Introduction – Strategic Vision
Children’s environmental health genomics-2013
New interest group in children’s environmental health genomics
NIEHS supplement for pilot project to Tonellato, Laiosa, Carvan
Construction of Pipeline-undergoing testing
TALENS-Carvan, Heideman
West end facility to stimulate conversion to specific pathogen-free facility
Biobanking of zebrafish tissues has begun.
Personal air pollution sensing: collaboration of Chen and Etzel
IR detection of metabolism of NO, O2, etc (Hirschmugl)
New programs/activities described in 2012 are activated in 2013
1. Mission
The vision of the (NIEHS) is to provide global leadership for innovative research that improves public
health by preventing disease and disability from our environment. (NIEHS) will require partnerships and
coordinated strategies to achieve these Strategic Goals..........................NIEHS Strategic Plan
The mission of the Children’s Environmental Health Sciences Core Center (CEHSCC) is to contribute
powerfully to the prevention of environmentally-related diseases and disorders that affect development during
the period from conception to maturation and to do so particularly among City of Milwaukee children. The
Center sees itself as a regional partner with NIEHS, supporting the Institute’s national leadership aims. This
section describes how Center members, assets, programs, and activities work together to achieve this mission.
2. Overall Objectives and Specific Aims
Primary objective The Center will stimulate and sustain the development of the regional community of
scientists that conducts significant and innovative research and community engagement in environmental
health impacting children in Milwaukee and elsewhere. Working individually and in teams, scientists will
conduct research along the basic, translational, clinical/public health science continuum. Their findings will
move the Center toward national leadership in research on identifying and addressing environmental
contributions to childhood disease.
Complementary objective The CEHSCC will convert scientific understanding into effective strategies
to prevent environmentally-induced childhood disease. In cooperation with partners, the community outreach
arm of the CEHSCC will engage with local and regional communities effectively to understand the burden of
environmentally-related childhood diseases and to act in effective ways to reduce them.
The following specific aims serve as the framework to meet these objectives.1 The Center will [1]
provide a rich program that attracts leading and promising scientists from diverse disciplines into a stimulating
research community; [2] encourage researchers to address and collaborate on significant problems in
children’s environmental health; [3] enhance investigators’ research and engagement with a wealth of
resources and professional staff; and [4] offer investigators multiple options to link their expertise and
knowledge with communities through outreach and engagement.
3. Children’s Environmental Health - the Challenge and Opportunity
Human development, beginning with embryogenesis and continuing through adolescence, is a
particularly sensitive period during which environmental factors play a pivotal role in immediate health status
and lifetime health outcomes (1). Children may confront a daunting array of challenges that severely
compromises their health and longevity. These include exposure to toxic contaminants, inadequate nutrition,
and adverse environmental and social conditions in the home and surrounding environment (2-6). Research
indicates that environmental factors contribute to birth defects, asthma, learning and behavioral deficits, and
possibly, obesity (7-10). Moreover, it is increasingly clear that some adult diseases find their origin in fetal and
early childhood development (11). There is strong evidence, for example, that low birth weight results from
environmental exposures during gestation, predisposing infants to diseases as adults (12,13).
Of particular concern are health inequities that children suffer in families with lower socio-economic
status, typically, racial/ethnic minorities. For example, exposure to tobacco smoke and addictive drugs (low
birth weight, stunted development); household allergens (asthma); lead (depressed learning and other
neurological outcomes), etc. are all substantially higher in children born into poverty (14-18). Milwaukee
mirrors the health problems and inequities that children face in urban centers across the country and is, in
some respects, among the worst in the nation. Thus, City of Milwaukee infant mortality rates for all
races/ethnicities, as well as for non-Hispanic blacks and Hispanics in 2005-2007 and 2008-2010 were
significantly higher than the comparable U.S. infant mortality rates in 2005-2007 (the most recently available
data) (19a,b). Preterm birth is the major contributor (68%) to infant mortality in the U.S (19b). In Milwaukee, at
least a 2-fold difference exists between zip codes in infant mortality rates (2-2.5-fold), and the prevalence of
preterm birth and low birth weight (19a,c).
4. Overall Vision for the Center
1
Abbreviations: AAF, Aquatic Animal Facility; AAMFC, Aquatic Animal Models Facility Core; App, Appendix; CDC, Centers for
Disease Control and Prevention; CDP, Career Development Program; CEHSCC, Children’s Environmental Health Sciences Core
Center; CHHS, Children’s Hospital and Health System; COEC, Community Outreach and Engagement Core; CRI, Children’s Research
Institute; EBAC, Exposure and Biological Analysis Core; ICO, Institutional Commitment and Organization; IHS, Institute for Health and
Society; IHSFC, Integrative Health Sciences Facility Core; LSIP, Laboratory System Improvement Program; MCW, Medical College of
Wisconsin; MeHg, methylmercury; MFBS Center, Marine and Freshwater Biomedical Sciences Center; MHD, Milwaukee Health
Department; NBTF, Neurobehavioral Toxicology Facility; PAH, polycyclic aromatic hydrocarbon; NIEHS, National Institute of
Environmental Health Sciences; SFS, School of Freshwater Sciences (UWM); TALEN, transcription activator-like effector nuclease;
UWM, University of Wisconsin-Milwaukee; WSLH, Wisconsin State Laboratory of Hygiene; ZSPH, Zilber School of Public Health
4.1. Background The NIEHS Children’s Environmental Health Sciences Core Center (CEHSCC)
evolved from a predecessor NIEHS Center, the Marine and Freshwater Biomedical Sciences (MFBS) Center
(1978-2008) when it formed a partnership with the Children’s Research Institute (CRI) in 2006 to support joint
research and community engagement (Figure 1). The aim was to establish a powerful, cohesive program of
research and community engagement involving basic, translational, public health and clinical investigators to
improve the health of children in general and, particularly, in the immediate region.
To realize this vision, a strategic inter-institutional
partnership
was established between the University of
NIEHS
CHHS
Wisconsin-Milwaukee
(UWM) and the CRI of Children’s
MFBS Center
CRI
UWM
MCW
1978-2008
Hospital and Health System (CHHS) and the Medical College
2006
of Wisconsin (MCW) (Figure 1).
As the CEHSCC
commenced
in
2009,
UWM
and
its
partner
institutions were
CHHS
MFBS
CRI
UWM
Center
about to experience significant expansion of their academic
MCW
programs and faculty. With the Center’s formative support,
UWM has inaugurated two new schools, the Zilber School of
Public Health (ZSPH) and the School of Freshwater Sciences
CHHS
NIEHS Children ’s
UWM
EHSC Center
(SFS) that play important roles in the alliance. Soon, a thriving
MCW
2009
research community emerged as the Center became the
U WM Zilber Sc hool
MCW CTSI
of Public H ealth
organizational hub for regional investigators who are engaged
C R I U nex plained
Infant D eath
U WM Sc hool of
in children’s environmental health studies.
Center
Fres hwater
NIEHS
4.2.
