A5085451699- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Pluripotent Stem Cells Research
- Tissue Engineering and Regenerative Medicine
- SARS-CoV-2 and COVID-19 Research
- Immune responses and vaccinations
- Immune cells in cancer
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- COVID-19 Clinical Research Studies
- Reproductive System and Pregnancy
- Mosquito-borne diseases and control
- interferon and immune responses
- Mesenchymal stem cell research
- IL-33, ST2, and ILC Pathways
- Herpesvirus Infections and Treatments
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- vaccines and immunoinformatics approaches
- Neuroscience and Neural Engineering
- 3D Printing in Biomedical Research
- Immune Response and Inflammation
- Influenza Virus Research Studies
- Viral Infections and Vectors
University of Minnesota Medical Center
2018-2024
University of Minnesota
2019-2024
Fred Hutch Cancer Center
2016-2021
Cancer Research Center
2019-2021
Minot State University
2021
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2016-2019
University of Washington
2016-2017
Seattle University
2017
WiCell
2009-2012
Morgridge Institute for Research
2009-2012
Human induced pluripotent stem (iPS) cells hold great promise for cardiovascular research and therapeutic applications, but the ability of human iPS to differentiate into functional cardiomyocytes has not yet been demonstrated. The aim this study was characterize cardiac differentiation potential generated using OCT4, SOX2, NANOG, LIN28 transgenes compared embryonic (ES) cells. ES were differentiated embryoid body (EB) method. time course developing contracting EBs comparable cell lines,...
Cardiomyocytes (CMs) differentiated from human pluripotent stem cells (PSCs) are increasingly being used for cardiovascular research, including disease modeling, and hold promise clinical applications. Current cardiac differentiation protocols exhibit variable success across different PSC lines primarily based on the application of growth factors. However, extracellular matrix is also fundamentally involved in development earliest morphogenetic events, such as gastrulation.We sought to...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Neutralizing Abs target receptor binding domain of spike (S) protein, a focus successful vaccine efforts. Concerns have arisen that S-specific immunity may fail to neutralize emerging variants. We show vaccination with human adenovirus type 5 vector expressing SARS-CoV-2 nucleocapsid (N) protein can establish protective immunity, defined by reduced weight loss and viral load, in both Syrian...
Numerous observations indicate that resident memory T cells (TRM) undergo unusually rapid attrition within the lung. Here we demonstrate contraction of lung CD8+ cell responses after influenza infection is contemporized with egress CD69+/CD103+ to draining mediastinal LN via lymphatic vessels, which term retrograde migration. Cells retained canonical markers TRM, including CD103 and CD69, lacked Ly6C expression (also a feature TRM), maintained granzyme B expression, did not equilibrate among...
Respiratory tract resident memory T cells (T
Abstract The magnitude of SARS-CoV-2–specific T cell responses correlates inversely with human disease severity, suggesting involvement in primary control. Whereas many COVID-19 vaccines focus on establishing humoral immunity to viral spike protein, vaccine-elicited may bolster durable protection or cross-reactivity variants. To better enable mechanistic and vaccination studies mice, we identified a dominant CD8 SARS-CoV-2 nucleoprotein epitope. Infection ACE2 transgenic mice elicited robust...
Abstract Chronological aging correlates with epigenetic modifications at specific loci, calibrated to species lifespan. Such ‘epigenetic clocks’ appear conserved among mammals, but whether they are cell autonomous and restricted by maximal organismal lifespan remains unknown. We used a multilifetime murine model of repeat vaccination memory T transplantation test tracks cellular replication if such clocks continue ‘counting’ beyond Here we found that tick independently host age through four...
The oral mucosa is a frontline for microbial exposure and juxtaposes several unique tissues mechanical structures. Based on parabiotic surgery of mice receiving systemic viral infections or co-housing with microbially diverse pet shop mice, we report that the harbors CD8+ CD103+ resident memory T cells (TRM), which locally survey without recirculating. Oral antigen re-encounter during effector phase immune responses potentiated TRM establishment within tongue, gums, palate, cheek. Upon...
