A5072678549- Bone Metabolism and Diseases
- NF-κB Signaling Pathways
- Bone health and treatments
- T-cell and Retrovirus Studies
- Vector-Borne Animal Diseases
- Animal Disease Management and Epidemiology
- RNA Research and Splicing
- Fungal and yeast genetics research
- Ubiquitin and proteasome pathways
- Radiopharmaceutical Chemistry and Applications
- Diet and metabolism studies
- Pancreatic function and diabetes
- Renal Transplantation Outcomes and Treatments
- Cardiac Structural Anomalies and Repair
- Transplantation: Methods and Outcomes
- TGF-β signaling in diseases
- Chemokine receptors and signaling
- Respiratory viral infections research
- Multiple Myeloma Research and Treatments
- Mechanical Circulatory Support Devices
- CRISPR and Genetic Engineering
- Cardiovascular Issues in Pregnancy
- Adipose Tissue and Metabolism
- Genomics and Chromatin Dynamics
Lucile Packard Children's Hospital
2024
Amgen (United States)
2004-2007
IDEX Corporation (United States)
1999-2002
Fred Hutch Cancer Center
1996
Colorado State University
1993-1994
The physiological role of the TNF receptor (TNFR) family member, RANK, was investigated by generating RANK-deficient mice. RANK(-/-) mice were characterized profound osteopetrosis resulting from an apparent block in osteoclast differentiation. RANK expression not required for commitment, differentiation, and functional maturation macrophages dendritic cells their myeloid precursors but provided a necessary specific signal differentiation myeloid-derived osteoclasts. also exhibited marked...
Signaling through receptor activator of nuclear factor-κB (RANK) is essential for the differentiation and activation osteoclasts, cell principally responsible bone resorption. Animals genetically deficient in RANK or cognate ligand are profoundly osteopetrotic because lack resorption remodeling. provokes biochemical signaling via recruitment intracellular tumor necrosis factor receptor-associated factors (TRAFs) after binding oligomerization. To understand RANK-mediated signal transduction...
Abstract BACKGROUND Metastases to bone are a frequent complication of human prostate cancer and result in the development osteoblastic lesions that include an underlying osteoclastic component. Previous studies rodent models breast have established receptor activator NF‐κB ligand (RANKL) inhibition decreases lesion tumor growth bone. RANK is essential for osteoclast differentiation, activation, survival via its expression on osteoclasts their precursors. has also been observed some cell...
Transcription repression by the basic region-helix-loop-helix-zipper (bHLHZip) protein Mad1 requires DNA binding as a ternary complex with Max and mSin3A or mSin3B, mammalian orthologs of Saccharomyces cerevisiae transcriptional corepressor SIN3. The interaction between mSin3 is mediated three potential amphipathic alpha-helices: one in N terminus Mad (mSin domain, SID) two within second paired helix domain (PAH2) mSin3A. Mutations that alter structure SID inhibit vitro inactivate Mad's...
The Tax protein, encoded by the human T-cell leukemia virus type I, is a potent activator of viral and cellular gene transcription. does not bind DNA directly but appears to trans-activate through an interaction with host-cell transcription factors that recognize sequences within promoters Tax-responsive genes. Cellular transcriptional activators implicated in mediating trans-activation include members activating factor/cAMP response element binding protein (ATF/CREB) family proteins, serum...
RANK and RANKL, the key regulators of osteoclast differentiation activation, also play an important role in control proliferation mammary epithelial cells during pregnancy. Here, we show that protein expression is strictly regulated a spatial temporal manner gland development. overexpression under mouse tumor virus (MMTV) promoter transgenic model results increased cell pregnancy, impaired lobulo-alveolar structures, decreased milk proteins β-casein whey acidic protein, deficient lactation....
Abstract Tumor cells induce excessive osteoclastogenesis, mediating pathologic bone resorption and subsequent release of growth factors calcium from matrix, resulting in a “vicious cycle” breakdown tumor proliferation. RANK ligand (RANKL) is an essential mediator osteoclast formation, function, survival. In metastatic prostate cancer models, RANKL inhibition directly prevents osteolysis via blockade osteoclastogenesis indirectly reduces progression skeletal burden by reducing local factor...
Signaling through the receptor activator of nuclear factor κB (RANK) is required for both osteoclast differentiation and mammary gland development, yet extent to which RANK utilizes similar signaling pathways in these tissues remains unclear. Mice expressing a kinase-inactive form inhibitor kinase α (IKKα) have defects those RANK-null mice apparently normal function. Because that completely lack IKKα severe skin skeletal are not associated with IKKα-kinase activity, we wished directly...
Abstract Development of new therapies for myeloma has been hindered by the lack suitable preclinical animal models disease in which widespread tumor foci skeleton can be detected reliably. Traditional means detecting skeletal infiltration such as histopathology are cumbersome and labor-intensive do not allow temporal monitoring progression or regression response to therapy. To resolve this problem, we modified Radl 5TGM1 model bone that fluorescent tumors optically imaged situ. Here, show...
Abstract Receptor activator of NF-κB (RANK) and its ligand (RANKL) are essential for osteoclast formation, function, survival. Osteoprotegerin (OPG) inhibits RANK signaling by sequestering RANKL. This study evaluated the antiosteoclast immunoregulatory effects mouse rRANK-Fc, which, similar to OPG, can bind The effect RANKL inhibition RANK-Fc on function was determined vitamin D3 (1,25(OH)2D3)-induced hypercalcemia. Mice were injected with a single dose 0, 10, 100, 500, or 1000 μg RANK-Fc;...
The human T-cell leukemia virus type I (HTLV-I) oncoprotein Tax is a potent activator of viral and cellular gene transcription. does not bind DNA directly but utilizes transcription factors to mediate activation. In this report, we examine the role basic helix-loop-helix (bHLH) proteins in deregulation expression, as these play critical progression through cell cycle have been implicated neoplastic disease. We show that bHLH do activation, instead repression expression presence Tax. further...
Abstract Background Disparities in pediatric heart transplant outcomes based on socioeconomic status (SES) have been previously observed. However, there is a need to reevaluate these associations contemporary settings with advancements therapies and increased awareness of health disparities. This retrospective study aims investigate the relationship between SES for patients. Methods Data were collected through chart review 176 patients who underwent first orthotopic transplantation (OHT) at...