Randy L. Jirtle

University of Bedfordshire, Luton, England, United Kingdom

Are you Randy L. Jirtle?

Claim your profile

Publications (240)1430.29 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Lead exposure during early development causes neurodevelopmental disorders by unknown mechanisms. Epidemiologic studies have focused recently on determining associations between lead exposure and global DNA methylation; however, such approaches preclude the identification of loci that may alter human disease risk. The objective of this study was to determine if maternal, postnatal and early childhood lead exposure alter the differentially methylated regions (DMRs) that control the monoallelic expression of imprinted genes involved in metabolism, growth and development. Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study from birth to 78 months. During adulthood, peripheral blood DNA was used to quantify CpG methylation in peripheral blood leukocytes at DMRs of 22 human imprinted genes using Sequenom EpiTYPER assays. Statistical analyses were conducted using linear regression. Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation, (β=-0.0014, 95% CI:-0.0023, -0.0005, p=0.002), stronger in males, (β=-0.0024, 95% CI:-0.0038, -0.0009, p=0.003) than females (β=-0.0009, 95% CI:-0.0020, 0.0003, p=0.1). Elevated mean childhood blood lead concentration was also associated with a significant decrease in IGF2/H19 (β=-0.0013, 95% CI:-0.0023, -0.0003, p=0.01) DMR methylation, but primarily in females, (β=-0.0017, 95% CI:-0.0029, -0.0006, p=0.005) than males, (β=-0.0004, 95% CI:-0.0023, 0.0015, p=0.7). Elevated blood lead concentration during the neonatal period was associated with higher PLAGL1/HYMAI DMR methylation regardless of sex, (β=0.0075, 95% CI:0.0018, 0.0132, p=0.01). The magnitude of associations between cumulative lead exposure and CpG methylation remained unaltered from 30 to 78 months. Our findings provide evidence for early childhood lead exposure resulting in sex-dependent and gene-specific DNA methylation differences in the DMRs of PEG3, IGF2/H19 and PLAGL1/HYMAI in adulthood.
    Environmental Health Perspectives 06/2015; DOI:10.1289/ehp.1408577 · 7.98 Impact Factor
  • Cancer Research 12/2014; 74(23 Supplement):28-28. DOI:10.1158/1538-7445.CANSUSC14-28 · 9.33 Impact Factor
  • Cancer Epidemiology Biomarkers & Prevention 11/2014; 23(11 Supplement):B22-B22. DOI:10.1158/1538-7755.DISP13-B22 · 4.13 Impact Factor
  • Cancer Epidemiology Biomarkers & Prevention 11/2014; 23(11 Supplement):C65-C65. DOI:10.1158/1538-7755.DISP13-C65 · 4.13 Impact Factor
  • Cancer Epidemiology Biomarkers & Prevention 11/2014; 23(11 Supplement):CN02-03-CN02-03. DOI:10.1158/1538-7755.DISP13-CN02-03 · 4.13 Impact Factor
  • Randy L Jirtle
    Epigenomics 10/2014; 6(5):447-450. DOI:10.2217/epi.14.58 · 4.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In infants exposed to maternal stress in utero, phenotypic plasticity through epigenetic events may mechanistically explain increased risk of preterm birth (PTB), which confers increased risk for neurodevelopmental disorders, cardiovascular disease, and cancers in adulthood. We examined associations between prenatal maternal stress and PTB, evaluating the role of DNA methylation at imprint regulatory regions. We enrolled women from prenatal clinics in Durham, NC. Stress was measured in 537 women at 12 weeks of gestation using the Perceived Stress Scale. DNA methylation at differentially methylated regions (DMRs) associated with H19, IGF2, MEG3, MEST, SGCE/PEG10, PEG3, NNAT, and PLAGL1 was measured from peripheral and cord blood using bisulfite pyrosequencing in a sub-sample of 79 mother-infant pairs. We examined associations between PTB and stress and evaluated differences in DNA methylation at each DMR by stress. Maternal stress was not associated with PTB (OR = 0.98; 95% CI, 0.40-2.40; P = 0.96), after adjustment for maternal body mass index (BMI), income, and raised blood pressure. However, elevated stress was associated with higher infant DNA methylation at the MEST DMR (2.8% difference, P < 0.01) after adjusting for PTB. Maternal stress may be associated with epigenetic changes at MEST, a gene relevant to maternal care and obesity. Reduced prenatal stress may support the epigenomic profile of a healthy infant.
