A5009172988- HIV Research and Treatment
- Virus-based gene therapy research
- Genetics and Neurodevelopmental Disorders
- Viral Infectious Diseases and Gene Expression in Insects
- Neural dynamics and brain function
- SARS-CoV-2 detection and testing
- HIV/AIDS Research and Interventions
- Olfactory and Sensory Function Studies
- Congenital heart defects research
- Hepatitis C virus research
- Neuroscience and Neuropharmacology Research
- Single-cell and spatial transcriptomics
- Biosensors and Analytical Detection
- RNA modifications and cancer
- Memory and Neural Mechanisms
- HIV/AIDS drug development and treatment
- Hepatitis B Virus Studies
- Advanced biosensing and bioanalysis techniques
- Protein Kinase Regulation and GTPase Signaling
- Photoreceptor and optogenetics research
- Viral gastroenteritis research and epidemiology
- Pain Management and Placebo Effect
- CAR-T cell therapy research
- HIV-related health complications and treatments
- Biochemical Analysis and Sensing Techniques
University of North Carolina at Chapel Hill
2000-2024
North Carolina State University
2023-2024
Janelia Research Campus
2013-2022
University of North Carolina Health Care
2021
Howard Hughes Medical Institute
2016-2021
George Washington University Virginia Campus
2021
Helix (United States)
2013-2021
Rockefeller University
2008-2011
Hepatitis B Foundation
2010
Johns Hopkins University Center for AIDS Research
2004-2005
Placebo effects are notable demonstrations of mind-body interactions
ABSTRACT The viral determinants that underlie human immunodeficiency virus type 1 (HIV-1) neurotropism are unknown, due in part to limited studies on viruses isolated from brain. Previous suggest brain-derived macrophage tropic (M-tropic) and principally use CCR5 for entry. To better understand HIV-1 neurotropism, we primary autopsy brain, cerebral spinal fluid, blood, spleen, lymph node samples AIDS patients with dementia encephalitis. Isolates were characterized determine coreceptor usage...
Vav and Vav2 are members of the Dbl family proteins that act as guanine nucleotide exchange factors (GEFs) for Rho proteins. Whereas expression is restricted to cells hematopoietic origin, widely expressed. Although share highly related structural similarities high sequence identity in their homology domains, it has been reported they active GEFs with distinct substrate specificities toward members. displayed GEF activity Rac1, Cdc42, RhoA, RhoG, was exhibit RhoB, RhoG but not Rac1 or Cdc42....
Hepatitis C virus (HCV) replicates primarily in the liver, but HCV RNA has been observed association with other tissues and cells including B T lymphocytes, monocytes, dendritic cells. We have taken advantage of a recently described, robust system that fully recapitulates entry, replication production vitro to re-examine issue infection blood cell subsets. The replicase inhibitor 2'C-methyl adenosine was used distinguish from persistence. Whereas culture-grown replicated Huh-7.5 hepatoma...
Hepatitis C virus (HCV) remains a major public health problem, affecting approximately 130 million people worldwide. HCV infection can lead to cirrhosis, hepatocellular carcinoma, and end-stage liver disease, as well extrahepatic complications such cryoglobulinemia lymphoma. Preventative therapeutic options are severely limited; there is no vaccine available, nonspecific, IFN-based treatments frequently ineffective. Development of targeted antivirals has been hampered by the lack robust cell...
Objectives: To characterize HIV-1 env compartmentalization between cerebrospinal fluid (CSF) and peripheral blood plasma over all stages of the disease course, to determine relationship extent CSF clinical neurologic status. Design: Paired specimens were collected from 66 HIV-infected patients cross-sectionally representing major relating HIV-associated disease, including primary infection, asymptomatic chronic infection with minor global impairment, immune deficiency dementia. Methods:...
