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People

  • Principal Investigator

    Elizabeth Mears and House Jameson Professor of Psychiatry; Deputy Chair for Translational Research, Psychiatry; Director, Yale OCD Research Clinic; Director, Neuroscience Research Training Program, Yale Department of Psychiatry

    Chris Pittenger earned his MD and Ph.D. degrees from Columbia University, where his graduate work was done with Nobel Prize recipient Eric Kandel. He returned to Yale University, his undergraduate alma mater, for residency and research training in psychiatry in 2003. He joined the faculty as an Assistant Professor in 2007 and is now a tenured Associate Professor and Assistant Chair for Translational Research in the Department of Psychiatry .During his Ph.D. studies in basic neurobiology, he became fascinated by the brain's ability to go on autopilot -- to perform complex series of actions or thoughts, after sufficient rehearsal, with almost no conscious effort. Then, during his clinical training, he recognized how this process, when disrupted by disease, can lead to the maladaptive and disruptive automaticity seen in many neuropsychiatric disorders. His research, both with patients and in animal models, aims to elucidate the mechanisms of learned automatic behaviors and to better understand the consequences when they go awry, with the ultimate goal of developing new understandings and better treatments for a variety of neuropsychiatric conditions.Dr. Pittenger's research and clinical work have been acknowledged by a number of prestigious awards, including grant funding from the National Institute of Mental Health, the National Institute of Neurological Disease and Stroke, NARSAD, the Tourette Syndrome of America, the Doris Duke Charitable Trust, and other organizations.  He has won a number of honorific awards, including from the National Institute of Mental Health, the Society for Neuroscience, the American College of Neuropsychopharmacology, the American Psychiatric Association, and the American College of Psychiatrists. He is a member of the Scientific Advisory Board of the International OCD Foundation and Chair of both their Grant Review Committee and their Annual Research Symposium Planning Committee.  He is a Fellow of the American College of Neuropsychopharmacology, the American Psychiatric Association, and the American Neurological Association.

Lab Members

  • Research Assistant

    Elizabeth began her career at Yale working in animal husbandry. Since then she has had the privilege to work in several labs that cover a wide range of specialty areas. There have also been brief periods working with the Surgery department, the Office of Diversity and Inclusion, and the Sterling Library which allowed her to further explore all that Yale has to offer. Currently she is enjoying assisting with OCD research being done in both the research lab and clinic.
  • Associate Research Scientist of Psychiatry