Moving forward The Center’s vision is to
Sc ienc es
Children’s
Other
U niv er s ities
EHSC
Center
accelerate
the
development of the regional children’s
Milw auk ee
2012
H ealth D ept.
environmental health community into a system of resources,
Laboratory
of H y giene
interactions, and collaborations that addresses key
Figure 1. Evolution of the CEHSCC
environmental health problems, developing in and/or emerging
during childhood. The Center’s deliberate will continue to
encourage individual and multi-disciplinary teams of scientists to work on the vexing health problems of
children living in adverse environments. Its distributive and diverse institutional and scientific foundation
makes possible the Center’s broad portfolio of research, extending from basic to human studies and promotes
many opportunities in the realm of community engagement. To illustrate, the UWM School of Freshwater
Science (SFS) brings together environmental and environmental health scientists to address issues of
freshwater and children’s health. Zilber School of Public Health (ZSPH) scientists provide robust translational
expertise in the sphere of children’s population health, epidemiology, and health inequities. CRI and MCW
researchers offer access and depth in pediatric medicine.
To serve the public, Center members’ collective scientific knowledge needs to reach the Milwaukee
regional community and beyond. Thus, the CEHSCC is committed to engaging with ethnic communities and
related governmental bodies and officials, teachers and students, and health professionals in order to improve
children’s environmental health understanding and outcomes. The process begins with a career development
model that emphasizes community engagement as an integral part of the professional life of scientists and
links this with the programs of the Center’s Community Outreach and Engagement Core (COEC).
5. Overview of Research Base
The CEHSCC considers its basic
mission to advance and sustain a regional
Figure 2. Regional Full Membership and Disciplinary Expertise
community of scientists that strongly
contributes to children’s environmental
UWM (23)1 behavioral, developmental, and reproductive biology,
health research and engagement. Science
bioinformatics, biochemistry, biophysics, endocrinology, microbiology,
neuroscience, public health nursing, public health policy and law, physics,
thrives on the combination of long-term,
toxicology
focused research and inquiries into new
MCW (25) biostatistics, cell biology, genetics, molecular biology,
areas and questions. The Center facilitates
pathology, pediatrics, physiology, toxicology
depth and novelty by supporting a research
UW-Madison (4) molecular genetics, nutrition, toxicology
community that attracts investigators from
Marquette U (3) biology, biomedical science, microbiology
Concordia U (3) analytical chemistry, biophysical chemistry, toxicology
various institutions and many backgrounds.
MKE Health Dept. (1) environmental health, microbiology
Figure 2 summarizes the breadth of
organizations and disciplines represented in
1Number of members. Membership list in Table 1 (NIEHS Table B) of
the Center’s membership.
Included are
Administrative Core, section 4.
three major and one local university, a
nationally recognized medical school, a first rank Children’s Hospital, and the Milwaukee Health Department.
With the participation of scientists from the ZSPH and SFS at UWM and key units within MCW/Children’s
Hospital (CRI and Unexplained Infant Death Center [UIDC]) etc., members with many backgrounds come
together in a unique inter-institutional research community (Figure 2). The resulting concentration of expertise
provides the capacity and opportunity to form diverse research teams and the flexibility to find new
collaborators as interests evolve. Section 7 summarizes the blend of deepening research, novel initiatives,
and new and established collaborations that is occurring within the CEHSCC community.
6. Introduction to Research Portfolio and Environmental Health Identity
The Center’s environmental health identity stems from the wealth of multi-disciplinary expertise that is
gathered into three major areas of research in children’s environmental health and extending along the
translational pathway from basic to children’s research (Figure 3). At the level of “Pathways of Toxicity,”
interests
coalesce
around
gene-environment
Communities
interactions and other basic mechanisms of toxicity,
the zebrafish model organism as a key tool for studying
developmental toxicity, and the generation of novel
methods that support toxicological study. In the area
Children
Children
Children’s Health
of “Developmental Toxicology,” scientists seek to
& Inequities
understand
organ-based
toxicity,
including
Lab Animals
Lab Animals
neurobehavioral toxicity and pathology that originates
Pathways
Developmental
in waterborne exposures. Finally, “Children’s Health
of
Toxicology
Toxicity
and Inequities” research seeks (1) to understand the
underlying etiology of children’s health inequities in the
urban environment, particularly the city of Milwaukee
Cells & tissues
Cells & tissues
and (2) to contribute formatively to the emerging area
Biomolecules
of children’s environmental genomics, and the
understanding of the epigenetic origins of childhood
Figure 3. Major themes of the Center’s Research Portfolio
and adult diseases.
Impact of research on environmental health
The Center’s long-term research objective is to favorably impact children’s health. To approach this goal in
the near- and mid-term, the Center will support strong, innovative research projects and encourage the
formation of scientific teams that connect basic and translational researchers. In order for this strategy to
deliver changes in children’s health, two additional tactics must be implemented. First, high impact research
that is potentially high risk needs to be encouraged. Second, collaboration with experts in community outreach
and engagement and environmental health policy must be increasingly emphasized (long-term impact).
7. Center Investigator Research and Engagement Portfolio
7.1. Relationship of Research and Engagement to NIEHS Strategic Plan 2012 The Center
assesses its research portfolio in part in relationship to the NIEHS Strategic Plan 2012
(www.niehs.nih.gov/about/strategicplan/). Focal areas of Center
research that overlap with the Strategic Plan are listed in Figure 4.
Figure 4. NIEHS Strategic Plan 2012:
7.2. Introduction to Research and Engagement Research
Areas of congruence with Center research
portfolio
progress reports by Center investigators are gathered in Appendix
(App) 1. Some of the strengths and highlights of research progress
Fundamental Science: child development,
and/or plans for future research by Center members are described
life-span analysis, model organisms, geneenvironment interactions, high throughput
below by focal area of collective strength as illustrated in Figure 3.
methods
In toto, the summaries portray the environmental health identity of
Exposure
Science:
new
tools
and
the CEHSCC and its impact on children’s environmental health.
technologies,
analytical
measurements,
Where possible, results across the translational research-community
sensors, linkage with ”omics” technologies
Translational Science: bench to bedside
engagement continuum are included. The role of Center support in
and community, public health policy and
advancing research and engagement is woven into the narrative.
practice, gene-environment interactions in
7.3. Pathways of Toxicity Zebrafish model organism
medicine
(Fundamental, Exposure, and Translational Science, Figure 4)
Health Disparities: vulnerable populations
Model organisms provide opportunities to study living systems.
and interaction of chemicals, infectious
agents, nutritional factors, and social
Mammals play key roles.
