John Manis
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View article: Challenges and limitations of mobilization and stem cell collection for gene therapy of sickle cell disease
Challenges and limitations of mobilization and stem cell collection for gene therapy of sickle cell disease Open
Sickle cell disease (SCD) is a hemolytic anemia that afflicts millions of people worldwide and continues to carry high morbidity and reduced life expectancy. Allogeneic hematopoietic stem cell transplantation was the only standard-of-care …
Improved hematopoietic stem cell mobilization for gene therapy using single agent motixafortide in sickle cell disease Open
While the development and approval of gene therapies (GT) for sickle cell disease (SCD) has transformed treatment options for patients, a critical limitation remains in the ability to obtain sufficient autologous hematopoietic stem cells (…
View article: In Vivo correction of the sickle cell disease mutation in hematopoietic stem cells using RNA gene writers
In Vivo correction of the sickle cell disease mutation in hematopoietic stem cells using RNA gene writers Open
Tessera Therapeutics is pioneering a novel approach to in vivo genome editing that uses RNA Gene Writers and delivery of all RNA-based components to introduce precise edits into the genome of cells in vivo by target-primed reverse transcri…
View article: Efficacy of motixafortide plus G-CSF versus plerixafor plus G-CSF for stem cell mobilization and collection in multiple myeloma: A single-center comparative analysis and interim Results from a prospective study in poor mobilizers
Efficacy of motixafortide plus G-CSF versus plerixafor plus G-CSF for stem cell mobilization and collection in multiple myeloma: A single-center comparative analysis and interim Results from a prospective study in poor mobilizers Open
Introduction Stem cell collection after 4–8 cycles of induction therapy remains standard for multiple myeloma (MM), supporting autologous stem cell rescue/transplantation (ASCT) following high-dose melphalan. The recent growth of cell ther…
View article: Analyzing long-read CRISPR experiments with CRISPRLungo
Analyzing long-read CRISPR experiments with CRISPRLungo Open
Long-read sequencing can characterize complex genome editing-induced DNA sequence changes such as large deletions, insertions, and inversions that are difficult to detect using short-read sequencing. However, PCR amplification and sequenci…
View article: Discovery of A Small Molecule non-IMiD Degrader of ZBTB7A for the Treatment of β-hemoglobinopathies
Discovery of A Small Molecule non-IMiD Degrader of ZBTB7A for the Treatment of β-hemoglobinopathies Open
Sickle cell disease and β-thalassemia, two major β-hemoglobinopathies, pose significant clinical challenges globally. Current treatments often face limitations in efficacy and tolerability. The transcription factor ZBTB7A has emerged as a …
View article: The Red Blood Cell-Improving Transfusions for Chronically Transfused Recipients (RBC-IMPACT) study: protocol description of an international multi-site observational clinical study.
The Red Blood Cell-Improving Transfusions for Chronically Transfused Recipients (RBC-IMPACT) study: protocol description of an international multi-site observational clinical study. Open
This study will be the most detailed and granular evaluation of the predictive variables that may optimize RBC effectiveness and safety in these chronically transfused patient populations.
View article: Bone Marrow Adipokine Mediates Hematopoietic Regeneration and Stem Cell Fitness
Bone Marrow Adipokine Mediates Hematopoietic Regeneration and Stem Cell Fitness Open
Summary Bone marrow (BM) hematopoietic stem cells (HSCs) are exquisitely sensitive to cues from the BM microenvironment (ME), which is critical for their engraftment and regeneration following myeloablative stress. Retinoic acid signaling,…
View article: A progranulin variant causing childhood interstitial lung disease responsive to anti-TNF-α biologic therapy
A progranulin variant causing childhood interstitial lung disease responsive to anti-TNF-α biologic therapy Open
This work was supported by a grant from the Chan Zuckerberg Initiative Patient-Partnered Collaboration for single-cell analysis of rare inflammatory pediatric disease, the Corkin Family Fund for Research, and in part by cooperative agreeme…
View article: UM171 enhances fitness and engraftment of gene-modified hematopoietic stem cells from patients with sickle cell disease
UM171 enhances fitness and engraftment of gene-modified hematopoietic stem cells from patients with sickle cell disease Open
Hematopoietic stem cell (HSC) transplantation with lentiviral vector (LVV)-transduced autologous cells has proven an effective therapeutic strategy for sickle cell disease (SCD). However, ex vivo culture or proliferative stress associated …
View article: Antibody-mediated antigen loss switches augmented immunity to antibody-mediated immunosuppression
Antibody-mediated antigen loss switches augmented immunity to antibody-mediated immunosuppression Open
Antibodies against fetal red blood cell (RBC) antigens can cause hemolytic disease of the fetus and newborn (HDFN). Reductions in HDFN due to anti-RhD antibodies have been achieved through use of Rh immune globulin (RhIg), a polyclonal ant…
View article: Gene editing without<i>ex vivo</i>culture evades genotoxicity in human hematopoietic stem cells
Gene editing without<i>ex vivo</i>culture evades genotoxicity in human hematopoietic stem cells Open
SUMMARY Gene editing the BCL11A erythroid enhancer is a validated approach to fetal hemoglobin (HbF) induction for β-hemoglobinopathy therapy, though heterogeneity in edit allele distribution and HbF response may impact its safety and effi…
