A5012126522- Sarcoma Diagnosis and Treatment
- Cancer Research and Treatments
- HIV Research and Treatment
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Cytomegalovirus and herpesvirus research
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- Infant Nutrition and Health
- HIV/AIDS Research and Interventions
- Protein Degradation and Inhibitors
- Cancer Cells and Metastasis
- Gastrointestinal Tumor Research and Treatment
- Immune cells in cancer
- Bone Tumor Diagnosis and Treatments
- Cardiac tumors and thrombi
- Herpesvirus Infections and Treatments
- SARS-CoV-2 and COVID-19 Research
- Breastfeeding Practices and Influences
- Inflammatory Biomarkers in Disease Prognosis
- Clostridium difficile and Clostridium perfringens research
- Radiopharmaceutical Chemistry and Applications
- Gut microbiota and health
- Infant Health and Development
Duke University
2015-2025
Duke Medical Center
2015-2024
Duke University Hospital
2019-2023
City of Hope
2017
Beckman Research Institute
2017
Nearly two-thirds of cancer patients are treated with radiation therapy (RT), often the intent to achieve complete and permanent tumor regression (local control). RT is primary treatment modality used local control for many malignancies, including locally advanced cervical cancer, head neck lung cancer. The addition concurrent platinum-based radiosensitizing chemotherapy improves patient survival. Enhanced outcomes chemoradiotherapy may result from increased direct killing cells effects on...
Abstract Immunotherapy fails to cure most cancer patients. Preclinical studies indicate that radiotherapy synergizes with immunotherapy, promoting radiation-induced antitumor immunity. Most preclinical immunotherapy utilize transplant tumor models, which overestimate patient responses. Here, we show sarcomas are cured by PD-1 blockade and radiotherapy, but identical treatment in autochthonous sarcomas, demonstrate immunoediting, decreased neoantigen expression, tumor-specific immune...
Sarcoma is a rare, aggressive and highly metastatic disease. The efficacy of current treatment approaches including surgery, chemotherapy radiation limited hence the recent focus in novel immunotherapy. However, immunotherapy research for sarcoma impeded by our understanding antitumor immune responses, largely due to lack faithful mouse models expressing known neoantigens. Here, we combined CRISPR/Cas9 sleeping beauty transposase technology develop an autochthonous orthotopic murine model...
Abstract African green monkeys (AGMs) are natural primate hosts of simian immunodeficiency virus (SIV). Interestingly, features the envelope-specific antibody responses in SIV-infected AGMs distinct from that HIV-infected humans and rhesus monkeys, including gp120-focused rapid development autologous neutralization. Yet, lack genetic tools to evaluate B-cell lineages hinders potential use this unique non-human model for HIV vaccine development. Here we define AGM Ig loci compare proportion...
Breast milk HIV-1 transmission is currently the predominant contributor to pediatric HIV infections. Yet, only ~10% of breastfeeding infants born untreated HIV-infected mothers become infected. This study assessed protective capacity natural envelope-specific antibodies isolated from women in an infant rhesus monkey (RM), tier 2 SHIV oral challenge model. To mimic placental and maternal antibody transfer, RMs were i.v. infused orally treated at time with a single weakly neutralizing...
Human cytomegalovirus (HCMV) is the most common congenital infection worldwide and leading infectious cause of neurologic deficits hearing loss in newborns. Development a maternal HCMV vaccine to prevent vertical virus transmission high priority, yet protective immune responses following acute are poorly understood. To characterize humoral response primary CMV infection, we investigated plasmablast early antibody repertoire using nonhuman primate model with two acutely rhesus...
The initial phases of acute human immunodeficiency virus type 1 (HIV-1) infection may be critical for development effective envelope (Env)-specific antibodies capable impeding the establishment latent pool HIV-1-infected CD4(+) T cells, preventing virus-induced immune hyperactivation to limit disease progression and blocking vertical transmission. However, systemic HIV-1 Env-specific antibody response targets gp41 epitopes fails control acute-phase viremia. African-origin, natural simian...
Abstract This study aims to investigate whether adding neoadjuvant radiotherapy (RT), anti-programmed cell death protein-1 (PD-1) antibody (anti–PD-1), or RT + anti-PD-1 surgical resection improves disease-free survival for mice with soft tissue sarcomas (STS). We generated a high mutational load primary mouse model of STS by intramuscular injection adenovirus expressing Cas9 and guide RNA targeting Trp53 3-methylcholanthrene (MCA) into the gastrocnemius muscle wild-type (p53/MCA model)....
Radiation therapy (RT) is frequently used to treat cancers, including soft-tissue sarcomas. Prior studies established that the toll-like receptor 9 (TLR9) agonist cytosine-phosphate-guanine oligodeoxynucleotide (CpG) enhances response RT in transplanted tumors, but mechanisms of this enhancement remain unclear. Here, we CRISPR/Cas9 and chemical carcinogen 3-methylcholanthrene (MCA) generate autochthonous sarcomas with high tumor mutation burden. Treatment a single fraction 20 Gy 2 doses CpG...
Abstract Despite impressive responses in some patients, immunotherapy fails to cure most cancer patients. Preclinical studies indicate that radiotherapy synergizes with immunotherapy, promoting radiation-induced antitumor immunity. Nearly all preclinical utilize transplant tumor models, but rates of models treated often overestimate patient responses. Here, we show tumors are cured by PD-1 blockade and radiotherapy, identical treatment autochthonous tumors. We generated a single-cell atlas...
Unlike human immunodeficiency virus type 1 (HIV-1)-infected humans, African-origin, natural simian (SIV) hosts, such as African green monkeys (AGMs), sustain nonpathogenic SIV infections and rarely vertically transmit to their infants. Interestingly, chronically SIV-infected AGMs have anatomically compartmentalized variants in plasma milk, whereas humans rhesus (RMs), Asian-origin nonnatural do not exhibit this compartmentalization. Thus, it is possible that AGM populations milk unique...
<p>SU2C-SARC032 clinical trial study design</p>
<p>Long-term survival of an autochthonous p53/MCA mouse model in immunocompetent 129/SvJae wild-type mice induced by CRISPR/Cas9</p>
<p>Additional lung abnormalities noted on CT and histology</p>
<p>Long-term metastases study of an autochthonous p53/MCA mouse model STS induced by Cre-LoxP technology using TRP53 fl/fl mice</p>
<p>Long-term survival of an autochthonous p53/MCA mouse model in immunocompetent 129/SvJae wild-type mice induced by CRISPR/Cas9</p>
<p>SU2C-SARC032 clinical trial study design</p>
<p>Long-term metastases study of an autochthonous p53/MCA mouse model STS induced by Cre-LoxP technology using TRP53 fl/fl mice</p>