The zebrafish is an excellent,
stressors in communities
complementary model for discovering pathways of vertebrate
Knowledge Management: bioinformatics,
developmental toxicity, screening (mixtures of) chemicals, and
computational tools, data integration
probing the impact of non-chemical environmental stressors. Its
attributes of rapid external development, large numbers of optically clear embryos, and facile genomics argue
for a central role in understanding gene-environment interactions that lead to disease in children. In the 1990s
the Center made a long-term, high risk commitment to advance the zebrafish model toward acceptance as a
regulatory model organism. Center members R. Peterson and W. Heideman were among the first to utilize the
favorable characteristics of this model organism for developmental toxicological studies (20, 21). Working with
J. Postelthwaite, M. Carvan and P. Tonellato constructed the first annotated genomic maps comparing
zebrafish, rat, and human chromosomal DNA sequences and demonstrated their striking gene and syntenic
similarities (22). D. Weber assembled powerful technology to study life-stage dependent behavior of zebrafish
in the Center’s Neurobehavioral Toxicology Facility (Aquatic Animal Models Facility Core, AAMFC, 4.5) (23,24).
H. Tomasiewicz and K. Kosteretz developed procedures to obtain the superb embryo survival rates needed to
support quantitative studies. In 2013, the Center assembled new resources that advance the zebrafish as a
prime toxicological model, including specific pathogen-free fish (AAMFC, 3.4) and transcription activator-like
effector nuclease (TALEN) gene-disruption methodology (AAMFC, 5.5.1). A bioinformatics pipeline for nextgeneration genome and transcriptome sequencing (Integrative Health Sciences Facility Core (IHSFC, 9.2.5)
and routine biobanking of zebrafish tissues (Exposure and Biological Analysis Core, EBAC, 4). have been
instituted. Together, they stimulate research, particularly linking environmental health with genomics.
Gene-environment Interactions (Fundamental and Translational Science, Knowledge
Management) The premise that health outcomes derive from gene-environment interactions underlies a
significant segment of members’ research. For example, across the translational path, beginning with basic
research, W. Heideman (genetics) and R. Peterson (toxicology) study TCDD as a developmental toxin (App1:
1.1.3,1.1.4). Having demonstrated the extensive similarity between the gene regulatory Ah receptor system in
mammals and zebrafish as well as the disruption of cranial-facial and cardiac development in zebrafish by
TCDD, they have shown that there is an epigenetic component to its effects and are investigating its
mechanism (25, 26). To facilitate epigenomic/transcriptomic research in zebrafish, Dr. Tonellato, Director,
Bioinformatics Subunit, IHFSC, has built the first workflow computational system for Next Generation
Sequencing data analysis (App1: 1.2.9). Several investigators are testing the system with pilot project funding.
Methylmercury (MeHg) is a potent neurotoxin that presents itself to the fetus through maternal
consumption of fish (27). M. Carvan, D. Weber, P. Tonellato, and co-investigators J. Dellinger, A. Udvadia,
and D. Petering have undertaken a far-reaching study of its effects on the neurobehavioral development of the
zebrafish (23,28). This medium-to-high risk (not used consistently below) project has been supported by a pilot
project and the AAMFC, EBAC, and IHSFC Cores (see abbreviations and 8.4.5). After exposing fish to nM
MeHg for brief periods during development, adverse effects on visual startle responses were identified in
adults (App1: 2.1.24). The results were explained by a MeHg-dependent increase in threshold activity levels
of retinal bipolar cells. Notably, dietary Se antagonizes this effect of MeHg (23,28). Subsequent generations
not exposed to MeHg retain similar behavioral and physiological deficits, revealing a serious epigenetic impact
(App1: 2.1.24). This is a highly provocative finding with major public health implication because many, if not
the majority, of fetuses are exposed to MeHg. The bio-chemical basis for these outcomes is being examined:
Carvan and Tonellato are conducting a detailed inquiry into the perturbations that MeHg causes within the
genome and transcriptome following exposure of larval zebrafish. Moreover, Carvan and D. Petering have
determined the organ distribution of MeHg (App1: 1.2.5), using special methods offered through the EBAC.
Hg concentrates in the eye. Future studies will use EBAC laser dissection to isolate segments of the eye for
proteomic analysis of binding sites of Hg and (epi)genomic/transcriptomic outcomes of MeHg exposure.
An inter-institutional partnership between N. Tabatabai and D. Petering demonstrated at the chemical
level how cadmium (Cd2+) causes a component of human kidney failure, urinary glucosuria (App1: 1.1.12).
Cd2+ down-regulates sodium-dependent transporter (SGLT) protein synthesis by inhibiting transcription of their
mRNA sequences (29). This process is disrupted when Cd2+ displaces Zn2+ from a key transcription factor,
Zn3-Sp1, that ordinarily binds to the sglt gene promoters (29,30). EBAC (P. North, MD, collaborator) provided
elegant immunocytochemical support for the intracellular location and quantification of SGLT transporters.
NEW The field of personalized medicine has emerged as a novel approach to individualize and improve
the diagnosis and treatment of patients through the use of genetic data. Under the leadership of Dr. P. North,
Children’s Hospital of Wisconsin is the first pediatric hospital in the country to routinely genotype all patients for
15 common conditions. Generally, current strategies focus on the use of genetic information. But this
approach has not been successful in linking genetic variation to common diseases (31-33). Other factors need
to be integrated with genetic information; in particular, patient environmental context. Thus, the Center has
established a new high risk initiative supported by EBAC (P. North, genomics), IHSFC (P. Tonellato,
bioinformatics), and AAMFC (zebrafish model) to integrate environmental health discoveries with pediatric
genomics, based upon the gene-environment paradigm. Members, who constitute the Translational GeneEnvironment research interest group, include A. Pelech who focuses on the genetic and environmental etiology
of cardiac birth defects (App1: 3.17), R. Lane, newly appointed Chair of Pediatrics who studies the epigenetics
of fetal growth restriction (App1: 1.1.10), C. Bradfield with interests in transcriptomic signatures of children’s
diseases (App1: 1.1.1), MCW, H. Jacob, Director of the Human and Molecular Genetics Center and a leader in
individualized pediatric genomics, MCW (App1: 1.1.9), M. Carvan, who studies gene-environment interactions
in zebrafish (App1:2.1.2) along with Drs. North and Tonellato, and M. Laiosa, conducting a comparative
mouse-zebrafish study of the genetic impact of MeHg (App1: 1.--). The effort will leverage the research
expertise and tools of these investigators. For example, a major resource is the Cardiac Birth Defect Registry,
founded by Center member, Dr. A. Pelech. The Registry is unusual in that it contains 2000 medical records
with extensive data about environmental conditions of children with heart defects and their blood samples
available for genetic analysis, and (34).
In the engagement arena, Center members have engaged with Hmong, Native American, and African
American communities during the past decade to communicate the risks of fish consumption in relation to
exposure to MeHg and polychlorinated biphenyls (35,36). Recently, J. Hewitt, R. Hutz, and M. Carvan
developed and tested a new approach to such risk analysis in the local African American community (37).
Reciprocally, the research focus within the Center on MeHg developed in part because of the concern within
Hmong and Native American communities about the safety of fish contaminated by MeHg.
