A5030405143- CRISPR and Genetic Engineering
- Spaceflight effects on biology
- Liver physiology and pathology
- Microbial Inactivation Methods
- T-cell and B-cell Immunology
- Virus-based gene therapy research
- Magnetic and Electromagnetic Effects
- Organ Transplantation Techniques and Outcomes
- Cellular Mechanics and Interactions
- Pluripotent Stem Cells Research
- RNA Interference and Gene Delivery
- Hepatocellular Carcinoma Treatment and Prognosis
- Genetics, Aging, and Longevity in Model Organisms
- Microfluidic and Bio-sensing Technologies
- 3D Printing in Biomedical Research
- Immunotherapy and Immune Responses
- Hedgehog Signaling Pathway Studies
- Pharmacological Effects and Toxicity Studies
- HIV/AIDS drug development and treatment
- Pancreatic function and diabetes
- MicroRNA in disease regulation
- Antibiotics Pharmacokinetics and Efficacy
- Wnt/β-catenin signaling in development and cancer
- Epilepsy research and treatment
- Phagocytosis and Immune Regulation
University of Michigan
2001-2025
University of California, San Francisco
2016-2025
University of Illinois Urbana-Champaign
2022
Beckman Research Institute
1998-2020
City of Hope
1998-2020
City Of Hope National Medical Center
2006-2016
San Francisco VA Medical Center
2008
Harvard University
1999-2003
Brigham and Women's Hospital
1999-2003
Justus-Liebig-Universität Gießen
2003
Abstract The inducible costimulatory (ICOS) molecule is expressed by activated T cells and has homology to CD28 CD152. ICOS binds B7h, a APC with CD80 CD86. To investigate regulation of expression its role in Th responses we developed anti-mouse mAbs ICOS-Ig fusion protein. Little freshly isolated mouse cells, but rapidly up-regulated on most CD4+ CD8+ following stimulation the TCR. Strikingly, up-regulation significantly reduced absence CD86 can be restored stimulation, suggesting that...
Understanding cell biology of three-dimensional (3D) biological structures is important for more complete appreciation in vivo tissue function and advancing ex organ engineering efforts. To elucidate how 3D structure may affect hepatocyte cellular responses, we compared global gene expression human liver hepatocellular carcinoma line (HepG2) cells cultured as monolayers on culture dishes (TCDs) or spheroids within rotating wall vessel (RWV) bioreactors. HepG2 grown RWVs form up to 100 μm...
Matrix rigidity has important effects on cell behavior and is increased during liver fibrosis; however, its effect primary hepatocyte function unknown. We hypothesized that matrix in fibrotic livers would activate mechanotransduction hepatocytes lead to inhibition of liver-specific functions. To determine the physiologically relevant ranges stiffness at cellular level, we performed detailed atomic force microscopy analysis across lobules from normal livers. determined was around 150 Pa 1-6...
The importance of B7 costimulation in regulating T cell expansion and peripheral tolerance suggests that it may also play a significant regulatory role the development autoimmune disease. It is unclear whether involved only autoreactive cells periphery, or if required for effector activation target organ mediating tissue injury propagating In this study, B7–CD28 relative costimulators induction phases experimental encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG)...
This study tested the hypothesis that transcription of immediate early genes is inhibited in T cells activated μg. Immunosuppression during spaceflight a major barrier to safe, long-term human space habitation and travel. The goals these experiments were prove μg was cause impaired cell activation spaceflight, as well understand mechanisms controlling activation. from four donors stimulated with Con A anti-CD28 on board ISS. An on-board centrifuge used generate 1g simultaneous control...
The T cell response to the 65-kD mycobacterial heat-shock protein (Bhsp65) has been implicated in pathogenesis of autoimmune arthritis. Adjuvant arthritis (AA) induced Lewis rat (RT-1l) by injection Mycobacterium tuberculosis serves as an experimental model for human rheumatoid (RA). However, immunological basis regulation acute AA, or susceptibility/resistance AA is not known. We have defined specificity proliferative responses Bhsp65 during course rat. During early phase disease (6–9 d...
Plasma levels of diphenylhydantoin and the urinary excretion its hydroxylated metabolite were studied in 6 normal adults following single intravenous doses 0.25 Gm. DPH‐sodium. The high initial plasma dropped rapidly to a mean value 6.3 µg per milliliter 20 minutes after dosing 5.2 one hour; half‐life later time periods was about 15 hours (range 11 29 hours). Urinary free conjugated HPPH 5 subjects, measured by new gas‐chromatography procedure, accounted for 76 cent dose 65 81 cent) over...
