A5018345025- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- HIV/AIDS drug development and treatment
- Evolution and Genetic Dynamics
- HIV, Drug Use, Sexual Risk
- Hepatitis C virus research
- Topological and Geometric Data Analysis
- Mathematical and Theoretical Epidemiology and Ecology Models
- Evolutionary Game Theory and Cooperation
- Cancer Genomics and Diagnostics
- Immune Cell Function and Interaction
- Bioinformatics and Genomic Networks
- Glioma Diagnosis and Treatment
- HIV-related health complications and treatments
- Cytomegalovirus and herpesvirus research
- Respiratory viral infections research
- Influenza Virus Research Studies
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 and COVID-19 Research
- T-cell and B-cell Immunology
- Genomics and Chromatin Dynamics
- Drug Transport and Resistance Mechanisms
- Herpesvirus Infections and Treatments
- Metabolomics and Mass Spectrometry Studies
- Single-cell and spatial transcriptomics
Columbia University
2014-2024
Merck & Co., Inc., Rahway, NJ, USA (United States)
2018-2023
United States Military Academy
2022
Columbia University Irving Medical Center
2014-2018
Harvard University
2010-2015
Evolutionary Genomics (United States)
2012-2015
Harvard University Press
2012
The problem of achieving widespread immunity to infectious diseases by voluntary vaccination is often presented as a public-goods dilemma, an individual's contributes herd immunity, protecting those who forgo vaccination. temptation free-ride brings the equilibrium level below social optimum. Here, we present evolutionary game-theoretic approach this problem, exploring roles individual imitation behaviour and population structure in To end, integrate epidemiological process into simple...
Reversal of HIV-1 latency by small molecules is a potential cure strategy. This approach will likely require effective drug combinations to achieve high levels reversal. Using resting CD4+ T cells (rCD4s) from infected individuals, we developed an experimental and theoretical framework identify latency-reversing agent (LRA) combinations. Utilizing ex vivo assays for intracellular mRNA virion production, compared 2-drug leading candidate LRAs identified multiple that effectively reverse...
A latent reservoir for HIV-1 in resting CD4
Massive research efforts are now underway to develop a cure for HIV infection, allowing patients discontinue lifelong combination antiretroviral therapy (ART). New latency-reversing agents (LRAs) may be able purge the persistent reservoir of latent virus in resting memory CD4+ T cells, but degree reduction needed remains unknown. Here we use stochastic model infection dynamics estimate efficacy LRA prevent viral rebound after ART interruption. We incorporate clinical data population-level...
Infections with rapidly evolving pathogens are often treated using combinations of drugs different mechanisms action. One the major goal combination therapy is to reduce risk drug resistance emerging during a patient's treatment. Although this strategy generally has significant benefits over monotherapy, it may also select for multidrug-resistant strains, particularly long-term treatment chronic infections. these strains present an important clinical and public health problem. Complicating...
Monitoring the efficacy of novel reservoir-reducing treatments for HIV is challenging. The limited ability to sample and quantify latent infection means that supervised antiretroviral therapy (ART) interruption studies are generally required. Here we introduce a set mathematical statistical modeling tools aid in design interpretation ART-interruption trials. We show how likely size remaining reservoir can be updated real-time as patients continue off treatment, by combining output laboratory...
Most observation of human respiratory virus carriage is derived from medical surveillance; however, the infections documented by this surveillance represent only a symptomatic fraction total infected population. As role asymptomatic infection in transmission still largely unknown and rates shedding are not well constrained, it important to obtain more-precise estimates through alternative sampling methods. We actively recruited participants among visitors New York City tourist attraction....
Meiotic recombination is a fundamental evolutionary process driving diversity in eukaryotes. In mammals, known to occur preferentially at specific genomic regions. Using topological data analysis (TDA), branch of applied topology that extracts global features from large sets, we developed an efficient method for mapping fine scales. When compared standard linkage-based methods, TDA can deal with larger number SNPs and genomes without incurring prohibitive computational costs. We 1,000...
Antiretroviral therapy inhibits HIV-1 replication but is not curative due to establishment of a persistent reservoir after virus integration into the host genome. Reservoir reduction therefore an important cure strategy. Some nonnucleoside reverse transcriptase inhibitors induce selective cytotoxicity in vitro require concentrations far exceeding approved dosages. Focusing on this secondary activity, we found bifunctional compounds with HIV-1–infected cell kill potency at clinically...
Viral infections are one of the major causes death worldwide, with HIV infection alone resulting in over 1.2 million casualties per year. Antiviral drugs now being administered for a variety viral infections, including HIV, hepatitis B and C, influenza. These therapies target specific phase virus's life cycle, yet their ultimate success depends on factors, such as adherence to prescribed regimen emergence drug resistance. The epidemiology evolution resistance have been extensively...
Quantitative viral outgrowth assays (QVOA) use limiting dilutions of CD4+ T cells to measure the size latent HIV-1 reservoir, a major obstacle curing HIV-1. Efforts reduce reservoir require that can reliably quantify its in blood and tissues. Although QVOA is regarded as "gold standard" for measurement, little known about accuracy precision or how cell storage conditions laboratory-specific practices affect results. Owing this lack knowledge, confidence intervals around estimates-as well...