Active Projects
Human brain development and its alterations in neurodevelopmental and neuropsychiatric disorders
A BRAIN Initiative Resource: The Neuroscience Multi-omic Data Archive
NIH/NIMH, R24 MH114788, 9/15/17 – 7/31/27 (Owen White, PI)
The NeMO Archive serves as the genomics data archive for the BRAIN Initiative. We build infrastructure for the BRAIN Initiative Cell Atlas Network and contribute to atlases for cell type diversity in the developing and adult brain.
Multi-scale consequences of variants in the neuropsychiatric risk gene SETD1A in a population isolate.
NIH/NIMH, R01 MH129343, 8/15/22 – 5/31/27 (Seth Ament, PI)
This R01 supports collaborative studies with the Amish Research Program to investigate population-enriched variants in the Old Order Amish founder population and their clinical, cellular, and genomic mechanisms.
Endocannabinoids Regulate Microglia in Developing Brain
NIH/NIDA, R01 DA039062, 6/1/22 – 5/31/27 (Peg McCarthy, PI)
Neuroinflammation, Epigenetics and Male Vulnerability
NIH/NIMH, 2 R01 MH052716, 7/1/22 – 6/30/27 (Peg McCarthy, PI)
These collaborative projects with Dr. Peg McCarthy, a leading expert on neuroimmunology and sex differences in the brain, investigate roles for immune cells in brain development, primarily using rat models.
The role of NPRL2 loss in focal cortical dysplasia
NIH/NINDS, R01 NS131223, 4/15/23 – 3/31/28 (Phil Iffland, PI)
Many mutations in the mTOR pathway cause neurodevelopmental disorders characterized by malformations of cortical development and autistic and epileptic features. This R01 with Phil Iffland investigates mutations in one such mTORopathy, focal cortical dysplasia resulting from mutations in Nprl2, using a mouse model. The Ament lab is collaborating on spatial transcriptomic studies to investigate molecular mechanisms underlying cortical dyslamination in this model and the ability to rescue these developmental changes via mTOR inhibition.
Internal dynamics of the post-synaptic density
NIH/NIMH, R37 MH080046, 11/18/24 – 8/31/29 (Tom Blanpied, PI)
The Blanpied Lab studies the structure and function of synapses in the mammalian brain using super-resolution microscopy and live-cell imaging of single synapses. AI-based analyses of these data yield high-dimensional data describing the features of many thousands of synapses. We are collaborating with Tom's lab to analyze these data to describe synaptic diversity and the structure features that predict differences in function.
Dissecting the role of Ca2+ channel dysfunction in the pathogenesis of neurodevelopmental disorders
NIH/NIMH, R01MH137160, 4/1/25 – 3/31/30 (Ivy Dick, PI)
Mutations in the L-type voltage gated calcium channel (CaV 1.2, CACNA1C) cause Timothy syndrome, a developmental disorder associated with autistic features, as well as heart arhythmia. This R01 with Ivy Dick investigates physiological mechanisms, using both iPSCs and mouse models. We are using Patch-seq, snRNA-seq, and spatial multimodal profiling of neurons with Timothy syndrome mutations to understand their cell type-specific molecular mechanisms.
Convergent effects of genetic and inflammatory risk factors for autism spectrum disorders on the development of human Purkinje cells
MSCRF, 2025-R2-MSCRFD-00029, 7/1/25 – 6/30/27 (Seth Ament, PI)
This project develops a human cerebellar organoid model to understand how genetic and immune risk factors for autism spectrum disorder converge on the development of the cerebellum.
A Human Neurodevelopmental Model for Investigating the role of STRADA in Inhibitory Neuron Cortical Lamination and Epilepsy
MSCRF, 7/1/25 – 6/30/27 (Whitney Parker, PI)
Loss-of-function mutations in STRADA cause mTOR hyperactivation, cortical dyslamination, and epilepsy. Dr. Whitney Parker is a pediatric neurosurgeon and surgeon-scientist who treats patients with epilepsy in her clinical practice. This study investigates the effects of STRADA mutations on the development and migration of inhibitory neurons, using patient-derived iPSCs.
