A5064011327- Viral-associated cancers and disorders
- Cytomegalovirus and herpesvirus research
- Ubiquitin and proteasome pathways
- Lymphoma Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- HIV Research and Treatment
- Parvovirus B19 Infection Studies
- Cancer-related gene regulation
- Viral gastroenteritis research and epidemiology
- Gut microbiota and health
- Bacteriophages and microbial interactions
- Herpesvirus Infections and Treatments
- Clostridium difficile and Clostridium perfringens research
- Immunotherapy and Immune Responses
- Kawasaki Disease and Coronary Complications
- 14-3-3 protein interactions
- Viral Infections and Outbreaks Research
- Fibroblast Growth Factor Research
- Virology and Viral Diseases
- COVID-19 Clinical Research Studies
- Eosinophilic Disorders and Syndromes
- T-cell and Retrovirus Studies
- Immune Cell Function and Interaction
- Advanced Biosensing Techniques and Applications
- T-cell and B-cell Immunology
New York Medical College
2023-2024
University of North Carolina at Chapel Hill
2009-2022
UNC Lineberger Comprehensive Cancer Center
2011-2018
North Carolina State University
2006-2007
COVID-19, an infectious respiratory illness, is caused by infection with the SARS-CoV-2 virus. Individuals underlying medical conditions are at increased risk of developing serious illnesses such as long COVID. Recent studies have observed Epstein-Barr virus (EBV) reactivation in patients severe illness or COVID, which may contribute to associated symptoms. We determined frequency EBV COVID-19 positive compared negative patients. 106 blood plasma samples were collected from and was detection...
Epstein⁻Barr virus (EBV) infects up to 95% of the adult human population, with primary infection typically occurring during childhood and usually asymptomatic. However, EBV can cause infectious mononucleosis in approximately 35⁻50% cases when occurs adolescence early adulthood. is also associated several B-cell malignancies including Burkitt lymphoma, Hodgkin post-transplant lymphoproliferative disease. A number antiviral drugs have proven be effective inhibitors replication, yet resulted...
ABSTRACT PCNA is monoubiquitinated in response to DNA damage and fork stalling then initiates recruitment of specialized polymerases the tolerance pathway, translesion synthesis (TLS). Since reported associate with Epstein-Barr virus (EBV) during its replication, we investigated whether EBV deubiquitinating (DUB) enzyme encoded by BPLF1 targets ubiquitinated disrupts TLS. An N-terminal fragment (a construct containing first 246 amino acids [BPLF1 1-246]) associated attenuated ubiquitination...
Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1), the principal viral oncoprotein and a member of tumor necrosis factor receptor superfamily, is constitutively active signaling that regulates multiple signal transduction pathways via its C-terminal-activating region (CTAR1) CTAR2, also less-studied CTAR3. Because sumoylation among other posttranslational modifications may regulate many induced by LMP1, we investigated whether during EBV latency LMP1 processes control cellular...
ABSTRACT A newly discovered virally encoded deubiquitinating enzyme (DUB) is strictly conserved across the Herpesviridae . Epstein-Barr virus (EBV) BPLF1 encodes a tegument protein (3,149 amino acids) that exhibits activity lost upon mutation of active-site cysteine. However, targets for herpesviral DUBs have remained elusive. To investigate predicted interaction between EBV and ribonucleotide reductase (RR), functional clone first 246 N-terminal acids (BPLF1 1-246) was constructed....
As a herpesvirus, Epstein-Barr virus (EBV) establishes latent infection that can periodically undergo reactivation, resulting in lytic replication and the production of new infectious virus. Latent membrane protein-1 (LMP1), principal viral oncoprotein, is latency-associated protein implicated regulating reactivation maintenance latency. We recently found LMP1 hijacks SUMO-conjugating enzyme Ubc9 via its C-terminal activating region-3 (CTAR3) induces sumoylation cellular proteins. Because...
ABSTRACT BPLF1 of Epstein-Barr virus (EBV) is classified as a late lytic cycle protein but also found in the viral tegument, suggesting its potential involvement at both initial and stages infection. possesses deubiquitinating deneddylating activity located N-terminal domain involved processes that affect infectivity, DNA replication, repair, immune evasion. A recently constructed EBV BPLF1-knockout (KO) was used conjunction with humanized mouse model can be infected EBV, enabling first...
Deubiquitinating enzymes (DUBs) are involved in the regulation of distinct critical cellular processes. Ubiquitin C-terminal Hydrolase L1 (UCH L1) has been linked to several neurological diseases as well human cancer, but physiological targets and UCH expression vivo have largely unexplored. Here we demonstrate that up-regulates β-catenin/TCF signaling: forms endogenous complexes with β-catenin, stabilizes it β-catenin/TCF-dependent transcription. We also show that, reciprocally, signaling...
