A5003258065- Organ Transplantation Techniques and Outcomes
- Renal Transplantation Outcomes and Treatments
- Transplantation: Methods and Outcomes
- Liver Disease and Transplantation
- Xenotransplantation and immune response
- Organ Donation and Transplantation
- Virus-based gene therapy research
- Pancreatic function and diabetes
- Viral Infections and Immunology Research
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- RNA Interference and Gene Delivery
- Liver Disease Diagnosis and Treatment
- T-cell and B-cell Immunology
- Diversity and Career in Medicine
- HIV/AIDS drug development and treatment
- Tissue Engineering and Regenerative Medicine
- HIV Research and Treatment
- Complement system in diseases
- Viral gastroenteritis research and epidemiology
- Viral-associated cancers and disorders
- Clinical Nutrition and Gastroenterology
- Polyomavirus and related diseases
- Innovations in Medical Education
- Adenosine and Purinergic Signaling
Duke University
2017-2025
Duke Medical Center
2018-2025
Yahoo (United Kingdom)
2024
Durham Technical Community College
2023
Shaanxi University of Chinese Medicine
2022-2023
Duke University Hospital
2021-2022
Johns Hopkins University
2013-2014
Prior studies of anti-CD40 ligand (CD40L)–based immunosuppression demonstrated effective prevention islet and kidney allograft rejection in nonhuman primate models; however, clinical development was halted because thromboembolic complications. An anti-CD40L-specific monoclonal antibody, AT-1501 (Tegoprubart), engineered to minimize risk complications by reducing binding Fcγ receptors expressed on platelets while preserving CD40L. tested both a cynomolgus macaque model intrahepatic...
Current desensitization and maintenance immunosuppression regimens for kidney transplantation in sensitized individuals show limited ability to control the posttransplant humoral response, resulting high rates of antibody-mediated rejection (ABMR) graft failure. Here, we showed that anti-CD154 monoclonal antibody (mAb)–based more effectively controlled allograft rebound a highly nonhuman primate model compared with tacrolimus-based standard-of-care (SOC) immunosuppression. Desensitization an...
To investigate trends in long-term graft and patient outcomes following liver transplantation using grafts from donors ≥60 years old.The scarcity of donor livers has led to increased utilization organs old. However, few studies have examined how transplant older evolved over time.The OPTN/UNOS database was queried for all first-time isolated adult transplants. We identified 14,796 ≧60-year-old suitable analysis 1990 2014. Cohorts were then developed based on 5-year intervals date....
Machine preservation (MP) has emerged as a promising technology in liver transplantation, but the cellular processes occurring during MP have not been characterized. Recent studies noted presence of inflammatory molecules generated MP. We hypothesized that there is metabolism‐dependent accumulation damage‐associated molecular patterns (DAMPs) and cytokines these provoke inflammation graft. To stratify groups by metabolic rate, was performed on rat livers from standard donors at 3 different...
Background. Ex vivo kidney perfusion is an evolving platform that demonstrates promise in preserving and rehabilitating the grafts. Despite this, there little consensus on optimal conditions. Hypothermic offers limited functional assessment, whereas normothermic requires a more complex mechanical system perfusate. Subnormothermic machine (SNMP) has potential to combine advantages of both approaches but undergone investigation. Therefore, present study sought determine suitability SNMP for...
The human immunodeficiency virus type 1 (HIV-1)-encoded virion infectivity factor (Vif) is required to inactivate the host restriction APOBEC3 by engaging Cullin 5 (Cul5)-RING ubiquitin ligase (CRL5). Core binding beta (CBF-β) a novel regulator of Vif-CRL5 function; as yet, its mechanism regulation remains unclear. In present study, we demonstrate that CBF-β promotion assembly independent influence on Vif stability and also conserved feature primate lentiviral proteins. Furthermore, critical...
HIV-1 Vif promotes the degradation of host anti-retroviral factor family, APOBEC3 proteins via recruitment a multi-subunit E3 ubiquitin ligase complex. The complex is composed scaffold protein, Cullin 5 (Cul5), RING-box protein (Rbx), SOCS box binding complex, Elongins B/C (Elo B/C), as well newly identified co-factor, core beta (CBF-β). Cul5 has previously been shown to bind amino acids within an HCCH domain PPLP motif at C-terminus Vif; however, it unclear whether requires additional...
Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) restricts human immunodeficiency virus type (HIV-1) infection in myeloid cells but is inactivated by certain classes of simian (SIV) Vpx proteins. proteins recruit the DCAF1-CRL4 E3 ubiquitin ligase to trigger species-specific SAMHD1 degradation. Determinants SIV Vpx-mediated primate degradation have been mapped its C terminus. In this study, we identified N terminus as a major determinant suppression. The SIVmnd2 SIVrcm...
Porcine islet xenografts have the potential to provide an inexhaustible source of islets for β cell replacement. Proof-of-concept has been established in nonhuman primates. However, significant barriers xenoislet transplantation remain, including poorly understood instant blood-mediated inflammatory reaction and a thorough understanding early xeno-specific immune responses. A paucity data exist comparing responses with alloislet (AI) We recently developed dual transplant model, which enables...
Abstract Background Membrane cofactor protein CD46 attenuates the complement cascade by facilitating cleavage of C3b and C4b. In solid organ xenotransplantation, organs expressing have been shown to resist hyperacute rejection. However, incremental value human expression for islet xenotransplantation remains poorly defined. Methods This study attempted delineate role in early neonatal porcine engraftment comparing Gal‐knocked out (GKO) hCD46‐transgenic (GKO/CD46) islets a dual transplant...
Abstract Background Thrombosis is a known consequence of intraportal islet transplantation, particularly for xenogeneic islets. To define the origins thrombosis after xenotransplantation and relate it to early inflammation, we examined porcine islets transplanted into non‐human primates using dual‐transplant model directly compare characteristics. Methods α1,3‐Galactosyltransferase gene‐knockout (GTKO) with without expression human complement regulatory transgene CD46 (hCD46) were studied....
Porcine islet xenotransplantation is a viable strategy to treat diabetes. Its translation has been limited by the pre-clinical development of clinically available immunosuppressive regimen. We tested two relevant induction agents in non-human primate (NHP) model compare depletional versus nondepletional immunosuppression. Neonatal porcine islets were isolated from GKO or hCD46/GKO transgenic piglets and transplanted via portal vein infusion diabetic rhesus macaques. Induction therapy...