Quantifying cerebellar multi-omic and synaptic features in autism spectrum disorders
NIH/NIMH, R01 MH139606, 4/1/26 – 12/30/30 (Seth Ament and Tom Blanpied, PIs)
Changes in synapses and neuronal connectivity are through to be core mechanisms underlying neuropsychiatric and neurodevelopmental disorders, yet there have been almost no direct measurements of synapses in the brains of humans with NDDs. This collaboration with Tom Blanpied's lab combines spatial transcriptomics and super-resolution STED microscopy to investigate coordinated changes in cell type-specific gene expression and synaptic structure in post-mortem brains of donors with autism and related disorders, leveraging unique brain tissue resources from the University of Maryland Baltimore Brain and Tissue Biobank.
High-throughput spatial multimodal genetic screens in human and mouse neurons
MSCRF, 2026-MSCRFD-6688, 7/1/26 – 6/30/28 (Seth Ament, PI)
The goal of this study -- a collaboration with Tom Blanpied and Wei Li -- is to develop new high-throughput approaches to co-assay transcriptomic, morphological, and physiological characteristics of thousands of cultured neurons in parallel. This technology also enables multimodal genetic screens by co-culturing neurons from multiple human donors (cell villages) or with many distinct engineered mutations (spatial Perturb-seq).
Genomic mechanisms of substance use disorders and addiction
Genomic profiling mediating the protective effect of social reward on opioid craving
NIH/NIDA, R01 DA056440, 8/1/22 – 6/30/27 (Marco Venniro, Mary Kay Lobo, and Seth Ament, PIs)
Social environments strongly influence patterns of substance use and relapse. In an animal model developed by our collaborator, Dr. Marco Venniro, rats given the opportunity to interact with a social partner display reduced behavioral signs of opioid craving. This study aims to characterize genomic and neural circuit mechanisms mediating these protective effects.
Lasting Neurological Effects of Perinatal Opioids
NIH/NIDA, 1R01DA054905, 9/30/22 – 7/31/27 (MK Lobo, Asaf Keller, and Seth Ament, PIs)
The opioid epidemic has led to dramatically higher rates of opioid use during pregnancy. Infants exposed to opioids during pregnancy display withdrawal signs after birth and are at risk for a wide range of adverse neurological outcomes that persist through childhood. Drs. Mary Kay Lobo and Asaf Keller developed a mouse model for perinatal fentanyl exposure. In this R01, we are using this model to investigate the persistent effects of perinatal fentanyl on the development of the cortex and striatum. Parallel studies in the Ament lab investigate genetic and genomic factors associated with withdrawal severity in opioid-exposed infants, a collaboration with Dr. Dina Metwally and the Neonatal Intensive Care Unit at the University of Maryland Medical Center. We are also developing a human iPSC-derived model for the effects of opioids on neurodevelopment and physiology.
NeMO Archive: SCORCH Support, Coordination and Outreach
NIH/NIDA, UM1 DA052244, 8/1/25 – 6/30/30 (Owen White, Anup Mahurkar, and Seth Ament, PIs)
The Single-Cell Opioid Responses in the Context of HIV (SCORCH) consortium aims to characterize molecular adaptations associated with substance use disorders, as well as the effects of comorbid HIV infections, spanning multiple brain regions in humans and animal models. The NeMO-SCORCH Data Coordination Center establishes the consortium's data infrastructure and leads working groups toward a joint analysis of the entire data compendium. It has been a privilege to collaborate with Dr. Owen White and Anup Mahurkar on the development of NeMO projects for many years.
Joint decomposition of SCORCH mulit-omic data to explore the impact of SUD and HIV on reward circuitry and neuroinflammation
NIH/NIDA, R01 DA063090, 9/1/25 – 5/31/30 (Brian Herb and Carlo Colantuoni, PIs)
The SCORCH program is supporting several R01s for joint analysis of genomic and clinical data produced by the consortium. This project led by IGS faculty Brian Herb and Carlo Colantuoni is applying innovative data decomposition techniques to characterize gene networks influenced by opioids and other addictive substances across hundreds of genomic datasets. The project also supports the development of web resources for the visualization and analysis of these gene networks using the NeMO Analytics platform.
Brain injury and neurodegeneration
Bidirectional Brain-Gut interactions, chronic neuroinflammation and neurodegeneration after traumatic brain injury
NIH/NINDS, R01 NS124687, 8/1/22 – 7/31/27 (Bogdan Stoica, PI)
NOX2 drives microglia-dependent neurodegeneration after traumatic brain injury
NIH/NINDS, R01 NS129094, 8/1/22 – 7/31/27 (Bogdan Stoica, PI)
We collaborate with Bogdan Stoica and other researchers in the Center for Shock Trauma and Anesthesiology Research to investigate genomic mechanisms underlying recovery from traumatic and non-traumatic brain injuries.