Reprogramming Stars #25:Modeling Brain Aging with Direct Reprogramming of Skin Cells into Neurons—An Interview with Dr. Jerome Mertens
REPROGRAMMING STAR: Dr. Jerome Mertens is an Associate Professor at the Department of Neurosciences at the University of California San Diego (UCSD), USA. Dr. Mertens’s lab applies neuronal direct reprogramming and induced pluripotent stem cell (iPSC) generation to develop informative models of human biological aging and its intersection with age-related diseases, investigating the effects of epigenetic aging, rejuvenation, and stability of adult neuronal identity. With the goal of identifying key molecular players at the interface of human biological aging and disease to develop new treatments for age-related neurodegeneration, the lab relies on a patient-centric approach supported by cellular neuroscience and big data biology. By employing multi-omics strategies, functional genetics, and cell biology approaches to characterize human patient-based reprogramming models, Dr. Mertens’s work elucidates the interplay between non-genetic and age-related cellular changes and disease pathways.
Reprogramming Stars #24:Pluripotency and Oncogenic Transformation:A Series of Intermingling Events—An Interview with Dr. Fabrice Lavial
REPROGRAMMING STAR: Dr. Fabrice Lavial is the team leader of the Cellular Reprogramming, Stem Cells, and Oncogenesis Laboratory at the Cancer Research Center of Lyon, France, and a research director at INSERM. Dr. Lavial’s lab joins the fields of developmental biology, cellular reprogramming, cancer biology, and bioinformatics to mechanistically understand embryonic development and the establishment of cellular identities. They explore the molecular mechanisms that control cell fate conversions in early development, reprogramming to pluripotency, transdifferentiation, and oncogenic transformation. Focusing on the regulation of cellular identity and plasticity, Dr. Lavial is interested in deciphering cellular and molecular networks that will lead to the development of nontumorigenic approaches for cell fate conversions in situ. Specifically, he and his group are trying to understand how we can harness the benefits of cellular reprogramming while avoiding cancer development.
Dr. Lavial’s lab is divided into two main themes: (1) control of cellular identity during reprogramming and oncogenic transformation and (2) pluripotent stem cell dynamics. The team’s first line of research aims to dissect the early molecular events of cellular reprogramming and transformation, using multi-omics approaches at the single-cell scale, 2D cellular models, 3D organoids, and murine genetic models. The second research subject focuses on understanding the molecular mechanisms controlling the self-renewal of pluripotent stem cells, as well as their ability to polarize and self-assemble. For that, the team uses models of embryonic or induced stem cells, cultured in 2D or induced to form 3D epiblast-like structures, as well as synthetic embryos.
Reprogramming Stars #23: Charting Cell Fate Crossroads from the Interplay Between Epigenetics, Transcription, and 3D Chromatin Architecture—An Interview with Dr. Effie Apostolou
REPROGRAMMING STAR: Dr. Effie Apostolou is an Associate Professor of Molecular Biology at Weill Cornell Medicine, New York, US, and the Group Leader of the Chromatin Organization & Cell Fate Decisions Lab. The main focus of the Apostolou lab is to dissect the critical interplay between TFs, 3D chromatin organization, and transcription during either (i) maintenance of cell fate (selfrenewal) or (ii) transition to a new fate. Their goal is to build 4D molecular roadmaps to address specific questions such as, How do cells maintain or change identity? What factors dictate cell fate decisions? What is the interplay between transcription, epigenetic factors, and 3D chromatin organization in development and disease?
Dr. Apostolou’s group uses several dynamic cellular systems, including induced pluripotent stem cell (iPSC) reprogramming, differentiation, immune response, tumorigenesis, and cell cycle. They use high throughput sequencing technologies such as 4C-Seq, HiC, HiChIP, ChIP-seq, andPRO-seq and integrative computational analysis to address regulatory mechanisms of cell type-specific gene expression programs. In addition, they employ advanced CRISPR/(d)Cas9-based genetic and epigenetic approaches for precise modulation and functional testing. Dr Apostolou’s lab is also tackling functional heterogeneity and rare stem-like populations in vivo and ex vivo by expanding into single-cell technologies.
