Faculty & Research

Molecular Biology Faculty

Daniel A. Notterman

Lecturer with rank of Professor in Molecular Biology
Daniel A. Notterman 
This email address is being protected from spambots. You need JavaScript enabled to view it.
Phone (609) 258-7185
locationLewis Thomas Lab, 205
Faculty Assistant
Carolynne Lewis-Arévalo
This email address is being protected from spambots. You need JavaScript enabled to view it.
Phone (609) 258-2933

Research Focus

Genetic, epigenetic, and environmental interactions with child development and health.

Dan is interested in the reciprocal interactions between genetic variants and environmental signals in the developing behavioral, cognitive and emotional phenotype of the child.  Over the past decade, technical advances in our ability to specify and analyze both genetic variants and epigenetic modifications to DNA and histones have enabled a new field that can be termed, social and behavioral genomics.  Although this field is in its infancy, we already understand that there are robust interactions between specific genetic variants, environmental signals, and resulting behavioral and health outcomes.   For example, we 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.” These reactive alleles are the biological substrate, perhaps, for Belsky’s “Differential Sensitivity Hypothesis.”   It is also known that variations in environmental input induce longstanding behavioral changes by affecting the methylation state of DNA. For example, rat pups raised by inattentive as opposed to attentive mothers have hypermethylated promoters for the GC receptor gene expressed in the hypothalamus—this reduces expression of that receptor, thereby upregulating the activity of the cortisol stress pathway in these pups.  There is great excitement around findings such as this, 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, we 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.

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.    

A second area of focus is the genetics of autism. We have developed a cohort of families in which more than one sibling has an autism spectrum disorder. Currently, we are analyzing whole genome sequence data on monozygotic and dizygotic twins (and their parents and siblings), some of whom have discordant phenotypes.

Selected Publications

Mitchell C, Hobcraft J, McLanahan SS, Siegel SR, Berg A, Brooks-Gunn J, Garfinkel I, Notterman D. Social disadvantage, genetic sensitivity, and children's telomere length. Proc Natl Acad Sci U S A. 2014.

Mitchell C, McLanahan S, Brooks-Gunn J, Garfinkel I, Hobcraft J, Notterman D. Genetic differential sensitivity to social environments: implications for research. Am J Public Health. 2013 Oct;103 Suppl 1:S102-10.

Lee D, Brooks-Gunn J, McLanahan SS, Notterman D, Garfinkel I. The Great Recession, genetic sensitivity, and maternal harsh parenting. Proc Natl Acad SciU S A. 2013 Aug 20;110(34):13780-4.

Giacobbe A, Bongiorno-Borbone L, Bernassola F, Terrinoni A, Markert EK, Levine AJ, Feng Z, Agostini M, Zolla L, Agrò AF, Notterman DA, Melino G, Peschiaroli A. p63 regulates glutaminase 2 expression. Cell Cycle. 2013 May 1;12(9):1395-405.

Shand J, Berg J, Bogue C; Committee for Pediatric Research; Committee on Bioethics. Human embryonic stem cell (hESC) and human embryo research. Pediatrics. 2012 Nov;130(5):972-7.

Mitchell C, Notterman D, Brooks-Gunn J, Hobcraft J, Garfinkel I, Jaeger K, Kotenko I, McLanahan S. Role of mother's genes and environment in postpartum depression. Proc Natl Acad Sci U S A. 2011 May 17;108(20):8189-93.

Postel EH, Zou X, Notterman DA, La Perle KM. Double knockout Nme1/Nme2 mouse model suggests a critical role for NDP kinases in erythroid development. Mol Cell Biochem. 2009 Sep;329(1-2):45-50.

Sheffer M, Bacolod MD, Zuk O, Giardina SF, Pincas H, Barany F, Paty PB, Gerald WL, Notterman DA, Domany E. Association of survival and disease progression with chromosomal instability: a genomic exploration of colorectal cancer. Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7131-6.

Postel EH, Wohlman I, Zou X, Juan T, Sun N, D'Agostin D, Cuellar M, Choi T, Notterman DA, La Perle KM. Targeted deletion of Nm23/nucleoside diphosphate kinase A and B reveals their requirement for definitive erythropoiesis in the mouse embryo. Dev Dyn. 2009 Mar;238(3):775-87.

Bacolod MD, Schemmann GS, Giardina SF, Paty P, Notterman DA, Barany F. Emerging paradigms in cancer genetics: some important findings from high-density single nucleotide polymorphism array studies. Cancer Res. 2009 Feb 1;69(3):723-7. doi: 10.1158/0008-5472.CAN-08-3543.

Cheng YW, Pincas H, Bacolod MD, Schemmann G, Giardina SF, Huang J, Barral S, Idrees K, Khan SA, Zeng Z, Rosenberg S, Notterman DA, Ott J, Paty P, Barany F. CpG island methylator phenotype associates with low-degree chromosomal abnormalities in colorectal cancer. Clin Cancer Res. 2008 Oct 1;14(19):6005-13.

MolBio Events

Contact Us

Lewis Thomas Laboratory at Princeton University

119 Lewis Thomas Laboratory
Washington Road, Princeton, NJ  08544-1014

Need help? Contact us

Fax: (609) 258-3980
Website:  molbio.princeton.edu