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Neutralizing antibodies target receptor binding domain of spike (S) protein, a focus successful vaccine efforts. Concerns have arisen that S-specific immunity may fail to neutralize emerging variants. We show vaccination with HAd5 expressing nucleocapsid (N) protein can establish protective immunity, defined by reduced weight loss and viral load, in both Syrian hamsters k18-hACE2...
Tissue-resident memory CD8 T cells (CD8 TRM) are critical for maintaining barrier immunity. TRM have been mainly studied in the skin, lung and gut, with recent studies suggesting that signals control tissue residence phenotype highly dependent. We examined cell compartment healthy human cervicovaginal (CVT) found most were granzyme B+ TCF-1- To address if this is driven by CVT residence, we used a mouse model to environmental factors. Using localized systemic infection models, gradually...
Abstract Given the rapid spread of flaviviruses such as West Nile virus (WNV) and Zika virus, it is critical that we develop a complete understanding key mediators an effective anti-viral response. We previously demonstrated WNV infection mice deficient in mitochondrial antiviral-signaling protein (MAVS), signaling adaptor for RNA helicases RIG-I, resulted increased death dysregulated immunity, which correlated with failure Treg expansion following infection. Thus, sought to determine if...
Abstract Respiratory tract resident memory T cells (Trm), typically generated by local vaccination or infection, can accelerate control of pulmonary infections that evade neutralizing antibody. It is unknown whether mRNA establishes respiratory Trm. We a self-amplifying vaccine encoding the influenza A virus nucleoprotein encapsulated in modified dendron-based nanoparticles. Here we report how routes immunization mice, including contralateral versus ipsilateral intramuscular boosts,...
Abstract Tissue-resident memory CD8 T cells (CD8 RM ) are critical for maintaining barrier immunity. have been mainly studied in the skin and gut with recent studies suggesting that signals control tissue-residence phenotype highly tissue-dependent. We examined cell compartment healthy human cervicovaginal tissue (CVT) found most were granzyme B + TCF-1 - . To address if this is driven by CVT tissue-residence, we used a mouse model to environmental factors. Using localized systemic infection...
Abstract Regulatory T-cells (Tregs) limit autoimmunity and immunopathology using a variety of suppressive mechanisms, but their roles during pathogen-directed immune responses remain unclear. Following Herpes Simplex virus-2 (HSV-2) infection, mice lacking Tregs fail to control viral replication, pointing role for in facilitating productive responses. Using adoptive transfer TCR transgenic CD4 into Treg-sufficient or Treg-depleted prior HSV-2 we found that are required timely accumulation...
Abstract Memory T cell migration facilitates whole-body immunosurveillance and protection against recurrent infections cancer. In the absence of inflammation, tissue resident memory cells (TRM) patrol non-lymphoid tissues (NLT) while effector central (TEM TCM) are mostly restricted to blood blood/lymph system respectively. that retain ability recirculate through all compartments rare poorly characterized. Thus, function these as well their entry egress requirements under homeostatic...
Abstract As the immune system ages, protective capacity from established immunological memory wanes over time and is often referred to as senescence. Yet molecular hallmarks of lymphocyte age replicative senescence remain largely undefined. Here we report our use a multi-lifetime murine model repeat vaccination define core epigenetic signature coupled T cells that evade Through adoptive transfer boosting period approximately four mouse lifetimes, became enriched for repressive DNA...
Abstract Resident memory T cells (TRM) constitute a recently identified lymphocyte lineage that occupies non-lymphoid tissues (NLT) without recirculating. In murine models, upon antigenic rechallenge, TRM trigger antiviral responses in neighboring innate and adaptive immune cells, recruit effectors from circulation. Collectively this is referred to as ‘sensing alarm’ function. However, the full range of functions has not been assessed, non-human primate/human function remains almost entirely...
Human induced pluripotent stem (iPS) cells hold great promise for cardiovascular research and therapies, but the lentiviral generated iPS contain transgene vector sequences inserted into genome that could result in insertional mutagenesis. The recent generation of using oriP/EBNA1(Epstein-Barr nuclear antigen-1)-based episomal vectors avoids genomic integrations brings closer to clinical applications. However, ability vector-free generate cardiomyocytes (CMs) is unknown. aim this study was...