Reprogramming Stars #22: Cellular Reprogramming as a Route for Decoding Neurodegenerative Disorders—An Interview with Dr. Janelle Drouin-Ouellet
REPROGRAMMING STAR: Dr. Janelle Drouin-Ouellet is an associate professor at the Université de Montréal, Canada, a neuroscientist, and a Canada Research Chair in Direct Neural Reprogramming. Her research group works with direct neural reprogramming to study neurodegenerative disorders and identify new therapeutic targets. Uncovering age-related drivers of neurodegeneration through cellular reprogramming, Dr. Drouin-Ouellet’slab uses specific approaches such as highcontent confocal microscopy, gene expression profiling, and proteomics. To study the interplay between cellular aging and Parkinson’s disease, in addition to using direct cellular reprogramming, her group investigates approaches to accelerate cellular aging in induced pluripotent stem cells (iPSCs)- derived immune cells such as microglia. Her group is working on understanding the mechanisms of neuronal reprogramming a means to improve current direct neuronal reprogramming methods and generate subtypespecific neurons resembling more closely the neuronal populations of the central nervous system to improve disease modeling and brain repair strategies.
Reprogramming Stars #21:RNA Regulatory Mechanisms That Instruct Cell Identity—An Interview with Dr. Bruno Di Stefano
REPROGRAMMING STAR: Dr. Bruno Di Stefano is an Assistant Professor in the Department of Molecular and Cellular Biology at Baylor College of Medicine (Houston, Texas, USA). His research centers on the pivotal role of post-transcriptional regulation in mammalian cell fate decisions. Cell fate transitions are essential during embryonic development and for tissue homeostasis in adults. These transitions largely occur without changes in genomic content, highlighting the importance of RNAbased regulatory mechanisms in development and lineage specification. Despite recent advances, the contribution of post transcriptional regulation to lineage specification remains incompletely understood. The Di Stefano lab focuses on several outstanding questions: (1) How do RNA condensates orchestrate the establishment and maintenance of cell identity? (2) What mechanisms guide the crosstalk between chromatin architecture and RNA processing in cell fate? (3) How do RNA modifications instruct human cell fate decisions? By addressing these fundamental questions, research in the Di Stefano lab aims to uncover general principles of cell fate control and cancer development across tissue contexts while pioneering innovative RNA-based therapeutic strategies.
Reprogramming Stars #20:Attenuating Cancer Cell Memory and Discovering Cancer Biomarkers with Cellular Reprogramming—An Interview with Dr. Jungsun Kim
REPROGRAMMING STAR: Dr. Jungsun Kim is a member of the Early Detection Advanced Research Center and Cancer Biology Program at Knight Cancer Institute, Oregan, USA. Her research group is interested in the reversibility of regulatory mechanisms in cancer development and progression, with the long-term goal of applying the generated knowledge in early cancer therapy. Defined combinations of transcription factors (TFs) can reprogram somatic cells into induced pluripotent stem cells (iPSCs) through epigenetic rewiring of the landscape of “starting” somatic cells, established by cell fate decisions during normal development. Dr. Kim’s lab explores TF-mediated reprogramming to rewire and reverse aberrant epigenetic alterations in cancer cells. They have demonstrated proof of principle of a pancreatic cancer reprogramming model, providing a unique platform to study different stages of human pancreatic cancer. Essentially, Dr. Kim’s research group addresses the following questions: To what extent and reproducibility aberrant cancer transcriptional networks can be destabilized through TF-mediated reprogramming? How do cells that fail reprogramming regain an aggressive tumor phenotype? What chromatin regulators maintain a cancer cell state? Addressing these questions can provide understanding of how cancer cells establish and maintain cancer identity.
Reprogramming Stars #17:Breaking Down the Barriers of Direct Reprogramming Using a Model Organism—An Interview with Dr. Baris Tursun
REPROGRAMMING STAR: Prof. Dr. Baris Tursun leads the Molecular Cell Biology unit at the University of Hamburg’s Institute of Cell and Systems Biology of Animals. His group uses the nematode Caenorhabditis elegans (C. elegans) to study direct reprogramming of cells in vivo. Their aim is to identify and better understand cellular processes that limit the conversion of cell identities. The genetic factors identified by the Tursun group contribute to safeguard cell fates and thereby act as reprogramming barriers. Using C. elegans facilitates unbiased genetic screening for such factors. By interrogating all 20,000 genes of the worm, the Tursun group identifies unanticipated molecular mechanisms that counteract cell conversion, ensuring the maintenance of cell function and health. Tursun’s research focuses on epigenetic and physiological mechanisms in cellular reprogramming and aging
Reprogramming Stars #19:Upgrading Cell Fate Conversions with Engineered Reprogramming Factors—An Interview with Dr. Ralf Jauch
REPROGRAMMING STAR: Professor Ralf Jauch leads the protein and cell engineering laboratory at the School of Biomedical Sciences in the Faculty of Medicine of the University of Hong Kong (HKUMed). His group aims to boost cellular reprogramming with the help of unconventional factors from exotic species and reengineered biomolecules. To achieve this, they look at the natural evolution of pioneer transcription factors, perform direct molecular evolution in mammalian cells, and use structural information for protein design. With this toolkit, they aim to make new types of stem cells that can help to model and revert age linked disease, enhance the developmental potential of stem cells, and direct stem cell differentiation. The team aims to translate their technologies within the Centre for Translational Stem Cell Biology (CTSCB).