Exposure Methods Research (Exposure Science, Knowledge Management) Center investigators
are devising methods to measure exposure and outcomes of exposure to environmental chemicals. For
example, there is wide ranging need to define molecular binding sites of metals and metalloids: M. Carvan and
D. Lobner study Hg (23, 38); C. Myers, Cr (39); N. Tabatabai and Petering, Cd (29, 30); D. Weber, Pb (40),
and Ramchandran, As (App: 1.1.11). In response, D. Petering has undertaken high risk, innovative research
to develop methods that define the localization of toxic metals and metalloids in zebrafish and their protein
targets in cells and tissues (toxico-metalloproteome) (App1: 1.2.5). Using a new gel electrophoresis method
that maintains relatively native protein structure and provides excellent protein band resolution, the distribution
of toxic metals and metalloids among proteins can, in principle, be defined by laser ablation inductively coupled
plasma mass spectrometry (EBAC) and relevant proteins identified by mass spectrometry (41).
NEW J. Chen, M. Gajdardziska-Josifovska,C. Hirschmugl, and M. Weinert are engineers and physicists
who are designing next generation nano-sensors that selectively measure gaseous pollutants with high
sensitivity (App1:1.2.2) (42). A key finding is that two-dimensional graphene (carbon) surfaces have favorable
properties to serve as such sensors (43). Research has extended their range to the aqueous phase and water
soluble pollutants. This is high risk research because of the difficulty in producing practical sensors. By joining
the Center, these scientists will find partners across the translational path, such as R. Etzel, who provide
complementary research expertise needed for their work. Once developed, such devices will greatly advance
the capability to measure air pollutant and other ambient exposures of children (IHSFC, EBAC).
7.4. Developmental Toxicology The Center’s research portfolio emphasizes understanding the
impact of chemicals on embryonic and early development (Figure 3). Commonly, these studies are reversetranslational, starting with diseases and disorders in infants and children that are hypothesized to involve
environmental exposures and then testing the strength of such relationships in model systems.
Neurotoxicology (Fundamental and Translational Science) Several researchers provide the Center
with a robust base of research on the development of the zebrafish nervous system. J. Gutzman studies the
control of brain morphogenesis (start-up support). Abnormalities resulting from abnormal brain morphogenesis
include neural tube defects and mental health disorders such as autism and schizophrenia. This research
provides the basis for investigating environmental contributors to these problems.
Zebrafish have been used by several scientists to investigate if embryonic exposure to chemicals
results in adult neurological deficits (Carvan, Svoboda, Weber). To illustrate with Pb 2+, a metallic contaminant
of great consequence for children, , D. Weber has used new high-speed videography capability in the AAMFC
to demonstrate that developmental exposure to 10 nM (2 ppb) Pb2+ (2-24 h post fertilization) results in a
deranged startle response in adulthood without compromising long-term survival (App1: 2.1.22) (40).
Dr. Weber has also partnered with R. Tanguay (Oregon State University) on an inter-center pilot project
funded by the CEHSCC, to characterize the neurobehavioral toxicology of bisphenol A (BPA), a constituent of
many plastics and, therefore, a contaminant of processed food and water (App1: 2.1.21). Embryonic exposure
to nM BPA resulted in larval behavioral dysfunction and subsequent pronounced learning deficits in adults (44).
As with other agents, early exposure that does not compromise overt development causes subtle neurological
injury that persists into adulthood (AAMFC support).
Selective serotonin reuptake inhibitors (SSRIs) are anti-depressant drugs designed to inhibit serotonin
reuptake, thereby influencing signaling mechanisms within the brain. Low levels of such compounds have been
found in the freshwater environment and in drinking water systems. In the work of R. Klaper, supported by the
Director’s Opportunity Fund and the AAMFC, exposure to the SSRI fluoxetine causes fathead minnows to
become aggressive at the beginning of exposure (App1: 2.1.8) (45). During chronic exposure, behavior
changes to obsessive, e.g. nest cleaning, quantitatively increases. Parallel transcriptomic changes in genes
involved in neurogenesis and plasticity are observed. These high profile results sustain the concern that
pharmaceuticals in freshwater may exert toxic effects on the community’s health, especially children.
A. Kalkbrenner is an environmental health epidemiologist who recently joined the ZSPH. She extends
the neurotoxicology theme to the level of children with her studies aimed at testing potential connections
between air pollution (outdoor and passive smoking) and the development of behavioral problems in children,
including the on-set of autism spectrum diseases (App1: 2.1.5-2.1.7) (46).
Neurotoxicological research has been abundantly translated to communities. COEC’s key participation
in the Milwaukee Community’s Cleaner Valley Coalition (J. Hewitt and K. Bartholomew) provided the scientific
voice about Hg toxicity that helped to convince WE Energies to convert its downtown coal-burning power plant
to natural gas. Recently, the coalition received a major award for its success (COEC, 4.4). Research has also
been translated into experiment modules implemented by high school students in COEC’s pre-college
education program (COEC, 5.2) (47, 48). M. Carvan, K. Svoboda, D. Petering, H. Tomasiewicz, and D. Weber
have contributed to this engagement program. Notably, the stimulus for Dr. Weber’s research on the
behavioral toxicology of Pb was COEC’s feed-back from the community about the large numbers of children
with elevated blood Pb concentrations. In turn, some of his work has inspired student experiments.
Embryonic Toxicity-Neural Crest Developmental Outcomes (Fundamental and Translational
Science) During development, the neural crest provides progenitor cells for a variety of tissues. Several
Center members have focused their research on understanding how genes, environmental chemicals, and
nutritional factors combine to cause developmental deficits related to neural crest cell differentiation in
zebrafish and other model organisms. Unexpectedly, K. Svoboda and V. Lee, an expert in neural crest
development, have shown in a high risk pilot project involving zebrafish and mouse models that nicotine
exposure targets neural crest cell differentiation, leading to abnormal cranial-facial development (AAMFC,
EBAC) (App1: 2.2.2). This is highly significant research that supports a prominent role of nicotine in birth
defects. S. Smith and M. Carvan jointly use zebrafish and chick models to understand the genomic-ethanol
interactions that disrupt neural crest differentiation (AAMFC, EBAC) (App1: 2.2.1). Dr. Smith has also
discovered a strong nutritional synergy in a rat model between ethanol exposure and iron-deficiency in the
mother during gestation and outcomes of altered neuro-behavior including learning (49). Research in this area
moves into community engagement through the Center’s pre-college education program and its emphasis on
zebrafish as a model for fetal alcohol syndrome (COEC, 5.2) (47). Similarly, other research by K. Svoboda
undergirds the pre-college program’s focus on the embryo toxicity of nicotine.
Cardiovascular Toxicology
(Fundamental, Translational Science)
Cardiac abnormalities
constitute the major cause of spontaneous abortion during pregnancy and birth defects. Dr. A. Pelech, a
surgeon who operates on infants with cardiac birth defects, has established the Wisconsin Cardiac Birth
Registry and leads an on-going effort to probe whether environmental chemicals are a cause of abnormal
cardiac development (34, 50). Recently, J. McGraw and A. Pelech were awarded a pilot project to probe the
relationship between polybrominated diphenyl ethers, nutritional factors and such birth anomalies, using
biological samples from infants born with hyperplastic left heart syndrome (HLHS) (App1: 2.3.3). They have
discovered high levels of a PBDE metabolite correlates with this cardiac birth defect. With IHSFC support, G.
