About our lab
We are a multidisciplinary group united by a passion for vision restoration. We develop novel therapies for glaucoma, traumatic optic neuropathies, optic pathway glioma, and other diseases characterized by retinal ganglion cell and photoreceptor loss. To achieve this audacious goal, we combine the achievements in regenerative medicine, retinal cell biology and development, advanced transcriptomics, transplantation, and functional imaging of the retinal neurons on a single cell level.
We employ automation, artificial intelligence, and quantitative strategies to produce retinal and other organoids from human, tree shrew, and mouse stem cells. We are particularly interested in using this fascinating model to test therapies, study cell-cell interaction, model diseases, such as Alzheimer's, LHON, NAION, and glaucoma.
We perform deep advanced analysis of single-cell RNA-, ATAC-, ChIP-, VDJ-, and spatial-seq data, focusing on cell specification, maturation, and cell-to-cell communication in disease and regeneration. Species include humans, dogs, mice, and axolotl. The ultimate goal is to create a “digital eye” - in silico platform to model, explore and predict cell behavior in changing ecosystem.
Organoids: retina and beyond
Integrated multi-omics analysis
Competences
Transplantation and cell therapy development
The retina of the eye provides a unique setting to study and control donor cell fate on a single level. The lab focuses on cell and organoid transplantation, emphasizing the microenvironment and its role in donor cell maturation and integration.
Team
Petr Baranov
Head of the Lab
My lab is committed to search for novel therapies for glaucoma, traumatic optic neuropathies and other diseases characterized by retinal ganglion cell loss. We explore cell replacement and neuroprotection strategies. To achieve this audacious goal we combine the achievements in regenerative medicine, retinal cell biology and development, transplantation and functional imaging of the retinal neurons on single cell level.
Nikita Bagaev
Student Intern
I am focused on optic pathway glioma biology exploring and mechanisms of tumorogenesis revealing in neurofibromatosis type 1 (NF1) patients using analysis of single-cell transcriptomics data (scRNA-seq, cell-cell interaction analysis) and experimental data obtained from mouse models. This combined approach let understand the way in which interaction of the complex genetics and tumor microenvironment results in clinical manifestations seen in NF1.
Emil Kriukov
Lead Bioinformatician
My primary goal of the research is to build the biggest picture possible of cell ontogeny in dynamics using multiomics data and computational approaches. By the ontogeny, cell-fate-wise, I understand all the changes occurring, including development, aging, disease, and, of course, the route retinal ganglion cells have to undergo from differentiation to their functional integration upon transplantation.
Volha Malechka
Postdoctoral fellow, MD
My long-term career goal is to contribute to ophthalmology field in improving and restoring human vision by constantly building up strong scientific knowledge and clinical skills.
Aubin Mutschler
Summer Student
Having conducted research in age-related macular degeneration prior to joining, I aim to increase my exposure to all types of ophthalmic pathologies and decipher ways to combat diseases that have posed particular resistance in the face of treatment. I get especially excited about leveraging new technological advances to solve problems that have impeded progress in the field and unlock new understandings of complex mechanisms that may one day lead to improving patient care.
Jonathan Soucy
Postdoctoral fellow, PhD
I am focused on improving the structural and functional integration of donor retinal ganglion cells by directing neural migration, controlling their microenvironment, and manipulating host neurons. I believe that we need a better understanding of fundamental principles that control donor neuron integration in the retina and brain to guide RGCs to their natural connecting points and improve cell replacement therapy outcomes. These include homophilic cell-cell interactions, chemokine signal cues, neurotrophic factors, migration modes, and neural activity.
Alumni
  • Christian Akotoye, BS 06/2021 – 07/2021 MD student, Case Western Reserve University
  • Volha (Olga) Malechka, MD 02/2022 – present, Postdoc, SERI/HMS
  • Sophia Bauer, BS 09/2021 – 08/2022 MS student, Northeastern University
  • John Dayron Rivera, BS 04/2022 – 09/2023, SERI/HMS
  • Emil Kriukov, 07/2022 – present, Research Fellow, SERI/HMS
  • Sergio Pestun, 07/2023 – 09/2023, scholar student
  • Simatul Rashid, 07/2023 – 09/2023, student intern
  • Josy Augustine, 07/2023 – 09/2023, visiting postdoc
  • Nikita Bagaev, 05/2024 - present, student intern
  • Aubin Mutscler, 06/2024 - present, student intern
  • Julia Oswald, PhD 10/2016 – 05/2021 Scientist II, Ring Therapeutics
  • Tatiana Perepelkina, MD 11/2016 – 07/2019 Ophthalmology Resident, LSU Health Shreveport
  • Evgenii Kegeles, BS 10/2018 – 08/2019 PhD Student, Harvard University
  • Monichan Phay, PhD 08/2019 – 04/2022 Research Scientist, Leal Therapeutics
  • John Masland, BS 09/2019 - 08/2020 Research Assistant
  • Jonathan Soucy, PhD 07/2020 – present Postdoc, SERI/HMS
Publications
    Featured publications
    The “in silico–in vitro–in vivo” funnel holds significant potential for identifying targets to control cellular processes in research and clinical applications. In this report, we describe a framework for identifying, selecting, and applying chemokines to direct retinal neuron migration in vivo within the adult mouse retina.
    Controlling donor and newborn neuron migration and maturation in the eye through microenvironment engineering

