A5071956292- Pancreatic function and diabetes
- Mosquito-borne diseases and control
- interferon and immune responses
- Viral Infections and Vectors
- Diabetes and associated disorders
- RNA regulation and disease
- Viral Infections and Immunology Research
- Diabetes Management and Research
- Viral Infections and Outbreaks Research
- Single-cell and spatial transcriptomics
- Error Correcting Code Techniques
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- Genetic Associations and Epidemiology
- Immune cells in cancer
- RNA Research and Splicing
- Chemokine receptors and signaling
- Herpesvirus Infections and Treatments
University of California, Los Angeles
2022-2024
UCLA Health
2023
University of California, San Diego
2019-2021
Palo Alto Veterans Institute for Research
2018
VA Palo Alto Health Care System
2018
Glioblastoma (GBM) is the least treatable type of brain tumor, afflicting over 15,000 people per year in United States. Patients have a median survival 16 months, and 95% die within 5 years. The chemokine receptor ACKR3 selectively expressed on both GBM cells tumor-associated blood vessels. High tumor expression correlates with poor prognosis potential treatment resistance, making it an attractive therapeutic target. We engineered single chain FV-human FC-immunoglobulin G1 (IgG1) antibody,...
The tripartite motif (TRIM) family of E3 ubiquitin ligases is well known for its roles in antiviral restriction and innate immunity regulation, addition to many other cellular pathways. In particular, TRIM25-mediated ubiquitination affects both carcinogenesis response. While individual substrates have been identified TRIM25, it remains unclear how regulates diverse processes. Here we characterized a mutation, R54P, critical TRIM25 catalytic activity, which successfully utilized “trap”...
Abstract Genetic risk variants for complex, multifactorial diseases are enriched in cis -regulatory elements. Single cell epigenomic technologies create new opportunities to dissect type-specific mechanisms of variants, yet this approach has not been widely applied disease-relevant tissues. Given the central role pancreatic islets type 2 diabetes (T2D) pathophysiology, we generated accessible chromatin profiles from 14.2k islet cells and identified 13 clusters including multiple alpha, beta...
The host interferon pathway upregulates intrinsic restriction factors in response to viral infection. Many of them block a diverse range viruses, suggesting that their antiviral functions might have been shaped by multiple families during evolution. Host-virus conflicts led the rapid adaptation and proteins at interaction hotspots. Hence, we can use evolutionary genetic analyses elucidate mechanisms domain factors. Zinc finger protein (ZAP) is factor against RNA viruses such as alphaviruses,...
The authors report a large genome-wide association study (GWAS) of type 1 diabetes (T1D) in 18 942 cases and 501 638 controls, finding 92 T1D-associated genomic loci (59 known 33 novel). Furthermore they analyse DNA chromatin patterns pancreas peripheral white blood cells to help identify the underlying genes. were linked genes that are active T cells, but also acinar ductal exocrine pancreas.
ABSTRACT Translating genome-wide association studies (GWAS) of complex disease into mechanistic insight requires a comprehensive understanding risk variant effects on disease-relevant cell types. To uncover type-specific mechanisms type 1 diabetes (T1D) risk, we combined genetic mapping and single epigenomics. We performed the largest to-date GWAS T1D in 489,679 samples imputed 59.2M variants, which identified 74 novel signals including several large-effect rare variants. Fine-mapping 141...
Abstract Despite their role as innate sentinels, macrophages are cellular reservoirs for chikungunya virus (CHIKV), a highly pathogenic arthropod-borne alphavirus that has caused unprecedented epidemics worldwide. Here, we took interdisciplinary approaches to elucidate the CHIKV determinants subvert into virion dissemination vessels. Through comparative infection using chimeric alphaviruses and evolutionary selection analyses, discovered first time glycoproteins E2 E1 coordinate efficient...
ABSTRACT The tripartite motif (TRIM) family of E3 ubiquitin ligases is well known for its roles in antiviral restriction and innate immunity regulation, addition to many other cellular pathways. In particular, TRIM25-mediated ubiquitination affects both carcinogenesis response. While individual substrates have been identified TRIM25, it remains unclear how regulates diverse processes. Here we characterized a mutation, R54P, critical TRIM25 catalytic activity, which successfully utilized...
The host interferon pathway upregulates intrinsic restriction factors in response to viral infection. Many of them block a diverse range viruses, suggesting that their antiviral functions might have been shaped by multiple families during evolution. Virus-host conflicts led the rapid adaptation and proteins at interaction hotspots. Hence, we can use evolutionary genetic analyses elucidate mechanisms domain factors. Zinc finger protein (ZAP) is factor against RNA viruses such as alphaviruses,...
Abstract Despite their role as innate sentinels, macrophages can serve cellular reservoirs of chikungunya virus (CHIKV), a highly-pathogenic arthropod-borne alphavirus that has caused large outbreaks among human populations. Here, with the use viral chimeras and evolutionary selection analysis, we define CHIKV glycoproteins E1 E2 critical for virion production in THP-1 derived macrophages. Through proteomic analysis functional validation, further identify signal peptidase complex subunit 3...