The Pittenger Laboratory at Yale University is seeking 2 new postdoctoral associates to join an NIH-funded research program focused on using preclinical models (primarily in mice) to advance understanding of the normal functions of the corticostriatal circuitry and their dysregulation in neuropsychiatric disease, with a particular focus on Tourette syndrome, autism, and obsessive-compulsive disorder. Recent work has focused on two models that capture aspects of the pathophysiology of TS, one genetic and one based on post-mortem findings (see references below). Ongoing funded work will combine molecular techniques (CRISPR-generated mice; viruses; analysis of signaling and gene expression), chemogenetic and targeted pharmacological manipulation, behavioral analysis, and other approaches to further analyze several aspects of these models, including stress effects, sexual dimorphism, and mechanisms of striatal modulation by neuromodulators and cortical and thalamic afferents. A dense network of collaborators, both at Yale and at other institutions, broadens our technical repertoire to incorporate ex vivo and in vivo MRI imaging, electrophysiology, proteomics and transcriptomics, and others. Several other pathophysiological models are currently in development, all based on observations drawn from clinical material.
Work in the Pittenger laboratory is loosely coordinate with clinical research in Dr. Pittenger's clinical research program, the Yale OCD Research Clinic, which encompasses a broad range of clinical research approaches: functional and structural neuroimaging; pharmacology; cognitive testing; neurofeedback; neuroeconomic approaches; epidemiology; treatment development. This makes our group an unusually rich place to learn translational approaches to neuroscience and keeps our basic and mechanistic work tethered to relevant questions.
This breadth of perspective is captured in a recent comprehensive book, Obsessive-Compulsive Disorder: Phenomenology, Pathophysiology, and Treatment. Pittenger (editor), 2017. New York: Oxford University Press.
Relevant recent papers:
Hdc knockout genetic model
Pittenger, C. (2017). Histidine decarboxylase knockout mice as a model of the pathophysiology of Tourette syndrome and related conditions. In Hattori, Y. and Seifert, R. (eds), Handbook of Experimental Pharmacology: Histamine and Histamine Receptors in Health and Disease. Berlin: Springer-Verlag.
Castellan Baldan, L., Williams, K.A., Gallezot, J.-D., Pogorelov, V., Rapanelli, M., Crowley, M., Anderson, G.M., Loring, E., Gorczyca, R., Billingslea, E., Wasylink, S., Panza, K.E., Ercan-Sencicek, A.G., Krusong, K., Leventhal, B.L., Ohtsu, H., Bloch, M.H., Hughes, Z.A., Krystal, J.H., Mayes, L., de Araujo, I., Ding, Y.-S., State, M.W., and Pittenger, C. (2014). Histidine decarboxylase deficiency causes Tourette syndrome: parallel findings in humans and mice. Neuron 81:77-90. doi: 10.1016/j.neuron.2013.10.052.
Rapanelli, M., Frick, L.R., Horn, K.D., Schwarcz, R., Pogorelov, V., Nairn, A.C., and Pittenger, C. (2016). The histamine H3 receptor differentially modulates MAPK and Akt signaling in striatonigral and striatopallidal neurons. J. Biol. Chem. 291:21042-52.
Rapanelli, M.,* Frick, L.,* Bito, H., and Pittenger, C. (2017). Histamine modulation of the basal ganglia circuitry in the development of pathological grooming. Proc. Natl. Acad. Sci. USA 114:6599-6604. doi: 10.1073/pnas.1704547114
Striatal interneuron model
Xu, M., Kobets, A., Du, J.C., Lennington, J., Li, L., Banasr, M., Duman, R.S., Vaccarino, F.M., DiLeone, R.J., and Pittenger, C. (2015). Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome. Proc. Natl. Acad. Sci. USA, 112:893-8.
Rapanelli, M., Frick, L.R., Xu, M., Groman, S.M., Jindachomthong, K., Tamamaki, N., Tanahira, C., Taylor, J.R., and Pittenger, C. (2017). Targeted interneuron depletion in the dorsal striatum produces autism-like behavioral abnormalities in male but not female mice. Biological Psychaitry, EPub; doi: 10.1016/j.biopsych.2017.01.020.
Ph.D. in neurobiology, psychology (with experience in animal work), or related area.
Strong record of research productivity and publication.
Experience with one or more core methodologies used in the laboratory: mouse behavioral analysis; molecular genetics/biochemistry/immunohistochemistry; stereotactic surgery/viral manipulations of the brain/chemogenetics.
Interest in translational studies of neuropsychiatric disease.
Additional Salary Information: Postdoctoral salaries are commensurate with experience and are set by the University; for more information see http://postdocs.yale.edu/policies/compensation. Benefits are set by the University; details may be found at http://postdocs.yale.edu/postdocs/benefits.