    Education & Training: Bsc. Genetics, Fudan University, Shanghai, China (2000) PhD. Molecular Biology, Fudan University, Shanghai, China (2005) Research interest: My research focuses on translational work examining the role of STriatal Enriched Protein tyrosine phosphatase (STEP) in neuropsychiatric disorders, including Alzheimer’s disease (AD) and schizophrenia (SZ).Selected publications:1. Peer-reviewed articlesXu J, Kurup P, Baguley TD, Foscue E, Ellman JA, Nairn AC, Lombroso PJ (2015) Inhibition of the tyrosine phosphatase STEP61 restores BDNF expression and reverses motor and cognitive deficits in phencyclidine-treated mice.Cell Mol Life Sci doi:10.1007/s00018-015-2057-1. [Epub ahead of print]Jang SS, Royston SE, Xu J, Cavaretta JP, Vest MO, Lee KY, Lee S, Jeong HG, Lombroso PJ, Chung HJ (2015) Regulation of STEP61 and tyrosine-phosphorylation of NMDA and AMPA receptors during homeostatic synaptic plasticity. Mol Brain 8:55. Xu J, Kurup P, Azkona G, Baguley TD, Saavedra A, Nairn AC, Ellman JA, Pérez-Navarro E, Lombroso PJ (2015) Down-regulation of BDNF in cell and animal models increases striatal-enriched protein tyrosine phosphatase 61 (STEP61 ) levels.J Neurochem doi: 10.1111/jnc.13295. [Epub ahead of print]Xu J, Kurup P, Foscue E, Lombroso PJ (2015) Striatal-enriched protein tyrosine phosphatase regulates the PTPα/Fyn signaling pathway. J Neurochem 134:629-641. Kurup PK, Xu J, Videira RA, Ononenyi C, Baltazar G, Lombroso PJ, Nairn AC (2015) STEP61 is a substrate of the E3 ligase parkin and is upregulated in Parkinson's disease. Proc Natl Acad Sci U S A 112:1202-1207.Xu J, Chatterjee M, Baguley TD, Brouillette J, Kurup P, Ghosh D, Kanyo J, Zhang Y, Seyb K, Ononenyi C, Foscue E, Anderson GM, Gresack J, Cuny GD, Glicksman MA, Greengard P, Lam TT, Tautz L, Nairn AC, Ellman JA, Lombroso PJ. Inhibitor of the Tyrosine Phosphatase STEP Reverses Cognitive Deficits in a Mouse Model of Alzheimer’s Disease. PLoS Biol 12:e1001923.Gladding CM, Fan J, Zhang LY, Wang L, Xu J, Li EH, Lombroso PJ, Raymond LA (2014) Alterations in STriatal-Enriched protein tyrosine Phosphatase expression, activation, and downstream signaling in early and late stages of the YAC128 Huntington's disease mouse model. J Neurochem 130:145-159.Darcq E, Hamida SB, Wu S, Phamluong K, Kharazia V, Xu J, Lombroso P, Ron D (2014) Inhibition of striatal-enriched tyrosine phosphatase 61 in the dorsomedial striatum is sufficient to increased ethanol consumption. J Neurochem 129:1024-1034.Dabrowska J, Hazra R, Guo JD, Li C, Dewitt S, Xu J, Lombroso PJ, Rainnie DG (2013) Striatal-Enriched Protein Tyrosine Phosphatase-STEPs Toward Understanding Chronic Stress-Induced Activation of Corticotrophin Releasing Factor Neurons in the Rat Bed Nucleus of the Stria Terminalis. Biol Psychiatry 74:817-826.Xu J, Kurup P, Nairn AC, Lombroso PJ (2012) Striatal-enriched protein tyrosine phosphatase in Alzheimer's disease. Adv Pharmacol 64:303-325.Carty NC, Xu J, Kurup P, Brouillette J, Goebel-Goody SM, Austin DR, Yuan P, Chen G, Correa PR, Haroutunian V, Pittenger C, Lombroso PJ (2012) The tyrosine phosphatase STEP: Implications in schizophrenia and the molecular mechanism underlying antipsychotic medications. Transl Psychiatry 2:e137.Xu J, Kurup P, Bartos JA, Patriarchi T, Hell JW, Lombroso PJ (2012) STriatal-enriched protein tyrosine phosphatase (STEP) regulates Pyk2 activity. J Biol Chem 287:20942-20956.Sergienko E1, Xu J1, Liu WH, Dahl R, Critton DA, Su Y, Brown BT, Chan X, Yang L, Bobkova EV, Vasile S, Yuan H, Rascon J, Colayco S, Sidique S, Cosford ND, Chung TD, Mustelin T, Page R, Lombroso PJ, Tautz L (2012) Inhibition of hematopoietic protein tyrosine phosphatase augments and prolongs ERK1/2 and p38 activation. ACS Chem Biol 7(2):367-377.