    Jonathan R. Soucy, Levi Todd, Emil Kriukov, Monichan Phay, Volha V. Malechka, John Dayron Rivera, Thomas A. Reh, Petr Baranov | PNAS | 2023
    We identify DNA methyltransferase 3a (DNMT3a) as a potent inhibitor of axon regeneration in mouse and human retinal explants. Selective suppression of DNMT3a in retinal ganglion cells (RGCs) by gene targeting or delivery of shRNA leads to robust, full-length regeneration of RGC axons through the optic nerve and restoration of vision in adult mice after nerve crush injury.
    Suppressing DNMT3a Alleviates the Intrinsic Epigenetic Barrier for Optic Nerve Regeneration and Restores Vision in Adult Mice


    Wai Lydia Tai, Kin-Sang Cho, Emil Kriukov, ..., Joshua R. Sanes, Petr Baranov, Dong Feng Chen | bioRxiv | 2023
    Using the retina as an example, we discuss common reasons for artifactual labeling of endogenous host neurons with donor cell reporters and suggest strategies to prevent erroneous conclusions based on misidentification of cell origin.
    The importance of unambiguous cell origin determination in neuronal repopulation studies


    Johnson TV, Calkins DJ, Fortune B, Goldberg JL, La Torre A, Lamba DA, Meyer JS, Reh TA, Wallace VA, Zack DJ, Baranov P. | iScience| 2023
    We identify an immune regulator, IGFBPL1, that plays a pivotal role as a master switch, turning inflammatory microglia to their homeostatic state to prevent excessive neuroinflammation. IGFBPL1 presents potent and lasting therapeutic effects of neuroprotection, delivering functional benefits in the treatment for neurodegenerative disorders.
    IGFBPL1 is a master driver of microglia homeostasis and resolution of neuroinflammation in glaucoma and brain tauopathy
    L. Pan, ..., E. Kriukov, P. Baranov, D. F. Chen | Cell Reports | 2023
    Optic neuropathies, including glaucoma, are a group of neurodegenerative diseases, characterized by the progressive loss of retinal ganglion cells (RGCs), leading to irreversible vision loss. While previous studies demonstrated the potential to replace RGCs with primary neurons from developing mouse retinas, their use is limited clinically.
    Transplantation of miPSC/mESC-derived retinal ganglion cells into healthy and glaucomatous retinas

