center for Children’s Environmental Health (CCEH) builds upon the discovery of immunologic and molecular biomarkers specific to children with autism found in 2-5 year olds enrolled in the CHARGE (Childhood Autism Risks from Genetics and Environment) Study.
(1) First, newborn blood spots from children in each of three groups (i.e., autism, developmental delay, and general population controls) will be analyzed in Project 2 for a variety of immune biomarkers and in Core 3 (Analytical Chemistry) for metal concentrations. The data obtained from newborn bloodspots, when compared to data already collected from the same individuals in early childhood, will provide important information for the period shortly before birth about immune dysfunction and metal exposures or metabolism in children who are later diagnosed with autism. In other words, the Center will extend the investigation of post-diagnosis differences to the pre-diagnostic period.
- The hypothesis being tested is that children with autism can be distinguished from those without autism by markers of immune dysregulation (at birth, as well as post-diagnosis) and by prenatal, immunologically relevant events and exposures.
(2) Second, in collaboration with Core 3, investigators will determine if children with and without autism differ with regard to exposures, body burdens, and excretion of xenobiotics, including metals, pesticides and PBDEs. Exposures are based on questionnaire information and environmental databases covering toxic emissions, hazardous air pollutants and pesticide applications. Body burdens are measured in blood or plasma, and excretion is evaluated in hair or urine; these measurements are performed in the Core 3 laboratories.
(3) Third, the UC Davis Children’s Center will test the hypothesis that transcriptional genomic profiles of children with autism differ from those of children without autism. Particular attention will be placed on genes related to biotic and xenobiotic metabolism.
(4) Fourth, Projects 1 and 2 in collaboration with the Community Outreach and Translation Core (COTC – Core 2) will collect a second set of blood samples from 375 children who enrolled in the CHARGE study in the first project period. This study (CHARGE-BACK) will examine stability over time in the immune cell markers that were determined when these children were 2-5 years old. CHARGE-BACK blood samples will provide peripheral immune cells to study how autism alters properties of cell activation, and susceptibility to known immunotoxicants (Project 2 and Core 4).
(5) Fifth, Project 1 will launch a new
cohort study that tracks 200 women at high risk of giving birth
to a child who develops autism, starting from early pregnancy
and following the pregnancies and the babies to the age of
three years. This new cohort study is called Markers
of Autism Risk
in Babies – Learning Early Signs
(MARBLES). Fieldwork for the MARBLES study will be tightly
integrated with the COTC (Core 2) efforts, and the specimens
will be evaluated in Cores 3 and 4, and in Project 2. The
goal is to determine early predictors of autism, whether they
be immunologic, genomic, or environmental.
For detailed information on this study, see:
Review Article – Hertz-Picciotto I, Croen LA, Hansen R, Jones CR, van de Water J, Pessah IN 2006. The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism. Environ Health Perspect. 2006 Jul;114(7):1119-25.
Project 2: Immunological Susceptibility to Autism
Recent studies indicate that immune function in children with autism spectrum disorder (ASD) is profoundly altered compared to developmentally healthy controls. There is a strong interface between the immune system and the neurologic network, and successful neurodevelopment is contingent upon a successful interaction between these two systems.
We have identified several aspects of immune dysfunction in patients
with autism compared with typically developing controls. These
include a reduced response to vaccine antigens of bacterial origin,
altered cytokine levels in plasma and upon stimulation of PBMC,
increased levels of leptin in patients with early onset autism,
and autoantibodies to brain antigens. This wide and complex variety
of immune anomalies noted in the first funding period (2001-2006)
is in keeping with the broad range of phenotypes encompassed
by the autism spectrum. Thus, we will build upon our earlier
findings of both serologic and cellular changes in immune function.
While our studies in the first project period were aimed at a
broad analysis of immune function in patients with autism, the
current proposal addresses the mechanisms responsible for the
numerous alterations in immune homeostasis uncovered in our earlier
studies. Therefore, our primary focus will be on the mechanisms
responsible for such anomalies in immune function through an
in-depth analysis of cellular immune function.
- The overall hypothesis is that patients with autism have a fundamental defect at the cellular level that ultimately leads to abnormalities in immune function and heightened susceptibility to environmental triggers.
To examine this, we propose to: (1) examine longitudinally the serologic profile of children with ASD to ascertain whether the various immune changes noted in our first studies are maintained and/or deteriorating further; (2) determine which immune cell population(s) plays a critical role in the immune dysfunction seen in patients with autism; and (3) fully characterize the autoantibody response in a subpopulation of children with ASD and some mothers of children with ASD. It must be noted that due to the highly heterogeneous nature of autism, there will potentially be immunologic differences that relate to sub-groups of patients with autism. Therefore, we will carefully define the study groups based on our current data to include children with early onset autism, children with delayed onset/regressive autism, general population controls, and children with developmental disorders without ASD. The studies will be performed on CHARGE subjects formerly analyzed by our laboratory (CHARGE-BACK study). This will allow us to extend our prior studies longitudinally to determine if the immune dysregulation, such as increased leptin levels in the early onset patients, remains over time. The following aims address both the serologic and cellular aspects of immune function in patients with autism.