Abstract Spinal muscular atrophy (SMA) is one of the most common autosomal recessive disorders in humans and a genetic cause infant mortality. The disease caused by loss survival motoneuron (SMN) protein, resulting degeneration alpha motoneurons spinal cord limbs trunk. One function SMN involves RNA splicing. It unclear why deficiency housekeeping such as splicing causes profound effects only on but not other cell types. difficulty studying SMA scarcity patient's samples. discovery that...
We evaluated the effect of water-soluble vitamin E (d-α-tocopheryl polyethylene glycol 1000 succinate [TPGS]; Liqui-E) on oral pharmacokinetics cyclosporine, a poorly available (~30%) drug, in healthy volunteers. Ten subjects were given two doses cyclosporine (10 mg/kg) separated by 7-day washout period. Oral TPGS (2.6 IU/kg) was administered concomitantly with one randomized order. A significant increase observed area under blood concentration-time curve (AUC; mean ± SD) concomitant...
Altered immune function has been demonstrated in astronauts during spaceflights dating back to Apollo and Skylab; this could be a major barrier long-term space exploration. We tested the hypothesis that spaceflight causes changes microRNA (miRNA) expression. Human leukocytes were stimulated with mitogens on board International Space Station using an onboard normal gravity control. Bioinformatics showed miR-21 was significantly up-regulated 2-fold early T-cell activation gravity, gene...
The health risks of a dysregulated immune response during spaceflight are important to understand as plans emerge for humans embark on long-term space travel Mars. In this first-of-its-kind study, we used adoptive transfer T-cell receptor transgenic OT-II CD4 T cells track an in vivo antigen-specific that was induced the course spaceflight. Experimental mice destined and remained ground received transferred cognate peptide stimulation with ovalbumin (OVA) 323-339 plus inflammatory adjuvant,...
CRISPR-Cas9 has been developed into a powerful molecular tool for genome engineering, and it revolutionized the field of biomedical research. Despite tremendous potential in research, precise control over dose exposure time is important to expand its applications. In this study, we fused Cas9 with peptide termed small molecule-assisted shut-off (SMASh) consisting protease domain degron derived from hepatitis C virus (HCV). The presence SMASh allows tight stability via clinically approved HCV...
This technical paper introduces a novel organ preservation system based on isochoric (constant volume) supercooling. The is designed to enhance the stability of metastable supercooling state, offering potential long-term large biological organs at subfreezing temperatures without need for cryoprotectant additives. Detailed designs and usage protocols are provided researchers interested in exploring this field. also presents control thermodynamics freezing, utilizing pressure monitoring...
This study was motivated by the increasing interest in finding ways to preserve organs a supercooled state for transplantation. Previous research with small volumes suggests that isochoric (constant volume) thermodynamic enhances stability of solutions. The primary objective this investigate feasibility storing large organ, such as pig liver, metastable clinically relevant durations. To achieve this, we designed new technology employs system consisting two domains separated an interior...
Background: Rho-associated kinases 1 and 2 (ROCK1 ROCK2) regulate critical cell functions, including actomyosin contractility, apoptosis, proliferation. Some studies suggest that ROCK inhibition may serve as a treatment for liver fibrosis. More investigation is needed to understand the role of hepatocyte signaling in vivo, especially context profibrotic injury. Methods: Rock1 fl/fl , Rock2 ; mice were given adeno-associated virus serotype 8 (AAV8)-thyroid hormone-binding globulin (TBG)-Cre...
Abstract Human induced pluripotent stem cell (iPSC)-derived liver organoids serve as models of organogenesis, disease, drug screening, and regenerative medicine. Prevailing methods for generating rely on Matrigel, whose batch-to-batch variability xenogeneic source pose challenges to mechanistic research translation human clinical therapy. In this report, we demonstrate that self-assembled Matrigel-free iPSC-derived developed in rotating wall vessels (RWVs) exhibit greater hepatocyte-specific...
Abstract Background Naturally occurring dietary patterns, a major contributor to health, are not well described among those with cardiovascular disease (CVD) – particularly in light of socioeconomic vulnerability. We sought identify patterns the US and their distribution by CVD, social risk factors, Supplemental Nutrition Assistance Program (SNAP) participation. Methods This was cross-sectional study 32,498 noninstitutionalized adults from National Health Examination Survey (2009-2020). used...