McCarver has completed an important prospective study (high impact) of infants born with cardiac defects.
Intrauterine exposure to 14 volatile organic compounds and 4 halogenated hydrocarbons was determined by
measuring their concentrations in offspring meconium (App1: 2.3.2). Exposure to high levels of two
trichoroethylene (TCE) metabolites (trichloroacetic acid and/or dichloroacetic acid) were associated with a 3-4
fold increase in the risk of particular cardiac defects. In addition, high level exposure to these TCE metabolites
was linked with an increase of congenital heart disease among children of mothers with at least one copy of
ADH1C*2, a genetic variant that influences how efficiently these metabolites are produced.
Lung Toxicology (Fundamental, Translational Science) Bronchopulmonary dysplasia (BPD), a
debilitating lung disease that develops in 20-25% of very low birth-weight infants (birth-weight < 1500 grams),
remains the major cause of pulmonary morbidity and mortality in infancy. The Toll-Like Receptor (TLR)
signaling pathway plays critical roles in regulating protective pulmonary responses against environmental
toxicants, oxidative stress and bacterial-derived toxins. V. Sampath and R. Hines hypothesized that functional
genetic variation in the TLR signaling pathway genes would modulate susceptibility or severity of BPD in
premature infants (App1: 2.4.4). Their clinical study, supported by a Center pilot project, demonstrated that
polymorphisms in the TLR pathway correlated with the incidence of BPD (51). These results supported the
hypothesis that TLR pathway genetic variants modulate vulnerability to environmental lung injury in premature
infants. Sampath is now addressing the hypothesis that environmental suppression of the immune system by
polycyclic aromatic hydrocarbons contributes to bacterial pathogenesis in newborn infants (App1: 2.6.5).
Freshwater Toxicology (Fundamental, Translational, Health Disparities Science) The CEHSCC
has its roots in the NIEHS MFBS Center and continues to emphasize toxicological issues related to freshwater
toxic exposures (Figure 1). Both D. Lobner and T. Miller study neurotoxins synthesized by algae that are
becoming prevalent in lakes due to climate change. Dr. Lobner has determined that β-methylamino-L-alanine
(BMAA), a non-protein amino acid that causes human neurodegenerative disease, acts synergistically with
MeHg to damage fetal mouse neurons (App1: 2.1.14). It appears to do so by depleting cellular glutathione
and, thereby, stimulating oxidative stress (52). Miller, recently funded by NIEHS and supported with Director’s
Funds, seeks to establish whether toxins such as BMAA bioaccumulate in edible fish (App1: 2.7.13). He has
partnered with M. Carvan and K. Svoboda to measure the neurotoxicity of algal toxins in zebrafish (AAMFC).
These studies are significant because of increasing algal blooms and the potential for exposure of children.
M. Gorelick and S. McLellan have conducted an important study (high impact) of the built environment
to understand the relationship between admittances of children to Children’s Hospital with acute gastroenteritis
and the water distribution system in Milwaukee (Pilot Project, App1: 2.7.12) (53). Spikes follow heavy rain
events. Using McLellan’s expertise in finger printing pathogenic bacteria, it appears that inflow into the
compromised water delivery system stimulated by heavy rains contaminates the drinking water, leading to
illness. Such results raise the possibility that during these and perhaps less severe events, children and others
are exposed to elevated concentrations of chemical pollutants as well as microorganisms (IHSFC, AAMFC).
This research became the basis for a State of Wisconsin study of the potential human health consequences of
increased storms due to climate change (App1: 2.7.3, 2.7.10). Dr. McLellan’s work also stimulated a highly
original analysis of the impact of the Gulf of Mexico oil spill on beach microbial integrity (AAMFC, IHSFC)
(App1: 2.7.11) (54). Dr. Hewitt sits on the External Advisory Board for the University of Texas Medical
Branch’s work that provides follow-up with Vietnamese and Houma Nation fishers affected by the spill.
7.6. Children’s Health and Health Inequities NEW Children’s Health Inequities Research
(Translational and Health Disparities Science) Introduction Children in Milwaukee face disease, disorders,
even death among African American infants at rates worse than those seen in many developing nations (19d).
The Milwaukee community, starting with the Mayor, has urgently called for action to reduce the health
inequities suffered by its children. The CEHSCC has the responsibility to assume scientific leadership in
addressing this dismal situation. It has made a long term commitment to support and integrate environmental
and social epidemiologic research and community engagement to resolve these issues.
A coalition of Center investigators has initiated community-based, epidemiologic research to
understand the environmental-social basis of these health inequities in Milwaukee. Two new Center members
play leading roles in environmental health equity research during the next grant period. Ruth Etzel, a world
leader in children’s environmental health, brings a record of distinguished research-development of cotinine as
the prime biomarker of exposure to cigarette smoke; recognition (and removal) of volatile mercury in indoor
house paint; first in-depth investigation of Native Alaskan health and disease, their underlying determinants,
and more (55-57). In the spring of 2013, she began an environmental epidemiological study of apparent life
threatening events among children in the city of Milwaukee supported by Center start-up funds (App1: 3.3).
Included in this study is a focus on new biomarkers of lung injury in relation to infant death. Dr. Etzel’s arrival
has stimulated a new collaboration with the Milwaukee Health Dept. in which she and Raymond Hoffmann
(MCW) will work with Eric Gass, Research Director, MHD, D. Petering and D. Weber, experts in metal/lead
toxicology, to design an analysis of the Health Department’s extensive records to test the hypothesis that
childhood Pb exposure adversely affects later teen pregnancy outcomes in the City of Milwaukee (58).
Lorraine Malcoe also has a distinguished record of research addressing both environmental and social
determinants of health. Dr. Malcoe is well known for her superfund-related research into Pb poisoning among
Native American children in Oklahoma (59). She and A. Kalkbrenner are conducting an analysis of linked
environmental (air pollution)-social determinants of children’s health in Milwaukee (pilot project) (App1: 3.8).
Other research Dr. P. North has organized the Unexplained Infant Death Center (UIDC) in the
Children’s Research Institute (Appendix 2). Beginning its second year, the UIDC researchers investigate the
underlying causes of the epidemic of infant deaths in Milwaukee. Other Center investigators focus on air
pollution and mortality and morbidity in children. J. Hewitt has undertaken an epidemiological study in
Milwaukee County that assesses the contribution of air pollution and traffic on risk of preterm and low birth
weight, leading factors in infant mortality among African American infants (App1: 3.6) (IHSFC). In a related
study evolving from a pilot project, V. Sampath, MD, has begun to test his hypothesis that exposure to PAHs
leads to the development of bronchodysplasia in infants (App1: 2.4.4). J. Meurer and R. Hoffmann have
played major roles in defining the environmental health status of Milwaukee children, particularly their rates of
asthma and environmental conditions within the home that promotes the disease (60). At a more general level,
A. Kalkbrenner examines the linkages between exposure to cigarette smoke or air pollution and
neurobehavioral outcomes in children (App1: 2.1.5-2.1.7) and has just received a pilot project to include
Milwaukee children in her studies (App1: 3.8).
