Jeffrey C. Way

Durability of the Benefit of Vagus Nerve Stimulation in Markedly Treatment-Resistant Major Depression: A RECOVER Trial Report

Charles R. Conway, A. John Rush, Scott T. Aaronson, Mark T. Bunker et autres

ABSTRACT Importance Greater levels of treatment resistance in major depressive disorder (MDD) are associated with lower rates of initial benefit and higher rates of relapse (lower durability). Objective Characterize depressive symptoms, function, and quality of life (QoL) over 24 months of adjunctive …

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A long-lasting prolactin stimulates galactopoiesis in mice

Kasia M. Kready, Kailyn E. Doiron, Katherine Redfield Chan, Jeffrey C. Way et autres

Prolactin is the main hormonal driver of mammalian lactation. To sustain milk production, basal prolactin levels must remain elevated compared to nonpregnant states. However, prolactin (23 kDa) is short-lived in circulation due to rapid renal excretion. Here, we design and test the …

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An Fc-SPINK1 fusion protein inhibits pancreatic inflammation in a mouse model

Jeffrey C. Way, Daniel Heid, Maria Theiss, Simon Flyvbjerg Nørrelykke et autres

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Rational design of selective bispecific EPO-R/CD131 agonists

Kailyn E. Doiron, Jeffrey C. Way, Pamela A. Silver

Erythropoietin (EPO) suppresses apoptosis and promotes survival by signaling through EPO-R/EPO-R on hematopoietic progenitors or EPO-R/CD131 on non-hematopoietic cells. However, EPO signaling through EPO-R/CD131 is controversial and there is no solved structure of a complex. Here, we constructed a structural model of …

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An Fc-SPINK1 fusion protein inhibits pancreatic inflammation in a mouse model

Jeffrey C. Way, Daniel Heid, Maria Theiss, Lucas Barck et autres

Abstract Pancreatitis results from premature activation and impaired inactivation of pancreatic proteases, primarily trypsin, leading to self-digestion, tissue necrosis, fibrosis, and inflammation. SPINK1 is a pancreas-specific inhibitor of trypsin that prevents premature trypsin activation, and could be a candidate therapeutic. However, because …

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Linker minimization and characterization of Fc-fused interleukin-17A for increased in vivo half-life

Qiu Chang Wu, Jungmin Lee, Aishwarya Swaminathan, Ashley Winward et autres

Interleukin-17A (IL-17A) is a cytokine involved in pro-inflammatory responses and tissue regeneration, with potential therapeutic and research applications. However, its short serum half-life limits in vivo use. Here, we report the systematic design of fc-IL-17A fusion proteins for extended half-life. Through computational …

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Rational design of selective bispecific EPO-R/CD131 agonists

Kailyn E. Doiron, Jeffrey C. Way, Pamela A. Silver

Erythropoietin (EPO) suppresses apoptosis and promotes survival by signaling through EPO-R/EPO-R on hematopoietic progenitors or EPO-R/CD131 on non-hematopoietic cells. However, EPO signaling through EPO-R/CD131 is controversial and there is no solved structure of a complex. Here, we constructed a structural model of …

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Tardigrade secretory proteins protect biological structures from desiccation

Samuel T. Lim, Charles B. Reilly, Zeina Barghouti, Benedetto Marelli et autres

Tardigrades, microscopic animals that survive a broad range of environmental stresses, express a unique set of proteins termed tardigrade-specific intrinsically disordered proteins (TDPs). TDPs are often expressed at high levels in tardigrades upon desiccation, and appear to mediate stress adaptation. Here, we …

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A long-acting prolactin to combat lactation insufficiency

Kasia M. Kready, Kailyn E. Doiron, Katherine Redfield Chan, Jeffrey C. Way et autres

. Here, we engineer a variant of the naturally-occurring driver of lactation, the hormone Prolactin, to increase its serum half-life and produce a viable drug candidate. Our engineered variant, Prolactin-eXtra Long-acting (Prolactin-XL), is comprised of endogenously active human prolactin fused to an …

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Tardigrade secretory proteins protect biological structures from desiccation

Samuel T. Lim, Charles B. Reilly, Zeina Barghouti, Benedetto Marelli et autres

Abstract Tardigrades, microscopic animals that survive a broad range of environmental stresses, express a unique set of proteins termed tardigrade-specific intrinsically disordered proteins (TDPs). TDPs are often expressed at high levels in tardigrades upon desiccation, and appear to mediate stress adaptation. Here, …

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ASCEND: A randomized controlled trial of titration strategies for vagus nerve stimulation in drug-resistant epilepsy

Anto I. Bagic, Ryan S. Verner, Pegah Afra, Selim R. Benbadis et autres

Vagus Nerve Stimulation (VNS) therapy is widely understood to provide clinically meaningful improvements in seizure control to patients with drug-resistant epilepsy, and has been a staple in the clinical armamentaria available to epileptologists for over 25 years. Despite the long history of …

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High spontaneous integration rates of end-modified linear DNAs upon mammalian cell transfection

Samuel T. Lim, R. Rogers Yocum, Pamela A. Silver, Jeffrey C. Way

In gene therapy, potential integration of therapeutic transgene into host cell genomes is a serious risk that can lead to insertional mutagenesis and tumorigenesis. Viral vectors are often used as the gene delivery vehicle, but they are prone to undergoing integration events. …

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