Charney Laboratory

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The Brain and Data Sciences Lab (Charney 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

Alexander Charney, MD, PhD
Associate Professor | Psychiatry, Neuroscience, Neurosurgery, Genetics and Genomic Sciences
Director | Charles Bronfman Institute for Personalized Medicine
Executive Director | Blau Center
alexander.charney@mssm.edu

Research

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).

The Blau Center

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.

Active research studies in the Blau Center include both interventional and observational studies that enrolled inpatients and outpatients with psychosis throughout the Mount Sinai Health System.

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.

COVID-19 Biobank

The COVID-19 Biorepository Research Program was a multi-center research initiative that aimed 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 aimed to find a cure to COVID-19.

Recruitment for this study has closed and the project has moved to data analysis.

PGC3

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.

RECOVER

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 began recruiting subjects in December of 2021.

Meet Our Team

Alex Charney | Associate Professor | alexander.charney@mssm.edu

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!

Isotta Landi | Assistant Professor | isotta.landi@mssm.edu

Isotta joined the lab in September 2020 as a Postdoctoral Fellow, and joined faculty in 2022. 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 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 | Assistant Professor | eric.vornholt@mssm.edu

Eric Vornholt, PhD, joined the lab 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 | lauren.lepow@mssm.edu

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.

Carolina Cappi | Instructor | carolina.cappi@mssm.edu

Carolina joined the lab as a Postdoctoral Fellow in December 2023. She completed her PhD at the University of São Paulo (USP), which included an internship under Dr. Mathew State at Yale University, resulting in two pioneering studies on the role of rare and de novo genomic variants in the risk of OCD. Carolina possesses substantial experience in the data collection of mental illnesses. Currently, she leads the Obsessive-Compulsive Working Group (GTTOC) in Brazil, which is dedicated to research and clinical practice. The GTTOC’s mission is to investigate the genetics of OCD within families across the diverse states of Brazil, which are characterized by varied migrations and ethnicities. In 2023, Carolina received the prestigious K99/R00 award from NIMH to study common and rare genomic variants in psychiatric disorders, including in diverse populations. Outside work, Carolina enjoys walking her dog, exploring New York City’s culinary scene, and spending time in nature.

Nicole Bussola | Postdoctoral Fellow | nicole.bussola@mssm.edu

Nicole joined the lab as a Postdoctoral Fellow in June 2023. She obtained her B.Sc. and M.Sc. in Mathematics – Mathematical Sciences curriculum – at the University of Trento, Italy. She then earned her PhD in Biomolecular Sciences – Expertus in Computational Biology from the Center for Integrative Biology, University of Trento, with a joint scholarship from the Bruno Kessler Foundation. Her PhD research focused on AI algorithms for multimodal data in Precision Medicine, specifically on predictive models using high-throughput omics and bioimaging data to improve patient stratification for diagnostic and prognostic endpoints. Nicole also possesses practical experience as a Data Scientist with an AI service company in Rovereto, Italy, where she supervised AI projects related to implement software solutions for precision medicine. In the Charney lab, Nicole contributes to the Living Brain Project by analyzing gene expression data to identify blood-based brain biomarkers.

Lora Liharska | Bioinformatician II | lora.liharska@mssm.edu

Lora obtained her PhD in the lab and is now a Bioinformatician II in the Blau Center, leading all genetic analyses in our schizophrenia and rare variant carrier cohorts.

Nicole Simons | Blau Center Program Manager and PhD Candidate | nicole.simons@mssm.edu

Nicole joined the lab in 2020 after her redeployment to Dr. Charney’s COVID-19 Biobank research team. Nicole manages the Blau Center and is also a PhD candidate. Her dissertation work involves examining the clinical and neurobiological effects of rare, protein-truncating variants that confer risk for schizophrenia through a family study. Nicole’s favorite part of her job is interacting with patients and their families. Her favorite parts of life include her family, mountains, vanilla candles, and summer.

Anina Lund | PhD Student | anina.lund@mssm.edu

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 fourth year Neuroscience PhD student co-mentored by Dr. Noam Beckmann, Dr. Alex Charney and Dr. Eric Nestler studying the integration of gene expression and imaging from human patients enrolled in the Living Brain Project. Outside of lab, Anina is always up for coffee and going on adventures.

Alissa Valentine | PhD Student | alissa.valentine@mssm.edu

Alissa (she/they) is currently a third year Neuroscience PhD student mentored by Dr. Isotta Landi and Dr. Alex Charney. Alissa studied Psychology, Neuroscience, and Health Studies at Haverford College before earning her master’s degree in Bioinformatics from Northeastern University. Alissa’s dissertation is on the topic of clinical bias detection in clinical notes of psychiatric patients, and her favorite research sits at the intersection of AI ethics and health disparity mitigation. Alissa is part of the oSTEM and 1stGen student groups and spends her free time taking photos with her analog camera, chilling in nature, building lego plants, and discovering new bakeries.

