A5085912489- HIV Research and Treatment
- Virus-based gene therapy research
- HIV/AIDS drug development and treatment
- Herpesvirus Infections and Treatments
- HIV/AIDS Research and Interventions
- Viral Infectious Diseases and Gene Expression in Insects
- Monoclonal and Polyclonal Antibodies Research
- Cell Adhesion Molecules Research
- Virology and Viral Diseases
- Mosquito-borne diseases and control
- Biochemical and Structural Characterization
- Cytomegalovirus and herpesvirus research
- Viral Infections and Immunology Research
- Tardigrade Biology and Ecology
- Chemical Reactions and Mechanisms
- Antimicrobial Peptides and Activities
- RNA Interference and Gene Delivery
- Viral gastroenteritis research and epidemiology
- Cancer Research and Treatments
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Viral Infections and Vectors
- Protist diversity and phylogeny
- CRISPR and Genetic Engineering
- Synthesis and Catalytic Reactions
Lehigh University
2024
University of Florida
2009-2023
Beth Israel Deaconess Medical Center
2014-2020
Ragon Institute of MGH, MIT and Harvard
2017
Harvard University
2014
Rutgers, The State University of New Jersey
2008
The development of an effective AIDS vaccine has been challenging because viral genetic diversity and the difficulty generating broadly neutralizing antibodies (bnAbs). We engineered trispecific (Abs) that allow a single molecule to interact with three independent HIV-1 envelope determinants: CD4 binding site, membrane-proximal external region (MPER), V1V2 glycan site. Trispecific Abs exhibited higher potency breadth than any previously described bnAb, showed pharmacokinetics similar those...
A combination of HIV-1–specific broadly neutralizing antibodies is necessary to protect rhesus monkeys against a mixed SHIV challenge.
Neutralizing antibodies to the HIV-1 envelope V2 apex protect macaques against SHIV challenge at very low serum concentrations.
Recently, a convincing body of evidence has accumulated suggesting that the overexpression carbonic anhydrase isozyme IX (CA IX) in some cancers contributes to acidification extracellular matrix, which turn promotes growth and metastasis tumor. These observations have made CA an attractive drug target for selective treatment certain cancers. Currently, there is no available X-ray crystal structure IX, this lack availability hampered rational design inhibitors. In light these on basis...
Adeno-associated virus (AAV)-derived vectors are promising gene delivery systems, and a number of design strategies have been pursued to improve their performance. For example, genetic insertion proteins into the capsid may be used achieve vector retargeting, reduced immunogenicity, or track transport. Unfortunately, rational approaches experienced limited success due unpredictable context-dependent nature protein folding complexity capsid's macroassembly. We report construction use...
ABSTRACT Human and chimpanzee adenovirus vectors are being developed to circumvent preexisting antibodies against common such as Ad5. However, baseline immunity these still exists in human populations. Traditional cloning of new vaccine is a long cumbersome process that takes 2 months or more requires rare unique restriction enzyme sites. Here we describe novel, enzyme-independent method for rapid reduces the total procedure 1 week. We 14 novel from rhesus monkeys can be grown high titers...
The development of a panel mucosally transmissible simian-human immunodeficiency virus (SHIV) challenge stocks from multiple clades would facilitate preclinical evaluation candidate HIV-1 vaccines and therapeutics. majority SHIV that have been generated to date derived clade B env sequences viruses isolated during chronic infection typically required serial animal-to-animal adaptation for establishing mucosal transmissibility pathogenicity. To capture essential features transmission C...
Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies. However, administration of purified bNAbs poses challenges in resource-poor settings, where the disease burden is greatest. In vivo vector-based production represents an alternative strategy. We investigated adenovirus serotype 5 (Ad5) adeno-associated virus 1 (AAV1) vectors to deliver HIV-1-specific bNAb PGT121 wild-type immunocompromised C57BL/6 mice as well HIV-1-infected bone...
Simian-human immunodeficiency virus (SHIV) challenge stocks are critical for preclinical testing of vaccines, antibodies, and other interventions aimed to prevent HIV-1. A major unmet need the field has been lack a SHIV stock expressing circulating recombinant form 01_AE (CRF01_AE) env sequences. We therefore sought develop mucosally transmissible containing HIV-1 CRF01_AE derived from acutely infected individuals Thailand. SHIV-AE6, SHIV-AE6RM, SHIV-AE16 contained sequences that were >99%...
Adeno-associated virus (AAV) is a nonenveloped single-stranded DNA (ssDNA) icosahedral T=1 being developed as vector for clinical gene delivery systems. Currently, there are approximately 160 AAV trials, with AAV2 the most widely studied serotype. To further understand system, this study investigates role of viral protein (VP) symmetry interactions on capsid assembly, genome packaging, stability, and infectivity. A total 25 (seven 2-fold, nine 3-fold, 5-fold interface) VP variants were...
Adenoviral vectors have shown significant promise as vaccine delivery due to their ability elicit both innate and adaptive immune responses. α-defensins are effector molecules of the response been modulate natural infection with adenoviruses, but majority α-defensin-adenovirus interactions studied date only analyzed in vitro. In this study, we evaluated role α-defensin 5 (HD5) modulating adenovirus immunogenicity using various serotype mice. We screened a panel human adenoviruses including...
We sought to enhance the infectivity of three SHIV stocks by optimization a key residue in human immunodeficiency virus type 1 (HIV-1) Env (Env375). developed following new simian-human (SHIV) stocks: SHIV-SF162p3S/wild type, SHIV-AE16W, and SHIV-325cH. SHIV-SF162p3S could not be optimized, SHIV-AE16W proved comparable parental virus, SHIV-325cH demonstrated markedly enhanced replicative capacity compared with virus.
Abstract The majority of preclinical and clinical human immunodeficiency virus type 1 (HIV-1) vaccine development efforts have focused on HIV-1 subtype B strains from the western world. However, overwhelming HIV/AIDS-related deaths occur in developing world are other strains. Therefore, we sought to develop generate first mucosally transmissible simian-human (SHIV) challenge stocks AE env sequences. sequences were identified acutely infected individuals Southeast Asia. efficiently rhesus...