A5067154927- Lung Cancer Treatments and Mutations
- CAR-T cell therapy research
- Lung Cancer Research Studies
- Lymphoma Diagnosis and Treatment
- Cancer therapeutics and mechanisms
- Brain Metastases and Treatment
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Diagnosis and Treatment
- CNS Lymphoma Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- Cutaneous lymphoproliferative disorders research
- Cancer Genomics and Diagnostics
- Nuclear Receptors and Signaling
- Glioma Diagnosis and Treatment
- Integrated Circuits and Semiconductor Failure Analysis
- Chemical Reactions and Isotopes
- Glutathione Transferases and Polymorphisms
- Macrophage Migration Inhibitory Factor
- Toxin Mechanisms and Immunotoxins
- Childhood Cancer Survivors' Quality of Life
- Advancements in Semiconductor Devices and Circuit Design
- PI3K/AKT/mTOR signaling in cancer
- Immune Cell Function and Interaction
- Multiple Myeloma Research and Treatments
- Eosinophilic Disorders and Syndromes
University of Pennsylvania
2012-2025
Memorial Sloan Kettering Cancer Center
2019-2024
Kettering University
2019-2023
Cornell University
2021
Massachusetts General Hospital
2017-2020
Harvard University
2017-2018
Pfizer (United States)
2017
Veterans Health Administration
2014
Haverford College
2009-2011
King's College London
2011
NR4A1 (Nur77) is a nuclear receptor that expressed in macrophages and within atherosclerotic lesions, yet its function atherosclerosis unknown.Nur77 regulates the development of monocytes, particularly patrolling Ly6C(-) monocytes may be involved resolution inflammation. We sought to determine how absence subfamily 4, group A, member 1 (NR4A1) hematopoietic cells affected development.Nur77(-/-) chimeric mice on Ldlr(-/-) background showed 3-fold increase when fed Western diet for 20 weeks,...
Abstract The cornerstone of treatment for advanced ALK-positive lung cancer is sequential therapy with increasingly potent and selective ALK inhibitors. third-generation inhibitor lorlatinib has demonstrated clinical activity in patients who failed previous To define the spectrum mutations that confer resistance, we performed accelerated mutagenesis screening Ba/F3 cells expressing EML4–ALK. Under comparable conditions, N-ethyl-N-nitrosourea (ENU) generated numerous crizotinib-resistant but...
Purpose The ROS1 tyrosine kinase is activated through gene rearrangements in 1% to 2% of non–small-cell lung cancers (NSCLCs), which confer sensitivity treatment with the anaplastic lymphoma (ALK)/ROS1/mesenchymal-epithelial transition factor inhibitor crizotinib. Currently, insights into patterns metastatic spread and mechanisms crizotinib resistance among patients ROS1-positive disease are limited. Patients Methods We reviewed clinical radiographic imaging data ROS1- ALK-positive NSCLC...
Acquired resistance to next-generation ALK tyrosine kinase inhibitors (TKIs) is often driven by secondary mutations. Here, we investigated utility of plasma genotyping for identifying mutations at relapse on TKIs.We analyzed 106 specimens from 84 patients with advanced ALK-positive lung cancer treated second- and third-generation TKIs using a commercially available sequencing (NGS) platform (Guardant360). Tumor biopsies TKI-resistant lesions underwent targeted NGS identify mutations.By...
ALK rearrangements predict for sensitivity to tyrosine kinase inhibitors (TKIs). However, responses TKIs are generally short-lived. Serial molecular analysis is an informative strategy identifying genetic mediators of resistance. Although multiple studies support the clinical benefits repeat tissue sampling, utility longitudinal circulating tumor DNA has not been established in ALK-positive lung cancer.Using a 566-gene hybrid-capture next-generation sequencing (NGS) assay, we performed...
Abstract Purpose: Current standard initial therapy for advanced, ROS proto-oncogene 1, receptor tyrosine kinase fusion (ROS1)-positive (ROS1+) non–small cell lung cancer (NSCLC) is crizotinib or entrectinib. Lorlatinib, a next-generation anaplastic lymphoma kinase/ROS1 inhibitor, recently demonstrated efficacy in ROS1+ NSCLC, including crizotinib-pretreated patients. However, mechanisms of lorlatinib resistance disease remain poorly understood. Here, we assessed to and lorlatinib....
