Daniel A. Notterman

Senior Advisor to the Provost for Biomedical Affairs
Contact
dan1@princeton.eduFaculty Assistant
Ellen Brindle-ClarkResearch Area
Genetics & GenomicsResearch Focus
Genetic, epigenetic, and environmental interactions with child development and healthDan is a pediatrician by clinical training and a biologist whose research examines interactions between genetic variants and environmental signals in the developing behavioral, cognitive and emotional phenotype of the child. He wishes to understand the interactions between specific genetic variants, environmental signals, and resulting behavioral and health outcomes. For example, his group recently showed that women with a short, hypomorphic form of the promotor region of HTT (serotonin transporter) are more likely to experience post-partum depression in stressful socioeconomic circumstances then they are in more stable environments. However, women with the major allele of this gene (long promotor) do not display this environment-based difference in rate of postpartum depression. This is consistent with the idea that some gene variants express proteins that enhance an organism's sensitivity to the environment—so called "reactive alleles."
It is also known that variations in environmental input induce longstanding behavioral changes by affecting the methylation state of DNA. There is great excitement around these sorts of findings because it points the way to a biological understanding—invoking epigenetic mechanisms—of the relationship between adverse or favorable early environments and lifelong behavioral traits.
Notterman's lab is engaging these issues through several collaborations with social scientists and pediatricians. The lab serves as the genomics/epigenomics resource for the Fragile Family and Child Wellbeing Study (FFS), based at the Woodrow Wilson School at Princeton. The FFS is following a cohort of nearly 5,000 children born in large U.S. cities between 1998 and 2000 (roughly three-quarters of whom were born to unmarried parents). The study is in its 15th year, and we have collected DNA from participants at year and 9 and again at year 15. This enables us to make detailed correlations between genetic and epigenetic states and social, behavioral, health, and demographic data.
Using this information, his group recently showed that adverse early environments are associated with accelerated loss of telomeres by age 9 years, and that the extent of loss is moderated by genetic variants in serotonergic pathways. This is again consistent with the hypothesis that the products of these genes modulate the organism's environmental sensitivity and was featured in a commentary in Nature. Since early life telomere length is associated with both adult health and with lifespan, this research suggests a mechanism for the known effect of social disparity on well being throughout the lifespan.
Major projects include the comprehensive genotyping of more than 7500 DNA samples from the FFS cohort (mothers and children). Accompanying this project is a complementary effort to measure the methylation of DNA CpG sites. At a more mechanistic level, his group is trying to understand the biological mechanism that seems to link telomere erosion to stress.
A second area of focus is the genetics of autism. His group has developed a cohort of families in which more than one sibling has an autism spectrum disorder. Currently, we are analyzing whole genome sequence data, as well as exam and methylation data on monozygotic and dizygotic twins (and their parents and siblings), some of whom have discordant phenotypes. This will enable us to make detailed correlations between the autistic phenotype and various genetic and epigenetic abnormalities.
-
Assessment of Patient Health-Related Quality of Life and Functional Outcomes in Pediatric Acute Respiratory Distress Syndrome. Pediatr Crit Care Med. 2022 ;23(7):e319-e328. .
-
Complicated Grief, Depression and Post-Traumatic Stress Symptoms Among Bereaved Parents following their Child's Death in the Pediatric Intensive Care Unit: A Follow-Up Study. Am J Hosp Palliat Care. 2022 ;39(2):228-236. .
-
Lower respiratory tract infections in children requiring mechanical ventilation: a multicentre prospective surveillance study incorporating airway metagenomics. Lancet Microbe. 2022 ;3(4):e284-e293. .
-
Impact of paternal education on epigenetic ageing in adolescence and mid-adulthood: a multi-cohort study in the USA and Mexico. Int J Epidemiol. 2022 ;51(3):870-884. .
-
COVID-19 and EVALI: Considerations regarding two concurrent public health crises. Am J Emerg Med. 2022 ;56:389-390. .
-
Characterization of Inhaled Nitric Oxide Use for Cardiac Indications in Pediatric Patients. Pediatr Crit Care Med. 2022 ;23(4):245-254. .
-
The Longitudinal Associations Between Paternal Incarceration and Family Well-Being: Implications for Ethnic/Racial Disparities in Health. J Am Acad Child Adolesc Psychiatry. 2022 ;61(3):423-433. .
-
Post-Traumatic Growth in Parents following Their Child's Death in a Pediatric Intensive Care Unit. J Palliat Med. 2022 ;25(2):265-273. .
-
Prevalence of Pathogenic and Potentially Pathogenic Inborn Error of Immunity Associated Variants in Children with Severe Sepsis. J Clin Immunol. 2022 ;42(2):350-364. .
