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Jacob V. Layer
Harvard University
ImmunologyB cellDNAPolymeraseBiology
8Publications
3H-index
68Citations
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Publications 9
Newest
#2Yinan KanH-Index: 4
Last. Luhan YangH-Index: 16
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Xenotransplantation, specifically the use of porcine organs for human transplantation, has long been sought after as an alternative for patients suffering from organ failure. However, clinical application of this approach has been impeded by two main hurdles: 1) risk of transmission of porcine endogenous retroviruses (PERVs) and 2) molecular incompatibilities between donor pigs and humans which culminate in rejection of the graft. We previously demonstrated that all 25 copies of the PERV element...
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#1Jacob V. Layer (Harvard University)H-Index: 3
#2J. Patrick Cleary (Harvard University)H-Index: 2
Last. Tovah A. Day (Harvard University)H-Index: 7
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Chromosomal rearrangements, including translocations, are early and essential events in the formation of many tumors. Previous studies that defined the genetic requirements for rearrangement formation have identified differences between murine and human cells, most notably in the role of classic and alternative nonhomologous end-joining (NHEJ) factors. We reported that poly(ADP)ribose polymerase 3 (PARP3) promotes chromosomal rearrangements induced by endonucleases in multiple human cell types. ...
2 CitationsSource
#1Tovah A. DayH-Index: 7
#2Jacob V. LayerH-Index: 3
Last. David M. WeinstockH-Index: 44
view all 14 authors...
Nature Communications 8: Article number: 15110 (2017); Published: 27 Apr 2017; Updated: 13 Jun 2017 In this Article, the antibody ‘BG4’ is consistently referred to incorrectly as ‘hf2’. These errors appear in the Results and Methods. Additionally, the Article incorrectly cites reference 52 in the sentences ‘A recent study described hf2, an engineered single-chain antibody specific for G4 DNA52’ and ‘pSANG10-3F-BG4 (Addgene 55756)52 was transformed into….
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#1Tovah A. Day (Harvard University)H-Index: 7
#2Jacob V. Layer (Harvard University)H-Index: 3
Last. David M. Weinstock (Harvard University)H-Index: 44
view all 14 authors...
Chromosomal rearrangements are essential events in the pathogenesis of both malignant and nonmalignant disorders, yet the factors affecting their formation are incompletely understood. Here we develop a zinc-finger nuclease translocation reporter and screen for factors that modulate rearrangements in human cells. We identify UBC9 and RAD50 as suppressors and 53BP1, DDB1 and poly(ADP)ribose polymerase 3 (PARP3) as promoters of chromosomal rearrangements across human cell types. We focus on PARP3 ...
12 CitationsSource
#1Caron A. JacobsonH-Index: 15
#2Nadja KoppH-Index: 13
Last. David M. Weinstock (MIT: Massachusetts Institute of Technology)H-Index: 44
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The Bruton tyrosine kinase (BTK) inhibitor ibrutinib induces responses in 70% of patients with relapsed and refractory mantle cell lymphoma (MCL). Intrinsic resistance can occur through activation of the nonclassical NF-kappa B pathway and acquired resistance may involve the BTKC481S mutation. Outcomes after ibrutinib failure are dismal, indicating an unmet medical need. We reasoned that newer heat shock protein 90 (HSP90) inhibitors could overcome ibrutinib resistance by targeting multiple onco...
15 CitationsSource
#1Loretta S. Li (Harvard University)H-Index: 7
#2Nadja Kopp (Harvard University)H-Index: 13
Last. David M. Weinstock (Harvard University)H-Index: 44
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Approximately 10% of B-ALLs harbor CRLF2 rearrangements and have a poor prognosis. Although these leukemias are addicted to JAK2 signaling, ATP-competitive type I JAK2 inhibitors have limited activity (Weigert et al . J Exp Med 2012). This may result from heterodimerization of JAK2 with other JAK family members (Koppikar et al . Nature 2012). Type II inhibitors bind JAK2 in the inactive conformation and may have non-cross resistance with type I inhibitors. In Ba/F3 cells dependent on CRLF2 and t...
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#1Shuo-Chieh Wu (Harvard University)H-Index: 3
#2Loretta S. Li (Harvard University)H-Index: 7
Last. David M. Weinstock (Broad Institute)H-Index: 44
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Summary A variety of cancers depend on JAK2 signaling, including the high-risk subset of B cell acute lymphoblastic leukemias (B-ALLs) with CRLF2 rearrangements. Type I JAK2 inhibitors induce paradoxical JAK2 hyperphosphorylation in these leukemias and have limited activity. To improve the efficacy of JAK2 inhibition in B-ALL, we developed the type II inhibitor CHZ868, which stabilizes JAK2 in an inactive conformation. CHZ868 potently suppressed the growth of CRLF2- rearranged human B-ALL cells,...
38 CitationsSource
#1Loretta S. Li (Harvard University)H-Index: 7
#2Shuo-Chieh Wu (Harvard University)H-Index: 3
Last. David M. Weinstock (Harvard University)H-Index: 44
view all 20 authors...
Approximately 10% of B-ALLs harbor CRLF2 rearrangements, which may portend a poor prognosis. Although these leukemias are addicted to JAK2 signaling, ATP-competitive type I JAK2 inhibitors have limited activity in vitro or in vivo (Weigert et al . J Exp Med 2012). This may result from heterodimerization of JAK2 with other JAK family members (Koppikar et al . Nature 2012). Type II inhibitors bind JAK2 in the inactive conformation, which may overcome this resistance. When assayed in MHH-CALL4 cell...
1 CitationsSource
#1Jordy C. Van der Zwet (Harvard University)H-Index: 1
#2Jacob V. Layer (Harvard University)H-Index: 3
Last. David M. Weinstock (Harvard University)H-Index: 44
view all 7 authors...
Approximately 50% of myeloproliferative neoplasms (MPNs) harbor the JAK2 V617F mutation while approximately 50% of B-cell acute lymphoblastic leukemias (B-ALLs) with CRLF2 rearrangements harbor JAK2 exon 16 mutations that primarily involve R683. Multiple enzymatic inhibitors of JAK2 are in clinical development for the treatment of patients with malignant and nonmalignant conditions that depend on constitutive JAK2 signaling. Most of these drugs are ATP-mimetics that block JAK2 signaling in the a...
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