    Genetics & Epigenetics 09/2014; 6:37-44. DOI:10.4137/GEG.S18067
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Epigenetic mechanisms are proposed to link maternal concentrations of methyl group donor nutrients with the risk of low birth weight. However, empirical data are lacking. We have examined the association between folate and birth weight and assessed the mediating role of DNA methylation at nine differentially methylated regions (DMRs) of genomically imprinted genes in these associations. Compared with newborns of women with folate levels in the lowest quartile, birth weight was higher in those newborns of mothers in the second (β = 143.2, se = 63.2, P = 0.02), third (β = 117.3, se = 64.0, P = 0.07), and fourth quartile (β = 133.9, se = 65.2, P = 0.04), consistent with a threshold effect. This pattern of association did not vary by race/ethnicity but was more apparent in newborns of non-obese women. DNA methylation at the PLAGL1, SGCE, DLK1/MEG3 and IGF2/H19 DMRs was associated with maternal folate levels and also birth weight, suggestive of threshold effects. A role for methylation in the mediation of the association between maternal folate levels and birth weight was significant only for the MEG3 DMR (P<0.05). While the small sample size and partial scope of examined DMRs limit our conclusions, our data suggest that, with respect to birth weight, no additional benefits may be derived from increased maternal folate concentrations, especially in non-obese women. These data also support epigenetic plasticity as a key mechanistic response to folate availability during early fetal development.
    Epigenetics: official journal of the DNA Methylation Society 05/2014; 9(8). DOI:10.4161/epi.29332 · 4.78 Impact Factor
  • Epigenetics 05/2014; 9(8). · 4.78 Impact Factor
  • Source
    Adelheid Soubry · Cathrine Hoyo · Randy L Jirtle · Susan K Murphy
    [Show abstract] [Hide abstract]
    ABSTRACT: Literature on maternal exposures and the risk of epigenetic changes or diseases in the offspring is growing. Paternal contributions are often not considered. However, some animal and epidemiologic studies on various contaminants, nutrition, and lifestyle-related conditions suggest a paternal influence on the offspring's future health. The phenotypic outcomes may have been attributed to DNA damage or mutations, but increasing evidence shows that the inheritance of environmentally induced functional changes of the genome, and related disorders, are (also) driven by epigenetic components. In this essay we suggest the existence of epigenetic windows of susceptibility to environmental insults during sperm development. Changes in DNA methylation, histone modification, and non-coding RNAs are viable mechanistic candidates for a non-genetic transfer of paternal environmental information, from maturing germ cell to zygote. Inclusion of paternal factors in future research will ultimately improve the understanding of transgenerational epigenetic plasticity and health-related effects in future generations.
    BioEssays 04/2014; 36(4). DOI:10.1002/bies.201300113 · 4.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Insulin-like growth factor 2 receptor (IGF2R) and insulin-like growth factor 2 (IGF2) genetic variants have been inconsistently associated with low birth weight and birth length in Caucasian and Asian infants, however few studies have included African Americans (AA). Generalized linear models and logistic regression models were used to examine associations between IGF2R single nucleotide polymorphisms (SNP) rs629849 and rs8191754, and IGF2 SNP rs680 and infant anthropometric measurements, in a racially diverse birth cohort in Durham County, North Carolina. Caucasian American (CA) carriers of the IGF2R SNP rs629849 were heavier (P = 0.02) and longer (P = 0.003) at birth, however body size at age 1 yr was similar to that of AA. Birth length significantly differed between carriers and non-carriers of the IGF2 rs680 variant in both AA (P = 0.04) and CA infants (P = 0.03). Both AA and CA carriers were 1 cm shorter at birth compared to non-carriers. We found no evidence for an association between rs8191754 and infant anthropometric measurements. Associations between SNPs andone year weight gain were only observed for rs680; CA infant carriers of rs680 variants weighed less than non-carriers at year one (P = 0.03); however, no associations were found in AA infants at year one. Larger studies using ancestral markers are required to disentangle these associations.
