A5022151380- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Acute Myeloid Leukemia Research
- CAR-T cell therapy research
- Polyomavirus and related diseases
- Plant Virus Research Studies
- Bacteriophages and microbial interactions
- Peptidase Inhibition and Analysis
- Hematological disorders and diagnostics
- Monoclonal and Polyclonal Antibodies Research
- Bone and Joint Diseases
- Cancer Immunotherapy and Biomarkers
- Corneal Surgery and Treatments
- T-cell and B-cell Immunology
- RNA and protein synthesis mechanisms
- DNA Repair Mechanisms
- Mesenchymal stem cell research
- Bone Metabolism and Diseases
- Hematopoietic Stem Cell Transplantation
- Immune Cell Function and Interaction
- Ocular Surface and Contact Lens
- Cellular Mechanics and Interactions
- Galectins and Cancer Biology
- Histone Deacetylase Inhibitors Research
- Bone and Dental Protein Studies
Thomas Jefferson University
2022-2025
AbbVie (United States)
2025
Northwestern University
2024
Pulmonary Associates
2023
Dana-Farber Cancer Institute
2018-2022
The University of Texas MD Anderson Cancer Center
2014-2018
Harvard University
2018
Colby College
2017-2018
Leukemia Research Foundation
2015-2017
Synthetic lethality exploits the genetic vulnerabilities of cancer cells to enable a targeted, precision approach treat cancer1. Over past 15 years, synthetic lethal target discovery approaches have led clinical successes PARP inhibitors2 and ushered several next-generation therapeutic targets such as WRN3, USP14, PKMYT15, POLQ6 PRMT57 into clinic. Here we identify, in human cancer, novel interaction between PELO-HBS1L SKI complexes mRNA quality control pathway. In distinct contexts,...
Genotypic and phenotypic alterations in the bone marrow (BM) microenvironment, particular osteoprogenitor cells, have been shown to support leukemogenesis. However, it is unclear how leukemia cells alter BM microenvironment create a hospitable niche. Here, we report that acute myeloid (AML) but not normal CD34+ or CD33+ induce osteogenic differentiation mesenchymal stromal (MSCs). In addition, AML inhibited adipogenic of MSCs. Mechanistic studies identified AML-derived BMPs activate Smad1/5...
MS is the most effective method to directly identify peptides presented on human leukocyte antigen (HLA) molecules. However, current standard approaches often use 500 million or more cells as input achieve high coverage of immunopeptidome, and therefore, these methods are not compatible with limited amounts tissue available from clinical tumor samples. Here, we evaluated microscaled basic reversed-phase fractionation separate HLA peptide samples offline followed by ion mobility coupled...
Abstract Tumor epitopes – peptides that are presented on surface-bound MHC I proteins - provide targets for cancer immunotherapy and have been identified extensively in the annotated protein-coding regions of genome. Motivated by recent discovery translated novel unannotated open reading frames (nuORFs) using ribosome profiling (Ribo-seq), we hypothesized cancer-associated processes could generate nuORFs can serve as a new source tumor antigens harbor somatic mutations or show tumor-specific...
Although local tissue-based immune responses are critical for elucidating direct tumor-immune cell interactions, peripheral increasingly recognized as occupying an important role in anticancer immunity. We evaluated serial blood samples from patients with advanced epithelial ovarian cancer (EOC) undergoing standard-of-care neoadjuvant carboplatin and paclitaxel chemotherapy (including dexamethasone prophylaxis of paclitaxel-associated hypersensitivity reactions) to characterize the evolution...
Cancers avoid immune surveillance through an array of mechanisms, including perturbation HLA class I antigen presentation. Merkel cell carcinoma (MCC) is aggressive, HLA-I-low, neuroendocrine the skin often caused by polyomavirus (MCPyV). Through characterization 11 newly generated MCC patient-derived lines, we identified transcriptional suppression several presentation genes. To systematically identify regulators HLA-I loss in MCC, performed parallel, genome-scale, gain- and...
Mesenchymal stromal cells (MSC) support acute myeloid leukemia (AML) cell survival in the bone marrow (BM) microenvironment. Protein expression profiles of AML-derived MSC are unknown. Reverse phase protein array analysis was performed to compare 151 proteins from AML-MSC (n=106) with healthy donors (n=71). differed significantly between two groups 19 over-expressed and 9 normal cells. Unbiased hierarchical clustering samples using these 28 revealed three constellations whose variation...
α-catenin (α-cat) displays force-dependent unfolding and binding to actin filaments through direct indirect means, but features of adherens junction structure function most vulnerable loss these allosteric mechanisms have not been directly compared. By reconstituting an α-cat F-actin-binding domain mutant known exhibit enhanced (α-cat-H0-FABD
Inflammation in the eye is tightly regulated to prevent vision impairment and irreversible blindness. Emerging evidence shows that immune cells are specifically recruited lens capsule response autoimmune uveitis, yet potential they have a role regulating this inflammatory disease remained unexplored. Here, an immunolocalization approach combined with high-resolution confocal microscopy was used investigate whether become stably associated eyes of C57BL/6J mice experimental uveitis (EAU)...
The eye is an immune-privileged site, with both vasculature and lymphatics absent from the central light path. Unique adaptations have made it possible for immune cells to be recruited this region of in response ocular injuries pathogenic insults. induction such responses typically activated by tissue resident cells, considered sentinels system. We discovered that, despite absence embedded vasculature, embryonic lens becomes populated cells. paths which they travel during development were...
Recurrent epithelial erosions develop in the cornea due to prior injury or genetic predisposition. Studies of recurrent animal models allow us gain insight into how form and are resolved. While slowing corneal cell migration reducing their proliferation following treatment with mitomycin C reduce erosion formation mice after sterile debridement injury, additional factors have been identified related cytokine expression immune activation. The relationship between recruitment cells region...
Abstract Personal vaccines directed at neoantigens arising from tumor mutations can induce neoepitope-specific T cell responses in patients with highly mutated tumors such as melanoma. It remains unknown if this approach be successfully applied low mutation frequency. We conducted a phase 1/1b study to determine the safety and feasibility of patient-specific neoantigen-targeting vaccination newly diagnosed, methylguanine methyltransferase (MGMT) unmethylated glioblastoma, administered...
Somatic mutations in cancer cells can generate neoantigens which be recognized by immune and trigger an response. Patients vaccinated with neoantigen-based peptides display expanded neoantigen-specific T cells, suggesting that this could a promising avenue for treatment. Currently, neoantigen predictions are based on detected whole exome sequencing, covers pre-determined set of annotated exons, often falls short cancers few somatic mutations.Ribosome profiling (Ribo-seq), allows to monitor...