A5032500370- Radiation Therapy and Dosimetry
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Advanced Radiotherapy Techniques
- Cerebrovascular and Carotid Artery Diseases
- Sarcoma Diagnosis and Treatment
- Prostate Cancer Diagnosis and Treatment
- Particle accelerators and beam dynamics
- Cytokine Signaling Pathways and Interactions
- Pituitary Gland Disorders and Treatments
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- Estrogen and related hormone effects
- ATP Synthase and ATPases Research
- Growth Hormone and Insulin-like Growth Factors
- Multiple Sclerosis Research Studies
- Electromagnetic Fields and Biological Effects
- Effects of Radiation Exposure
- CRISPR and Genetic Engineering
- Cancer Genomics and Diagnostics
- Nanoplatforms for cancer theranostics
- Mitochondrial Function and Pathology
- Prostate Cancer Treatment and Research
Massachusetts General Hospital
2023-2024
Harvard University
2023-2024
Boston University
2024
Dana-Farber Brigham Cancer Center
2023
Brigham and Women's Hospital
2023
Dana-Farber Cancer Institute
2023
Radiation Oncology Associates
2023
Duke Medical Center
2016-2022
Duke University Hospital
2017-2021
Duke University
2017-2020
Estrogen has well-documented neuroprotective effects in a variety of clinical and experimental disorders the CNS, including autoimmune inflammation, traumatic injury, stroke, neurodegenerative diseases. The beneficial estrogens CNS include mitigation symptoms, as well attenuation histopathological signs neurodegeneration inflammation. cellular mechanisms that underlie these are uncertain, because number different cell types express estrogen receptors peripheral immune system CNS. Here, we...
Estrogens can signal through either estrogen receptor α (ERα) or β (ERβ) to ameliorate experimental autoimmune encephalomyelitis (EAE), the most widely used mouse model of multiple sclerosis (MS). Cellular targets estrogen-mediated neuroprotection are still being elucidated. Previously, we demonstrated that ERα on astrocytes, but not neurons, was critical for ligand-mediated in EAE, including decreased T-cell and macrophage inflammation axonal loss. Here, determined whether ERβ astrocytes...
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...
Cancer development is influenced by hereditary mutations, somatic mutations due to random errors in DNA replication, or external factors. It remains unclear how distinct cell-intrinsic and -extrinsic factors affect oncogenesis within the same tissue type. We investigated murine soft-tissue sarcomas generated oncogenic alterations (KrasG12D activation p53 deletion), carcinogens (3-methylcholanthrene [MCA] ionizing radiation), both a potentially novel model (MCA plus deletion). Whole-exome...
ATRX is one of the most frequently altered genes in solid tumors, and mutation especially frequent soft tissue sarcomas. However, role tumor development response to cancer therapies remains poorly understood. Here, we developed a primary mouse model sarcoma showed that Atrx-deleted tumors were more sensitive radiation therapy oncolytic herpesvirus. In absence Atrx, irradiated sarcomas had increased persistent DNA damage, telomere dysfunction, mitotic catastrophe. Our work also Atrx deletion...
Abstract Background Recipients of radiation therapy (RT) for head and neck cancer (HNC) are at significantly increased risk carotid artery stenosis (CAS) cerebrovascular disease (CVD). We sought to determine (1) cumulative incidences CAS CVD among HNC survivors after RT (2) whether is associated with a dose response effect. Methods This single‐institution retrospective cohort study examined patients nonmetastatic who completed (chemo)RT from January 2000 through October 2020 subsequently...
Carbon ion therapy (CIT) offers several potential advantages for treating cancers compared with X-ray and proton radiotherapy, including increased biological efficacy more conformal dosimetry. However, CIT potency has not been characterized in primary tumor animal models. Here, we calculate the relative effectiveness (RBE) of carbon ions X-rays an autochthonous mouse model soft tissue sarcoma. We used Cre/loxP technology to generate sarcomas
Multiple sclerosis (MS) is an autoimmune disease characterized by inflammation and neurodegeneration. Current MS treatments were designed to reduce in rather than directly prevent Estrogen has well‐documented neuroprotective effects a variety of disorders the CNS, including experimental encephalomyelitis (EAE), most widely used mouse model MS. Treatment with estrogen receptor‐β (ERβ) ligand known ameliorate clinical effectively provide neuroprotection EAE. However, protective this ERβ have...
Abstract: Genetically engineered mouse models (GEMMs) are valuable research tools that have transformed our understanding of cancer. The first GEMMs generated in the 1980s and 1990s were knock-in knock-out single oncogenes or tumor suppressors. advances made these possible catalyzed both technological conceptual shifts way cancer was conducted. As a result, dozens exist today, covering nearly every tissue type. advantages inherent to compared vitro vivo transplant compounded preclinical...
Background: Gold nanostars are unique nanoplatforms that can be imaged in real time and transform light energy into heat to ablate cells. Adipose-derived stem cells migrate toward tumor niches response chemokines. The ability of adipose-derived integrate tumors makes them ideal vehicles for the targeted delivery cancer nanotherapeutics. Methods: To test labeling efficiency gold nanostars, undifferentiated were incubated with a commercially available nanoparticle (Qtracker), then using...
Background Single-agent immunotherapy has shown remarkable efficacy in selected cancer entities and individual patients. However, most patients fail to respond. This is likely due diverse immunosuppressive mechanisms acting a concerted way suppress the host anti-tumor immune response. Combination approaches that are effective such poorly immunogenic tumors mostly rely on precise knowledge of antigenic determinants tumor cells. Creating an antigen-agnostic combination for which determinant...
Abstract Cancer therapies targeting metabolism have been limited due to a lack of understanding the controlling properties vulnerable pathways. The Na + /K ATPase is responsible for large portion cellular energy demands but how these influence and create metabolic liabilities are not known. Using metabolomic approaches, we first show that digoxin, cardiac glycoside widely used in humans, acts through disruption central carbon via on target inhibition was fully recovered by expression an...
Abstract Radiation therapy 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 radiation (RT) in transplanted tumors, but mechanism(s) remain unclear. Here, we CRISPR/Cas9 and chemical carcinogen 3-methylcholanthrene (MCA) generate autochthonous sarcomas with high tumor mutation burden. Treatment a single fraction of 20 Gy RT two doses...