Epstein-Barr virus (EBV) encodes BPLF1, a lytic cycle protein with deubiquitinating activity that is contained in its N-terminal domain and conserved across the Herpesviridae. EBV replication associated cellular DNA repair factors, initiation of induces damage response, which can be regulated at least part by BPLF1. The pathway, translesion synthesis (TLS), disrupted deubiquitinates processivity factor, PCNA, inhibits recruitment TLS polymerase, polymerase eta (Pol eta), after to UV...
Although many drugs inhibit the replication of Epstein-Barr virus (EBV) in cell culture systems, there is still no drug that effective and approved for use primary EBV infection. More recently, maribavir (MBV), an l-ribofuranoside benzimidazole, has been shown to be a potent nontoxic inhibitor have mode action quite distinct from acyclic nucleoside analogs such as acyclovir (ACV) based primarily on MBV's ability block phosphorylation target proteins by human cytomegalovirus protein kinases....
Maribavir (MBV) inhibits Epstein-Barr virus (EBV) replication and the enzymatic activity of viral protein kinase BGLF4. MBV also expression multiple EBV transcripts during lytic infection. Here we demonstrate, with use a BGLF4 knockout virus, that effects on transcription take place primarily through inhibition genome copy numbers infectivity to levels similar exceeding produced by virus.
Increasing evidence shows that exosomes are key regulators in cancer cell-to-cell communication. Several reports on Epstein-Barr virus (EBV)-related malignancies demonstrate latent membrane protein 1 (LMP1) secreted by derived from EBV- or LMP1-positive cells can promote progression and metastasis. However, the mechanism which LMP1 is loaded into still poorly understood. Here, we examined whether process of loading linked to multifunctional molecule ubiquitin system-ubiquitin C-terminal...
Normally ubiquitin C-terminal hydrolase L1 (UCH-L1) is expressed in the central nervous and reproductive systems of adults, but its de novo expression has been detected many human cancers. There a growing body evidence that UCH-L1 de-ubiquitinating (DUB) activity plays major pro-metastatic role certain carcinomas. Here we tested anti-metastatic effects small-molecule inhibitor DUB activity, LDN-57444, cell lines from advanced oral squamous carcinoma (OSCC) as well invasive nasopharyngeal...
In most individuals, EBV maintains a life-long asymptomatic latent infection. However, can induce the formation of B cell lymphomas in immune suppressed individuals including people living with HIV (PLWH). Most who acquire are already infected as infection is primarily acquired during childhood and adolescence. Although antiretroviral therapy (ART) has substantially reduced incidence AIDS-associated malignancies, positive PLWH at an increased risk developing compared to general population....
Epstein-Barr virus (EBV) infection and lytic replication are known to induce a cellular DNA damage response. We previously showed that the virally encoded BPLF1 protein interacts with regulates several members of translesion synthesis (TLS) pathway, tolerance these factors enhance viral infectivity. is late cycle gene, but also packaged in tegument, indicating may function both early during infection. The expresses deubiquitinating activity strictly conserved across Herpesviridae; mutation...
Sindbis virus is a single-stranded positive-sense RNA virus. It composed of 240 copies three structural proteins: E1, E2, and capsid. These proteins form mature particle two nested T=4 icosahedral shells. A complex network disulfide bonds in the E1 E2 glycoproteins developed through series intermediates as maturation occurs (M. Mulvey D. T. Brown, J. Virol. 68:805-812, 1994; M. Carleton et al., 71:1558-1566, 1997). To better understand nature this network, cysteinyl residues were labeled...
Herpesviral deubiquitinating enzymes (DUBs) were discovered in 2005, are highly conserved across the family, and proving to be increasingly important players herpesviral infection. EBV's DUB, BPLF1, is known regulate both cellular viral target activities, yet remains largely unstudied. Our work has implicated BPLF1 a wide range of processes including infectivity, DNA replication, repair. Additionally, knockout delays reduces human B-cell immortalization lymphoma formation humanized mice....
Despite recent advances in therapy, allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option for a range of high-risk hematologic malignancies. However, acute graft-versus-host disease (aGVHD) continues to limit long-term success HSCT, and new therapies are still needed. We previously demonstrated that aGVHD depends on ability donor conventional T cells (Tcons) express lymph node trafficking receptor, CC-Chemokine Receptor 7 (CCR7). Consequently, we examined...