A5051236525- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- HIV Research and Treatment
- Pneumocystis jirovecii pneumonia detection and treatment
- Immune cells in cancer
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Glioma Diagnosis and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Multi-Objective Optimization Algorithms
- Antimicrobial Resistance in Staphylococcus
- Adolescent Sexual and Reproductive Health
- Economic and Financial Impacts of Cancer
- Manufacturing Process and Optimization
- Breast Cancer Treatment Studies
- Histone Deacetylase Inhibitors Research
- Global Cancer Incidence and Screening
- Pneumonia and Respiratory Infections
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Tuberculosis Research and Epidemiology
- vaccines and immunoinformatics approaches
- Simulation Techniques and Applications
- HIV/AIDS Research and Interventions
- Reproductive System and Pregnancy
Salk Institute for Biological Studies
2019-2024
Yale University
2017-2018
University of Alabama at Birmingham
2013-2016
Emory University
2009-2015
Boeing (Australia)
2006
Mechanisms of acquired resistance to immune checkpoint inhibitors (ICI) are poorly understood. We leveraged a collection 14 ICI-resistant lung cancer samples investigate whether alterations in genes encoding HLA Class I antigen processing and presentation machinery (APM) components or interferon signaling play role PD-1 PD-L1 antagonistic antibodies. Recurrent mutations copy-number changes were not detected our cohort. In one case, we found homozygous loss B2M that caused lack cell-surface...
The biological determinants of sensitivity and resistance to immune checkpoint blockers are not completely understood. To elucidate the role intratumoral T-cells their association with tumor genomic landscape, we perform paired whole exome DNA sequencing multiplexed quantitative immunofluorescence (QIF) in pre-treatment samples from non-small cell lung carcinoma (NSCLC) patients treated PD-1 axis blockers. QIF is used simultaneously measure level CD3+ infiltrating lymphocytes (TILs), situ...
Eliciting effective antitumor immune responses in patients who fail checkpoint inhibitor therapy is a critical challenge cancer immunotherapy, and such patients, tumor-associated myeloid cells macrophages (TAMs) are promising therapeutic targets. We demonstrate an autochthonous, poorly immunogenic mouse model of melanoma that combination with agonistic anti-CD40 mAb CSF-1R potently suppressed tumor growth. Microwell assays to measure multiplex protein secretion by single identified untreated...
Exhausted T cells (TEX) in cancer and chronic viral infections undergo metabolic epigenetic remodeling, impairing their protective capabilities. However, the impact of nutrient metabolism on modifications that control TEX differentiation remains unclear. We showed shifted from acetate to citrate by downregulating acetyl-CoA synthetase 2 (ACSS2) while maintaining ATP-citrate lyase (ACLY) activity. This switch increased citrate-dependent histone acetylation, mediated acetyltransferase...
ABSTRACT Streptococcus pneumoniae is a significant bacterial pathogen that expresses >90 capsule serotypes. Conventional serotyping methods assume each serotype genetically and antigenically distinct entity; however, recent investigations have revealed pneumococcal isolates cannot be unambiguously serotyped because they share the properties of more than one serotype. Here, we employed novel method NMR spectroscopy to examine clinical sharing serotypes 11A 11E. These ambiguous were...
Delays in treatment for breast cancer can lead to poorer patient outcome. We analyzed time among female patients receiving breast-conserving surgery two different hospital settings, public versus private. Retrospective chart review revealed 270 diagnosed during 2004-2008. Three consecutive intervals were defined (Initial abnormal imaging [I] core biopsy [II] /pathology staging [III] oncology evaluation adjuvant treatment). Multivariate analyses investigated type and demographic factors....
Antiretroviral therapy, antibody and CD8+ T cell-mediated responses targeting human immunodeficiency virus-1 (HIV-1) exert selection pressure on the virus necessitating escape; however, ability of CD4+ cells to selective remains unclear. Using a computational approach HIV gag/pol/nef sequences HLA-II allelic data, we identified 29 associated sequence polymorphisms or adaptations (HLA-AP) in an African cohort chronically HIV-infected individuals. Epitopes encompassing predicted adaptation...
Abstract Prior work has demonstrated that HIV-1–specific CD8 T cells can cross-recognize variant epitopes. However, most of these studies were performed in the context chronic infection, where presence viral quasispecies makes it difficult to ascertain true nature original antigenic stimulus. To overcome this limitation, we evaluated extent cell cross-reactivity patients with acute HIV-1 clade B infection. In each case, determined transmitted founder virus sequence identify autologous...
HIV-1 frequently escapes from CD8 T cell responses via HLA-I restricted adaptation, leading to the accumulation of adapted epitopes (AE). We previously demonstrated that AE compromise during acute infection and are associated with poor clinical outcomes. Here, we examined impact on their biological relevance in chronic HIV (CHI). In contrast infection, majority immunogenic CHI. Longitudinal analyses CHI showed an increased frequency magnitude AE-specific IFNγ compared NAE-specific ones....
Epidemiologic studies have demonstrated that HIV-1 discordant couples who share HLA-B alleles were more likely to transmit HIV-1. These data lead us hypothesize individuals match at both should a reduced allogeneic response than those are not matched. We observed diminished killing of CD4+ target cells only when propose for cell-associated transmission, the ability recipient eliminate infected from donor partner may be enhanced different between partners. findings suggest novel mechanism...
Summary The limited efficacy of immunotherapies against glioblastoma illustrates the urgent need to better understand interactions between central nervous system and immune system. Here, we showed that a protective response αCTLA-4 therapy depended on mutualistic relationship microglia CD4 + T cells. Suppression gliomas by cells did not require tumor-intrinsic MHC-II expression, but rather was dependent selective expression antigen presentation local in turn, sustained cell tumoricidal...
Abstract HIV readily mutates and many of these mutations can be predicted based on the human leukocyte antigen class I (HLA-I) allele infected individual. Majority HLA-associated polymorphisms may represent escape whereby epitope adapts to HLA-restricted pressure in every Though adapted epitopes have escaped recognition by some CD8 T cells, others recognize them. However, truly answer question as whether induce cell responses (primary response), acutely patient samples must tested where we...
<p>APM mutation and copy number alterations</p>
<p>Table with Details of Patient Characteristics</p>
<p>Supplementary Figures S1-S8</p>
<p>Legends for Figures S1-S8</p>
<p>Interferon pathway mutation and copy number alterations</p>
<p>Methods for quantitative immunofluorescence and IFN gamma treatment of PDXs</p>
<p>Legends for Figures S1-S8</p>
<p>Table with Details of Patient Characteristics</p>