A5030219410- Lung Cancer Treatments and Mutations
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cancer Genomics and Diagnostics
- Cardiac Valve Diseases and Treatments
- Immunotherapy and Immune Responses
- Colorectal Cancer Treatments and Studies
- RNA modifications and cancer
- Cancer Immunotherapy and Biomarkers
- Chemokine receptors and signaling
- Protein Degradation and Inhibitors
- Endometrial and Cervical Cancer Treatments
- PI3K/AKT/mTOR signaling in cancer
- Economic and Financial Impacts of Cancer
- Lung Cancer Research Studies
- IL-33, ST2, and ILC Pathways
- Ferroptosis and cancer prognosis
- Genetic factors in colorectal cancer
- Infective Endocarditis Diagnosis and Management
- Cancer Mechanisms and Therapy
- Orthopaedic implants and arthroplasty
- Health Systems, Economic Evaluations, Quality of Life
- Pancreatic function and diabetes
- Cardiac, Anesthesia and Surgical Outcomes
- Diabetes and associated disorders
Cho Ray Hospital
2025
University of Colorado Anschutz Medical Campus
2016-2024
University of Colorado Denver
2010-2024
Children's Hospital Colorado
2018-2024
Dana-Farber Cancer Institute
2017-2023
Harvard University
2020-2021
Gladstone Institutes
2020
University of Houston
2018
The University of Texas Health Science Center at Houston
2017-2018
Memorial Hermann
2018
Molecular mechanisms of acquired resistance to MET tyrosine kinase inhibitors (TKI) are poorly understood. We aimed characterize the genomic type I and II TKIs their impact on sequential TKI therapy outcomes in patients with metastatic exon 14-mutant NSCLC.Genomic alterations occurring at time progression were studied using plasma tissue next-generation sequencing (NGS).A total 20 had or available for analysis a TKI. Genomic known suspected be detected 15 (75%). On-target resistance,...
Abstract Lung carcinogenesis is a complex and stepwise process involving accumulation of genetic mutations in signaling oncogenic pathways via interactions with environmental factors host susceptibility. Tobacco exposure the leading cause lung cancer, but its relationship to clinically relevant composite tumor mutation burden (TMB) has not been fully elucidated. In this study, we investigated dose–response retrospective observational study 931 patients treated for advanced-stage non–small...
More than one-half of the ~50 human chemokines have been associated with or implicated in pathogenesis type 1 diabetes, yet their actual expression patterns islet environment diabetic patients remain, at present, poorly defined. Here, we integrated a culture system, murine models virus-induced and spontaneous histopathological examination pancreata from organ donors goal providing foundation for informed selection potential therapeutic targets within chemokine/receptor family. Chemokine (C-C...
Abstract Purpose: BRAF mutations are divided into functional classes distinguished by signaling mechanism and kinase activity: V600-mutant kinase-activating monomers (class I), dimers II), kinase-inactivating heterodimers III). The relationship between class disease characteristics in BRAF-mutant non–small cell lung cancer (NSCLC) has not been fully explored. Experimental Design: We performed a retrospective analysis of NSCLCs treated at 2 institutions from 2005 to 2017 determine...
The pleiotropic actions of interleukin-2 (IL-2) are essential for regulation immune responses and maintenance tolerance. IL-2 receptor (IL-2R) is composed IL-2Rα, IL-2Rβ, IL-2Rγ subunits, with defects in IL-2Rα their downstream signaling effectors resulting known primary immunodeficiency disorders. Here, we report the first human defect occurring two infant siblings a homozygous IL2RB mutation WSXWS motif, manifesting as multisystem autoimmunity susceptibility to CMV infection. hypomorphic...
Increasing costs and medical complexity are significant challenges in modern oncology. We explored the use of clinical pathways to support decision making manage resources prospectively across our network.We created customized lung cancer partnered with a commercial vendor provide Web-based platform for real-time post-treatment data aggregation. Dana-Farber Cancer Institute (DFCI) Pathways non-small cell (NSCLC) were introduced January 2014. identified all DFCI patients who diagnosed treated...
Despite the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in a subset patients, consistent and easily obtainable predictors remain elusive.
Implementing cancer precision medicine in the clinic requires assessing therapeutic relevance of genomic alterations. A main challenge is systematic interpretation whole-exome sequencing (WES) data for clinical care.One hundred sixty-five adults with metastatic colorectal and lung adenocarcinomas were prospectively enrolled CanSeq study. WES was performed on DNA extracted from formalin-fixed paraffin-embedded tumor biopsy samples matched blood samples. Somatic germ-line alterations ranked...
Metabolic imbalance leading to inflammatory hypoxia and stabilization of hypoxia-inducible transcription factors (HIFs) is a hallmark bowel diseases. We hypothesize that HIF could be stabilized in CD4+ T cells during intestinal inflammation alter the functional responses via regulation microRNAs. Our assays reveal markedly increased cell-intrinsic protein experimental colitis. microRNA screen primary points us towards miR-29a our subsequent studies identify selective role for HIF-2α...