    J. Oswald, E. Kegeles, T. Minelli, P. Volchkov, P. Baranov | Mol Ther Methods Clin Dev. | 2021
    We have developed a deep learning-based computer algorithm to recognize and predict retinal differentiation in stem cell-derived organoids based on bright-field imaging. The three-dimensional "organoid" approach for the differentiation of pluripotent stem cells (PSC) into retinal and other neural tissues has become a major in vitro strategy to recapitulate development.
    Convolutional Neural Networks Can Predict Retinal Differentiation in Retinal Organoids

    E. Kegeles, A. Naumov, E. Karpulevich, P. Volchkov, P. Baranov | Front Neurosci. | 2020
    Three-dimensional strategy for the differentiation of pluripotent stem cells to the retina has been widely used to study retinal development, although the cell production and drug discovery applications are limited by the throughput. Here we attempted to scale up the protocol using a semiautomated approach.
    Semi-Automated Approach for Retinal Tissue Differentiation

    E. Kegeles, T. Perepelkina, P. Baranov | Transl Vis Sci Technol. | 2020
    A common event in optic neuropathies is the loss of axons and death of retinal ganglion cells (RGCs) resulting in irreversible blindness. Mammalian target of rapamycin (mTOR) signaling pathway agonists have been shown to foster axon regeneration and RGC survival in animal models of optic nerve damage.
    Multifarious Biologic Loaded Liposomes that Stimulate the Mammalian Target of Rapamycin Signaling Pathway Show Retina Neuroprotection after Retina Damage

    A. Eriksen, R. Eliasen, J. Oswald, P. Kempen, F. Melander, T. Andersen, M. Young, P. Baranov, A. Urquhart | ACS Nano | 2018
    Regenerative medicine in the retina: from stem cells to cell replacement therapy
    J. Oswald, P. Baranov | Ther Adv Ophthalmol. | 2018
    Following the fast pace of the growing field of stem cell research, retinal cell replacement is finally emerging as a feasible mean to be explored for clinical application. Although neuroprotective treatments are able to slow the progression of retinal degeneration caused by diseases such as age-related macular degeneration and glaucoma, they are insufficient to fully halt disease progression and unable to recover previously lost vision.
    Degenerative diseases of the retina, such as retinitis pigmentosa and age-related macular degeneration, are characterized by the irreversible loss of photoreceptors. Several growth factors, including glial cell derived neurotrophic factor (GDNF), have been shown to rescue retinal neurons.
    A Novel Neuroprotective Small Molecule for Glial Cell Derived Neurotrophic Factor Induction and Photoreceptor Rescue

    P. Baranov, H. Lin, K. McCabe, D. Gale, S. Cai, B. Lieppman, D. Morrow, P. Lei, J. Liao, M. Young | J Ocul Pharmacol Ther. | 2017
    Development of an effective cell-based therapy is highly dependent upon having a reproducible cell source suitable for transplantation. One potential source, isolated from the developing fetal neural retina, is the human retinal progenitor cell (hRPC). One limiting factor for the use of hRPCs is their in vitro expansion limit.
    Low-oxygen culture conditions extend the multipotent properties of human retinal progenitor cells

    P. Baranov, B. Tucker, M. Young | Tissue Eng Part A. | 2014
    We need your ideas and expertise to make Vision Restoration possible. Send your CV and short personal statement to Petr @ Mass Eye and Ear if you believe that the Journey is the Reward.
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    Partnership
    The support from funding agencies allows us to develop novel cell-based therapies for blinding diseases, educate patients, families and invest in the next generation of brilliant scientists, ophthalmologists, physicians and entrepreneurs. We are grateful to The Gilbert Family Foundation, National Eye Institute, BrightFocus Foundation, Massachusetts Lions Club, The Iraty Award, Research to Prevent Blindness and private donors. Each contribution brings us a step closer to our Audacious Goal of Vision Restoration.
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    We believe that the therapy development is a collaborative effort. We have extensive experience in partnering with pharmaceutical, biotech and academic labs around the world to move ideas from conception to clinical trial.
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