Project 3: Models of Neurodevelopmental Susceptibility
The long range goal of this project is to determine if exposure to environmental toxicants early in development contributes to the etiology of neurodevelopmental disorders such as autism. A related goal is to determine whether susceptibility to autoimmune disease increases the neurotoxicity of environmental contaminants and increases the risk for developing disorders such as autism.
Understanding how exposure to environmental toxicants may contribute to the etiology of neurodevelopmental disorders is important so that the exposure risks can be identified and minimized. If immune system dysfunction is found to increase the risk of exposure to environmental toxicants, then exposure limits to toxic substances can be lowered, and children with immune system dysfunction who may be at increase risk can be identified and protected.
The specific aims are to expose mouse strains with low (C57BL/6J) or high (SJL mice) susceptibility to autoimmunity perinatally to either methylmercury (MeHg), polychlorinated biphenyl 95 (PCB 95) or polybrominated diphenyl ether 47 (BDE 47). We will then compare the effects of toxicant exposure between these mouse strains on brain development, complex social behaviors, and immune system function. The hypothesis is that perinatal exposure to each of these toxic substances will impair brain development and behavior, and that suscepbility to autoimmune disease will increase the neuro- and immunotoxicity of these agents.
The Center will also explore a potentially new model of autism in mice injected prenatally with unique autoantibodies isolated from the serum of mothers who have given birth to two more more autistic children. Brain development will be examined histologically using stereological procedures and immunohistochemistry. Complex social behaviors will be studied using behavioral testing procedures established in our laboratory that measure social recognition, social interaction and social communication in mice. Immune system status will be established by measuring cytokines, chemokines, immunoglobulins, and quantifying immune system response to antigenic stimulation. In addition, seizure susceptibility will be measured in toxicant-exposed mice as well as measures of synaptic excitibility and plasticity in hippocampal brain slices.
These studies will provide critical new information on the role of the immune system and its interaction with environmental contaminants in autism and other neurodevelopmental disorders.
Major scientific and professional achievements of CCEH scientists are highlighted below:
- The Center has established credible and trusting relationships with a wide range of local stakeholders, including parents and autism advocacy organizations (e.g., Participants of CHARGE and MARBLES, Families for Early Autism Treatment, Learning Disabilities Association; Parents Helping Parents, SF Chapter of Autism Society of America, and the Alameda Developmental Disabilities Council, and Cure Autism Now), State health/developmental service providers (CA Departments of Developmental Services and Health Services, CA Regional Centers, and CA Office of Environmental Health Hazard Assessment).
- The UC Davis Center has established the first population-based case-control study (Childhood Autism Risk from Genetics and the Environment, or CHARGE Study) of autism in 2002. By September 2006, more than 700 families were enrolled, had been assessed using standardized instruments, and had donated a variety of samples collected for analysis of xenobiotic, immune biomarkers, transcriptome, and SNP analyses (Hertz-Picciotto et al 2006 Environ Health Perspect. 2006 Jul;114(7):1119-25).
- The CHARGE Study has generated numerous spin-offs, including the M.I.N.D. Institute’s Autism Phenome Project, which includes add-ons such as brain imaging and more detailed psychometric assessments of children with autism, MARBLES and CHARGE-BACK.
- The Center has established the first sample and data archive consisting of age-matched children with autism, children with developmental delay, and children from the general population (2-5 years), also including samples from siblings, and parents
- The Center has completed and submitted a rigorous analysis of statewide time trends for autism in California. (Hertz-Picciotto and Delwiche 2006, submitted)
- The UC Davis Center has conducted a comparative analysis of CHARGE study cohort sociodemographic characteristics with targeted pool for autism, developmental delay and general population controls in California completed. (manuscript in preparation)
- Evaluation of head circumference at birth in autism completed. (manuscript in preparation)
- Sleep patterns and cognitive development in autism study completed. (manuscript in preparation)
- Completed initial transcriptional analysis of CHARGE participants. Children with autism are found to possess significantly higher levels of natural killer (NK) cell and CD8+ markers compared to comparison groups. (Gregg et al 2006 submitted)
- Elevated leptin levels identified in early onset autism. (Van DeWater et al 2006 submitted)
- Completed initial analysis of metal levels in CHARGE study index children comparing children with vs. without autism. Validated questionnaire data on fish consumption, nasal sprays and dental amalgams as predictors of blood mercury concentrations. (manuscript in preparation)
- Methods developed using laser ablation-ICP MS to obtain mercury data from blood spots and hair (manuscript in preparation).
- Development of an on-line SPE-HPLC-tandem mass spectrometry method to analyze urinary neuroactive peptides in autism. (Dettmer et al 2006 Anal. Bioanal. Chem., in press)
- Assessment of PBDE concentrations in CHARGE Study children launched,
with supporting funding from Cure
Autism Now .
- Identified and categorized distinct patterns of autoantibodies to fetal brain protein in serum collected from women who have mothered an autistic child.
