PhD (2014), UCLA Postdoc (2014-2019), UCSF
Characterizing sex-differential risk mechanisms in autism and other neuropsychiatric disorders using functional genomics, human genetics and bioinformatics approaches
- 2018 UCSF Psychiatry Trainee Research Award
- 2018 Simons Foundation Autism Research Initiative (SFARI) Bridge to Independence Award
Autism Spectrum Disorder (ASD) is currently diagnosed 3-5 times more frequently in males than females and this is one of the most consistent, yet mechanistically unexplained, features of ASD. Many other neurodevelopmental and neuropsychiatric conditions such as ADHD, Tourette Syndrome, schizophrenia, and major depression, also show striking sex differences in their prevalence or presentation that are similarly unaccounted for. In contrast, human genetics studies have successfully identified many genetic loci and individual genes that are involved in risk for neuropsychiatric disorders.
However, a statistical link between a gene and a trait is only a first step toward understanding disease mechanisms. The Werling Lab is interested in investigating the key neurobiological mechanisms involved in the etiology of ASD and other neuropsychiatric disorders, including the dimensions of genetic variation, development, and sex-differential biology, and interactions between them. We apply genome-wide genetics, functional genomics, and bioinformatics approaches (e.g. RNA-seq, single cell analyses, eQTLs) in human tissue and model systems to identify and characterize the mechanisms involved in sex-differential and disorder-associated neurobiology. The long-term goal of our research program is to uncover fundamental causal pathways in both sexes that will facilitate treatment development and benefit affected individuals and their families.
Representative Publications (Google Scholar | PUBMED)
Werling DM*, Pochareddy S*, Choi J*, An J-A*, Sheppard B, Peng M, Li Z, Dastmalchi C, Santpere G, Sousa AMM, Tebbenkamp ATN, Kaur N, Gulden FO, Breen MS, Liang L, Gilson MC, Zhao X, Dong S, Klei L, Cicek AE, Buxbaum JD, Adle-Biassette H, Thomas J-L, Aldinger KA, O’Day DR, Glass IA, Zaitlen NA, Talkowski ME, Roeder K, State MW, Devlin B, Sanders SJ, and Sestan N. Whole-genome and RNA sequencing reveal variation and transcriptomic coordination in the developing human prefrontal cortex. Cell Reports, 31, 1-17 (2020). https://doi.org/10.1016/j.celrep.2020.03.053. *These authors contributed equally to this work.
Werling DM*, Brand H*, An J-A*, Stone MR*, Zhu L*, Glessner JT, Collins RL, Dong S, Layer RM, Markenscoff- Papadimitriou E-C, Farrell A, Schwartz GB, Wang HZ, Currall BB, Zhao X, Dea J, Duhn C, Erdman C, Gilson M, Yadav R, Handsaker RE, Kashin S, Klei L, Mandell JD, Nowakowski TJ, Liu Y, Pochareddy S, Smith L, Walker MF, Waterman MJ, He X, Kriegstein AR, Rubenstein JL, Sestan N, McCarroll SA, Neale BM, Coon H, Willsey AJ, Buxbaum JD, Daly MJ, State MW, Quinlan A, Marth GT, Roeder K, Devlin B, Talkowski ME, Sanders SJ. An analytical framework for whole-genome sequence data and its implications for autism spectrum disorder. Nature Genetics, 50, 727-736 (2018). https://doi.org/10.1038/s41588-018-0107-y. PMID: 29700473. *These authors contributed equally to this work.
Werling DM, Parikshak NN, & Geschwind DH. Gene expression in human brain implicates sexually dimorphic pathways in autism spectrum disorders. Nature Communications, 7, 10717 (2016). https://doi.org/10.1038/ncomms10717. PMID: 26892004.
Werling DM & Geschwind DH. Recurrence rates provide evidence for sex-differential, familial genetic liability for autism spectrum disorders in multiplex families and twins. Molecular Autism, 6, 27 (2015). https://doi.org/10.1186/s13229-015-0004-5. PMID: 25973164.