Reprogramming Stars #18:Engineering Cell Fates and Preventing Diseaseby Repressing Unwanted Plasticity—An Interview with Dr. Moritz Mall
REPROGRAMMING STAR: Dr. Moritz Mall is a research group leader at the Hector Institute for Translational Brain Research (HITBR) and the German Cancer Research Center (DKFZ). The Mall lab employs mouse models, pluripotent stem cells, organoids, and cell fate engineering to reconstruct and investigate human development and disease. Their mission is to understand the mechanisms that determine and maintain cell fate, with the goal of treating diseases associated with increased cellular plasticity. Their immediate research goal is to understand the role of cell plasticity in brain disorders and cancer, with a focus on autism spectrum disorders and the emerging field of phenotypic plasticity in cancer.
Reprogramming Stars #16:Reprogramming, from Cells to Embryos—An Interviewwith Dr. José Silva
REPROGRAMMING STAR: Dr. José Silva is a full time Principal Investigator at the Guangzhou National Laboratory in Guangzhou, China. He leads a team that is developing new mouse and human embryo models to generate relevant cell types and tissues that are molecularly and functionally identical to their in vivo counterparts. Their approach combines reprogramming with developmental biology principles and an array of advanced tools to generate high-quality, relevant cell types for potential medical applications
Reprogramming Stars #15:Colliding Cellular Reprogramming Paths—An Interview with Dr. Stefan Stricker
ReprogrammingStar: Prof. Dr. Stefan H. Stricker leads the Epigenetic Engineering group at the Institute of Stem Cell Research, Helmholtz Munich, and concurrently holds the position of Professor of Reprogramming and Regeneration at the Biomedical Center of LMU Munich. Their primary objective is to uncover and manipulate mediators and barriers of cell identity conversion, leveraging these insights to enhance both established and innovative reprogramming strategies. Their multifaceted approach integrates computational analyses, epigenome editing techniques, transcriptional engineering, and advanced single-cell methodologies to propel their research toward achieving transformative outcomes in regenerative medicine.
Reprogramming Stars #14:Fast-Forwarding Cellular Reprogramming—An Interview with Dr. Mark Kotter
Reprogramming Star: Dr. Mark Kotter is a stem cell biologist and neurosurgeon at the University of Cambridge and a serial entrepreneur. As a neurosurgeon, he treats patients with spinal cord injury. He is CEO and founder of bit.bio, the cell coding company generating human cells for research, drug discovery, and cell therapy, cofounder of Meatable and clock.bio and cofounder and trustee of myelopathy.org, the first charity dedicated to a common yet often overseen condition causing a ‘‘slow motion spinal cord injury.’’ Mark set up bit.bio to democratize access to human cells for research, drug discovery, and cell therapies.
Reprogramming Stars #13:Establishing Connections with Cellular Reprogramming–An Interview with Dr. Daniella Rylander Ottosson
Reprogramming Star: Dr. Rylander Ottosson is an Associate Professor at the Lund University and Wallenberg Academy Fellow. The Ottosson laboratory studies cell fate specification toward GABAergic interneurons from human neuronal progenitor cells and somatic cells using neuronal differentiation and reprogramming approaches. The long-term goal is in brain repair and rewiring of altered brain plasticity in disorders such as Schizophrenia and Alzheimer’s disease. Her laboratory includes cell-based models, mouse in vivo model, and human organotypic cultures with a clear focus on the functional and integrational aspects of in vivo reprogrammed cells. In parallel the laboratory applies in vitro reprogramming of patient skin fibroblast to develop interneuron disease models for pathologies related to these neurons.
