The Brain and Data Sciences Lab is known for using multiple types of genomic data to dissect the clinical features of schizophrenia and bipolar disorder, developing a novel framework for human brain research with the Living Brain Project, and advocating for the rapid translation of genomic findings to early-phase clinical trials of experimental therapeutics.
The Living Brain Project, a multiscale, data-driven investigation of the human brain wherein a single living population is being studied using all of the tools available for human-subject neuroscience, including the tools of molecular and cellular neurobiology that to date have been applied primarily in the post-mortem setting.
The lab is also a leader of the Psychiatric Genomics Consortium Targeted Schizophrenia Sequencing Study, a sequencing study of over 20,000 individuals that, when combined with existing data, will constitute the largest assessment of the role of rare damaging genetic variants to the risk of schizophrenia. It also leads the Mount Sinai site of the PsychEMERGE consortium, which is a large coordinated effort amongst the largest academic biobanks in the United States to integrate electronic medical records and genetics to better elucidate risk factors for mental illness.
Funding: National Institute of Aging/NIH, Michael J. Fox Foundation, Virginia Polytechnic Institute and State University
Brain & Data Sciences Lab
Alexander Charney, M.D., PhD
Assistant Professor | Genetics and Genomic Sciences | Psychiatry | Neuroscience | Neurosurgery
Icahn Medical Institute L3-70D and Annenberg Building 22-38
Icahn School of Medicine at Mount Sinai
1 Gustave L. Levy Pl, New York, NY 10029
The Living Brain Project
To understand the human brain, scientists use clinical observation, neuropharmacology, neuroimaging, neurophysiology, neuromodulation and molecular-cellular neuroscience. However, applications of molecular-cellular neuroscience have traditionally been limited to post-mortem specimens or cultured neural cells, whereas the other approaches require interactive living subjects. As a result, it is rare that a single cohort is studied using the full human subject neuroscience toolkit. The biological foundations of neuropsychiatric traits therefore remain largely unknown, and understanding the inner workings of the human brain continues to be one of the greatest scientific challenges.
The Living Brain Project is a multiscale, data-driven investigation of the human brain wherein a single living population is being studied using all of the tools available for human-subject neuroscience. Led by Drs. Alexander Charney and Brian Kopell, this study will enroll 500 men and women from young to old age receiving deep brain stimulation (DBS) over a 10-year period. Batteries of neuropsychological testing will survey all domains of cognition and mental health, while electronic medical records will create a high-resolution digital record of the health of each participant. Brain structure and function will be recorded through multi-modal neuroimaging, and during each of two DBS electrode implantation surgeries (one per hemisphere) specimens will be obtained from the participant’s brain, skin and blood for cutting-edge multiomic analyses. With this unique cohort, the Living Brain Project aims to discover how interactions between the various levels of neurobiology, neurophysiology and neuroanatomy assessed give rise not only to the chronic traits that have been probed in post-mortem studies (e.g., depression, dementia), but also acute states that can only be assessed in a living cohort (e.g., sadness, working memory).
Multimodal Neuroimaging Techniques in the Living Brain
The multimodal neuroimaging techniques, including but not limited to functional and structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) facilitate the diagnosis of psychiatric disorders and the development of new medications. Among the modalities, the structural MRI and DTI are widely utilized to investigate the gray matter and white matter anatomical anomalies for neurodegenerative disorders which may contribute to the cognitive deficiency in psychiatric disorders. Our project applies both structural MRI and DTI modalities to identify the microstructural features of gray matter and white matter to patients with Parkinson’s disease. The features include cortical thickness, cortical surface area, subcortical volume and the volume, average length, axial diffusivity, radial diffusivity, mean diffusivity, and fractional anisotropy of white matter fiber tracts, as well as topological features of anatomical network. The integration of neuroimaging, multiomics and neuropsychiatric phenotyping could contribute to identify the molecular mechanism that influence brain structure and function.
The COVID-19 Biorepository Research Program is a multi-center research initiative that aims to characterize the immune response to SARS-CoV-2. Through the collection of blood specimens from covid-positive pediatric and adult inpatients throughout the Mount Sinai Health System, this initiative aims to find a cure to COVID-19.
Our PGC3 project is a data-driven targeted sequencing approach to discovering rare single-nucleotide variants (rSNV) in genes with a causal role in schizophrenia (SCZ). By harnessing the corpus of SCZ genetic data currently available, our group has designed a novel, data-driven approach to targeted sequencing that allows us to increase the power for causal gene discovery at a fraction of the cost of whole exome sequencing, focusing only on genes with a high prior probability of having excess rare loss-of-function variants in SCZ. This data will be meta-analyzed with all other SCZ sequencing datasets, producing the largest sequencing study of SCZ to date and maximizing power to identify additional risk genes. This approach offers the promise to identify biologically, clinically and therapeutically meaningful information from the growing resource of available genetic information.
