The Laboratory of Molecular Neuropsychiatry, led by Joseph D. Buxbaum, PhD, studies human psychiatric and neurological diseases using methods of cell biology, molecular biology, genetics, genomics, and animal models. Currently, we are focusing on autism spectrum disorder (ASD), Alzheimer’s disease, and schizophrenia.
The ASD research group within the Laboratory of Molecular Neuropsychiatry is part of the Seaver Autism Center, directed by Dr. Buxbaum. The Seaver Autism Center conducts progressive research studies aimed at understanding the multiple causes of ASD. The multidisciplinary team is comprised of experts in the fields of genetics, molecular biology, model systems, neuroimaging, and experimental therapeutics who are dedicated to discovering the biological causes of ASD. The Center strives to develop innovative diagnostics and treatments for integration into the provision of personalized, comprehensive assessment and care for people with ASD.
The Laboratory of Molecular Neuropsychiatry is affiliated with a number of institutes and departments within the Icahn School of Medicine at Mount Sinai.
Mount Sinai, Ph.D.
Department of Cell, Developmental, & Regenerative Biology
Black Family Stem Cell Institute
Tisch Cancer Institute
Mindich Child Health and Development Institute
We are vigorously continuing the study of EKLF (KLF1) using a number of approaches, including biochemical and structure/function analyses of the EKLF protein, identification of its protein partners, examining its ability to extrinsically control erythropoiesis, and monitoring how EKLF expression itself is so precisely regulated during development.
Our most recent studies are focused on a number of areas: one, a continuing analysis of EKLF protein/protein interactions and how they result in altered transcriptional and epigenetic changes at target loci; two, on how these controls converge to regulate late events in erythropoiesis, particularly enucleation; three, on analysis of EKLF upstream regulators to help explain its exquisite tissue-restricted expression pattern, and to possibly link alteration of its expression level to aberrant red cell biology; four, on functional and phenotypic analyses of a neonatal anemia mouse mutant (Nan) that contains a mutation in one allele of EKLF; finally, on determining the mechanism by which a human mutation in EKLF leads to congenital dyserythropoietic anemia.
Varricchio, A. Planutis, D. Manwani, J. Jaffray, W.B. Mitchell, A.R. Migliaccio, Genetic disarray follows mutant KLF1-E325K expression in a congenital dyserythropoietic anemia patient, Haematologica, in press (2019). [highlighted in Hematopoiesis News]
M.N. Gnanapragasam, J.D. Crispino, A.M. Ali, R. Weinberg, R. Hoffman, A. Raza, Survey and evaluation of mutations in the human KLF1 transcription unit, Scientific Reports, 8, 6587 (2018).
Planutis, L. Xue, C.D. Trainor, M. Dangeti, K. Gillinder, M. Siatecka, L.L. Peters, A.C. Perkins, Neomorphic effects of the neonatal anemia (Nan-EKLF) mutation contribute to deficits throughout development, Development, 144, 430-440 (2017). [highlighted as an In this Issue preview; highlighted in Hematopoiesis News]
M.N. Gnanapragasam, K.E. McGrath, S. Catherman, L. Xue, J. Palis, EKLF/KLF1-regulated cell cycle exit is essential for erythroblast enucleation, Blood, 128, 1631-1641 (2016). [highlighted in Hematopoiesis News]
Lohmann*, M. Dangeti*, S. Soni, X. Chen, A. Planutis, M.H. Baron, K. Choi The DEK oncoprotein is a critical component of the EKLF/KLF1 enhancer in erythroid cells, Molecular and Cellular Biology, 35, 3726-3738 (2015). [*co-first authors] [highlighted in Exp Hem 43, 827 (15)]
Soni , N. Pchelintsev , P.D. Adams Transcription factor EKLF (KLF1) recruitment of the histone chaperone HIRA is essential for ß-globin gene expression, Proceedings of the National Academy of Sciences, 111, 13337-13342 (2014). [highlighted in Hematopoiesis News]