The chemokines are a large family of mainly secreted molecules involved in the regulation numerous physiological and pathophysiological processes. Despite many years investigation, precise cellular sources most have remained incompletely defined as consequence limited availability suitable reagents to visualize expression chemokine proteins at single-cell level. Here, we developed simple flow cytometry–based assay using commercially available chemokine-specific antibodies for efficient...
The choreography of complex immune responses, including the priming, differentiation, and modulation specific effector T cell populations generated in immediate wake an acute pathogen challenge, is part controlled by chemokines, a large family mostly secreted molecules involved chemotaxis other patho/physiological processes. cells are both responsive to various chemokine cues relevant source for certain chemokines themselves; yet, actual range, regulation, role cell-derived remains...
Despite the prevalence of Aspergillus-related disease in immune suppressed lung transplant patients, little is known host-pathogen interaction. Because mould's angiotropic nature and because its capacity to thrive hypoxic conditions, we hypothesized that degree Aspergillus invasion would increase with progressive rejection-mediated ischemia allograft. To study this relationship, utilized a novel orthotopic tracheal model infection, which it was possible assess effects tissue hypoxia on...
Inflammatory bowel disease [IBD] is characterised by a disruption of immune homeostasis, which tightly regulated to protect against harmful pathogens yet not react commensal antigens. Animal studies indicate that regulatory T cells [Treg] modulate the response prevent IBD development. Lactoferrin [LF] an endogenous anti-inflammatory pleiotropic protein secreted at high concentrations in colostrum and mucosal sites. However, effect LF on specific lymphocyte populations has been studied. Here,...
Abstract The clinical significance of gene fusions detected by DNA-based next generation sequencing remains unclear as resistance mechanisms to EGFR tyrosine kinase inhibitors in mutant non-small cell lung cancer. By studying inhibitor-resistant patients treated with a combination an inhibitor and drug targeting the putative resistance-causing fusion oncogene, we identify who benefit those do not from this treatment approach. Through evaluation including RNA-seq potential...
<title>Abstract</title> <bold>Purpose</bold> The increase in carbapenem-resistant Enterobacterales (CRE) strains has shown significant variations over time and geographical regions. types of Carbapenemase-producing genes CRE Southern Vietnam have not yet been completely known; therefore, this study provides knowledge the epidemiology compares findings with global strains.<bold>Methods</bold> This utilizes whole-genome sequencing to analyze 195 from patients at Cho Ray Hospital, a major...
Oncogenic metabolism depends on multifaceted mechanisms, including bidirectional inter-organelle communication between mitochondria and the nucleus, facilitating cellular adaptation at transcriptomic, proteomic, metabolomic levels. The mitochondrial protein complex composed of apoptosis-inducing factor (AIF) coiled-coil-helix-coiled-coil-helix domain-containing 4 (CHCHD4) is essential for this mitochondrio-nuclear communication. AIF/CHCHD4 mediates import cysteine-enriched nuclear...
The destruction of infected cells by cytotxic T lymphocytes (CTL) is integral to the effective control viral and bacterial diseases, CTL function at large has long been regarded as a distinctive property CD8+T cell subset. In contrast, despite their first description more than three decades ago, precise contribution cytotoxic CD4+T resolution infectious diseases remained matter debate. particular, activity pathogen-specific CD4+ "helper" constitutes single trait among diverse array other...
ABSTRACT The lymphocytic choriomeningitis virus (LCMV) system constitutes one of the most widely used models for study infectious disease and regulation virus-specific T cell immunity. However, with respect to activity costimulatory associated regulatory pathways, LCMV-specific responses have long been regarded as relatively independent thus distinct from immunity directed against many other viral pathogens. Here, we reevaluated contribution CD28-CD80/86 costimulation in LCMV by use...
3 Background: Oncologists face challenges associated with increasing cost and medical complexity. The Dana-Farber Cancer Institute (DFCI) has created a customized clinical pathways program that seeks to prospectively support guide decision-making across our network. It also allows the track learn from decisions made. We have analyzed outcomes data before after implementation of Pathways in thoracic oncology program. Methods: Our lung cancer group pathway for treatment non-small cell (NSCLC)....
Protective T cell memory is an acquired trait that contingent upon the preservation of its constituents and therefore vulnerable to potentially deleterious effects organismal aging. Here, however, we have found long-term in a natural murine host-pathogen system can substantially improve over time. Comprehensive molecular, phenotypic, functional profiling aging antiviral CD8+ cells (CD8+ TM) revealed pervasive remodeling process promotes gradual acquisition distinct molecular signatures,...
In nonsmall cell lung cancer (NSCLC), the threonine(790)-methionine(790) (T790M) point mutation of EGFR kinase is one leading causes acquired resistance to first generation tyrosine inhibitors (TKIs), such as gefitinib and erlotinib. Herein, we describe optimization a series 7-oxopyrido[2,3-d]pyrimidinyl-derived irreversible kinase. This led discovery compound 24 which potently inhibits gefitinib-resistant EGFR(L858R,T790M) with 100-fold selectivity over wild-type EGFR. Compound displays...