A5006524239- Polyomavirus and related diseases
- Plant Virus Research Studies
- Bacteriophages and microbial interactions
- Sarcoma Diagnosis and Treatment
- Neuroscience and Neuropharmacology Research
- Peptidase Inhibition and Analysis
- Receptor Mechanisms and Signaling
- Cancer, Stress, Anesthesia, and Immune Response
- RNA modifications and cancer
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Cancer Research and Treatments
- Cancer-related molecular mechanisms research
- Machine Learning in Materials Science
- RNA Research and Splicing
- Hedgehog Signaling Pathway Studies
- Radiomics and Machine Learning in Medical Imaging
- Tumors and Oncological Cases
- Galectins and Cancer Biology
- Plant Disease Resistance and Genetics
- Drug Transport and Resistance Mechanisms
- Gestational Trophoblastic Disease Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Glycosylation and Glycoproteins Research
- Photochromic and Fluorescence Chemistry
National Institute of Arthritis and Musculoskeletal and Skin Diseases
2019-2025
National Institutes of Health
2016-2025
National Cancer Institute
2016-2024
Georgetown University
2013-2015
University of Washington
2015
Georgetown University Medical Center
2014
Abstract Immunoconjugates targeting cell-surface antigens have demonstrated clinical activity to enable regulatory approval in several solid and hematologic malignancies. We hypothesize that a rigorous comprehensive surfaceome profiling approach identify osteosarcoma-specific can similarly development of effective therapeutics this disease. Herein, we describe an integrated proteomic transcriptomic proteins are highly expressed osteosarcoma but minimally on normal tissues. Using approach,...
Abstract Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer. Most MCCs contain polyomavirus (virus-positive MCC; VP-MCC), and the remaining are virus-negative (VN-MCC). Immune checkpoint inhibitors first-line treatment for metastatic MCC, but durable responses achieved in less than 50% of patients. To identify new treatments, we screen ~4,000 compounds their ability to reduce MCC viability demonstrate that VP-MCC VN-MCC exhibit distinct response profiles. Aurora kinase selectively...
Abstract Introduction: BT1718 is a targeted Bicycle peptide-conjugate designed to deliver the anti-tubulin agent, DM1 tumors expressing membrane type 1-matrix metalloprotease (MT1-MMP; MMP14; MT1). In vivo preclinical studies demonstrated that anti-tumor activity of dependent on level tumor MT1-MMP expression. patient expression has been reported in and stromal cells, both which may contribute potential for effects following dosing. currently being investigated Phase 1/2 clinical trial,...
Merkel cell carcinoma (MCC) is a rare, but aggressive skin cancer the incidence of which has increased significantly in recent years. The majority MCCs have incorporated polyomavirus (VP-MCC) while remainder are virus-negative (VN-MCC). Although variety therapeutic options shown promise treating MCC, there remains need for additional therapeutics as well probes better understanding MCC. A high-throughput screening campaign was used to assess ability > 25,000 synthetic and natural product...
The direct antitumour effects of mTOR inhibitors against cutaneous squamous cell carcinoma (SCC) have prompted a paradigm shift towards using sirolimus for allograft rejection prophylaxis in patients with high-risk SCC who had solid organ transplant (SOT). Patients an SOT are at higher risk Merkel (MCC), yet there is little evidence concerning potential immunosuppressive drugs MCC. Screening seven six MCC lines revealed that mycophenolate mofetil (MMF) strong activity (surpassing inhibitors)...
<b>Abstract ID 96154</b> <b>Poster Board 257</b> Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer with high case fatality rate. Currently, immune checkpoint inhibitors (ICI) are the first line of treatment for metastatic MCC, but 50% patients do not achieve durable responses. To identify novel treatments we screened 4,000 compounds their ability to reduce MCC viability. Using Area Under Dose-Response Curve, identified CDK as efficacious against multiple lines....
Melanoma cells that express metabotropic glutamate 1 (mGlu1) receptors depend on for their survival and proliferation. The dependence receptor properties of mGlu1 allow us to propose justify three promising approaches melanoma treatment: depletion, antagonism, targeting signaling.
