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Clinical Sciences

Joel Kleinman

M.D.,Ph.D.
Dscn2427kleinmansmall

Dr. Kleinman is Associate Director, Clinical Sciences, Lieber Institute for Brain Development (LIBD), Johns Hopkins University, Baltimore, MD.

Dr. Kleinman received three degrees from the University of Chicago (BS, 1966, MD, 1973 and PHD, 1974). He completed an internship at San Francisco General Hospital and residencies in psychiatry at Harvard and neurology at George Washington University, respectively. He subsequently was a tenured Section Chief in the NIMH.

He has spent the last 36 years in the NIH amassing what is widely regarded as one of the best collections of postmortem human brains for the study of the molecular biology of brain development and related disorders, especially schizophrenia. He has been both a pioneer and leader in this area of research with over 200 peer-reviewed papers on postmortem human brain. Recently, his research has focused on allelic variation, alternative transcripts and epigenetic modifications in both human brain development and schizophrenia. His lab has published a dozen papers that focus on prenatal brain development and its importance in risk for schizophrenia. Dr. Kleinman and his group at LIBD have also established one of the first, if not largest collections of postmortem brains of patients with PTSD.

 

Selected Publications

Akil M, Kolachana BS, Rothmond DA, Hyde TM, Weinberger DR and Kleinman JE: COMT genotype and dopamine regulation in the human brain. J Neuroscience 23: 2008-2013, 2003. PMID: 12657658

Egan MF, Straub RE, Goldberg TE, Yakub I, Callicott JH, Hariri AR, Mattay VS, Bertolino A, Hyde TM, Weickert CS, Akil M, Crook J, Vakkalanka RK, Balkissoon R, Gibbs RA, Kleinman JE and Weinberger DR: Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia. Proc Natl Acad. Sci USA 101: 12604-12609, 2004. PMID: 15310849

Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S, Kolachana BS, Hyde TM, Herman MM, Apud J, Egan MF, Kleinman JE and Weinberger DR: Functional analysis of genetic variation in COMT: Effects on mRNA, protein and enzyme activity in postmortem human brain. Am J Human Genet 75: 807- 821, 2004. PMID: 15457404

Law AJ, Lipska BK, Weickert CS, Hyde TM, Straub RE, Hashimoto R, Harrison PJ, Kleinman JE and Weinberger DR: Neuregulin 1 (NRG1) transcripts are differentially expressed in schizophrenia and regulated by 5’ SNPs associated with the disease. Proc Natl Acad  Sci USA 103: 6747-6752, 2006. PMID: 16618933  

Meyer-Lindenberg A, Straub RE, Lipska BK, Verchinski BA, Goldberg TE, Callicott JH, Egan MF, Huffaker SS, Mattay VS, Kolachana BS, Kleinman JE and Weinberger DR: Genetic evidence implicating DARPP-32 in human fronto-striatal structure, function and cognition. J Clin Invest 117: 672-682, 2007. PMID: 17290303

Huffaker SJ, Chen J, Nicodemus KK,  Sambataro F, Yang F, Mattay V, Lipska BK, Hyde TM, Song J, Rujescu D, Giegling I, Mayilyan K, Soghoyan A, Caforio G, Bertolino A, Meyer-Lindenberg A, Chang J, Egan M, Goldberg T, Kleinman JE, Lu B and Weinberger DR. A primate-specific, brain isoform of KCNH2: affects cortical physiology, neuronal repolarization, and risk of risk of schizophrenia. Nat Med 15: 509-518, 2009. PMID: 19412172  

Nakata K1, Lipska, BK1, Hyde TM, Ye T,  Newburn EN, Morita Y, Vakkalanka R, Barenboim M, Sei Y, Weinberger DR and Kleinman JE. (1 shared equally as first authors).  DISC1 splice variants are upregulated in schizophrenia and associated with risk polymorphisms.  Proc Natl Acad Sci USA  106: 15873-15878, 2009. PMID: 19805229

Bigos KL, Mattay VS, Callicott JH, Vakkalanka R, Kolachana B, Lipska B, Kleinman JE and Weinberger DR. Genetic variation in CACNA1C affects brain circuitries related to mental illness. Arch of Gen Psychiatry 67: 939-945, 2010. PMID: 20819988

Kao W-T, WangY, KleinmanJE, LipskaBK, HydeTM, WeinbergerDR and Law AJ. Common genetic variation in Neuregulin 3 (NRG3) influences risk for schizophrenia and impacts NRG3 expression in human brain. Proc Natl Acad Sci USA  107: 15619-15624, 2010. PMID: 20713722

Kleinman JE, Law AJ, Lipska BK, Hyde TM, Ellis JK, Harrison PJ and Weinberger DR. Genetic neuropathology of schizophrenia: new approaches to an old question and new uses for postmortem human brains. Biol Psychiatry 69: 140-145, 2011. PMID: 21183009

Hyde TM, Lipska BK, Ali T, Mathew SV, Law AJ, Metitiri OE, Straub RE, Ye T, Colantuoni C, Herman MM, Bigelow LB, Weinberger DR and Kleinman JE.  Expression of GABA signaling molecules KCC2, NKCC1, and GAD1 in cortical development and schizophrenia. J. Neuroscience 31: 11088-11095, 2011. PMID: 21795557

Kang HJ, Kawasawa YI, Cheng F, Zhu Y, Meyer A, Sedmak G, Guennel T, Shin Y, Johnson MB, Krsnik Z, Mayer S, Fertuzinhos S, Umlauf S, Vortmeyer A, Weinberger DR, Mane S, Hyde TM, Huttner A, Reimers M, Kleinman JE and Sestan N. Spatiotemporal transcriptome of the human brain. Nature 478: 483-489, 2011 PMID: 22031440

Colantuoni C1, Lipska BK1, Ye T, Hyde TM, Tao R, Leek JT, Colantuoni EA, Elkahloun AG, Herman MM, Weinberger, DR and Kleinman JE. (1 shared equally as first authors). Temporal dynamics and genetic control of transcription in the human prefrontal cortex. Nature 478: 519-523, 2011. PMID: 22031444

Numata S, Ye T, Hyde TM, Guitart-Navarro X, Tao R, Wininger M, Colantuoni C, Weinberger DR, Kleinman JE1 and Lipska BK1. (1 shared equally as senior authors). DNA methylation signatures in development and aging of the human prefrontal cortex. Am J Human Genet 90: 260-272, 2012. PMID: 22305529.

Zeng H, Shen EH, Hohmann JG, Oh SW, Bernard A, Royall JJ, Glattfelder KJ, Sunkin SM, Morris JA, Guillozet-Bongaarts AL, Smith KA, Ebbert AJ, Swanson B, Kuan L, Page DT, Overly CC, Lein ES, Hawrylycz MJ, Hof PR, Hyde TM, Kleinman JE, Jones AR. Large-scale cellular-resolution gene profiling in human neocortex reveals species-specific molecular signatures. Cell 149:483-96, 2012. PMID: 22500809.

Law AJ, Wang Y, Sei Y, O’ Donnell P, Piantadosi  P, Papaleo F, Huang W, Thomas CJ, Nicodemus KK, Straub RE, 1, Sambataro F,  Vakkalanka R, Besterman A, Lipska BK, Hyde TM, Harrison PJ, Kleinman JE and Weinberger DR. NRG1-ErbB4-p110δ signaling in schizophrenia and p110δ inhibition as a potential therapeutic strategy. Proc. Nat’l. Acad. Sci. USA 109: 12165-12170, 2012. PMID: 22689948.