- Purified IgGs isolated from women at risk and general population tested for developmental effects in nonhuman primate model. Pronounced stereotypes are identified in monkeys prenatally exposed to IgG from mothers of children with autism, but not IgG from mothers from the general population or those of children with MR/DD. (Martin et al J. Neurosci. submitted)
- Established extensive behavioral test battery for mice with particular emphasis on tasks that test social behaviors, anxiety, motor functioning.
- Behavioral analysis of Homer 1 knockout mouse completed. Homer is found to regulate gain of ryanodine receptors. (Jaubert et al Genes Brain Behav. 2006)
- Homer 1 and 2 found to regulate gain of ryanodine receptors. (Feng et al J. Biol Chem. 2002 277(47):44722-30.; Ward et al J Biol Chem. 2004 279(7):5781-7).
- Structure-activity relationship established for non-coplanar PCBs toward wild type and mutated ryanodine receptors. (Pessah et al Chem Res Toxicol 2006 19(1):92-101; Ta and Pessah 2006, NeuroToxicology (in press); Gafni et al 2004 Toxicol Sci 77(1):72-82; Howard et al. 2003)
- Developmental exposure of rats to non-coplanar PCB is found to disrupt normal tonotopic organization of primary auditory cortex, enhance hippocampal excitability and seizure susceptibility. Developmental exposure to non-coplanar PCBs has impacts on sociability in mice. (Kenet et al, submitted; Kim et al submitted)
- Mouse model piloted with maternal IgG from mothers of children with autism and general population. Autism IgG shows immunoreactivity toward mouse brain proteins.
- Initial pilot study of developmental exposure of human IgGs from CHARGE in mouse completed.
- Murine dendritic cells (DC) maturation in culture is found to be regulated by oxygen tension and extremely sensitive to organic mercury. (Goth et al. 2006).
- Thimerosal and/or vaccine study in SJL and C57/B6 strains completed. (Berman et al in preparation)
- Study of early neurodevelopmental toxicity of organic forms of mercury completed (with New Jersey CCEH). (Burke et al, NeuroToxicology, 2006 Dec;27(6):970-81.)
- Piloted the Markers of Autism Risk in Babies – Learning Early Signs (MARBLES) Study beginning August 2006. MARBLES is enrolling pregnant women for a longitudinal cohort study of high-risk fetuses/infants, namely those with an older sibling who has autism.
Participants of CHARGE and MARBLES
Families for Early Autism Treatment
Learning Disabilities Association
San
Francisco Bay Chapter of the Autism Society of America
Alameda
County Developmental Disabilities Council
State of California health/developmental service providers (CA Departments of Developmental Services and Health Services, CA Regional Centers, and CA Office of Environmental Health Hazard Assessment)
Feng W, Tu J, Yang T, Vernon PS, Allen PD, Worley PF, Pessah IN 2002. Homer regulates gain of ryanodine receptor type 1 channel complex. J Biol Chem. 2002 277(47):44722-30.
Gafni J, Wong PW, Pessah IN 2004. Non-coplanar 2,2',3,5',6-pentachlorobiphenyl (PCB 95) amplifies ionotropic glutamate receptor signaling in embryonic cerebellar granule neurons by a mechanism involving ryanodine receptors. Toxicol Sci. 77(1):72-82.
Goth SR, Chu RA, Gregg JP, Cherednichenko G, Pessah IN. 2006. Uncoupling of ATP-mediated calcium signaling and dysregulated interleukin-6 secretion in dendritic cells by nanomolar thimerosal. Environ Health Perspect. 2006 114:1083-1091.
Hertz-Picciotto I, Croen LA, Hansen R, Jones CR, van de WJ, Pessah IN 2006. The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism. Environ Health Perspect. 2006 114:1119-1125.
Howard AS, Fitzpatrick R, Pessah I, Kostyniak P, Lein PJ 2003. Polychlorinated biphenyls induce caspase-dependent cell death in cultured embryonic rat hippocampal but not cortical neurons via activation of the ryanodine receptor. Toxicol Appl Pharmacol 190:72-86.
Jaubert PJ, Golub MS, Lo YY, Germann SL, Dehoff MH, Worley PF, Kang SH, Schwarz MK, Seeburg PH, Berman RF 2006. Complex, multimodal behavioral profile of the Homer1 knockout mouse. Genes Brain Behav, in press.
Pessah IN, Hansen LG, Albertson TE, Garner CE, Ta TA, Do Z, Kim KH, Wong PW 2006. Structure-activity relationship for noncoplanar polychlorinated biphenyl congeners toward the ryanodine receptor-Ca2+ channel complex type 1 (RyR1). Chem Res Toxicol. 19(1):92-101.
Ta TA and Pessah IN 2006. Ryanodine receptor type 1 (RyR1) possessing malignant hyperthermia mutation R615C exhibits heightened sensitivity to dysregulation by non-coplanar 2,2',3,5',6-pentachlorobiphenyl (PCB 95). NeuroToxicology, in press.
Full List of Publications | Publications List from NIEHS PubMed Database
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