Developing a Genetically Based Precision Medicine Approach in Psychiatry
Our group aims to leverage genomics to improve outcomes for patients suffering from neuropsychiatric disorders. Towards building a precision medicine approach for psychiatry, we are constructing genomic predictive models of the human brain to understand how genetic variation affects the transcriptional and epigenetic landscape. Subsequently, we apply these models to:
- Existing genetic studies to understand more about the biology of disease and to improve existing drug development and repurposing approaches
- Biobanks with electronic health record information, such as the Million Veteran Program (MVP), BioMe and UK Biobank (UKBB) to identify disease subgroups, stratify risk and model medication response
We collaborate closely with the Roussos, Akbarian, Björkegren, Fanous, Harvey, Davis and Smoller laboratories towards common milestones in the field.
Georgios Voloudakis, M.D., Ph.D.
• Assistant Professor, Departments of Psychiatry and Genetics and Genomic Sciences
• Member, Pamela Sklar Division of Psychiatric Genomics
• Member, The Friedman Brain Institute
Current Projects
Towards achieving our long-term goal of building a framework for genetically based precision and personalized medicine approaches in psychiatry, we are developing and optimizing the necessary tools and strategies for:
- Improved genomic feature imputation
- Expanding imputation approaches beyond the transcriptome to include the epigenome and other multiomics datasets
- data-driven integration of imputed molecular features
- Deep phenotyping of individuals based on information of Electronic Health Records
- Computational drug repurposing and drug development
- Better collaboration between sites
Genetics of neuropsychiatric disorders. Via collaborations with multiple groups we are contributing to the elucidation of the genetic architecture of multiple disorders such as schizophrenia, bipolar disorder, suicidal behavior, etc. across diverse population groups.
Reducing the stigma of mental health disorders by understanding the pleiotropy of their risk variants. Neuropsychiatric disorders are moderately to highly heritable and a lot of genetic variants that confer risk have been identified over the past two decades. Some of these variants are quite common and it would make sense from an evolutionary perspective for them to have “survived” because they also have beneficial functions either for the individual or for the society. We aim to identify these trade-offs to understand the potentially beneficial impact they have in our world and to our societies.
Funding:
BBRF, Elucidating the genetic basis of suicidal behavior
NIH, NIMH, K08MH122911, Characterizing and targeting subphenotypes of schizophrenia and bipolar disorder via individually imputed tissue and cell-type specific transcriptomes
NIH, NIA, P50AG005138 (Parent), Pilot 35-3, Identifying genetically-driven microglial gene expression changes in AD (completed)
Leon Levy Foundation, Neuroscience Fellowship (completed)
Recent and Selected Publications
Studies focused on genomic feature imputation approaches
- Zhang W‡, Voloudakis G‡, Rajagopal VM, Reahead B, Dudley JT, Schadt EE, Bjorkegren JLM, Kim Y, Fullard JF, Hoffman GE, Roussos P. Integrative Transcriptome Imputation Reveals Tissue-Specific and Shared Biological Mechanisms Mediating Susceptibility to Complex Traits. Nat Commun. 2019 Aug 23;10(1):3834.
Functional Neurogenomics
- Hoffman GE, Bendl J, Voloudakis G, Montgomery KS, Sloofman L, Wang YC, Shah HR, Hauberg ME, Johnson JS, Girdhar K, Song L, Fullard JF, Kramer R, Hahn CG, Gur R, Marenco S, Lipska BK, Lewis DA, Haroutunian V, Hemby S, Sullivan P, Akbarian S, Chess A, Buxbaum JD, Crawford GE, Domenici E, Devlin B, Sieberts SK, Peters MA, Roussos P. CommonMind Consortium provides transcriptomic and epigenomic data for Schizophrenia and Bipolar Disorder. Sci Data. 2019 Sep 24;6(1):180.
- Fullard JF‡, Charney AW‡, Voloudakis G, Uzilov A, Haroutunian V, Roussos P. Assessment of somatic single-nucleotide variation in brain tissue of cases with schizophrenia. Transl Psychiatry. 2019 Jan;9(1):21
- Fullard JF, Giambartolomei C, Hauberg ME, Xu K, Voloudakis G, Shao Z, Bare C, Dudley JT, Mattheisen M, Robakis NK, Haroutunian V, Roussos P. Open chromatin profiling of human postmortem brain infers functional roles for non-coding schizophrenia loci. Hum Mol Genet. 2017 May 15;26(10):1942-1951.
- Roussos P‡, Mitchell AC‡, Voloudakis G, Fullard JF, Pothula VM, Tsang J, Stahl EA, Georgakopoulos A, Ruderfer DM, Charney A, Okada Y, Siminovitch KA, Worthington J, Padyukov L, Klareskog L, Gregersen PK, Plenge RM, Raychaudhuri S, Fromer M, Purcell SM, Brennand KJ, Robakis NK, Schadt EE, *Akbarian S, *Sklar P. A role for noncoding variation in schizophrenia. Cell Rep. 2014 Nov 20;9(4):1417-29.
Molecular Pathophysiology of Neuropsychiatric Disorders
- Yoon YJ‡, Voloudakis G‡, Doran N, Zhang E, Dimovasili C, Chen L, Shao Z, Darmanis S, Tang C, Tang J, Wang VX, Hof PR, Robakis NK, Georgakopoulos A. PS1 FAD mutants decrease ephrinB2-regulated angiogenic functions, ischemia-induced brain neovascularization and neuronal survival. Mol Psychiatry 2020. https://doi.org/10.1038/s41380-020-0812-7
- Warren NA, Voloudakis G, Yoon Y, Robakis NK, Georgakopoulos A. The product of the γ-secretase processing of ephrinB2 regulates VE-cadherin complexes and angiogenesis. Cell Mol Life Sci. 2018 Aug;75(15):2813-2826.
- Huang Q, Voloudakis G, Ren Y, Yoon Y, Zhang E, Kajiwara Y, Shao Z, Xuan Z, Lebedev D, Georgakopoulos A, Robakis NK. Presenilin1/γ-secretase protects neurons from glucose deprivation-induced death by regulating miR-212 and PEA15. FASEB J. 2018 Jan;32(1):243-253.
‡ Authors contributed equally to this work
Team
Sanan Venkatesh, BSc
Graduate student (GDS)
sanan.venkatesh {at} mssm.edu 07/01/2020 – Present
Co-mentor: Panos Roussos
– 12/2020 Society for Neuroscience (SfN) Trainee Professional Development Award (TPDA)
– 09/2020 Million Veteran Program (MVP) Early Stage Investigator (ESI) Award
david.burstein2 {at} mssm.edu
ciella.angel-lalanne {at} mssm.edu
07/01/2021 – Present
deepika.mathur {at} mssm.edu
11/01/2021 – Present
Want to join our team?
We are looking for talented scientists and engineers. Email: georgios.voloudakis {at} mssm.edu to discuss career opportunities.
Location
Hess CSM Floor 9
1470 Madison Ave
Phone:
Office: (212) 659-9282
Lab:
georgios.voloudakis {at} mssm.edu