Addressing other aspects of the local environment, S. Johnson, with the support of the IHSFC and
Biostatistics Division Director, R. Hoffmann, has undertaken a community-based participatory research pilot
project to understand the hazards associated with growing vegetables in soil contaminated with lead and other
toxic chemicals, a common activity within the city of Milwaukee (App1:3.7). Her early results have been
rewarded with a major grant to continue her research. In this vein, Simpson and Pelech received pilot funding
to examine the geographical relationship between toxic waste sites in Milwaukee and the homes of children
with cardiac birth defects (App1:3.20). Beyond the City, J. Dellinger heads a large program that focuses on
the impact of the environment, including MeHg and PCBs in edible fish, on maternal-child health in Native
Americans (App1: 3.1.17). Policy expert K. Bartholomew links research to improved housing (App1: 3.1).
7.7. Analysis of Research and Researchers The contents of Appendix 1 have been analyzed as
shown in Figure 5.
The 87 total
projects strike a good balance: 33% are
categorized as basic research; 38%
translational science; and 29% as public
health or clinical studies. Importantly,
the number of multi-investigator projects
approximates those involving single
investigators
along
the
entire
translational path. Equally significant,
many multi-investigator projects involve
scientists at different institutions-64% of
the basic studies, and close to 50% of
the rest. The CEHSCC emerged from a
MFBS Center.
Thus, it was not
surprising that many projects utilized
zebrafish [33].
Nevertheless, it is
important for the Center’s development
that many projects also utilize
mammalian model systems [22].
Significantly, supporting the Center goal to involve physician-scientists in children’s environmental health
research, 16 physician-scientists contribute to 24 projects, 28% of the total, and are well represented in multiinvestigator and inter-institutional research.
7.8. Community Outreach and Engagement The CEHSCC is committed to a model of scientific
inquiry that values relevant engagement with local communities. The COEC Director leads a coordinated effort
throughout the Center to communicate with three broad groups-ethnic communities, governmental and
business officials, and science educators and health professionals. COEC has established important
programs for each of the groups. These include (1) durable partnerships in African American and Hispanic
communities focused on local needs expressed in a 2009 Town Hall meeting with NIEHS officials; (2)
initiatives with community governmental and business representatives to improve health outcomes, and (3) a
premier, NIEHS-funded program for high school teachers and students, linking biology and children’s
environmental health and (4) an inter-center collaboration with the Harvard University COEC to educate health
professionals about environmental health (60). In each of these areas, Center members make important
contributions. In the future, COEC’s relationships and programs will increasingly focus on converting
education and engagement into effective public health outcomes that improve children’s health.
7.9. Research Grant Base and Relevance to Environmental Health Figure 6 lists the grant funding
of members that supports their current and proposed research activities (Appendix 1). The titles of the
awards make clear that the large majority of the grants are explicitly directed toward research problems in
environmental health (Table A.1). Others support basic biological research
Figure 6. Center Investigator Grant
in key areas of the Center’s scientific portfolio. In aggregate, current grants
Support 2013-2019
total $75,100,000 in direct cost funding. For the time frame of this application,
Current
$75,100,000
Center investigators have grant funding that is well distributed throughout the
20131
$17,900,000
2014-2018 period (Figure 6). Among the competitively funded grants are 11
2014
$24,600,000
2015
$16,300,000
from NIEHS, including 3 RO1s (Miller, Heideman, Peterson), 1 R00 (K99)
2016
$ 6,000,000
(Laiosa), 1 R25 (Petering), 1 R24 (North), and the current CEHSCC P30
2017
$10,300,000
NIEHS grants
11
grant, 25 from other NIH institutes and numerous other awards. The end
Other NIH grants
25
dates of 3 of the NIEHS grants (Heideman, Miller, and Peterson) fall beyond
Other Federal grants
11
the February 13, 2015 requirement. During 2009-14, the Center has
Other grants
25
averaged 5.5 R01 and R21 awards per year.
8. Strategic Program of the Center
8.1. Overview The CEHSCC is devoted to providing effective support for member’s research and
community engagement. It does so through the program that the Center offers. The program is introduced
here; other parts of the proposal provide the details to understand and evaluate it.
8.2. Organization (Aims 1-4, from section 2) Inter-institutional Foundation of the Center The
CEHSCC was founded as an inter-institutional alliance (Figure 1). It will continue to develop as a regional
center of children’s environmental health research and community engagement.
Center Organizational Structure The administrative structure organizes and delivers the Center’s
program support for research and community engagement (Figure 7). The Administrative Core oversees
three facility cores that provide an abundance of research support for members across the translational path
(8.4.5). Complementing the research infrastructure, the COEC integrates the Center’s scientific expertise with
the needs of local communities. In addition, the Administrative Core supervises a robust and effective Pilot
Project Program and leads the entire Center in supporting a diversity of career development initiatives for
members and others related to the mission of the Center. These programs and activities are discussed below
and elsewhere in the proposal.
Center Leadership: Center
NIEHS
Director,
Deputy Director, and
External Advisory
Others The leadership challenge
Administrative Core
Committee
Institutions
Directors: Petering, North
J. Stegeman, Chair
is to facilitate and integrate the
UWM, CRI
Ad. Staff: Schmidt, Gripentrog
MCW, Children’s
Pilot Project Program: Hoffmann, Petering
talents and resources distributed
Internal Advisory
Hospital
Career Development:Avner, Etzel, Sampath
Committee
among different physical sites and
across the translational research
spectrum. The executive team of
Integrative Health Sciences
Community Outreach
Exposure &
Aquatic Animal
Facility Core
& Engagement Core
Biological Analysis
Director and Deputy Director from
Models Facility Core
Hewitt
Etzel, Hoffmann, Tonellato,
Core
Tomasiewicz,
UWM and CRI/MCW bring to this
Weber,Kosteretz
-Epidemiology Research Unit
North, Tomasiewicz ,
-Aquatic Animal Facility
-Biostatistics and Bioinformatics
Petering
task complementary expertise and
Stakeholders
-Neurobehavioral
Research Unit
-Imaging and Histology
Advisory Board
common purpose. They contribute
Toxicology Facility
-Genomics
-Exposure Assessment
-Genome Modification
diverse backgrounds in basic and
Facility
translational
science,
deep
commitment
to
community
Figure 7. Center Administrative Structure
engagement, extensive, relevant
administrative experience, and, importantly, a history of working closely together within the Center.
