A5024272498- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- CRISPR and Genetic Engineering
- Immune responses and vaccinations
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- COVID-19 Impact on Reproduction
- Long-Term Effects of COVID-19
- Reproductive System and Pregnancy
- Cancer-related molecular mechanisms research
- Cytomegalovirus and herpesvirus research
- Cancer Immunotherapy and Biomarkers
- SARS-CoV-2 detection and testing
- IL-33, ST2, and ILC Pathways
University of Pennsylvania
2018-2024
Translational Therapeutics (United States)
2020-2022
Cornell University
2013-2021
Coronavirus disease 2019 (COVID-19) is currently a global pandemic, but human immune responses to the virus remain poorly understood. We used high-dimensional cytometry analyze 125 COVID-19 patients and compare them with recovered healthy individuals. Integrated analysis of ~200 ~50 clinical features revealed activation T cell B subsets in proportion patients. A subgroup had characteristic acute viral infection plasmablast reaching >30% circulating cells. However, another lymphocyte...
Abstract COVID-19 has become a global pandemic. Immune dysregulation been implicated, but immune responses remain poorly understood. We analyzed 71 patients compared to recovered and healthy subjects using high dimensional cytometry. Integrated analysis of ∼200 >30 clinical features revealed activation T cell B subsets, only in some patients. A subgroup had characteristic acute viral infection plasmablast could reach >30% circulating cells. However, another lymphocyte comparable...
Persistent viral infections and tumors drive development of exhausted T (TEX) cells. In these settings, TEX cells establish an important host-pathogen or host-tumor stalemate. However, erode over time, leading to loss pathogen cancer containment. We identified microRNA (miR)-155 as a key regulator sustained cell responses during chronic lymphocytic choriomeningitis virus (LCMV) infection. Genetic deficiency miR-155 ablated CD8 Conversely, enhanced expression promoted expansion long-term...
An early memory CD8 + T cell precursor with distinct genome maintenance capacity depends on inhibitory receptor signaling.
CD8 + T cells are classically recognized as adaptive lymphocytes based on their ability to recognize specific foreign antigens and mount memory responses. However, recent studies indicate that some antigen-inexperienced can respond innate cytokines alone in the absence of cognate cell receptor stimulation, a phenomenon referred bystander activation. Here, we demonstrate neonatal undergo robust diverse program activation, which corresponds enhanced innate-like protection against unrelated...
Microbial infection during various stages of human development produces widely different clinical outcomes, yet the links between age-related changes in immune compartment and functional immunity remain unclear. The ability system to respond specific antigens mediate protection early life is closely correlated with level diversification lymphocyte antigen receptors. We have previously shown that neonatal primary CD8+ T cell response replication competent virus significantly constricted...
Significance CD8 T cell exhaustion is a key underlying factor limiting immunity in chronic infections and cancer. Persistent antigen exposure antagonizes formation of functional memory cells that provide long-term protection and, instead, drives the development exhausted (T EX ). Improving persistence function major goal for reinvigorating immune responses against tumors. Here, we identify miR-29a as molecule attenuates enhances . Enforced expression alters transcriptome, resulting robust...
Abstract CMV is the most common congenital infection in United States. The major target of brain, with clinical manifestations including mental retardation, vision impairment, and sensorineural hearing loss. Previous reports have shown that CD8+ T cells are required to control viral replication significant numbers CMV-specific persist brain even after initial has been cleared. However, dynamics during latency remain largely undefined. In this report, we used TCR sequencing track development...
Summary Improving effector activity of antigen specific T cells is a major goal in cancer immunotherapy. Despite the identification several cell (T EFF )-driving transcription factors (TF), transcriptional coordination biology remains poorly understood. We developed an vivo CRISPR screening platform and identified novel mechanism restraining through ETS family TF, Fli1. Genetic deletion Fli1 enhanced responses without compromising memory or exhaustion precursors. restrained lineage...
Abstract The immune system is stratified into layers of specialized cells with distinct functions. Recently, Lin28b was shown to serve as a master regulator fetal lymphopoiesis, programming the development more innate-like lymphocytes in early life. However, it remains unclear whether specifies innate functions conventional adaptive lymphocytes. In this report, we discovered that promotes lineage CD8+ T capable protecting host against wide variety pathogens absence TCR stimulation. Using...
Abstract Exhausted CD8 T cells (TEX) are essential during chronic viral infections and cancer. Two TEX subpopulations including a progenitor more terminally exhausted subset cooperate to maintain an active immune response antigen persistence. However, non-overlapping delineations of these populations have suggested complex developmental biology. Here, using the LCMV mouse model infection, we identify four distinct subsets based on Ly108 (Slamf6) CD69 expression revealing novel stepwise...
Abstract Key features of the CD8+ T cell response to infection are robust clonal expansion and phenotypic diversification naïve precursors into effector memory cells. However, mechanisms that regulate fate cells after microbial challenge remain a subject controversy. Previous studies have suggested heterogeneity in pool is driven by differences TCR avidity, asymmetric division, environmental cues. one variable has not been closely examined developmental origin Notably, adult comprised...
Abstract We previously found that neonatal and adult CD8+ T cells adopt different fates after infection with specific pathogens because they are derived from a distinct progenitor cell is distinguished by expression of Lin28b. In this report, we investigated if respond differently to unrelated in early life. To start, compared gene profiles stimulation innate cytokines (IL-12 + IL-18). Interestingly, more responsive express cytokine profile their counterparts. examine the biological...
Improving effector activity of antigen specific T cells is a major goal in cancer immunotherapy. Despite the identification several cell (TEFF)-driving transcription factors (TF), transcriptional coordination TEFF biology remains poorly understood. We developed an vivo CRISPR screening platform and identified novel mechanism restraining through ETS family TF, Fli1. Genetic deletion Fli1 enhanced responses without compromising memory or exhaustion precursors. restrained lineage...
Abstract Exhaustion gradually establishes in chronically stimulated CD8s and this process is not reverted by current therapeutic approaches due to establishment of a stable epigenetic program. Recent advances have informed on the developmental exhaustion highlighted TOX as key lineage-defining TF process. Yet, little remains known molecular pathways capable antagonizing TOX-dependent By depicting transcriptional changes at steps exhaustion, we demonstrate an antagonistic role for STAT5...
Abstract Lin28b serves as a master regulator of fetal lymphopoiesis and promotes the development more innate-like lymphocytes in early life. However, it is still unclear how alters function CD8+ T cells protects host against infection. In this report we examined transcriptionally epigenetically programs neonatal for innate immune defense. We found that murine possess transcriptomes, are responsive to cytokines absence antigen produce broader spectrum compared their adult counterparts. This...