Reprogramming Stars #12:At the Heart of In Vivo Reprogramming—An Interview with Dr. Li Qian
Reprogramming Star: Dr. Li Qian is a Professor at the University of North Carolina. Dr. Qian’s laboratory is interested in developing innovative approaches to regenerate or repair an injured heart. Their goal is to understand the molecular basis of cardiomyocyte specification and maturation and apply this knowledge to improve efficiency and clinical applicability of cellular reprogramming in heart disease. To achieve these goals, they utilize in vivo modeling of cardiac disease in the mouse, including myocardial infarction, cardiac hypertrophy, chronic heart failure, and congenital heart disease. In addition, they take advantage of traditional mouse genetics, cell and molecular biology, biochemistry, reprogramming technologies, and the latest single-cell genomics approaches in combination with mathematical modeling to investigate the fundamental events underlying the progression of various cardiovascular diseases as well as to discover the basic mechanisms of cell reprogramming.
Reprogramming Stars #11: Teaming Up to Uncoverthe Epitranscriptomics of Reprogramming—An Interview with Dr. Miguel Fidalgo and Dr. Diana Guallar
Reprogramming Stars: Dr. Diana Guallar is an Assistant Professor at the Department of Biochemistry and Molecular Biology in the University of Santiago de Compostela (USC) and group leader at the Center for Research in Molecular Medicine and Chronic Diseases (CIMUS). The Guallar laboratory studies how epigenetic and epitranscriptomic cross talk is involved in the regulation of cell identity and plasticity in cellular rejuvenation and pluripotency. Her ultimate aim is to dissect critical pathways accompanying the loss of molecular fidelity observed during aging and in aging-related disorders that could be very valuable for clinical application. Dr. Miguel Fidalgo is an Associate Professor at the Department of Physiology (USC) and group leader at the CIMUS. The Fidalgo laboratory is focused on understanding how regulatory information encoded by the genome is integrated with the metabolic, epigenetic, and epitranscriptomic machineries to control cellular plasticity in the context of cell reprogramming and pluripotency, and how perturbations of these mechanisms could be associated with development and disease.
Reprogramming Stars #10:Modeling Cancer with Cellular Reprogramming—An Interview with Dr. Dung-Fang Lee
Reprogramming Star: Dr. Dung-Fang Lee is an assistant professor and CPRIT scholar in cancer research at the University of Texas Health Science Center at Houston. The Lee research laboratory is dedicated to understanding the pathological mechanisms behind cancer by applying patient-specific induced pluripotent stem cells (iPSCs) and/or engineered embryonic stem cells (ESCs) as models. The central directions of the Lee laboratory include (1) systems-level analyses and characterization of mutant p53 in Li–Fraumeni syndrome-associated tumor initiation, (2) systematic analyses of genome alterations during Li–Fraumeni syndrome-associated osteosarcoma development, and (3) modeling of familial cancer syndromes with a predisposition to osteosarcoma through patient-specific iPSC methods.
Reprogramming Stars #9:Spacing Out Cellular Reprogramming—An Interview with Dr. Valentina Fossati
Reprogramming Star: Dr. Valentina Fossati is a senior investigator at the New York Stem Cell Foundation Research Institute where she focuses on building human induced pluripotent stem cell (iPSC)-based models for studying progressive multiple sclerosis (MS) and other neurodegenerative diseases to investigate the role of glia in neuroinflammation and neurodegeneration. She has established protocols to generate human iPSCderived oligodendrocytes, astrocytes, microglia, and neuronal cell types and is developing organoids and coculture systems to study the crosstalk between neurons and glial cells.Her ultimate goal is to identify and target key glia-driven pathogenic mechanisms leading to neurodegeneration in progressive MS, Alzheimer’s disease, and other disorders of the central nervous system (CNS).
Reprogramming Stars #8:A Synthetic Biology Approach to Cellular Reprogramming—An Interview with Dr. Katie Galloway
Reprogramming star: Dr. Katie Galloway is the W.M. Keck Career Development Professor in biomedical engineering and chemical engineering at MIT. As a chemical engineer working in stem cell and molecular systems biology, her research focuses on elucidating the fundamental principles of constructing and integrating synthetic circuitry to drive cellular reprogramming. Her laboratory leverages synthetic biology to understand cell fate transitions with the goal of building genetic controllers that support disease modeling and cell-based therapies.
