A5078775033- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Erythropoietin and Anemia Treatment
- Glycosylation and Glycoproteins Research
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Radiopharmaceutical Chemistry and Applications
- T-cell and B-cell Immunology
- Chronic Lymphocytic Leukemia Research
- Cytokine Signaling Pathways and Interactions
- 3D Printing in Biomedical Research
- PARP inhibition in cancer therapy
- Renal and related cancers
- Virus-based gene therapy research
- Erythrocyte Function and Pathophysiology
- Acute Myeloid Leukemia Research
- Zebrafish Biomedical Research Applications
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Advanced Biosensing Techniques and Applications
- Cell death mechanisms and regulation
- Nanofabrication and Lithography Techniques
- Pancreatic function and diabetes
- RNA Interference and Gene Delivery
- Genetic and Kidney Cyst Diseases
IGM Biosciences (United States)
2019-2024
Amgen (United States)
2005-2015
Palmetto Hematology Oncology
2010
Whitehead Institute for Biomedical Research
2005
The University of Texas Southwestern Medical Center
2001-2003
Yale University
2003
Howard Hughes Medical Institute
2003
Aarhus University
2002
Wellcome Sanger Institute
2002
University of Cambridge
1999-2002
Polycystic kidney disease (PKD) is the most common genetic cause of renal failure in humans. Several proteins that are encoded by genes associated with PKD have recently been identified primary cilia tubular epithelia. These findings suggested abnormalities formation and function may play a role pathogenesis PKD. To directly determine whether essential to maintain integrity, we conditionally inactivated KIF3A, subunit kinesin-II for formation, Constitutive inactivation KIF3A produces...
Abstract Osteoclasts differentiate from the hemopoietic monocyte/macrophage cell lineage in bone marrow through cell-cell interactions between osteoclast progenitors and stromal/osteoblastic cells. Here we show another differentiation pathway closely connected with B lymphocyte differentiation. Recently TNF family molecule factor/receptor activator of NF-κB ligand (ODF/RANKL) was identified as a key membrane-associated factor regulating We demonstrate that B-lymphoid cells are major source...
Hepatocyte nuclear factor-1beta (HNF-1beta) is a Pit-1, Oct-1/2, UNC-86 (POU)/homeodomain-containing transcription factor that regulates tissue-specific gene expression in the liver, kidney, and other organs. Humans with autosomal dominant mutations of HNF-1beta develop maturity-onset diabetes young type 5 (MODY5) congenital cystic abnormalities kidney. Autosomal recessive polycystic kidney disease (ARPKD) an inherited disorder produces renal failure infants children caused by PKHD1. The...
SUMMARY The SCL gene encodes a basic helix-loop-helix transcription factor which is expressed in early haematopoietic progenitors throughout ontogeny and essential for the normal development of blood vessels. Transgenic studies have characterised spatially distinct 5’ enhancers direct lacZ expression to subdomains pattern, but same elements failed produce appropriate expression. We now describe an 3’ enhancer with unique properties. It directed transgenic mice extra-embryonic mesoderm...
Hepatocyte nuclear factor–1β (HNF-1β) is a Pit-1, Oct-1/2, UNC-86 (POU)/homeodomain-containing transcription factor that regulates tissue-specific gene expression in the liver, kidney, and other organs. Humans with autosomal dominant mutations of HNF-1β develop maturity-onset diabetes young type 5 (MODY5) congenital cystic abnormalities kidney. Autosomal recessive polycystic kidney disease (ARPKD) an inherited disorder produces renal failure infants children caused by PKHD1. The proximal...
Erythropoietin (Epo) is an essential hormone that binds and activates the Epo receptor (EpoR) resident on surface of erythroid progenitor cells, thereby promoting erythropoiesis. Recombinant human erythropoietin has been used successfully for over 20 years to treat anemia in millions patients. In addition erythropoiesis, also reported have other effects, such as tissue protection promotion tumor cell growth or survival. This became significant concern 2003, when some clinical trials cancer...
The CD33/CD3-bispecific T-cell engaging (BiTE) antibody construct, AMG 330, potently lyses CD33+ leukemic cells in vitro. Using specimens from 41 patients with acute myeloid leukemia (AML), we studied the factors that might contribute to clinical response or resistance. For this purpose, thawed aliquots of primary AML samples were immunophenotypically characterized and subjected various doses 330 presence absence healthy donor T-cells. After 48 hours, drug-specific cytotoxicity was...
Abstract Death receptor 5 (DR5) is an attractive target for cancer therapy due to its broad upregulated expression in multiple cancers and ability directly induce apoptosis. Though anti-DR5 IgG antibodies have been evaluated clinical trials, limited efficacy has attributed insufficient crosslinking. IGM-8444 engineered, multivalent agonistic IgM antibody with 10 binding sites DR5 that induces cell apoptosis through efficient multimerization. bound high avidity was substantially more potent...
The mouse hematopoietic marker Sca-1, encoded by the Ly-6E.1 and Ly-6A.2 genes, has been instrumental in enrichment characterization of stem cell for adult blood system. In studies reported here, we use genomic fragments to direct expression a lacZ transgene vivo study specific regulatory elements localize these cells developing embryo. We demonstrate that region approximately 9 kb downstream from transcriptional start site is required distinct, restricted pattern Ly-6E.1-lacZ within...
Erythropoietin receptor (EpoR) has been reported to be overexpressed in tumours and raised safety concerns regarding the use of erythropoiesis-stimulating agents (ESAs) treat anaemia cancer patients. To investigate potential for EpoR tumours, we have evaluated human amplification EPOR locus, levels transcripts, expression surface protein. Gene analysis 1083 solid found that locus was rare with frequencies similar other non-oncogenes. transcript tumour cell lines were low comparison bone...
Recombinant human erythropoietin (rHuEPO), such as the approved agents epoetin alfa and beta, has been used successfully for over 20 years to treat anemia in millions of patients. However, due relatively short half-life molecule (approximately 8 hours), frequent dosing may be required achieve hemoglobin levels. Therefore, a need was identified some anemic patient populations erythropoiesis stimulating with longer half-lives that less dosing. This led development second generation molecules...
Abstract Resistance to FLT3 inhibitors is a serious clinical issue in treating acute myelogenous leukemia (AML). AMG 925, dual FLT3/CDK4 inhibitor, has been developed overcome this resistance. It hypothesized that the combined inhibition of and CDK4 may reduce occurrence resistance mutations, thereby prolong responses. To test hypothesis, we attempted isolate AML cell clones resistant 925 or inhibitors. After selection over 8 months with could only partially clones. No new mutations were...
Aberrant activation of Wnt/β-catenin signaling occurs frequently in cancer. However, therapeutic targeting this pathway is complicated by the role Wnt stem cell maintenance and tissue homeostasis. Here, we evaluated antibodies blocking 6 10 human Wnt/Frizzled (FZD) receptors as potential therapeutics. Crystal structures revealed a common binding site for these monoclonal (mAbs) on FZD, interaction with palmitoleic acid moiety. mAbs displayed gastrointestinal toxicity or poor plasma exposure...