Abstract Introduction: BT5528 is a Bicycle® Toxin Conjugate (BTC) which contains an EphA2 binding peptide (Bicycle) conjugated through molecular spacer and cleavable linker to the antimitotic toxin MMAE. attractive tumor target; overexpression has been reported in multiple types. Preclinical activity of described previously, demonstrating increased efficacy associated with high cell expression levels xenograft models. Enrollment Phase I dose escalation study (BT5528-100) started patients...
Abstract Introduction: Bicycles® are a novel class of fully synthetic, short, constrained peptides. BT8009 consists bicyclic peptide targeting the tumor antigen Nectin-4, linked to cytotoxin monomethyl auristatin E (MMAE) via molecular spacer and cleavable linker. Nectin-4 is validated target highly expressed in wide range tumors. A Phase I/II dose escalation/expansion study, BT8009-100 (NCT04561362), enrolling patients with advanced solid tumors associated expression ongoing US. Here we...
Abstract Introduction: Toxin-conjugated agents targeting cell-surface antigens (e.g. antibody-drug conjugates) show promising clinical activity for some solid tumors, but none yet OS. There is an urgent need to identify high-confidence OS and evaluate the antitumor of toxin conjugates that can deliver cytotoxic payloads tumors expressing these targets. Methods: To proteins are highly expressed in not normal tissues, we prepared surface protein extracts from 4 standard, patient-derived cell...
<h3>Background</h3> <i>Bicycles</i> are fully synthetic constrained peptides with antibody-like affinities that target selectively, readily penetrate tumor tissue, have relatively short half-lives, and can be chemically linked together to generate multifunctional molecules. BT7480 is a <i>Bicycle</i> TICA™ binds both CD137 on immune cells Nectin-4 cancer deliver potent anti-tumor signal in expressing tumors. has been reported highly expressed wide range of human solid tumors, however the...
Abstract The purpose of this study was to elucidate the downstream signaling mGlu1 receptors involved in melanoma cell proliferation. Previously, using lines expressing receptors, we demonstrated that glutamate stimulation increases growth BRAF mutant, NRAS and BRAF/NRAS wild-type cells. Blockade receptor activation through depletion, knockdown, antagonism inhibited glutamate-stimulated growth, further identifying as a therapeutic target for treatment metastatic melanoma. Because antagonists...
Abstract We used an integrative oncogenomic approach to investigate the molecular etiology of Merkel Cell Carcinoma (MCC) in effort identify novel therapeutic targets and biomarkers for this highly aggressive neuroendocrine skin tumor. Because MCC is rare poorly understood, there are currently no effective treatment options patients with advanced disease. Approximately 80% tumors have polyomavirus (MCV) DNA integrated into host genome, viral oncogenes thought drive carcinogenesis. Moreover...
Supplementary Data from Comprehensive Surfaceome Profiling to Identify and Validate Novel Cell-Surface Targets in Osteosarcoma
Supplementary Figure from Comprehensive Surfaceome Profiling to Identify and Validate Novel Cell-Surface Targets in Osteosarcoma
<div>Abstract<p>Immunoconjugates targeting cell-surface antigens have demonstrated clinical activity to enable regulatory approval in several solid and hematologic malignancies. We hypothesize that a rigorous comprehensive surfaceome profiling approach identify osteosarcoma-specific can similarly development of effective therapeutics this disease. Herein, we describe an integrated proteomic transcriptomic proteins are highly expressed osteosarcoma but minimally on normal tissues....
<div>Abstract<p>Immunoconjugates targeting cell-surface antigens have demonstrated clinical activity to enable regulatory approval in several solid and hematologic malignancies. We hypothesize that a rigorous comprehensive surfaceome profiling approach identify osteosarcoma-specific can similarly development of effective therapeutics this disease. Herein, we describe an integrated proteomic transcriptomic proteins are highly expressed osteosarcoma but minimally on normal tissues....
Supplementary Figure from Comprehensive Surfaceome Profiling to Identify and Validate Novel Cell-Surface Targets in Osteosarcoma