- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Colorectal Cancer Treatments and Studies
- Genetic factors in colorectal cancer
- Immunotherapy and Immune Responses
- Cancer Cells and Metastasis
- Immune Cell Function and Interaction
- Brain Metastases and Treatment
- CAR-T cell therapy research
- Hippo pathway signaling and YAP/TAZ
- Cell Adhesion Molecules Research
- Ferroptosis and cancer prognosis
- Lymphoma Diagnosis and Treatment
- Cancer Research and Treatments
- Immune cells in cancer
- RNA modifications and cancer
- Acute Myocardial Infarction Research
- Radiomics and Machine Learning in Medical Imaging
- Single-cell and spatial transcriptomics
- Research on Leishmaniasis Studies
- Cancer, Stress, Anesthesia, and Immune Response
- Trypanosoma species research and implications
- Angiogenesis and VEGF in Cancer
- SARS-CoV-2 and COVID-19 Research
- Peptidase Inhibition and Analysis
Dana-Farber Cancer Institute
2018-2025
Weatherford College
2021
Harvard University
2020
University of Iowa
2011-2018
Loss of membrane MHC class I protein expression in most tumor cells advanced melanomas predicts primary resistance to anti–CTLA-4, but not anti-PD1, treatment.
<ns4:p><ns4:italic>Background: </ns4:italic>Given the demonstrated utility of Third Generation Sequencing [Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT)] long reads in many studies, a comprehensive analysis comparison their data quality applications is high demand. <ns4:italic>Methods: </ns4:italic>Based on transcriptome sequencing from human embryonic stem cells, we analyzed multiple features PacBio ONT, including error pattern, length, mappability technical...
Danshen, Salvia miltiorrhiza Bunge, is one of the most widely used herbs in traditional Chinese medicine, wherein its rhizome/roots are particularly valued. The corresponding bioactive components include tanshinone diterpenoids, biosynthesis which a subject considerable interest. Previous investigations S. transcriptome have relied on short-read next-generation sequencing (NGS) technology, and vast majority resulting isotigs do not represent full-length cDNA sequences. Moreover, these...
Novel approaches are needed to improve outcomes in patients with squamous cell carcinoma of the oral cavity. Neoadjuvant immunotherapy given prior surgery and combining programmed death protein 1 (PD-1) cytotoxic T-lymphocyte-associated 4 (CTLA-4) immune checkpoint inhibitors 2 strategies enhance antitumor responses that could be benefit.
Immune checkpoint blockade (ICB) therapy revolutionized cancer treatment, but many patients with impaired MHC-I expression remain refractory. Here, we combined FACS-based genome-wide CRISPR screens a data-mining approach to identify drugs that can upregulate without inducing PD-L1. screening identified TRAF3, suppressor of the NFκB pathway, as negative regulator not The Traf3-knockout gene signature is associated better survival in ICB-naïve and ICB response. We then screened for similar...
PURPOSE Although immune checkpoint inhibitors (ICI) have extended survival in patients with non–small-cell lung cancer (NSCLC), acquired resistance (AR) to ICI frequently develops after an initial benefit. However, the mechanisms of AR NSCLC are largely unknown. METHODS Comprehensive tumor genomic profiling, machine learning–based assessment tumor-infiltrating lymphocytes, multiplexed immunofluorescence, and/or HLA-I immunohistochemistry (IHC) were performed on matched pre- and post-ICI...
Highly multiplexed protein imaging is emerging as a potent technique for analyzing distribution within cells and tissues in their native context. However, existing cell annotation methods utilizing high-plex spatial proteomics data are resource intensive necessitate iterative expert input, thereby constraining scalability practicality extensive datasets. We introduce MAPS (Machine learning Analysis of Proteomics Spatial biology), machine approach facilitating rapid precise type...
The Leishmania species cause a variety of human disease syndromes. Methods for diagnosis and differentiation are insensitive many require invasive sampling. Although quantitative PCR (qPCR) methods reported leishmania detection, no systematic method to quantify parasites determine the in clinical specimens is established. We developed serial qPCR strategy identify rapidly differentiate or environmental specimens. SYBR green mainly employed, with corresponding TaqMan assays validation....
We developed an innovative hybrid sequencing approach, IDP-fusion, to detect fusion genes, determine sites and identify quantify isoforms. IDP-fusion is the first method study gene events by integrating Third Generation Sequencing long reads Second short reads. applied PacBio data Illumina from MCF-7 breast cancer cells. Compared with existing tools, detects genes at higher precision a very low false positive rate. The results show that will be useful for unraveling complexity of multiple...