    03/2014; 2(3):119-127. DOI:10.3233/PGE-13064
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background:Several epidemiologic studies have demonstrated associations between periconceptional environmental exposures and health status of the offspring in later life. Although these environmentally related effects have been attributed to epigenetic changes, such as DNA methylation shifts at imprinted genes, little is known about the potential effects of maternal and paternal preconceptional overnutrition or obesity.Objective:We examined parental preconceptional obesity in relation to DNA methylation profiles at multiple human imprinted genes important in normal growth and development: MEG3, MEST, PEG3, PLAGL1, SGCE/PEG10, and NNAT.Methods:We measured methylation percentages at the DMRs by bisulfite pyrosequencing in DNA extracted from umbilical cord blood leukocytes of 92 newborns. Preconceptional obesity, defined as BMI 30 kg/m(2), was ascertained through standardized questionnaires.Results:After adjusting for potential confounders and cluster effects, paternal obesity was significantly associated with lower methylation levels at the MEST (β=-2.57; s.e.=0.95; P=0.008), PEG3 (-1.71; SE=0.61; P=0.005), and NNAT (-3.59; SE=1.76; P=0.04) DMRs. Changes related to maternal obesity were detected at other loci: β-coefficient was +2.58 (s.e.=1.00; P=0.01) at PLAGL1 DMR, and -3.42 (s.e.=1.69; P=0.04) at the MEG3 DMR.Conclusion:We found altered methylation outcomes at multiple imprint regulatory regions in children born to obese parents, compared to children born to non-obese parents. In spite of the small sample size, our data suggest a preconceptional influence of parental life-style or overnutrition on the reprogramming of imprint marks during gametogenesis. More specifically, the significant and independent association between paternal obesity and the offspring's methylation status suggests the susceptibility of the developing sperm for environmental insults. The acquired imprint instability may be carried on to the next generation and increase the risk for chronic diseases in adulthood.International Journal of Obesity accepted article preview online, 25 October 2013; doi:10.1038/ijo.2013.193.
    International journal of obesity (2005) 10/2013; 39(4). DOI:10.1038/ijo.2013.193 · 5.00 Impact Factor
  • Randy L. Jirtle
    [Show abstract] [Hide abstract]
    ABSTRACT: Two epigenetically regulated targets involved in the developmental origins of disease susceptibility are genes that are imprinted and those with metastable epialleles. Genes with metastable epialleles have highly variable expressions that result from random allelic changes in the epigenome. The isogenic agouti viable yellow (Avy) mouse harbors a metastable Agouti gene. Maternal exposure of the Avy mouse during pregnancy with nutritional supplements (e.g., methyl donors and genistein), toxicological agents (e.g., bisphenol A), and physical agents (e.g., ionizing radiation) changes the coat color and adult disease incidence in the offspring by altering DNA methylation at the A vy locus. These studies clearly demonstrate that the developmental origins of disease risk can result from alterations in the epigenome. Genomic imprinting is an epigenetic form of gene silencing that results in monoallelic, parent-of-origin-dependent gene expression. It evolved in mammals with the advent of placentation and viviparity approximately 150 million years ago. Since only a single mutation or epigenetic event is required to alter imprinted gene function, these genes are implicated in a number of complex diseases and neurological conditions. Imprinting is controlled by parental-specific epigenetic marks that are established during gametogenesis and in early embryonic development. We refer to the complete set of these cis-acting epigenetic regulatory elements as the imprintome, a distinct and specially tasked subset of the epigenome. Significant species variation in the repertoire of imprinted genes and their epigenetic regulation mean that only humans can be used to define our imprintome.