Heritability of Gene Expression in the Brain
By using large datasets of gene expression in the brain, we intend to uncover mechanisms underlying the heritability of gene expression. This includes evaluating if the genetic architecture of expression is differentially dominated by cis or trans regulation. This study is to our knowledge amongst the largest studies to date of the genetic architecture of gene expression traits in the human brain. We hope this will contribute to the field’s understanding of the mechanisms underlying polygenicity, especially in neurological and psychiatric disorders.
Genome Wide Association Studies of Depression
This project involves the use of Genome-Wide Association Studies to investigate genes involved with depression etiology. By comparing the genotype between depressed patients and healthy controls, the hope is to identify single nucleotide polymorphisms that may contribute to depression.
Identifying the genetic targets of pro- and antipsychotic drugs
Is there an overlap between the genes that increase one’s risk of experiencing psychosis and the targets of drugs that cause and treat psychosis? My project studies the genetic underpinnings of schizophrenia and how we might identify potential genetic targets to develop drugs to treat patients with mental illness. We look at both rare and common variants implicated in schizophrenia and pair those variants with known genetic targets of various pro- and antipsychotic drugs.
The focus of the Blau Center will be on schizophrenia, one of the most debilitating conditions in the entire field of medicine. Over the past 15 years, a new understanding of its pathogenesis has emerged through genetics, epidemiology, and other disciplines. Yet, while knowledge has increased, there have been no breakthroughs in diagnosis, prevention, or treatment. Toward this end, the Blau Center will combine excellent clinical care with groundbreaking research in order to:
- Create a consultation and treatment center for patients with schizophrenia and those at increased risk to develop psychotic disorders
- Optimize the care of schizophrenia within the Mount Sinai Health System through clinical data science and artificial intelligence
- Accelerate the development of novel and breakthrough therapeutics for psychotic illnesses, including schizophrenia
- Develop, and participate in, trials examining and validating treatment interventions in psychosis and schizophrenia
- Expand translational research focusing on neurodevelopment in order to understand illness trajectories
Evidence across psychiatric disorders suggests that early intervention improves outcomes, but our incomplete understanding of the neurobiological underpinnings thwarts attempts at successful identification of those most at risk. Through the diligent research and comprehensive data compiled, the Blau Center aims to shed light on these disorders to provide better and more compassionate psychiatric care.
RECOVER is a national, multi-site study that aims to characterize PASC (post-acute sequelae of COVID-19, or long-covid). This is a large, NIH-funded longitudinal study that will begin recruiting subjects in December of 2021.
Meet Our Team
Alex Charney | Assistant Professor
Alexander Charney, MD, PhD is an Assistant Professor at the Icahn School of Medicine with primary appointments in the Departments of Psychiatry and Genetics & Genomic Sciences, as well as secondary appointments in the Departments of Neuroscience and Neurosurgery. He received his MD and PhD under the mentorship of Pamela Sklar, MD, PhD, and Eric Schadt, PhD, two of the world’s foremost experts on large-scale genomics and multiscale biology. He has been the lead data scientist on some of the largest genetic studies ever conducted on schizophrenia and bipolar disorder, including genome-wide association studies, copy number variant studies and rare sequencing variant studies. Currently, he leads several of the largest studies in the field of psychiatric genomics and has established a unique approach to human brain research as the founder and primary investigator of the Living Brain Project. As a physician-scientist specializing in the neurobiology of severe mental illness, his primary goal is to translate genomic discoveries to experimental therapeutics. Alex likes to kayak, work out, and play the drums and guitar!
Dongjing Liu | Postdoctoral Fellow | email@example.com
Dongjing is a postdoc in the Charney lab. She has a broad interest in human genetics and biostatistics, and her research focuses on using genomic data and statistical tools to elucidate the etiology of complex human traits and disorders. In the Charney lab, Dongjing leads a targeted sequencing study of large schizophrenia cohorts to identify novel disease genes. She also studies the immune regulation in the central nervous system and peripheral tissues by analyzing single-cell sequencing data from the Living Brain Project. Dongjing’s favorite part of her work is to come up with a puzzle and solve it using genetics.
Outside of work, Dongjing’s favorite things/activities include being out in the nature, incredible views from high up, fireplace in the winter, healthy eating, and scented candles.