Director David H. Petering is University Distinguished Professor of Chemistry and Biochemistry (UWM)
and Adjunct Professor of Pharmacology and Toxicology at the Medical College of Wisconsin. Dr. Petering
directed the NIEHS P30 MFBS Center between 1987 and 2009 and has overseen its transition to a full
CEHSCC. He has been continuously funded by NIEHS for more than 30 years. In 2005 Petering ranked in
the top 5% of investigators in cumulative NIH funding since 1980 (personal communication, Pierre Azoulay,
MIT Sloan School of Management). With 220 publications in the broad area of metals in biological systems,
Petering has an extensive record of research in metal toxicology, including studies of (i) the chemical-biological
mechanism of cadmium inhibition of sodium-dependent nutrient transporters in kidney proximal tubule (29,30);
(ii) chemical, biochemical, and cellular properties of the heavy metal binding protein, metallothionein that
participates in protection against metals, oxidants and electrophiles (61); (iii) chemical and cellular
mechanisms of heavy metal interaction with zinc-finger transcription factors (29, 62); and (iv) analytical tools to
define the essential and toxic metal proteomes (30). A hallmark of his work is its interdisciplinary character,
involving multiple collaborators in order to address questions ranging from the structure and reactivity of
biomolecules to molecular and cellular biology. He is regularly called upon to write expert reviews (61, 62).
Recently, Dr. Petering was named to the Editorial Board of Chemical Research in Toxicology, the premier
journal focused on chemical mechanisms of toxicity. Petering also leads a long term, successful pre-college
education program in environmental health funded by NIH/NIEHS. His collective experience has motivated the
development of the CEHSCC as a highly interactive, first rate research organization complemented by an
excellent engagement program.
Paula North, MD-PhD (MCW), Deputy Director, is Medical Director of the Dept. of Pathology at
Children’s Hospital of Wisconsin and Chief of Pediatric Pathology at MCW. She is the Director of the EBAC
research Core, PI of an NIEHS R24 grant to establish a GeoHealth Hub for environmental health in Peru, and
leads the Unexplained Infant Death Center. North provides the CEHSCC with significant laboratory research
experience on children’s health and is a highly respected leader within the CRI and the CHHS. Dr. North
brings great strength to the Center’s objective to develop physician-scientists.
The Center has also attracted into leadership positions other stellar scientists. Ruth Etzel, MD,PhD,
Professor of Public Health, UWM, has become Director of the IHSFC. Dr. Etzel is internationally recognized in
children’s environmental epidemiology and global environmental health (55-57,64). Exploiting her research
background, support for community and clinical studies is unified within the Epidemiology Unit. The
Biostatistics and Bioinformatics Research Unit within the IHSFC has attracted an international leader in
bioinformatics, Peter Tonellato, to lead the new bioinformatics focus (65).
8.3. Center Membership (Aim 1) The Center maintains two categories of membership, Full Member
scientists are fully engaged in and supported to conduct children’s environmental health research and include
pilot project awardees (Administrative Core, 4). They have complete access to core resources. Associate
Member designation connotes others with strong interests in children’s environmental health but who have not
achieved independent research status. Such members do not have free access to Cores. This category of
membership permits the Center to play a significant part in fostering the careers of promising young scientists
and influencing investigators to focus their research on environmental health. Currently, the Center has 59 full
members and 14 Associate members representing 23 academic disciplines (Figure 2).
A primary responsibility of the Center Director and Deputy Director is to continually upgrade the quality
of the Center membership roster. They can be effective to the extent that the CEHSCC is recognized as an
important avenue for career development. Careers of excellent research and engagement flourish with the aid
of early funding, access to critical infrastructure, and, often, important collaborators. A summary of the
Center’s manifold support for career development is offered below. Administrative Core, Career Development
Program, Pilot Project Program, and IHSFC sections provide full details of these support mechanisms.
8.4. Research and Community Engagement Capacity (Aims 1-3) A primary function of the
CEHSCC is to enhance the capacity of member scientists to conduct meaningful research on problems in
children’s environmental health and to connect their findings with various communities. In practice, this means
(i) attracting strong investigators to the Center, (ii) stimulating interactions among them that generate an
effective scientific community, including research collaborations and communication, and (iii) providing a
wealth of supportive infrastructure that enhances research and engagement. During the past 3-4 years, the
Center has established the foundation for intense, region-wide research collaboration in children’s
environmental health. The sections below describe the Center’s ongoing strategy.
8.4.1. Regional Organizations Contributing to the CEHSCC Membership and Program
The Administrative Core section details the Center’s relationship with the groups and organizations shown in
Figure 1. Here, some of the initiatives supporting membership and program are briefly listed.
UWM Zilber School of Public Health The ZSPH will hire two faculty each in Environmental and
Occupational Health and Epidemiology in 2013-14. Most of the hires are anticipated to become Center
members.
School of Freshwater Sciences A key development for the Center’s future was the arrival in
2012 of the School’s founding Dean, David Garman. Already, the Dean has allocated significant institutional
commitment to the Center in the form of additional space for the Aquatic Animal Models Facility Core
(Institutional Organization and Commitment (IOC), 3.2.1).
Children’s Research Institute-Children’s Hospital Of special importance is the Unexplained Infant
Death Center, Paula North, Director, which serves as a partner in the children’s health inequities research
initiative (7.6) (Appendix 2). It is providing funds for the Center’s pilot project program (IOC, 3.3).
NEW Clinical Translational Sciences Institute The Center has arranged to partner with the CTSI to
provide key clinical services for the Integrative Health Sciences Facility Core (IHSFC, 4).
Milwaukee Health Department Director Petering has taken a lead role in the MHD (Public Health)
Laboratory System Improvement Program, including acting as co-chair of its research committee. As this
initiative matures, partnerships will increase in the area of children’s environmental public health.
NEW Wisconsin State Laboratory of Hygiene The Laboratory of Hygiene (WSLH) is a joint
governmental-university unit of the State of Wisconsin. As part of its academic role, the Environmental Health
Division of the WSLH has agreed to provide chemical analytical services to Center members on a collaborative
basis. In so doing, the Center greatly enhances its research support capability (EBAC, 7).
8.4.2. Fostering Career Development and Research Community (Aims 1-3) The regional
children’s environmental health community begins with attracting researchers with diverse talents and skills
who value the Center for its support of their developing careers. It advances this goal by stimulating
interactions and collaborations among its members through a variety of means. The Center will continue to
grow as a highly interconnected community in the next grant period. To accomplish this trajectory, the Center
offers a range of support mechanisms.
Internal Advisory Committee The IAC is comprised of the executive leadership and heads of cores
and programs in the Center, augmented by representative members. All are senior leaders, recognized by
peers for their scientific background and expertise. Members meet monthly, work together, and model the
larger Center community. The IAC takes responsibility for identifying potential new members and advancing
superior cores and programs. Below we summarize enrichment activities that support the research community.
All-Investigator Gatherings A primary tool that the Center uses to insure that members from across
the region mingle, become acquainted, and begin to interact is the All-Investigator Gathering. Each year, the
entire membership has met twice a year from 5-8 PM at a central location for scientific exchange and dinner.