    Toxicology Letters 08/2013; 221:S19. DOI:10.1016/j.toxlet.2013.06.068 · 3.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: At birth, elevated IGF-I levels have been linked to birth weight extremes; high birth weight and low birth weight are risk factors for adult-onset chronic diseases including obesity, cardiovascular disease, and type 2 diabetes. We examined associations between plasma IGF-I levels and birth weight among infants born to African American and White obese and nonobese women. Prepregnancy weight and height were assessed among 251 pregnant women and anthropometric measurements of full term infants (≥37 weeks of gestation) were taken at birth. Circulating IGF-I was measured by ELISA in umbilical cord blood plasma. Linear regression models were utilized to examine associations between birth weight and high IGF-I, using the bottom two tertiles as referents. Compared with infants with lower IGF-I levels (≤3rd tertile), those with higher IGF-I levels (>3rd tertile) were 130 g heavier at birth, (β-coefficient = 230, se = 58.0, P = 0.0001), after adjusting for gender, race/ethnicity, gestational age, delivery route, maternal BMI and smoking. Stratified analyses suggested that these associations are more pronounced in infants born to African American women and women with BMI ≥30 kg/m(2); the cross product term for IGF-I and maternal BMI was statistically significant (P ≤ 0.0004). Our findings suggest that the association between IGF-I levels and birth weight depends more on maternal obesity than African American race/ethnicity.
    International Journal of Pediatrics 05/2013; 2013. DOI:10.1155/2013/191472
  • Sharon A Meyer · Randy L Jirtle
    [Show abstract] [Hide abstract]
    ABSTRACT: The decades-long quest for the phenobarbital (PhB) receptor that mediates activation of Cyp2B would appear fulfilled with the discovery by Mutoh et al., who found that PhB binds with pharmacological affinity to the epidermal growth factor receptor (EGFR). This finding provides a molecular basis for the suppression of hepatocyte EGFR signaling observed with PhB treatment, as previously noted in the context of tumor promotion. Although the PhB-mediated induction of Cyp2B expression through the association of a canonical nuclear receptor with the 5'-enhancer PBREM of Cyp2B is well known, direct binding of PhB to constitutive active androstane receptor (CAR, also known as NR1I3) typical of other xenobiotic-activated nuclear receptors has eluded detection. One EGF-activated pathway affected by the PhB-EGFR interaction is the loss of tyrosine phosphorylation of the scaffold protein RACK1. Dephosphorylated RACK1 provides the mechanistic link between the binding of PhB to EGFR and its effects on CAR by facilitating the interaction of serine/threonine phosphatase PP2A with inactive phosphorylated CAR. The dephosphorylation of CAR enables its translocation to the nucleus and activation of Cyp2B expression. Because EGFR and transducers RACK1, PP2A, and other partners are highly networked in numerous cellular pathways, this newly discovered partnership will surely reveal new fundamental roles for PhB beyond the regulation of drug metabolism.
    Science Signaling 05/2013; 6(274):pe16. DOI:10.1126/scisignal.2004239 · 6.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: Low birth weight (LBW) has been associated with common adult-onset chronic diseases, including obesity, cardiovascular disease, type II diabetes and some cancers. The etiology of LBW is multi-factorial. However, recent evidence suggests exposure to antibiotics may also increase the risk of LBW. The mechanisms underlying this association are unknown, although epigenetic mechanisms are hypothesized. In this study, we evaluated the association between maternal antibiotic use and LBW and examined the potential role of altered DNA methylation that controls growth regulatory imprinted genes in these associations. Methods: Between 2009–2011, 397 pregnant women were enrolled and followed until delivery. Prenatal antibiotic use was ascertained through maternal self-report. Imprinted genes methylation levels were measured at differentially methylated regions (DMRs) using bisulfite pyrosequencing. Generalized linear models were used to examine associations among antibiotic use, birth weight and DMR methylation fractions. Results: After adjusting for infant gender, race/ethnicity, maternal body mass index, delivery route, gestational weight gain, gestational age at delivery, folic acid intake, physical activity, maternal smoking and parity, antibiotic use during pregnancy was associated with 138 g lower birth weight compared with non-antibiotic use (β-coefficient=−132.99, s.e.=50.70, P=0.008). These associations were strongest in newborns of women who reported antibiotic use other than penicillins (β-coefficient=−135.57, s.e.=57.38, P=0.02). Methylation at five DMRs, IGF2 (P=0.05), H19 (P=0.15), PLAGL1 (P=0.01), MEG3 (P=0.006) and PEG3 (P=0.08), was associated with maternal antibiotic use; among these, only methylation at the PLAGL1 DMR was also associated with birth weight. Conclusion: We report an inverse association between in utero exposure to antibiotics and lower infant birth weight and provide the first empirical evidence supporting imprinted gene plasticity in these associations.