Parvalbumin and somatostatin inhibitory interneurons gate information flow in discrete cortical areas that compute sensory cognitive functions. Despite the considerable differences between areas, individual interneuron subtypes are genetically invariant thought to form canonical circuits regardless of which area they embedded in. Here, we investigate whether this is achieved through selective systematic variations their afferent connectivity during development. To end, examined development...
Projection neurons (PNs) in the mammalian olfactory bulb (OB) receive input from nose and project to diverse cortical subcortical areas. Morphological physiological studies have highlighted functional heterogeneity, yet no molecular markers been described that delineate PN subtypes. Here, we used viral injections into cortex fluorescent nucleus sorting enrich PNs for high-throughput single bulk RNA deep sequencing. Transcriptome analysis situ hybridization identified distinct mitral tufted...
Human immunodeficiency virus type 1 (HIV-1) exists as a complex population of multiple genotypic variants in persons with chronic infection. However, acute HIV-1 infection via sexual transmission is low-probability event which there thought to be low genetic complexity the initial inoculum. In order assess viral present during primary infection, V1/V2 and V3 variable regions env gene were examined by using heteroduplex tracking assay (HTA) capable resolving these variants. Blood plasma...
The human immunodeficiency virus type 1 (HIV-1) surface Env protein has been implicated in the development of HIV-1-associated dementia (HAD). HIV-1 env diversity was analyzed by heteroduplex tracking assay 27 infected subjects with various neurological statuses. compartmentalization between blood and cerebral spinal fluid (CSF) apparent all categories. However, HAD, significantly more CSF represented CNS-unique variants. Variants specialized for replication CNS may play a larger role HAD....
Adeno-associated viruses (AAVs) have acquired a central role in modern medicine as delivery agents for gene therapies targeting rare diseases. While new AAVs with improved tissue targeting, potency, and safety are being introduced, their biomanufacturing technology is lagging. In particular, the AAV purification pipeline hinges on protein ligands affinity-based capture step. featuring excellent binding capacity selectivity, these require strong acid (pH <3) elution conditions, which can...
Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) during primary infection and persists in this compartment by unknown mechanisms over course of infection. In study, we examined viral population dynamics four asymptomatic subjects commencing antiretroviral therapy to characterize cellular sources HIV-1 CNS. The inability monitor viruses directly brain poses a major challenge studying Studies cerebrospinal fluid (CSF) provide useful surrogate for sampling...
Loss of the maternal UBE3A allele causes Angelman syndrome (AS), a debilitating neurodevelopmental disorder. Here, we devised an AS treatment strategy based on reinstating dual-isoform expression human (hUBE3A) in developing brain. Kozak sequence engineering our codon-optimized vector (hUBE3Aopt) enabled translation both short and long hUBE3A protein isoforms at near-endogenous 3:1 (short/long) ratio, feature that could help to support optimal therapeutic outcomes. To model widespread brain...
Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder caused by monoallelic mutation or deletion in the transcription factor 4 ( TCF4 ) gene. Individuals with PTHS typically present first year of life developmental delay and exhibit intellectual disability, lack speech, motor incoordination. There are no effective treatments available for PTHS, but root cause disorder, haploinsufficiency, suggests that it could be treated normalizing gene expression. Here, we performed...
The worldwide coronavirus disease 2019 pandemic has had devastating effects on health, healthcare infrastructure, social structure, and economics. One of the limiting factors in containing spread this virus been lack widespread availability fast, inexpensive, reliable methods for testing individuals. Frequent screening infected often asymptomatic people is a cornerstone management plans. Here, we introduce 2 pH-sensitive "LAMPshade" dyes as novel readouts an isothermal Reverse Transcriptase...
We developed a novel Plasmodium falciparum genotyping strategy based on the heteroduplex tracking assay (HTA) method commonly used to genotype viruses. Because it can detect both sequence and size polymorphisms, we hypothesized that HTA is more sensitive than current methods. To test this hypothesis, compared ability of nested polymerase chain reaction (PCR) genetic diversity in 17 Thai samples. The detected MSP1 variants eight isolates (47%), less three (18%), an equal number six (35%),...