View article: Humanized V(D)J-rearranging and TdT-expressing mouse vaccine models with physiological HIV-1 broadly neutralizing antibody precursors
Humanized V(D)J-rearranging and TdT-expressing mouse vaccine models with physiological HIV-1 broadly neutralizing antibody precursors Open
Antibody heavy chain (HC) and light chain (LC) variable region exons are assembled by V(D)J recombination. V(D)J junctional regions encode complementarity-determining-region 3 (CDR3), an antigen-contact region immensely diversified through…
View article: Humanized V(D)J-rearranging and TdT-expressing Mouse Vaccine Models with Physiological HIV-1 Broadly Neutralizing Antibody Precursors
Humanized V(D)J-rearranging and TdT-expressing Mouse Vaccine Models with Physiological HIV-1 Broadly Neutralizing Antibody Precursors Open
Antibody heavy chain (HC) and light chain (LC) variable region exons are assembled by V(D)J recombination. V(D)J junctional regions encode complementarity-determining-region 3 (CDR3), an antigen-contact region immensely diversified through…
View article: Aging Predisposes B cells to Malignancy by Activating c-Myc and Perturbing the Genome and Epigenome
Aging Predisposes B cells to Malignancy by Activating c-Myc and Perturbing the Genome and Epigenome Open
Age is the single major risk factor for human cancer, but naturally occurring cancers are rarely studied in aging models. Like humans, mice spontaneously develop cancer with age, and standard laboratory strains are predisposed for B-cell l…
View article: Targeting multiple cell death pathways extends the shelf life and preserves the function of human and mouse neutrophils for transfusion
Targeting multiple cell death pathways extends the shelf life and preserves the function of human and mouse neutrophils for transfusion Open
Survival of neutrophils is prolonged, and their function is preserved by simultaneously targeting multiple cell death pathways.
View article: Post-Transcriptional Genetic Silencing of <i>BCL11A</i> to Treat Sickle Cell Disease
Post-Transcriptional Genetic Silencing of <i>BCL11A</i> to Treat Sickle Cell Disease Open
This study validates BCL11A inhibition as an effective target for HbF induction and provides preliminary evidence that shmiR-based gene knockdown offers a favorable risk-benefit profile in sickle cell disease. (Funded by the National Insti…
View article: Serine/threonine phosphatase PP2A is essential for optimal B cell function
Serine/threonine phosphatase PP2A is essential for optimal B cell function Open
Protein phosphatase 2A (PP2A), a serine/threonine phosphatase, has been shown to control T cell function. We found that in vitro-activated B cells and B cells from various lupus-prone mice and patients with systemic lupus erythematosus dis…
View article: Successful hematopoietic stem cell mobilization and apheresis collection using plerixafor alone in sickle cell patients
Successful hematopoietic stem cell mobilization and apheresis collection using plerixafor alone in sickle cell patients Open
Novel therapies for sickle cell disease (SCD) based on genetically engineered autologous hematopoietic stem and progenitor cells (HSPCs) are critically dependent on a safe and effective strategy for cell procurement. We sought to assess th…
View article: Hypomorphic Rag1 mutations alter the preimmune repertoire at early stages of lymphoid development
Hypomorphic Rag1 mutations alter the preimmune repertoire at early stages of lymphoid development Open
Key Points Mice with hypomorphic mutations in the Rag1 C-terminal domain are a model of leaky combined immunodeficiency with autoantibodies. Hypomorphic C-terminal domain Rag1 mutations cause repertoire skewing at the earliest stages of B-…
View article: Evaluation of the Role of <i>stat3</i> in Antibody and T <sub>H</sub> 17-Mediated Responses to Pneumococcal Immunization and Infection by Use of a Mouse Model of Autosomal Dominant Hyper-IgE Syndrome
Evaluation of the Role of <i>stat3</i> in Antibody and T <sub>H</sub> 17-Mediated Responses to Pneumococcal Immunization and Infection by Use of a Mouse Model of Autosomal Dominant Hyper-IgE Syndrome Open
Loss-of-function mutations in the signal transducer and activator of transcription 3 gene ( stat3 ) result in autosomal dominant hyper-IgE syndrome (AD-HIES), a condition in which patients have recurrent debilitating infections, including …
View article: Natural Killer Cells from Patients with Recombinase-Activating Gene and Non-Homologous End Joining Gene Defects Comprise a Higher Frequency of CD56bright NKG2A+++ Cells, and Yet Display Increased Degranulation and Higher Perforin Content
Natural Killer Cells from Patients with Recombinase-Activating Gene and Non-Homologous End Joining Gene Defects Comprise a Higher Frequency of CD56bright NKG2A+++ Cells, and Yet Display Increased Degranulation and Higher Perforin Content Open
Mutations of the recombinase-activating genes 1 and 2 (RAG1 and RAG2) in humans are associated with a broad range of phenotypes. For patients with severe clinical presentation, hematopoietic stem cell transplantation (HSCT) represents the …
View article: <i>EXTL3</i> mutations cause skeletal dysplasia, immune deficiency, and developmental delay
<i>EXTL3</i> mutations cause skeletal dysplasia, immune deficiency, and developmental delay Open
We studied three patients with severe skeletal dysplasia, T cell immunodeficiency, and developmental delay. Whole-exome sequencing revealed homozygous missense mutations affecting exostosin-like 3 (EXTL3), a glycosyltransferase involved in…