Jocelynn R. Pearl

Critical evaluation of compositions and clinical relevance of Wharton’s jelly-derived biologics

Annette M. Marleau, Jocelynn R. Pearl, Patricia Juárez, Paloma Almeida et autres

BACKGROUND: Wharton’s jelly, the mucoid connective tissue that surrounds umbilical cord vessels, contains both acellular and cellular components with recognized relevance to regenerative medicine. The acellular extracellular matrix (ECM) is composed of collagen fibers, hyaluronic acid, proteoglycans, glycosaminoglycans, that provides a scaffold …

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Hierarchical therapeutic potential in the mesenchymal stem cell landscape

Jocelynn R. Pearl, Annette M. Marleau, Vijay Mahant, J. Christopher Mizer et autres

Mesenchymal stem cells (MSCs) are heterogeneous and versatile cells comprising distinct subpopulations with varying regenerative potential. MSCs have been widely explored in clinical research owing to their regenerative, tissue trophic, immune modulatory, and anti-inflammatory properties. Tissue-sourced autologous and allogeneic MSCs including those …

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Altered huntingtin−chromatin interactions predict transcriptional and epigenetic changes in Huntington's disease

Jocelynn R. Pearl, Amol C. Shetty, Jeffrey P. Cantle, Dani E. Bergey et autres

While progressive striatal gene expression changes and epigenetic alterations are a prominent feature of Huntington's disease (HD), the mechanistic basis remains poorly understood. Using chromatin immunoprecipitation and sequencing (ChIP-seq), we show that the huntingtin protein (HTT) reproducibly occupies specific locations in the …

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A genome scale transcriptional regulatory model of the human placenta

Alison G. Paquette, Kylia Ahuna, Yeon Mi Hwang, Jocelynn R. Pearl et autres

Gene regulation is essential to placental function and fetal development. We built a genome-scale transcriptional regulatory network (TRN) of the human placenta using digital genomic footprinting and transcriptomic data. We integrated 475 transcriptomes and 12 DNase hypersensitivity datasets from placental samples to …

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A Genome Scale Transcriptional Regulatory Model of the Human Placenta

Alison G. Paquette, Kylia Ahuna, Yeon Mi Hwang, Jocelynn R. Pearl et autres

ABSTRACT Gene regulation is essential to placental function and fetal development. We report a genome-scale transcriptional regulatory network (TRN) of the human placenta built using digital genomic footprinting and transcriptomic data. We integrated 475 transcriptomes and 12 DNase hypersensitivity datasets from placental …

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Altered Huntingtin-Chromatin Interactions Predict Transcriptional and Epigenetic Changes in Huntington’s Disease Mouse Models

Jocelynn R. Pearl, Amol C. Shetty, Jeffrey P. Cantle, Dani E. Bergey et autres

Abstract Progressive striatal gene expression changes and epigenetic alterations are a prominent feature of Huntington’s disease (HD), but the mechanistic basis remains poorly understood. Using chromatin immunoprecipitation and sequencing (ChIP-seq), we show that the huntingtin protein (HTT) reproducibly occupies specific locations in …

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De novo design of protein logic gates

Zibo Chen, Ryan D. Kibler, Andrew C. Hunt, Florian Büsch et autres

Designer gates Signaling in cells can occur through protein-protein interactions. Chen et al. describe the design of logic gates that can regulate protein association. The gates were built from small, designed proteins that all have a similar structure but where one module …

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Promoter keyholes enable specific and persistent multi-gene expression programs in primary T cells without genome modification

Matthew S. Wilken, Christie Ciarlo, Jocelynn R. Pearl, Jordan Bloom et autres

Non-invasive epigenome editing is a promising strategy for engineering gene expression programs, yet potency, specificity, and persistence remain challenging. Here we show that effective epigenome editing is gated at single-base precision via 'keyhole' sites in endogenous regulatory DNA. Synthetic repressors targeting promoter …

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Quantitative dialing of gene expression via precision targeting of KRAB repressor

Matthew S. Wilken, Christie Ciarlo, Jocelynn R. Pearl, Elaine Schanzer et autres

Abstract Human genes are regulated quantitatively, yet the ability to specify the expression level of a native gene accurately and specifically using a defined reagent has remained elusive. Here we show that precise targeting of KRAB repressive domain within regulatory DNA unlocks …

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Allele-selective transcriptional repression of mutant HTT for the treatment of Huntington’s disease

Bryan Zeitler, Steven Froelich, Kimberly Marlen, David A. Shivak et autres

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Genome-Scale Transcriptional Regulatory Network Models of Psychiatric and Neurodegenerative Disorders

Jocelynn R. Pearl, Carlo Colantuoni, Dani E. Bergey, Cory C. Funk et autres

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Potent and Timed Epigenetic Repression of PD-1 in Human T Cells

Jocelynn R. Pearl, Fyodor D. Urnov, J Stamatoyannopoulos

Abstract T cell exhaustion mediated by checkpoint genes - most prominently PD-1 - is believed to play a major role in limiting the efficacy of chimeric antigen receptor (CAR) T cell therapies of hematologic malignancies. Clinically durable responses to CAR-T therapy of …

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