Isotta Landi | Postdoctoral Fellow | firstname.lastname@example.org
Isotta joined the lab in September 2020 as a Postdoctoral Fellow. Originally from Italy, she received her B.Sc. in Mathematics at the University of Pisa and M.Sc in Mathematics at the University of Trento (Italy). She then earned her PhD in Computational Psychology (University of Trento and Bruno Kessler Foundation) and researched unsupervised machine learning and natural language processing methods to disentangle complex disorders, such as Autism Spectrum Disorder, from clinical and behavioral data. In the Charney lab, her work focuses on the application of machine learning models to predict clinical outcomes in psychiatry. Her research also includes the implementation of natural language processing methods for clinical concept and temporal relation extraction from psychiatric notes, towards precision medicine.
Outside of work, Isotta enjoys coffee, climbing, and spending time in the mountains.
Eric Vornholt | Post-Doctoral Fellow | email@example.com
Eric Vornholt, PhD, joined the Department of Genetics and Genomic Sciences at Mount Sinai in January 2021 after earning his doctorate from the Virginia Institute for Psychiatric and Behavioral Genetics at Virginia Commonwealth University. While at VCU, Eric’s research centered on profiling the transcriptional landscape of postmortem brain tissue from chronic alcohol abusers. Now a Postdoctoral Fellow in the Charney Lab, Eric serves as one of the lead investigators for the Living Brain Project where he utilizes his experience assessing differential gene expression to perform multi-omic comparison analyses of postmortem vs. living brain tissue. Long-term, Eric plans to continue studying the biological signatures of neuropsychiatric and neurodegenerative disorders in order to better understand how genetic and environmental factors impact behavior. Outside of work, Eric is a foodie who enjoys writing music, playing board/video games, and socializing with friends.
Lauren Lepow | Psychiatry resident and PhD student | firstname.lastname@example.org
Lauren is a psychiatry resident at Mount Sinai in the NIMH-supported PhD+ neuroscience track. During college at Columbia, Lauren began studying the impact of the early environment on psychological development in the lab of Dr. Frances Champagne. She then completed medical school in Houston at McGovern- University of Texas learning about the intersection of neurology and psychiatry with Dr. Paul Schulz. Her eyes were opened to novel therapeutics at the NIMH Experimental Therapeutics & Pathophysiology Branch studying the mechanism of ketamine. Lauren is currently researching the psychological and biological mechanism of psychedelic-assisted psychotherapy in the lab of Dr. Rachel Yehuda. With Dr. Alex Charney and Dr. Ben Glicksberg, she is learning Natural Language Processing with EHR data to better characterize suicidality. In the future, she plans to apply NLP to patient narratives to better understand pathways to healing. Lauren is also passionate about biking, the never-ending discoveries to be made in NYC, and psychoanalysis.
Anina Lund | PhD Student | email@example.com
Anina graduated from the University of California Berkeley in 2020 majoring in Cognitive Science and minoring in Music. In undergrad she worked in Dr. Andrew Dillin’s lab performing research on the genetic and molecular mechanism that regulate aging and aging-related disease. Anina is currently a 2nd year Neuroscience PhD student co-mentored by Dr. Alex Charney and Dr. Eric Nestler studying the integration of gene expression, imaging, and microelectrode recordings from human patients enrolled in the Living Brain Project. Outside of lab Anina is always up for coffee and going on adventures.
Nicole Simons | Blau Center Program Manager; Ph.D. Student | Nicole.Simons@mssm.edu
Nicole joined the lab in June 2020 after her redeployment to Dr. Charney’s COVID-19 Biobank research team during the first coronavirus surge in New York City. She received her bachelor’s degree in psychology at Boston University and her master’s degree in Developmental Psychology from Columbia University. In addition to working on the Blau Center, she is also a first-year Ph.D. student studying breakthrough therapeutics for schizophrenia and psychotic illness trajectories under Dr. Charney’s mentorship.
Nicole’s favorite part of her job is interacting with patients and their families. Her favorite parts of life include her family, sea turtles, mountains, vanilla candles, and summer.
Esther Cheng | Lab Manager | firstname.lastname@example.org
Esther graduated from New York University, majoring in Molecular Biology she then completed her Master’s in Biomedical Sciences at Mount Sinai’s Icahn School of Medicine. During her Master’s, she studied in Dr. Kristen Brennand’s lab generating brain organoids to understand how genetic variations can impact schizophrenia risk. While completing her Master’s, she joined Dr. Alex Charney’s lab in September 2018 as a part time laboratory technician.
Esther was hired as the lab manager after she graduated from the Master’s program. Currently in Dr. Charney’s lab, Esther works with assisting the lab in multiple projects from the Living Brain Project to the newly added COVID-19 projects. For fun, Esther loves exploring different hobbies from crafting to cooking.
