Kevin S. Kao
A5086445311- Immune cells in cancer
- Hematopoietic Stem Cell Transplantation
- Acute Myeloid Leukemia Research
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- Phagocytosis and Immune Regulation
- SARS-CoV-2 and COVID-19 Research
- T-cell and B-cell Immunology
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Galectins and Cancer Biology
- Glycosylation and Glycoproteins Research
- Influenza Virus Research Studies
- COVID-19 Clinical Research Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Erythrocyte Function and Pathophysiology
- Complement system in diseases
- Mosquito-borne diseases and control
- Renal and related cancers
- Receptor Mechanisms and Signaling
- Hand Gesture Recognition Systems
- Neurogenesis and neuroplasticity mechanisms
- Hearing, Cochlea, Tinnitus, Genetics
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Stroke Rehabilitation and Recovery
Rockefeller University
2020-2024
Cornell University
2018-2024
Tri-Institutional PhD Program in Chemical Biology
2018-2024
Kyoto University
2024
Kobe University
2024
RIKEN Center for Biosystems Dynamics Research
2024
Stanford University
2016-2022
California Institute for Regenerative Medicine
2016-2021
Institute for Stem Cell Biology and Regenerative Medicine
2019
Kettering University
2019
Significance During the ongoing COVID-19 pandemic, protein engineering offers a rapid and powerful approach for building therapeutics to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. We use computational design, affinity maturation, fusion dimerization domains engineer “receptor traps” based on wild-type angiotensin-converting enzyme II (ACE2), target viral spike-mediated SARS-CoV-2 entry into cells. The optimized ACE2 receptor traps neutralize authentic...
Monoclonal antibodies with neutralizing activity against SARS-CoV-2 have demonstrated clinical benefits in cases of mild-to-moderate infection, substantially reducing the risk for hospitalization and severe disease1–4. Treatment generally requires administration high doses these monoclonal has limited efficacy preventing disease complications or mortality among hospitalized patients COVID-195. Here we report development evaluation anti-SARS-CoV-2 optimized Fc domains that show superior...
Abstract Macrophage-mediated programmed cell removal (PrCR) is a process essential for the clearance of unwanted (damaged, dysfunctional, aged, or harmful) cells. The detection and recognition appropriate target cells by macrophages critical step successful PrCR, but its molecular mechanisms have not been delineated. Here using models tissue turnover, cancer immunosurveillance, hematopoietic stem cells, we show that such as aging neutrophils living are susceptible to “labeling” secreted...
Significance This study demonstrates the efficacy of combining macrophage-checkpoint inhibition with tumor-specific antibodies for cancer immunotherapy. The combination anti-CD47 (magrolimab) and anti-HER2 (trastuzumab) eliminated HER2 + breast cells increased due to enhancement antibody-dependent cellular phagocytosis by macrophages, even when were tolerant trastuzumab-induced cytotoxicity natural killer cells. We believe these findings present a promising therapeutic approach treating...
ABSTRACT An investigational live influenza virus vaccine, FluMist, contains three cold-adapted H1N1, H3N2, and B viruses. The vaccine viruses are 6/2 reassortants, in which the hemagglutinin (HA) neuraminidase (NA) genes derived from circulating wild-type remaining six master donor strains. strains ensure attenuation, HA NA confer ability to induce protective immunity against contemporary genotypic stability of this was studied by employing clinical samples collected during an efficacy...
The Tabula Muris Consortium We have created a compendium of single cell transcriptome data from the model organism Mus musculus comprising more than 100,000 cells 20 organs and tissues. These represent new resource for biology, revealing gene expression in poorly characterized populations allowing direct controlled comparison types shared between tissues, such as T-lymphocytes endothelial distinct anatomical locations. Two technical approaches were used most tissues: one approach,...
Significance Gloeobacter violaceus ligand-gated ion channel (GLIC) is a proton-gated, cation-selective channel, Cys-loop family member of the pentameric channels (pLGICs). In pursuit to provide evidence function-related conformational changes pLGIC in membrane, at ambient temperature and pressure very same unlabeled molecules, we used high-speed atomic force microscopy (HS-AFM) combined with buffer exchange system visualize reversible supramolecular arrangement conformations GLIC during pH...
Key Points Upon injury, the mesothelium recruits neutrophils to peritoneal space, which contributes adhesion formation. Neutrophil recruitment and macrophage-depletion kinetics in adhesions differ from normal innate response.
GABRR1 is a rho subunit receptor of GABA, the major inhibitory neurotransmitter in mammalian brain. While most investigations its function focused on nervous system, regulatory role hematopoiesis has not been reported. In this study, we found mainly expressed subsets human and mouse hematopoietic stem cells (HSCs) megakaryocyte progenitors (MkPs). GABRR1-negative (GR-) HSCs led to higher donor-derived chimerism than GABRR1-positive (GR+) HSCs. GR+ but GR- MkPs respond GABA patch clamp...
An essential mechanism for SARS-CoV-1 and -2 infection begins with the viral spike protein binding to human receptor angiotensin-converting enzyme II (ACE2). Here we describe a stepwise engineering approach generate set of affinity optimized, enzymatically inactivated ACE2 variants that potently block SARS-CoV-2 cells. These optimized traps tightly bind domain (RBD) prevent entry into host We first computationally designed ACE2-RBD interface using two-stage flexible backbone design process...
Protein glycosylation is a crucial mediator of biological functions and tightly regulated in health disease. However, interrogating complex protein glycoforms challenging, as current lectin tools are limited by cross-reactivity while mass spectrometry typically requires biochemical purification isolation the target protein. Here, we describe method to identify characterize class nanobodies that can distinguish without reactivity off-target glycoproteins or glycans. We apply this technology...
Self-renewal and multipotency are essential functions of hematopoietic stem cells (HSCs). To maintain homeostatic hematopoiesis, functionally uniform HSCs have been thought to be an ideal cell-of-origin. Recent technological advances in the field allowed us analyze with single cell resolution implicate that functional heterogeneity may exist even within highly purified HSC compartment. However, due part technical limitations analyzing extremely rare populations our incomplete understanding...
Abstract Immunoglobulin G (IgG) antibodies contain a complex N -glycan embedded in the hydrophobic pocket between its heavy chain protomers. This glycan contributes to structural organization of Fc domain and determines specificity for Fcγ receptors, thereby dictating distinct cellular responses. The variable construction this structure leads highly-related, but non-equivalent glycoproteins known as glycoforms. We previously reported synthetic nanobodies that distinguish IgG Here, we present...
Myeloid-biased hematopoiesis is a well-known age-related alteration. Several possibilities, including myeloid-biased hematopoietic stem cell (HSC) clones, may explain this. However, the precise mechanisms remain controversial.Utilizing Hoxb5 reporter system to prospectively isolate long-term HSCs (LT-HSCs) and short-term (ST-HSCs), we found that young aged LT-HSCs co-transplanted into same recipients demonstrated nearly equivalent myeloid lineage output, contrary theory of HSC clones....
Abstract Monoclonal antibodies (mAbs) with neutralizing activity against SARS-CoV-2 have demonstrated clinical benefit in cases of mild to moderate infection, substantially reducing the risk for hospitalization and severe disease1-4. Treatment generally requires administration high doses these mAbs limited efficacy preventing disease complications or mortality among hospitalized COVID-19 patients5. Here we report development evaluation Fc-optimized anti-SARS-CoV-2 superior potency prevent...