Steven Ascolillo | Program Manager | steven.ascolillo@mssm.edu

Steven began working at Mount Sinai in 2019 as an Accessioning Specialist for the department of Genetics and Genomic Sciences. He 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 first COVID-19 surge. Steven is now a certified project manager and manages projects in the Charney Lab and the Charles Bronfman Institute for Personalized Medicine. 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!

Brian Fennessy | Bioinformatician II | brian.fennessy@mssm.edu

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 University of 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 in the Mount Sinai BioMe biobank, the clinical utility of polygenic risk scores, along with contributing to other projects. Outside of work, Brian is a dedicated runner, having completed nine marathons, stays active by frequenting the gym, loves animals, and enjoys exploring new dining experiences within the city.

Kate Keller | Clinical Research Coordinator II | katherine.keller@mssm.edu

Kate joined the lab in February 2023 as a Clinical Research Coordinator in the Blau Center. She graduated with degrees in Psychology and Music for Vocal Performance from SUNY Geneseo In 2019. As a former CRC at the Seaver Autism Center at Mount Sinai, Kate worked alongside Dr. Jennifer Foss-Feig to develop a novel assessment scale for autism spectrum disorders, as well as work to identify biomarkers of autism via EEG and eye tracking methods. Kate is broadly interested in the neural correlates of mental illness, as well as the implementation of music and arts therapies in severely mentally ill populations. Kate enjoys performing and writing music, going to shows, painting, and spending time outdoors.

Alice Hashemi | Clinical Research Coordinator II | alice.hashemi@mssm.edu

Alice joined the lab in August 2022 as a Clinical Research Coordinator and now manages the Living Brain Project. Alice graduated from Brandeis University in 2022 with a B.S. in Neuroscience. During her undergraduate career, she worked with researchers from Brandeis University and the University College of London, in order to study the efficacy of optogenetic devices as a tool for neuroscience research in animal models. Outside of the lab, Alice loves rock climbing, traveling, and music.

Henry Rogers | Senior Clinical Research Coordinator | henry.rogers@mssm.edu

Henry joined the lab in April 2023 as a Senior Clinical Research Coordinator. Before joining the lab, Henry graduated with a B.Sc. in Psychology from the University of Surrey and worked at King’s College London collecting data and samples for research across a number of clinical populations. Outside of work, Henry enjoys exploring NYC, watching sports and spending time with friends and family.

Renata Gonzalez Chong | Clinical Research Coordinator I | renata.gonzalezchong@mssm.edu

Renata joined the lab in September 2023 as a Clinical Research Coordinator. She graduated from Bowdoin College in 2023 with a B.S. in Neuroscience and a minor in Digital Computational Studies. Renata has experience working with labs from Bowdoin College, Columbia University, and the Spanish National Research Council, where she has developed skills in microscopy and histological methods. She is interested in neurotechnology and the ethical applications of AI in neuroscience. Renata loves having jam sessions with friends, playing rugby in the park, and traveling.

Janice Morinigo | Laboratory Manager | janice.morinigo@mssm.edu

Bio coming soon!

Vibhuti Patel | Laboratory Supervisor | vibhuti.patel@mssm.edu

Vibhuti joined the lab in July 2022 after obtaining her Master of Science degree in Biotechnology and Chemical Science from Roosevelt University in Chicago, IL. During her master’s, she worked on CRISPR/Cas9 and other molecular biology projects. In the lab, Vibhuti ensures the efficient and successful completion of multiple research projects and oversees wet-lab related experiments (e.g. PCR, genotype validation using sanger sequencing, electrophoresis, analyzing data, extraction, QC, and normalizing DNA). Vibhuti supervises and trains research associates in biospecimen processing and other wet lab work/assays. Outside of work, Vibhuti loves exploring new foods, traveling, cooking, and spending time with family and friends.

Rachel Jackson | Research Associate | rachel.jackson@mssm.edu

Rachel joined Dr. Charney’s lab in January 2022 as a Research Associate for the RECOVER project. Originally from the south, she attended the University of Oklahoma where she studied chemistry and psychology. During her time in Oklahoma, she worked alongside pediatric specialists at A Better Chance Clinic to provide developmental and behavioral therapy for children exposed to drugs and/or alcohol before birth. Rachel came to New York in January 2020 and began her career with Mount Sinai as a Clinical Research Coordinator for the IBD Center, where she was a part of highly innovative and successful clinical trials aimed to help patients with Crohn’s Disease and Ulcerative Colitis. Outside of the lab, Rachel enjoys reading, crocheting, and snowboarding.