    International journal of obesity (2005) 03/2013; 37(7). DOI:10.1038/ijo.2013.47 · 5.00 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Data from epidemiological and animal model studies suggest that nutrition during pregnancy may affect the health status of subsequent generations. These transgenerational effects are now being explained by disruptions at the level of the epigenetic machinery. Besides in vitro environmental exposures, the possible impact on the reprogramming of methylation profiles at imprinted genes at a much earlier time point, such as during spermatogenesis or oogenesis, has not previously been considered. In this study, our aim was to determine associations between preconceptional obesity and DNA methylation profiles in the offspring, particularly at the differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene. Methods We examined DNA from umbilical cord blood leukocytes from 79 newborns, born between July 2005 and November 2006 at Duke University Hospital, Durham, NC. Their mothers participated in the Newborn Epigenetics Study (NEST) during pregnancy. Parental characteristics were obtained via standardized questionnaires and medical records. DNA methylation patterns at two DMRs were analyzed by bisulfite pyrosequencing; one DMR upstream of IGF2 (IGF2 DMR), and one DMR upstream of the neighboring H19 gene (H19 DMR). Multiple regression models were used to determine potential associations between the offspring's DNA methylation patterns and parental obesity before conception. Obesity was defined as body mass index (BMI) ≥30 kg/m2. Results Hypomethylation at the IGF2 DMR was associated with paternal obesity. Even after adjusting for several maternal and newborn characteristics, we observed a persistent inverse association between DNA methylation in the offspring and paternal obesity (β-coefficient was -5.28, P = 0.003). At the H19 DMR, no significant associations were detected between methylation patterns and paternal obesity. Our data suggest an increase in DNA methylation at the IGF2 and H19 DMRs among newborns from obese mothers, but a larger study is warranted to further explore the potential effects of maternal obesity or lifestyle on the offspring's epigenome. Conclusions While our small sample size is limited, our data indicate a preconceptional impact of paternal obesity on the reprogramming of imprint marks during spermatogenesis. Given the biological importance of imprinting fidelity, our study provides evidence for transgenerational effects of paternal obesity that may influence the offspring's future health status.
    BMC Medicine 02/2013; 11(1):29. DOI:10.1186/1741-7015-11-29 · 7.25 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Imprinted genes form a special subset of the genome, exhibiting monoallelic expression in a parent-of-origin–dependent fashion. This monoallelic expression is controlled by parental-specific epigenetic marks, which are established in gametogenesis and early embryonic development and are persistent in all somatic cells throughout life. We define this specific set of cis-acting epigenetic regulatory elements as the imprintome, a distinct and specially tasked subset of the epigenome. Imprintome elements contain DNA methylation and histone modifications that regulate monoallelic expression by affecting promoter accessibility, chromatin structure, and chromatin configuration. Understanding their regulation is critical because a significant proportion of human imprinted genes are implicated in complex diseases. Significant species variation in the repertoire of imprinted genes and their epigenetic regulation, however, will not allow model organisms solely to be used for this crucial purpose. Ultimately, only the human will suffice to accurately define the human imprintome.