Attendance averages about 40. At a recent meeting, for example, MHD laboratory scientists were invited as a
means to introduce them to the community. Dr. Steven Gradus, Director of the Laboratory, reviewed major
local environmental health challenges and the Health Department’s role in resolving them. This was followed
by informal theme-based discussions at designated tables. Emerging from this meeting were new partners for
MHD scientists in the area of health inequities/infant mortality, including Dr. Venkatesh Sampath (MCW) and
Dr. Joseph McGraw (Concordia University). In the future, these meetings will be increased to 3 per year. The
formats will continue to vary–local or national speakers, posters, and multiple research and engagement
roundtable discussions (e.g. health inequities, neurotoxicology, freshwater, community engagement, etc.).
Research Interest Groups The Center supports interest groups that meet to discuss topical research
and mutual interests in the area. The Center underwrites refreshments. More significantly, it offers the groups
opportunities to invite external experts for seminars and to spend extra time with group members. Presently,
groups in neurotoxicology/immunotoxicology, zebrafish model organism studies, and unexplained infant death
convene at 1-2 month intervals. For example, this past year, Dr. Steven Ekker, Mayo Clinic, and Drs. C.
Konsitzke and Feng Wan, University of Wisconsin System Center for Biotechnology, presented seminars
focused on new genomic-based methodologies that can be applied to the zebrafish model. Moving forward,
other interest groups will be encouraged to form based on the area concentrations described in Appendix 1.
NEW-2013 Translational Research Committee-Multi-disciplinary Teams and Incentives Moving
beyond the informal opportunities presented by the All-Investigator Gathering, the IHSFC is leading the formal
effort to enhance translational research in the Center and the formation of multi-disciplinary research teams.
Comprised of senior scientists who have a grasp of the entire Center membership and research portfolio, the
Committee meets with (new) investigators and potential partners to consider possible collaborative Research
(IHSFC, 6.2.1). In addition, next year, the Center’s redesigned website will support this effort with a
searchable site (Research and Engagement Resource Directory) containing information about members’
interests in research and engagement.
NEW Mentoring of Faculty Supporting professional advancement of the next generation of
environmental health scientists is a special emphasis. They are arriving in numbers at the ZSPH, the School
of Freshwater Sciences, the Unexplained Infant Death Center, the CRI, etc. and offer great promise for
children’s environmental health. The Center will focus (i) on a mentoring program for this group of scientists
and (ii) on a Children Environmental Health Fellows program to develop physician-scientists (Career
Development Program (CDP), 2.3.4.1 and ----).
Seminar Program The CEHSCC seminar program provides members intellectual enrichment and
stimulation in the broad area of children’s environmental health as well as opportunities to meet one another
(CDP, 2.3.4.1). Moreover, seminars represent a primary means for the Center to promote interaction with the
larger scientific community. The Center partners with existing series in the Zilber School of Public Health, the
School of Freshwater Sciences, the Children’s Research Institute, etc.
Communications To build community, most meetings are conducted in person with tele-conferencing
as needed. Meetings take place at respective institutions or at a convenient central location in downtown
Milwaukee. The Center leadership uses an email list-serve to communicate with the membership as a whole.
This is complemented by information placed on the website, www.uwm.edu/CEHSC. Currently, the website is
being renovated to provide a user-friendly Research Support Directory that will guide viewers to all of the
Center’s resources and to a search tool of potential scientist collaborators (NEW) (Appendix 3). The website,
press releases, and other media provide publicity for members’ research and engagement activities.
8.4.3. Inter-Center Community At the Fall, 2009 Center Directors meeting in Milwaukee, the
CEHSCC led a session devoted to the question of inter-center cooperation. Would collaborations leveraging
the collective expertise and infrastructure of Centers provide important opportunities to advance research and
engagement? That discussion started a process culminating in a call from NIEHS for inter-center pilot projects
in Spring, 2012 and 2013. To catalyze sharing of methods and technologies among Centers, the CEHSCC will
offer services provided by our EBAC and AAMFC to other Centers at the same cost charged to its members.
8.4.4. Research Support (Aims 2,4) The CEHSCC offers an array of research support that (i)
supplies scientists with excellent staff and state-of-the-art methodology and instrumentation, distributed along
the translational research path; (ii) offers financial incentives to undertake multi-disciplinary research directed
at complex problems through the Pilot Project Program. Pilot projects serve as a vital incubator of innovative,
higher risk research; and (iii) provides start-up funding for new investigators to ensure that they have the
resources to properly initiate their studies. In order to sustain this level of support, the Center obtains
extraordinary commitment of resources from its institutional partners and will continue to acquire additional
assets-funding and infrastructure-from other sources (e.g. grants and fundraising) to supplement its NIEHS
grant award (ICO section).
8.4.5.
Research Support - Advanced
EBAC
Facility Cores (Aim 4) Successful implementation of the
- Imaging and histology
-Chemical analysis
Strategic Vision depends on provision of cutting-edge tools
-Genomics
and staff through the Center’s research Cores. The Cores
-Biobanking
Pathw ays of
continue to develop to meet the needs of Center scientists. In
Toxicity
IHSFC
many cases, research projects use multiple Cores that
- Epidemiology studies:
public health and clinical
provide complementary, comprehensive services. Figure 8
-Biostatistics
Childre n’s Health
qualitatively portrays relationships between broad research
-Bioinformatics
& Inequities
themes and Cores, emphasizing that the Cores are useful
AAM FC
across the three themes (based on review of Core usage
-Animal studies
-Behav ior
tables and Research Progress Report-Appendix 1). The
-Genomics
Dev elopmental
CEHSCC operates three multifaceted Cores: (i) the AAMFC,
Toxicology
COEC
comprised of the Aquatic Animal Facility, Neurobehavioral
-IHSFC partner
Toxicology Facility, and Genome Modification Facility; (ii) the
-Community engagement
EBAC, offering imaging, histology, genomics, chemical
Figure 8. Matching Cores and Research Projects
exposure assessment, and biobanking; and (iii) the IHSFC
with companion Epidemiology and Biostatistics and
Bioinformatics Units. As the research portfolio evolves, so do
the Facility Cores. Thus, in the next grant period the AAMFC will provide specific pathogen-free zebrafish,
added space for husbandry, and genome editing. The EBAC will offer new technical support for exposure
assessment and access to infrastructure to conduct genomic analyses. The IHSFC contributes a streamlined
Epidemiology Unit as well as a new Bioinformatics Subunit that supports genomic and database research.
8.5. Capacity for Community Outreach and Engagement (Aim 3) COEC plays the central role in
the Center’s central objective to apply its research knowledge and results to meet community environmental
health needs as described in 7.6. To succeed in facilitating bidirectional communication between the Center
and communities, Director J. Hewitt collaborates specifically with the Epidemiology Research Unit of the
IHSFC, with other Cores on an ad-hoc basis, and with numerous Center members (Figure 8). She and her
staff spend much time interacting with community leaders and members to facilitate transparent
communication and engagement in community-relevant environmental health initiatives. In this work, she is
assisted by skilled outreach specialists who are trusted members of the African American and Hispanic
communities. Providing oversight is a Stakeholder’s Advisory Board comprised of diverse members of
Milwaukee communities and governmental agencies. With a foundation of community relationships and
accomplishments in place, COEC will assume an increasingly prominent role in Center initiatives in the future.