Sattar Khoshkhoo
A5056411342- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Neuroscience and Neuropharmacology Research
- Single-cell and spatial transcriptomics
- Hedgehog Signaling Pathway Studies
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Neural dynamics and brain function
- Renal and related cancers
- Genetics and Neurodevelopmental Disorders
- Cancer-related cognitive impairment studies
- Cholinesterase and Neurodegenerative Diseases
- Epilepsy research and treatment
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Protein Tyrosine Phosphatases
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- Chromatin Remodeling and Cancer
- Genetic Associations and Epidemiology
- Photoreceptor and optogenetics research
- Galectins and Cancer Biology
- Cell Image Analysis Techniques
- Protein Kinase Regulation and GTPase Signaling
- Neuroscience and Music Perception
Broad Institute
2021-2024
Brigham and Women's Hospital
2018-2024
Boston Children's Hospital
2021-2024
Harvard University
2018-2024
Howard Hughes Medical Institute
2021-2023
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2021-2023
University of California, San Francisco
2016-2018
Massachusetts General Hospital
2018
University of California, Irvine
2018
University of California, Los Angeles
2009
During neocortical development, neurons exhibit highly synchronized patterns of spontaneous activity, with correlated bursts action potential firing dominating network activity. This early activity is eventually replaced by more sparse and decorrelated cortical neurons, which modeling studies predict a state that better suited for efficient neural coding. The precise time course mechanisms this crucial transition in have not been characterized vivo. We used vivo two-photon calcium imaging...
We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 schizophrenia, and 59 autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, had 20 60 detectable single-nucleotide mutations, but ~6% harbored hundreds mutations. Hypermutability was associated age damaging in genes implicated cancers and, some brains, reflected vivo clonal expansions. Somatic duplications, likely arising during development, were found ~5% normal...
Abstract The mammalian cerebral cortex shows functional specialization into regions with distinct neuronal compositions, most strikingly in the human brain, but little is known about how cellular lineages shape cortical regional variation and cell types during development. Here, we use somatic single nucleotide variants (sSNVs) to map of sub-types regions. Early-occurring sSNVs rarely respect Brodmann area (BA) borders, while late-occurring mark neuron-generating clones modest restriction,...
Alzheimer's disease (AD) is an age-associated neurodegenerative disorder characterized by progressive neuronal loss and pathological accumulation of the misfolded proteins amyloid-β tau1,2. Neuroinflammation mediated microglia brain-resident macrophages plays a crucial role in AD pathogenesis1-5, though mechanisms which age, genes, other risk factors interact remain largely unknown. Somatic mutations accumulate with age lead to clonal expansion many cell types, contributing cancer non-cancer...
Abstract When somatic cells acquire complex karyotypes, they often are removed by the immune system. Mutant that evade surveillance can lead to cancer. Neurons with karyotypes arise during neurotypical brain development, but neurons almost never origin of cancers. Instead, mutations in bring about neurodevelopmental disorders, and contribute polygenic landscape neuropsychiatric neurodegenerative disease. A subset human harbors idiosyncratic copy number variants (CNVs, “CNV neurons”),...
Germline mutations modulate the risk of developing schizophrenia (SCZ). Much less is known about role mosaic somatic in context SCZ. Deep (239×) whole-genome sequencing (WGS) brain neurons from 61 SCZ cases and 25 controls postmortem identified occurring during prenatal neurogenesis. showed increased variants open chromatin, with CpG transversions (CpG>GpG) T>G at transcription factor binding sites (TFBSs) overlapping a result not seen controls. Some these alter gene expression,...
Abstract Somatic mosaicism is defined as an occurrence of two or more populations cells having genomic sequences differing at given loci in individual who derived from a single zygote. It characteristic multicellular organisms that plays crucial role normal development and disease. To study the nature extent somatic autism spectrum disorder, bipolar focal cortical dysplasia, schizophrenia, Tourette syndrome, multi-institutional consortium called Brain Mosaicism Network (BSMN) was formed...
Recent studies demonstrate growing roles for genetic mosaicism in neurodevelopmental and neuropsychiatric disorders, with the paradigm being drug-resistant pediatric focal epilepsy related to activating somatic variants PI3K-mTOR pathway. While identifying genotype-associated changes at single-cell level is fundamental understanding disease pathophysiology, this remains technically challenging human tissue samples existing methods. Here, we performed single-nucleus RNA-sequencing (snRNA-seq)...
Abstract Importance Mesial temporal lobe epilepsy (MTLE) is the most common focal subtype and often refractory to anti-seizure medications. While MTLE patients do not have pathogenic germline genetic variants, contribution of post-zygotic (i.e., somatic) variants in brain unknown. Objective To test association between somatic hippocampus MTLE. Design This case-control study analyzed DNA derived from hippocampal tissue neurosurgically-treated with age- sex-matched neurotypical controls....
Abstract Background Alzheimer’s disease (AD), an age‐associated neurodegenerative disorder, is characterized by progressive neuronal loss and the accumulation of misfolded proteins such as amyloid‐β tau. While neuroinflammation, mediated microglia brain‐resident macrophages, plays a pivotal role in AD pathogenesis, intricate interactions among age, genes, other risk factors remain elusive. Somatic mutations, known to accumulate with instigate clonal expansion across diverse cell types,...
Abstract Germline pathogenic variants in the RAS/mitogen‐activated protein kinase (MAPK) signaling pathway are molecular cause of RASopathies, a group clinically overlapping genetic syndromes. RASopathies constitute wide clinical spectrum characterized by distinct facial features, short stature, predisposition to cancer, and variable anomalies nearly all major body systems. With increasing global recognition these conditions, 8th International Symposium spotlighted perspectives on care...