Faculty Profile

Dr. Herbert M. Lachman, M.D.

Herbert M. Lachman, M.D.

Professor, Department of Psychiatry and Behavioral Sciences

Professor, Department of Medicine (Hematology)

Associate Professor, Dominick P. Purpura Department of Neuroscience

Associate Professor, Department of Genetics

Areas of Research: We use induced pluripotent stem cell technology to study the molecular basis of schizophrenia and autism by RNA-seq and ChIP-seq. Patient-specific lines and isogenic knockout lines, generated by CRISP-Cas9 are used.

Professional Interests

Dr. Herbert Lachman is a physician and behavioral geneticist interested in the molecular and genetic basis of schizophrenia (SZ), autism spectrum disorders (ASD), bipolar disorder (BD), and intellectual and developmental disabilities (IDD). The lab’s primary research projects involve the use of induced pluripotent stem cells (iPSCs) for modeling neuropsychiatric disorders in vitro. Patient-specific iPCS are generated from skin fibroblasts or CD34+ white blood cells, which are ultimately induced to differentiate into neurons. Epigenetic analysis and gene expression profiling for protein-coding genes, long non-coding RNAs and microRNAs are then carried out. In addition, the lab also studies the effects of some candidate genes of interest on endosome recycling, innate immune phenomena, neurite outgrowth, and, in collaboration with members of the neuroscience department, electrophysiolgical properties of pure cultures of human glutamatergic neurons and GABAergic interneurons.

In addition, the lab uses gene knockdown and CRISPR knockout approaches to study the effects of SZ, ASD and IDD candidate genes on neurogenesis and gene expression. We are particularly interested in those candidate genes that function as transcription factors and chromatin remodeling complexes. The lab has also recently developed an interest in environmental factors that might play a role in SZ and ASD pathogenesis. The Lachman lab has developed iPSC models for 22q11.2 deletion syndrome, the most common abnormality found in SZ, CHD8 haploinsufficiency, which causes ASD, and Lowe Syndrome, an X-linked disorder that causes IDD and renal proximal tubulopathy. An iPSC model for PPM1D-related IDD is currently under development.

Dr. Lachman is board certified in Internal Medicine and has clinical responsibilities in the Einstein Division of Substance Abuse, where he is the director of the Medical Maintenance Program. He also teaches human genetics to first-year medical students and graduate students, and directs a course in human genetics in the Clinical Research Training Program.

Selected Publications

Selected publications since 2007

Herbert M. Lachman, Cathy S.J. Fann, Michael Bartzis, Oleg V. Evgrafov, Richard N. Rosenthal, Edward V. Nunes, Christian Miner, Maria Santana, Jebediah Gaffney, Amy Riddick, Chia-Lin Hsu, James Knowles (2007) Genomewide Suggestive Linkage of Opioid Dependence to Chromosome 14q. Human Molecular Genetics 16(11):1327-1334

Herbert M. Lachman Oriana A. Petruolo Erika Pedrosa, Tomas Novak, Karen Nolan, Pavla Stopkova (2008). Analysis of protocadherin alpha gene deletion variant in bipolar disorder and schizophrenia (in press: Psychiatric Genetics 18(3):110-115.

Erika Pedrosa, Radu Stefanescu, Oriana Petruolo, Yungtai Lo, Karen Nolan, Pavla Stopkova, Herbert M. Lachman (2008). Analysis of protocadherin alpha gene enhancer polymorphism in bipolar disorder and schizophrenia (Schizophrenia Research). 102 (1-3):210-219.

Rael D. Strous MD, Michael S. Ritsner MD PhD, Shmulik Adler BA, Yael Ratner MD, Rachel Maayan PhD, Moshe Kotler MD, Herbert Lachman MD, Abraham Weizman MD (2009) Improvement of Aggressive Behavior and Quality of Life Impairment Following S-Adenosyl-Methionine (SAM-e) Augmentation in Schizophrenia Eur. Neuropsychopharm. in press 19(1):14-22

Erika Pedrosa, Joseph Locker, Herbert M. Lachman (2009).Survey of schizophrenia and bipolar disorder candidate genes using chromatin immunoprecipitation and tiled microarrays (ChIP-chip) Journal of Neurogenetics, 18:1-12.