-
Inhaled Nitric Oxide Use and Outcomes in Critically Ill Children With a History of Prematurity. Respir Care. 2021 ;66(10):1549-1559. .
-
Growing Old Before Their Time: Measuring Aging. Pediatrics. 2021 ;147(6). .
-
Therapeutic Alliance Between Bereaved Parents and Physicians in the PICU. Pediatr Crit Care Med. 2021 ;22(4):e243-e252. .
-
Temporal airway microbiome changes related to ventilator-associated pneumonia in children. Eur Respir J. 2021 ;57(3). .
-
Early childhood psychosocial family risks and cumulative dopaminergic sensitizing score: Links to behavior problems in U.S. 9-year-olds. J Affect Disord. 2021 ;280(Pt A):432-441. .
-
Coming up short: Comparing venous blood, dried blood spots & saliva samples for measuring telomere length in health equity research. PLoS One. 2021 ;16(8):e0255237. .
-
Demographic and developmental patterns in telomere length across adolescence. Biodemography Soc Biol. 2020 ;66(3-4):208-219. .
-
Genetic analysis of the cooperative tumorigenic effects of targeted deletions of tumor suppressors , , , and in neuroendocrine tumors in mice. Oncotarget. 2020 ;11(28):2718-2739. .
-
Inhaled Nitric Oxide Use in Pediatric Hypoxemic Respiratory Failure. Pediatr Crit Care Med. 2020 ;21(8):708-719. .
-
Early Puberty and Telomere Length in Preadolescent Girls and Mothers. J Pediatr. 2020 ;222:193-199.e5. .
-
Telomere Time-Why We Should Treat Biological Age Cautiously. JAMA Netw Open. 2020 ;3(5):e204352. .
-
Variability in chest compression rate calculations during pediatric cardiopulmonary resuscitation. Resuscitation. 2020 ;149:127-133. .
-
Shared Reading at Age 1 Year and Later Vocabulary: A Gene-Environment Study. J Pediatr. 2020 ;216:189-196.e3. .
-
Structured Chart Review: Assessment of a Structured Chart Review Methodology. Hosp Pediatr. 2020 ;10(1):61-69. .
-
Two well-differentiated pancreatic neuroendocrine tumor mouse models. Cell Death Differ. 2020 ;27(1):269-283. .
-
A Multicenter Network Assessment of Three Inflammation Phenotypes in Pediatric Sepsis-Induced Multiple Organ Failure. Pediatr Crit Care Med. 2019 ;20(12):1137-1146. .
-
Survival and Cardiopulmonary Resuscitation Hemodynamics Following Cardiac Arrest in Children With Surgical Compared to Medical Heart Disease. Pediatr Crit Care Med. 2019 ;20(12):1126-1136. .
-
Ventilation Rates and Pediatric In-Hospital Cardiac Arrest Survival Outcomes. Crit Care Med. 2019 ;47(11):1627-1636. .
-
The association of immediate post cardiac arrest diastolic hypertension and survival following pediatric cardiac arrest. Resuscitation. 2019 ;141:88-95. .
-
Neighborhood Disadvantage and Telomere Length: Results from the Fragile Families Study. RSF. 2018 ;4(4):28-42. .
-
End-tidal carbon dioxide during pediatric in-hospital cardiopulmonary resuscitation. Resuscitation. 2018 ;133:173-179. .
-
Chest compression rates and pediatric in-hospital cardiac arrest survival outcomes. Resuscitation. 2018 ;130:159-166. .
-
Association Between Diastolic Blood Pressure During Pediatric In-Hospital Cardiopulmonary Resuscitation and Survival. Circulation. 2018 ;137(17):1784-1795. .
-
The Collaborative Pediatric Critical Care Research Network: Recent Progress and Future Directions. Pediatr Clin North Am. 2017 ;64(5):xvii-xix. .
-
Sleep Duration and Telomere Length in Children. J Pediatr. 2017 ;187:247-252.e1. .
-
Early-Life Experiences and Telomere Length in Adult Rhesus Monkeys: An Exploratory Study. Psychosom Med. 2016 ;78(9):1066-1071. .
-
DNA methylation, early life environment, and health outcomes. Pediatr Res. 2016 ;79(1-2):212-9. .
-
Epigenetics and Understanding the Impact of Social Determinants of Health. Pediatr Clin North Am. 2015 ;62(5):1227-40. .
-
Social disadvantage, genetic sensitivity, and children's telomere length. Proc Natl Acad Sci U S A. 2014 ;111(16):5944-9. .
-
Genetic differential sensitivity to social environments: implications for research. Am J Public Health. 2013 ;103 Suppl 1:S102-10. .
-
The Great Recession, genetic sensitivity, and maternal harsh parenting. Proc Natl Acad Sci U S A. 2013 ;110(34):13780-4. .