• Moscow Lomonosov University, Moscow, Russia, M.S. 1990 Biochemistry
• University of Lausanne, Lausanne, Switzerland, Ph.D. 1997 Molecular Immunology

PROFESSIONAL EXPERIENCE

• 1990-1991       Junior-investigator, Engelgart's Institute of Molecular Biology, Moscow, Russia,
• 1991-1996       Ph.D. student, University of Lausanne, Lausanne, Switzerland
• 1996-1997       Research Assistant, University of Lausanne, Lausanne Switzerland.
• 1998-2002       Postdoctoral fellow, Stanford University School of Medicine, Stanford, CA, USA.
• 2002-2006       Assistant Professor, Brain and Mind Institute, EPFL, Lausanne, Switzerland.
• 2006-2012       Assistant Professor, SBMRI, La Jolla, CA, USA.
• 2008-2014       Adjunct Professor, UCSD, Department of Pediatrics.
• 2018-present  Stemson Therapeutics, CSO and co-founder.
• 2014-present   Adjunct Professor, San Diego State University, Department of Biology.
• 2018-present   Stemson Therapeutics, CSO and co-founder.

HONORS AND AWARDS

• 1997       University of Lausanne - Ph.D. Thesis Faculty prize.
• 1997       Swiss National Foundation - Young Scientist award.
• 1998       Swiss National Foundation extended - Young Scientist award.
• 1998       Irvington Institute for Immunological Research - Postdoctoral Fellowship.
• 2003       Swiss National Foundation – Research Program award.
• 2004       National Institute of Health R21 award - Separation of Neural Stem Cells.
• 2005       Novartis Stiftung für med. biol. Forschung (Principle Investigator).
• 2006       California Breast Cancer Research Program award – MELK as a candidate marker for breast tumors.
• 2007       California Institute for Regenerative Medicine award – MEF2C directed neurogenesis from human stem cells.
• 2007       Department of Defense award – Development of covalent inhibitors of MELK.
• 2007       National Institute of Health, R21 award – Function of MELK in mammary tumors.
• 2008       National Institute of Health, PO1 award - Parkinson’s Disease Center.
• 2010       National Institute of Health, RO1 award – Role of MELK in glioblastoma Multiform.
• 2013       National Institute of Health, STTR award - Kinetic Image Cytometry Assays.
• 2014       California Institute for Regenerative Medicine award - Novel approaches to treatment of brain tumors (Glioblastoma).
• 2016       National Institute of Health, R21 award, Host-pathogen interactions in ZIKV infection leading to microcephaly.
• 2017       National Center for Advancing Translational Sciences - Director’s Award
• 2018       National Institute of Health, R41 sub-award, Development of MIEL- Neurodevelopment Assay.
• 2018       National Institute of Health, RO1 sub-award, Molecular Basis of Zika-induced Microcephaly
• 2019       National Institute of Health, RO1 award, Brain Pathology and Function in a Chronic Mouse Model of ZIKV Transmission

Personal Statement

          Over the past several years, my lab was focused on mechanism of neural stem cell self-renewal and neuronal differentiation. Primary cilium is a key structure mediating the function of Shh in hippocampal neurogenesis. To get insights into this pathway we established a physiological model of deficient hippocampal neurogenesis by ablating primary cilia in radial glial stem cells of the adult dentate gyrus (Amador-Arjona et al., 2011). Sox2 is a master regulator of neural stem cells biology. We discovered novel epigenetic mechanisms of Sox2 function in neural stem cell self-renewal and neuronal differentiation. In neural stem cells Sox2 supports the recruitment of the adaptor protein TRRAP and histone acetyl transferases (such as GCN5) to maintain the levels of H3K9me3 at the proximal promoters of genes critical for neural stem cell proliferation (Cimadamore et al., 2013). On the other hand, we found that Sox2 function is required for the appropriate activation of neurogenic genes (Cimadamore et al., 2011). Sox2 binds to the regulatory elements of poised neurogenic genes and regulates the and identified hits with improved activity compared to etoposide providing additional proof of continuity of our drug activity PRC2 complex and the levels of H3K27me3, thus enabling a robust activation of these genes upon neurogenic stimuli (Amador-Arjona et al., 2015).
         Over the past decade we developed a unique phenotypic screening approach: Microscopic Imaging of Epigenetic Landscapes (MIEL) captures patterns of nuclear staining of epigenetic marks from which derived texture features are used to compare different populations of cells or different cell treatments to generate discernable signatures of such states and to provide the accuracy of the result - Farhy et al., 2018, BioRxiv 348888 (preprint) available from: https://doi.org/10.1101/348888. MIEL enabled discrimination between cell types with high accuracy and derivation of image-based signatures of drug-induced perturbations. Based single cell imaging of epigenetic landscapes, we have successfully identified multiparametric signature of GBM differentiation induced by biologicals such as serum and BMP. Using such controls, we performed a pilot screening of the focused Prestwick chemical library validating the utility of MIEL approach in 384-well format. Critically, our preliminary results suggest that MIEL-based screening of compounds inducing GBM differentiation correlates well with hit prioritization based on the whole genome expression profiling, thus validating MIEL for screening large small molecule libraries to identify novel scaffolds and functions.
         As an alternative approach, we generated a small library of shape mimetics of etoposide (our best hit identified in Prestwick library) and identified a number of hits with the improved activity thus documenting our ability to march through the improvement and optimization steps using MIEL platform. More recently, we have documented MIEL’s power to derive epigenetic signatures for over 200 drug-induced perturbations in primary glioblastoma and provide functional information such as attribution to particular drug class or the mechanism of action, Farhy et al., 2019 - BioRxiv 541151 (preprint) available from: (https://doi.org/10.1101/541151). In the present application, joining efforts with the Lukyanov’s laboratory, we propose to advance arguably the most important direction for MIEL development – live imaging of epigenetic landscape in space and time (Live-MIEL). Rooted in the single cell analysis such approach will enable, for the first time, to get insights into the dynamics of epigenetic changes in single cells. By analogy, this will be equivalent to moving from bulk sequencing to single cell sequencing, with the huge advantage that we will actually gain in resolution and not lose (due to the loss of small amounts of RNA in single cells).