Erika Pedrosa, Karen A. Nolan, Radu Stefanescu, Pnina Hershcovitz, Tomas Novak, Ilja Zukov, Pavla Stopkova (2009) Herbert M. Lachman Analysis of a promoter polymorphism in the SMDF neuregulin 1 isoform in schizophrenia Neuropsychobiology 59:205-212.

Joshua T Kantrowitz, Karen Nolan, Srijan Sen, Arthur Simen, Herbert Lachman, Malcolm B Bowers (2009) Adolescent Cannabis Use, Psychosis and Catechol-O-Methyltransferase Genotype in African Americans and Caucasians. Psychiatr Q. 2009 Jul 25. [Epub ahead of print].

Erika Pedrosa, Abhishek Shah, Christopher Tenore, Michael Capogna, Catalina Villa, Herbert M. Lachman. Beta-catenin promoter ChiP-chip reveals potential schizophrenia and bipolar disorder gene network. J Neurogenet. 2010 Dec;24(4):182-93

Abhishek K. Shah, Nina M Tioleco, Karen Nolan, Joseph Locker, Katherine Groh, Catalina Villa, Tomas Novak, Pavla Stopkova, Erika Pedrosa, Herbert M. Lachman Rare NRXN1 promoter variants in patients with schizophrenia. Neuroscience Letters, 2010 475(2):80-4

Pedrosa E, Sandler V, Shah A, Carroll R, Chang C, Rockowitz S, Guo X, Zheng D, Lachman HM. Development of Patient-Specific Neurons in Schizophrenia Using Induced Pluripotent Stem Cells. J Neurogenet. 2011, 25(3):88-103

Mingyan Lin, Erika Pedrosa, Abhishek K. Shah, Anastasia Hrabovsky, Shahina Maqbool, Deyou Zheng, Herbert M. Lachman. Deep sequencing transcriptome analysis of human neurons derived from induced pluripotent stem cells identifies candidate long non-coding RNAs involved in neurogenesis and neuropsychiatric disorders. PLoS One, 2011;6(9):e23356.

Mingyan Lin, Anastasia Hrabovsky, Erika Pedrosa, Tao Wang, Deyou Zheng, Herbert M. Lachman. Allele-biased expression in differentiating human neurons: implications for neuropsychiatric disorders. PLoS One. 2012;7(8):e44017. Epub 2012 Aug 30.

Jian Chen, Mingyan Lin, John J. Foxe, Erika Pedrosa, Anastasia Hrabovsky, Reed Carroll, Deyou Zheng, Herbert M. Lachman Transcriptome comparison of human neurons generated using induced pluripotent stem cells derived from dental pulp and skin fibroblasts. PLoS One. 2013 Oct 3;8(10):e75682. doi: 10.1371/journal.pone.0075682. eCollection 2013. PMID: 24098394

Patch-Clamp Recordings Followed by Single-Cell PCR Reveal the Rise and Fall of 13 Genes in iPSC-Derived Human Neurons. Glenn S. Belinsky, Matthew T. Rich, Carissa L. Sirois, Shaina M. Short, Erika Pedrosa, Herbert M. Lachman, and Srdjan D. Antic. Stem Cell Res. 2014 Jan;12(1):101-18. PMID: 24157591

Characterization of Human Pseudogene-derived Non-coding RNAs for Functional Potential Xingyi Guo, Mingyan Lin, Shira Rockowitz, Herbert M. Lachman, and Deyou Zheng. PLOS ONE Published: April 03, 2014 DOI: 10.1371/journal.pone.0093972

Mingyan Lin, Dejian Zhao, Anastasia Hrabovsky, Erika Pedrosa, Deyou Zheng, Herbert M. Lachman. Gene expression profiling in an induced pluripotent stem cell model of the developing human telencephalon: effects of heat shock and its potential consequences in the development of neuropsychiatric disorders. PLoS One. 2014 Apr 15;9(4):e94968. doi: 10.1371/journal.pone.0094968. eCollection 2014.