Steven Ascolillo | Project Coordinator | email@example.com
Steven graduated from the City College of New York with a degree in Biology in 2020. During his junior year, Steven began working with Mount Sinai’s Genetic and Genomic Sciences Department’s PMO as an Accessioning Specialist. He spent his time supporting Project Managers on programs related to multiple myeloma, asthma, IBD, and CRISPR with a focus on sample tracking and management. Steven transitioned to the Charney lab in June of 2020, after providing support to Dr. Charney and the Mount Sinai COVID Informatics Center during New York’s COVID-19 surge. Steven now splits his time between the Charney Lab and the COVID Informatics Center. Coming to New York from Massachusetts, Steven enjoys spending his free time at sporting events, whenever his teams are in town. He also enjoys spending time with his dog Nanook, seeing shows on Broadway, and enjoying everything else New York City has to offer!
Agathe de Pins | Bioinformatician | firstname.lastname@example.org
Agathe is a bioinformatician in Dr. Charney and Dr. Huckins lab. She joined the lab in August 2019 after graduating from McGill University in 2018 to complete a Master’s degree in Biomedical Sciences. Her Master’s thesis was on estimating the heritability of gene expression in the dorsolateral prefrontal cortex. She was also involved in the PGC CNV group, investigating rare copy number variants in bipolar disorder.
Today, she is continuing her Master’s work as a bioinformatician in the lab and also pursuing a project that generates context-dependent eQTL in all tissues. She hopes to pursue a career in medicine soon. In her free time, Agathe likes to explore New York and find the best restaurants and rooftops in the city!
Lillian Wilkins | Research Associate
Lillian Wilkins joined the lab in October 2019 as an Associate Researcher. Before working for the Charney Lab, she graduated from Princeton University with a degree in Molecular Biology. While there, she worked with Dr. Girish Deshpande studying the role of the protein Germ Cell Less in germ cell formation during Drosophila embryogenesis. In the lab, Lillian processes samples collected from patients for multiple projects including the Living Brain Project and the World Trade Center Project. After working in the Charney Lab, she hopes to pursue a career in Science. When not in the Lab she enjoys eating pancakes, asking to pet people’s dogs, and dancing.
Brian Fennessy | Research Associate and Bioinformatician | email@example.com
Brian joined the lab in February 2020 as an Associate Researcher. Originally from Ireland, he earned his B.Sc. in Biomedical Science (Pharmacology major) and M.Sc. in Biomedical Genomics at the National University of Ireland, Galway. During his Master’s, he studied copy number alterations associated with chemoresistance in head and neck squamous cell carcinoma. In the Charney lab, Brian investigates treatment resistant depression (TRD) in the Mount Sinai BioMe biobank and examines the relationship between polygenic risk scores and TRD. Outside of work, Brian loves running, having completed five marathons, as well as traveling and exploring new places.
Kimia Ziafat | Clinical Research Coordinator | firstname.lastname@example.org
Kimia graduated from the University of British Columbia in 2020 with a major in Biology. She then pursued a Master of Science degree in Population and Public Health, where she worked under the supervision of Dr. Jane Buxton to better understand harm reduction and addiction treatment strategies across the province.
Kimia joined Dr. Charney’s lab in September 2021 as a clinical research coordinator, where she works on the Living Brain Project. Her favorite part of her job is interacting with patients and hearing their stories. Kimia hopes to pursue a career as clinician-scientist in the future.
Outside of work, Kimia loves cooking Persian food, dancing, and binge watching tv shows.
Gavin Hynes | Clinical Research Coordinator | email@example.com
Gavin joined the lab in December 2021 as a Clinical Research Coordinator in the Blau Center. He graduated with a BA in Psychology from University College Dublin in 2018 and with a MSc in Clinical Neuroscience from National University of Ireland, Galway in 2019. During his master’s degree, he studied the neural mechanism of social cognitive deficits in schizophrenia. His interests are in early intervention for psychosis and novel therapies in the treatment of psychosis. Gavin also has a strong interest in music and film and enjoys going to music concerts and the movie theatre.
- Julie Park
- Claudia Feng
- MK Rieder
- Hannah Silk
- Emily Moya
- Liam Cotter
- Konstantinos Mouskas
- Kishan Patel
- Khalifa Stafford
- Yuyang (Leo) Luo
- Brian H. Kopell, M.D.
- Navneet Dogra, PhD
- Jeff W. Lichtman, M.D., PhD
- Bojan Losic, PhD
- Panagiotis Roussos, M.D., PhD
- Eli Stahl, PhD
- Laura Huckins, PhD
Brain & Data Sciences Lab Alexander Charney, M.D., PhD Assistant Professor | Genetics and Genomic Sciences | Psychiatry | Neuroscience | Neurosurgery
Icahn Medical Institute L3-70D and Annenberg Building 22-38
Icahn School of Medicine at Mount Sinai
1 Gustave L. Levy Pl, New York, NY 10029