Prospective human data are lacking regarding safety, efficacy, and immunologic impacts of different radiation doses administered with combined PD-L1/CTLA-4 blockade.
Mechanisms of chimeric antigen receptor (CAR) T cell-mediated antitumor immunity and toxicity remain poorly characterized because few studies examine the intact tumor microenvironment (TME) following CAR cell infusion. Axicabtagene ciloleucel is an autologous anti-CD19 therapy approved for patients with large B lymphoma. We devised multiplex immunostaining ISH assays to interrogate cells other immune infiltrates in biopsies diffuse lymphoma axicabtagene found that a majority intratumoral...
Understanding the mechanisms of HIV tissue persistence necessitates ability to visualize microenvironments where infected cells reside; however, technological barriers limit our dissect cellular components these reservoirs. Here, we developed protein and nucleic acid in situ imaging (PANINI) simultaneously quantify DNA, RNA, levels within compartments. By coupling PANINI with multiplexed ion beam (MIBI), measured over 30 parameters across archival lymphoid tissues from healthy or simian...
Abstract Purpose: Eribulin modulates the tumor-immune microenvironment via cGAS-STING signaling in preclinical models. This non-randomized phase II trial evaluated combination of eribulin and pembrolizumab patients with soft-tissue sarcomas (STS). Patients Methods: enrolled one three cohorts: leiomyosarcoma (LMS), liposarcomas (LPS), or other STS that may benefit from PD-1 inhibitors, including undifferentiated pleomorphic sarcoma (UPS). was administered at 1.4 mg/m2 i.v. (days 1 8)...
<ns4:p><ns4:italic>Background: </ns4:italic>Given the demonstrated utility of Third Generation Sequencing [Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT)] long reads in many studies, a comprehensive analysis comparison their data quality applications is high demand. <ns4:italic>Methods: </ns4:italic>Based on transcriptome sequencing from human embryonic stem cells, we analyzed multiple features PacBio ONT, including error pattern, length, mappability technical...
Abstract Atezolizumab with chemotherapy has shown improved progression-free and overall survival in patients metastatic PD-L1 positive triple negative breast cancer (TNBC). anthracycline- taxane-based neoadjuvant also increased pathological complete response (pCR) rates early TNBC. This trial evaluated carboplatin paclitaxel or without atezolizumab clinical stages II-III The co-primary objectives were to evaluate if increase pCR rate tumor infiltrating lymphocyte (TIL) percentage compared...
Diffuse large B-cell lymphoma (DLBCL) not otherwise specified is the most common aggressive non-Hodgkin and a biologically heterogeneous disease. Despite development of effective immunotherapies, organization DLBCL tumor-immune microenvironment (TIME) remains poorly understood.We interrogated intact TIME 51 de novo DLBCLs with triplicate sampling to characterize 337 995 tumor immune cells using 27-plex antibody panel that captured cell lineage, architectural, functional markers. We spatially...
This study describes parasite kinetics in the blood of visceral leishmaniasis patients treated with liposomal amphotericin B (L-AmB) or a preformed fat emulsion (ApL) using real-time quantitative PCR (qPCR). Forty-six were single dose (15 mg/kg body weight) either L-AmB (n = 13) ApL 33). qPCR was used to estimate by detection Leishmania donovani DNA kinetoplast DNA-specific primers peripheral samples an absolute quantification method. The mean load decreased from baseline (day 0) values...
Visceral leishmaniasis (VL) is endemic in large cities Brazil, including Natal. We determined the prevalence of asymptomatic human infection with Leishmania infantum chagasi and associated environmental risks around Infection was detected by skin test (LST) anti-leishmanial antibodies humans dogs. Amongst 345 humans, 24.6% were seropositive, 38.6% LST-positive. Prevalence positive serology similar both sexes across all ages. However, LST responses increased age, suggesting that long-lasting...
Allele-specific expression (ASE) is a fundamental problem in studying gene regulation and diploid transcriptome profiles, with two key challenges: (i) haplotyping (ii) estimation of ASE at the isoform level. Existing analysis methods are limited by dependence on from laborious experiments or extra genome/family trio data. In addition, there lack for level analysis. We developed tool, IDP-ASE, full By innovative integration Third Generation Sequencing (TGS) long reads Second (SGS) short...