Shira Rockowitz, Wen-Hui Lien, Erika M Pedrosa, Gang Wei, Mingyan Lin, Keji Zhao, Herbert M Lachman, Elaine Fuchs, Deyou Zheng Comparison of REST cistromes across human cell types reveals common and context-specific functions. PLOS Computational Biology. 2014 ;10(6):e1003671

Jian Chen, Mingyan Lin, Anastasia Hrabovsky, Erika Pedrosa, Jason Dean, Swati Jain Deyou Zheng, Herbert M. Lachman ZNF804A transcriptional networks in differentiating human neurons derived from induced pluripotent stem cells. PLoS One. 2015 Apr 23;10(4):e0124597. doi: 10.1371/journal.pone.0124597. eCollection 2015.

Zhao D, Lin M, Chen J, Pedrosa E, Hrabovsky A, Fourcade HM, Zheng D, Lachman HM. MicroRNA Profiling of Neurons Generated Using Induced Pluripotent Stem Cells Derived from Patients with Schizophrenia and Schizoaffective Disorder, and 22q11.2 Del.PLoS One. 2015 Jul 14;10(7):e0132387. doi: 10.1371/journal.pone.0132387. eCollection 2015.PMID: 26173148

Wang P, Lin M, Pedrosa E, Hrabovsky A, Zhang Z, Guo W, Lachman HM, Zheng D. CRISPR/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in neurodevelopment. Mol Autism. 2015 Oct 19;6:55. doi: 10.1186/s13229-015-0048-6. eCollection 2015.

Lin M, Lachman HM, Zheng D. Transcriptomics analysis of iPSC-derived neurons and modeling of neuropsychiatric disorders. Mol Cell Neurosci. 2015 Nov 26. pii: S1044-7431(15)30035-X. doi: 10.1016/j.mcn.2015.11.009. [Epub ahead of print]

Nebel RA, Zhao D, Pedrosa E, Kirschen J, Lachman HM, Zheng D, Abrahams BS. Reduced CYFIP1 in Human Neural Progenitors Results in Dysregulation of Schizophrenia and Epilepsy Gene Networks. PLoS One. 2016 Jan 29;11(1):e0148039. doi: 10.1371/journal.pone.0148039. eCollection 2016.

Mingyan Lin, Erika Pedrosa, Ryan Mokhtari, Anastasia Hrabovsky, Jian Chen, Benjamin R. Puliafito, Stephanie R Gilbert, Deyou Zheng, Herbert M. Lachman. Integrative Transcriptome Network Analysis of iPSC-derived Neurons from Schizophrenia and Schizoaffective Disorder Patients with 22q11.2 Deletion. BMC Syst Biol. 2016 Nov 15;10(1):105.

Characteristics of allelic gene expression in human brain cells from single-cell RNA-seq data analysis. Zhao D, Lin M, Pedrosa E, Lachman HM, Zheng D. BMC Genomics. 2017 Nov 10;18(1):860. doi: 10.1186/s12864-017-4261-x.

Ping Wang, Ryan Mokhtari, Erika Pedrosa, Michael Kirschenbaum, Can Bayrak, Deyou Zheng, Herbert M. Lachman. CRISPR-Cas9 mediated knockout of the autism gene CHD8 and characterization of its transcriptional networks in cerebral organoids derived from iPS cells. Mol Autism. 2017 Mar 20;8:11. doi: 10.1186/s13229-017-0124-1

Dejian Zhao, Ryan Mokhtari, Erika Pedrosa, Rayna Birnbaum, Deyou Zheng, Herbert M. Lachman. Transcriptome analysis of microglia in a mouse model of Rett Syndrome: differential expression of genes associated with microglia/macrophage activation and cellular stressMol Autism. 2017 Mar 29;8:17. doi: 10.1186/s13229-017-0134-z.

Barnes J, Salas F, Mokhtari R, Dolstra H, Pedrosa E, Lachman HM. Mol Autism. Modeling the neuropsychiatric manifestations of Lowe syndrome using induced pluripotent stem cells: defective F-actin polymerization and WAVE-1 expression in neuronal cells. 2018 Aug 15;9:44. doi: 10.1186/s13229-018-0227-3. eCollection 2018.

Enriched expression of genes associated with autism spectrum disorders in human inhibitory neurons.Wang P, Zhao D, Lachman HM, Zheng D. Transl Psychiatry. 2018 Jan 10;8(1):13. doi: 10.1038/s41398-017-0058-6.

 

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