This cohort study evaluates the clinical outcomes in patients with metastatic lung cancer treated PD-1/PD-L1 inhibitors and thoracic radiotherapy.
Despite the increasing utilization of bridging radiotherapy (Br-RT), its impact on chimeric antigen receptor T-cell therapy (CAR-T) efficacy and toxicity remains poorly characterized. We retrospectively reviewed patients with relapsed/refractory B-cell lymphomas (r/r BCL) who received Br-RT followed by CAR-T from 2018-2020 across 10 institutions. toxicities were graded per CTCAE v5.0, cytokine release syndrome (CRS) immune effector cell-associated neurotoxicity (ICANS) ASTCT Consensus...
Greater tumor burden before CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy predicts lower complete response rate and shorter overall survival (OS) in patients with aggressive non-Hodgkin lymphoma (NHL). Recent patterns of failure studies have identified lesion characteristics, including size, standard uptake value (SUV), extranodal location, as associated post-CAR-T failure. Here we analyzed the effect bridging radiation-containing treatment (BRT) on pre-CAR-T lesion-...
Young breast cancer survivors in Mexico face distinct psychosocial challenges that have not been characterized. This study aims to describe the needs of young at 5 or more years survivorship, identifying areas focus for early interventions.
This case series reported survival, response, and safety outcomes for patients with mycosis fungoides or Sézary syndrome who received pembrolizumab at a single institution.
Regulatory T cells (Tregs) are CD4(+) that maintain immune homeostasis and prevent autoimmunity. Like all cells, Tregs require antigen-specific signals via cell receptor-major histocompatibility complex class II (TCR-MHCII) interactions for their development. However, the requirement MHCII in Treg tissues such as intestinal lamina propria (LP) is unknown. We examined LP a transgenic mouse model lacks peripheral TCR-MHCII generation of extrathymic (iTregs). Thymically generated entered...
Abstract Purpose: Greater disease burden is a well-established predictor of poorer outcomes following chimeric antigen receptor T-cell therapy (CART). While bridging (BT) widely used between leukapheresis and CAR T infusion, limited data has evaluated the impact BT on CART outcomes. In this study, we hypothesized that quantitative dynamics radiomic cytoreduction during are prognostic. Patients Methods: with large B-cell lymphoma (LBCL) treated CD19-CART from 2016-2022 were included....
9611 Background: Lorlatinib is a potent, brain-penetrant ROS1/ALK tyrosine kinase inhibitor (TKI), which has demonstrated efficacy in advanced ROS1 fusion-positive (ROS1+) non-small cell lung cancer (NSCLC), including patients (pts) previously treated with crizotinib. Despite initial benefit, however, most pts experience disease progression on lorlatinib. Mechanisms of resistance to lorlatinib ROS1+ NSCLC are poorly understood. Methods: We analyzed repeat tumor biopsies derived from...
Local therapy prolongs progression-free survival in patients with oligometastatic non-small-cell lung cancers treated chemotherapy. We previously reported that local also and time to next on tyrosine kinase inhibitors (TKIs) for EGFR-mutant adenocarcinomas. Here, we investigate the role of progressing TKIs ALK/ROS1/RET-rearranged adenocarcinomas.Patients advanced ALK/ROS/RET-rearranged adenocarcinomas who underwent radiation, surgery, or percutaneous thermal ablation from 2012 2020...
Major advances in myeloproliferative neoplasms the last decade have cast light on their complexity. The identification of JAK2 (V617F) briefly promised a unifying mechanism pathogenesis with single pathway that could be efficiently targeted. Instead, there been major understanding acquired and background genetic epigenetic contributors to this group disorders, refined risk prediction models experimental therapeutics provided more nuanced model disease. In aggregate these observations likely...
Introduction: Higher disease burden is associated with poor chimeric antigen receptor T-cell (CAR T) outcomes. Bridging therapy (BT) widely used to debulk or palliate between apheresis and CAR T infusion. We studied whether the dynamics of radiomic cytoreduction during bridging are prognostic. Methods: Large B-cell lymphoma (LBCL) patients (pts) treated anti-CD19 cells were stratified into 4 BT groups: (1) no (2) systemic (ST) (including steroids) (3) radiotherapy (RT) (4) combined ST/RT. To...