    ILAR journal / National Research Council, Institute of Laboratory Animal Resources 12/2012; 53(3-4):341-58. DOI:10.1093/ilar.53.3-4.341 · 2.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Humans are exposed to low-dose ionizing radiation (LDIR) from a number of environmental and medical sources. In addition to inducing genetic mutations, there is concern that LDIR may also alter the epigenome. Such heritable effects early in life can either be positively adaptive or result in the enhanced formation of diseases, including cancer, diabetes, and obesity. Herein, we show that LDIR significantly increased DNA methylation at the viable yellow agouti (A(vy)) locus in a sex-specific manner (P=0.004). Average DNA methylation was significantly increased in male offspring exposed to doses between 0.7 and 7.6 cGy, with maximum effects at 1.4 and 3.0 cGy (P<0.01). Offspring coat color was concomitantly shifted toward pseudoagouti (P<0.01). Maternal dietary antioxidant supplementation mitigated both the DNA methylation changes and coat color shift in the irradiated offspring. Thus, LDIR exposure during gestation elicits epigenetic alterations that lead to positive adaptive phenotypic changes that are negated with antioxidants, indicating they are mediated in part by oxidative stress. These findings provide evidence that in the isogenic A(vy) mouse model, epigenetic alterations resulting from LDIR play a role in radiation hormesis, bringing into question the assumption that every dose of radiation is harmful.-Bernal, A. J., Dolinoy, D. C., Huang, D., Skaar, D. A., Weinhouse, C., Jirtle, R. J. Adaptive radiation-induced epigenetic alterations mitigated by antioxidants.
    The FASEB Journal 11/2012; 27(2). DOI:10.1096/fj.12-220350 · 5.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Genomic imprinting is an epigenetic phenomenon resulting in parent-of-origin specific monoallelic gene expression. It is postulated to have evolved in placental mammals to modulate intrauterine resource allocation to the offspring. In this study, we determined the imprint status of metatherian orthologues of eutherian imprinted genes. Results L3MBTL and HTR2A were shown to be imprinted in Monodelphis domestica (the gray short-tailed opossum). MEST expressed a monoallelic and a biallelic transcript, as in eutherians. In contrast, IMPACT, COPG2, and PLAGL1 were not imprinted in the opossum. Differentially methylated regions (DMRs) involved in regulating imprinting in eutherians were not found at any of the new imprinted loci in the opossum. Interestingly, a novel DMR was identified in intron 11 of the imprinted IGF2R gene, but this was not conserved in eutherians. The promoter regions of the imprinted genes in the opossum were enriched for the activating histone modification H3 Lysine 4 dimethylation. Conclusions The phenomenon of genomic imprinting is conserved in Therians, but the marked difference in the number and location of imprinted genes and DMRs between metatherians and eutherians indicates that imprinting is not fully conserved between the two Therian infra-classes. The identification of a novel DMR at a non-conserved location as well as the first demonstration of histone modifications at imprinted loci in the opossum suggest that genomic imprinting may have evolved in a common ancestor of these two Therian infra-classes with subsequent divergence of regulatory mechanisms in the two lineages.
    BMC Genomics 08/2012; 13(1):394. DOI:10.1186/1471-2164-13-394 · 3.99 Impact Factor

Publication Stats

15k Citations
1,430.29 Total Impact Points


  • 2014
    • University of Bedfordshire
      • Department of Sport & Exercise Sciences
      Luton, England, United Kingdom
  • 1971–2014
    • University of Wisconsin–Madison
      • McArdle Laboratory for Cancer Research
      Madison, Wisconsin, United States
  • 1980–2013
    • Duke University Medical Center
      • • Department of Radiation Oncology
      • • Division of Medical Genetics
      • • Department of Medicine
      • • Department of Radiology
      • • Department of Pathology
      Durham, North Carolina, United States
  • 1981–2012
    • Duke University
      • • Department of Computer Science
      • • Department of Medicine
      • • Department of Electrical and Computer Engineering (ECE)
      Durham, North Carolina, United States
  • 2010
    • University of Michigan
      • Department of Environmental Health Sciences
      Ann Arbor, MI, United States
  • 2008
    • Catholic University of Korea
      • Department of Radiation Oncology
      Sŏul, Seoul, South Korea
  • 2005
    • University of North Carolina at Charlotte
      Charlotte, North Carolina, United States
  • 1995
    • Metamark Genetics
      Cambridge, Massachusetts, United States
  • 1994
    • Fred Hutchinson Cancer Research Center
      Seattle, Washington, United States
  • 1991
    • Eli Lilly
      Indianapolis, Indiana, United States
  • 1990
    • Emory University
      Atlanta, Georgia, United States
  • 1988
    • University of Salzburg
      Salzburg, Salzburg, Austria