Reprogramming Stars #7:Dynamic Pluripotent Stem Cell States and Their Applications–An Interview with Dr. Jun Wu
REPROGRAMMING STAR: Dr. Jun Wu is an Assistant Professor at the UT Southwestern Medical Center. The Wu lab mainly focuses on using stem cell models to gain novel insights in development and develop translational applications. The central directions of Wu lab include: 1) derive novel pluripotent stem cells; 2) study novel regulators of pluripotency; 3) identify and overcome the xenogeneic barrier to enable interspecies organogenesis; and 4) generate stem cell-based models of mammalian embryos.
Reprogramming Stars #6:A Venture Based in Cellular Reprogramming—An Interview with Dr. Cristiana Pires
REPROGRAMMING STAR: Dr. Cristiana F. Pires is CEO and co-founder of Asgard
Therapeutics. Asgard Therapeutics is a Swedish biotech company focusing on the development of groundbreaking cancer immunotherapies based on direct cell reprogramming technologies. Formed as a spinoff from Lund University, the company is pioneering a cancer gene therapy approach based on its proprietary TrojanDC technology. This is based on the expression of three transcription factors that convert somatic cells into dendritic cells. When reprogramming is applied to cancer cells, it induces efficient presentation of cancer own (neo-)antigens to the immune system, eliciting potent anticancer immune responses. Designed as an off-the-shelf gene therapy, Asgard’s approach overcomes many of the logistic and manufacturing hurdles of conventional cell-based therapies.
Reprogramming Stars #5:Regeneration, a Natural Reprogramming Process—An Interview with Dr. Nicholas Leigh
Reprogramming star: Dr. Nick Leigh is an associate senior lecturer (assistant professor) at Lund University. The Leigh laboratory is working to understand how the immune system of highly regenerative organisms, such as salamanders, facilitates extreme acts of complex multitissue regeneration (e.g., limb regeneration). He is studying regeneration through an immunological perspective and approach, understanding how salamander cells are able to effortlessly dedifferentiate and form progenitor cells capable of facilitating multitissue regeneration.
Reprogramming Stars #4:A Reprogramming Approach for Parkinson’s Disease—An Interview with Dr. Malin Parmar
Reprogramming star: Dr. Malin Parmar is a professor in cellular neuroscience at Lund University and an NYSCF-Robertson investigator. The Parmar laboratory studies cell fate specification in the developing brain and in human neural progenitor cells using cell-based models of neuronal differentiation. Her current focus is to learn how to direct and efficiently drive controlled differentiation of human stemcells into subtype-specific neurons. She also develops technologies for direct conversion of human fibroblasts into functional and subtype-specific neurons in vitro, and the conversion of endogenous glia into neurons in vivo. Her ultimate aim is to develop these cells and technologies for use in brain repair, with focus on Parkinson’s disease.
Reprogramming Stars #3:Mechanisms of iPSC Reprogramming—An Interview with Dr. Keisuke Kaji
Reprogramming Star: Dr. Keisuke Kaji is an MRC senior research fellow and a Professor of Biology of Reprogramming at the University of Edinburgh. The Kaji lab has developed one of the first non-viral iPSC reprograming systems and contributed to better understanding of molecular mechanisms of iPSC generation. The lab aims to apply the knowledge and the genetic manipulation techniques to other cell conversions and reprogramming in order to generate fully functional cell types.
Reprogramming Stars #2:Reprogramming Towards Neural Lineages—An Interview with Dr. Henrik Ahlenius
Reprogramming Star: Dr. Henrik Ahlenius is a principal investigator at the Department of Clinical Sciences and Lund Stem Cell Center at Lund University in Sweden. The Ahlenius lab uses novel stem cell, genome engineering and reprogramming technologies to study how aging and neurological disorders affect the formation and function of neural cells. The lab has recently been focused on reprogramming towards the astroglial lineage for investigating the role of astrocytes in neurodegenerative disease.
Reprogramming Stars #1: Genome Programming Through the Cell Cycle—An Interview with Dr. Tomomi Tsubouchi
Reprogramming Star: Dr. Tomomi Tsubouchi is an associate professor at the National Institute for Basic Biology. The Tsubouchi laboratory studies how pluripotency and genome integrity in embryonic stem cells are maintained and can be reacquired by differentiated somatic cells. Inspired by the fields of stem cell biology, cell cycle regulation, and genome maintenance mechanisms, the laboratory uses an interdisciplinary approach to mechanistically understand how the pluripotency network is established.