(1equal contribution)Gladding CM, Sepers MD, Xu J, Zhang LY, Milnerwood AJ, Lombroso PJ, Raymond LA (2012) Calpain and Striatal-Enriched Protein Tyrosine Phosphatase (STEP) Activation Contribute to Extrasynaptic NMDA Receptor Localization in a Huntington's Disease Mouse Model. Hum Mol Genet 21:3739-3752.Zhang Y, Kurup P, Xu J, Anderson GM, Greengard P, Nairn AC, Lombroso PJ (2011) Reduced levels of the tyrosine phosphatase STEP block β amyloid-mediated GluA1/GluA2 receptor internalization. J Neurochem 119:664-672.Saavedra A, Giralt A, Rué L, Xifró X, Xu J, Ortega Z, Lucas JJ, Lombroso PJ, Alberch J, Pérez-Navarro E (2011) Striatal-enriched protein tyrosine phosphatase expression and activity in Huntington's disease: a STEP in the resistance to excitotoxicity. J Neurosci 31(22):8150-8162.Zhang YF, Kurup P, Xu J, Carty NC, Fernandez S, Nygaard HB, Pittenger C, Greengard P, Strittmatter SM, Nairn AC, Lombroso PJ (2010) Genetic reduction of STEP tyrosine phosphatase reverses cognitive and cellular deficits in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci U S A 107:19014-19019.Kurup P, Zhang Y, Xu J, Venkitaramani DV, Haroutunian V, Nairn A.C, Paul Greengard, Lombroso PJ (2010) Abeta-mediated NMDAR endocytosis in Alzheimer’s disease involves ubiquitination of the tyrosine phosphatase STEP. J Neurosci 30: 5948-5957.Baum ML, Kurup P, Xu J, Lombroso PJ (2010) A STEP forward in neural function and degeneration. Commun Integr Biol 3:419-422.Kurup P, Zhang Y, Venkitaramani DV, Xu J, Lombroso PJ (2010) The role of STEP in Alzheimer's disease. Channels 4:347-350.Xu J, Kurup P, Zhang YF, Goebel-Goody SM, Wu PH, Hawasli AH, Baum ML, Bibb JA, Lombroso PJ (2009) Extrasynaptic NMDA receptors couple preferentially to excitotoxicity via calpain-mediated cleavage of STEP. J Neurosci 29:9330-9343.Braithwaite SP, Xu J, Leung J, Urfer R, Nikolich K, Oksenberg D, Lombroso PJ, Shamloo M (2008) Expression and function of striatal enriched protein tyrosine phosphatase is profoundly altered in cerebral ischemia. Eur J Neurosci 27: 2444-2452.Wang L1, Xu J1, Ji CN, Gu SH, Lv Y, Li S, Xu YR, Xie Y, Mao YM (2005) Cloning, expression and characterization of human glutathione S-transferase Omega 2. Int J Mol Med 16:19-27. (1equal contribution)Chen JX, Xu J, Zhao W, Hu GH, Cheng HP, Kang Y, Xie Y, Lu YC (2005) Characterization of human LNX, a novel ligand of Numb protein X that is downregulated in human gliomas. Int J Biochem Cell Biol 37 (11): 2273-2283.Xu J, He T, Wang L, Wu QH, Zhao EP, Wu MQ, Dou TH, Ji CN, Gu SH, Yin K, Xie Y, Mao YM (2004) Molecular cloning and characterization of a novel human BTBD8 gene containing double BTB/POZ domains. Int J Mol Med 13:193-197.Chen JX1, Xu J1, Ying K, Cao GT, Hu GH, Wang L, Luo C, Lou MQ, Mao YJ, Xie Y, Lu YC (2004) Molecular cloning and characterization of a novel human BTB domain-containing gene, BTBD10, which is down-regulated in glioma. Gene 340 (1): 61-69. (1equal contribution)Chen JX, Lu YC, Xu J, Huang Y, Cheng HP, Hu GH, Luo C, Lou MQ, Cao GT, Xie Y, Ying K (2004) Identification and characterization of NBEAL1, a novel human neurobeachin-like 1 protein gene from fetal brain, which is up regulated in glioma. Brain Res Mol Brain Res 125 (1-2): 147-155.Xu J, Gu SH, Wang S, Dai JL, Ji CN, Jin YS, Qian J, Wang L, Ye X, Xie Y, Mao YM (2003) Characterization of a novel splicing variant of KLHL5, a member of the kelch protein family. Mol Biol Rep 30:239-242.Xu J, Ji CN, Wang L, Cao YQ, Dai JL, Ye X, Zeng L, Dai JF, Wu QH, Xie Y, Mao YM (2003) Cloning and expression of a novel human C5orf12 gene, a member of the TMS_TDE family. Mol Biol Rep 30:47-52.Xu J, Wu H, Zhang CZ, Cao JQ, Wang L, Zeng L, Ye X, Wu QH, Dai JF, Xie Y, Mao YM (2002) Identification of a novel human DDX40 gene, a new member of the DEAH-box protein family. J Hum Genet 47:681-683.Xu J, Zhou ZX, Zeng L, Huang Y, Zhao W, Cheng C, Xu M, Xie Y, Mao YM (2001) Cloning, expression and characterization of a novel human REPS1 gene. Biochim Biophys Acta 1522:118-121.2. Book ChaptersKurup P, Xu J, Goebel-Goody S, Paul S, Lombroso PJ (2013) Striatal-Enriched Protein Tyrosine phosphatase (STEP). S. Choi (ed.), Encyclopedia of Signaling Molecules DOI 10.1007/978-1-4419-0461-4-630.