A5050435547- COVID-19 epidemiological studies
- SARS-CoV-2 and COVID-19 Research
- Evolution and Genetic Dynamics
- Radiomics and Machine Learning in Medical Imaging
- Evolutionary Game Theory and Cooperation
- vaccines and immunoinformatics approaches
- Animal Behavior and Reproduction
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Vaccine Coverage and Hesitancy
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- COVID-19 Digital Contact Tracing
- Viral Infections and Outbreaks Research
- COVID-19 and Mental Health
- COVID-19 Clinical Research Studies
- Infection Control and Ventilation
- Acute Myeloid Leukemia Research
- Cancer Genomics and Diagnostics
- Data-Driven Disease Surveillance
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Eosinophilic Disorders and Syndromes
- Animal Virus Infections Studies
- Cancer Treatment and Pharmacology
- Computational Drug Discovery Methods
Stanford University
2022-2025
Palo Alto University
2024
New York Genome Center
2022-2024
Cornell University
2022-2024
Weill Cornell Medicine
2022-2024
Dana-Farber Cancer Institute
2018-2022
Harvard University
2020-2021
Boston Children's Hospital
2020-2021
Center for Systems Biology
2020-2021
Harvard University Press
2021
Some cancers originate from a single mutation event in cell. Blood known as myeloproliferative neoplasms (MPNs) are thought to when driver is acquired by hematopoietic stem cell (HSC). However, the first occurs individuals and how it affects behavior of HSCs their native context not known. Here we quantified effect JAK2-V617F on self-renewal differentiation dynamics treatment-naive with MPNs reconstructed lineage histories individual using somatic patterns. We found that mutations occurred...
The spike protein receptor-binding domain (RBD) of SARS-CoV-2 is the molecular target for many vaccines and antibody-based prophylactics aimed at bringing COVID-19 under control. Such a narrow focus raises specter viral immune evasion as potential failure mode these biomedical interventions. With emergence new strains with altered transmissibility potential, critical question this: how easily can virus escape neutralizing antibodies (nAbs) targeting RBD? To answer this question, we combined...
Abstract B-cells are promising candidate autologous antigen-presenting cells (APCs) to prime antigen-specific T-cells both in vitro and vivo . However date, a significant barrier utilizing as APCs is their low capacity for non-specific antigen uptake compared “professional” such dendritic cells. Here we utilize microfluidic device that employs many parallel channels pass single through narrow constrictions high throughput. This microscale “cell squeezing” process creates transient pores the...
The rapid emergence of immune-evading viral variants SARS-CoV-2 calls into question the practicality a vaccine-only public-health strategy for managing ongoing COVID-19 pandemic. It has been suggested that widespread vaccination is necessary to prevent future mutants. Here, we examined proposition using stochastic computational models transmission and mutation. Specifically, looked at likelihood immune escape requiring multiple mutations impact on this process. Our results suggest rate...
Background: While the rapid deployment of SARS-CoV-2 vaccines had a significant impact on ongoing COVID-19 pandemic, viral immune evasion and waning neutralizing antibody titers have degraded vaccine efficacy. Nevertheless, manufacturers public health authorities number options at their disposal to maximize benefits vaccination. In particular, effect booster schedules performance bears further study. Methods: To better understand performance, we used an agent-based modeling framework...
Abstract As many prophylactics targeting SARS-CoV-2 are aimed at the spike protein receptor-binding domain (RBD), we examined risk of immune evasion from previously published RBD-targeting neutralizing antibodies (nAbs). Epitopes for nAbs overlap one another substantially and can give rise to escape mutants with ACE2 affinities comparable wild type that still infect cells in vitro . We used evolutionary modeling predict frequency before after widespread presence due vaccines, passive...
The rapid emergence and expansion of novel SARS-CoV-2 variants threatens our ability to achieve herd immunity for COVID-19. These often harbor multiple point mutations, conferring one or more evolutionarily advantageous traits, such as increased transmissibility, immune evasion longer infection duration. In a number cases, variant has been linked long-term infections in individuals who were either immunocompromised treated with convalescent plasma. this paper, we used stochastic evolutionary...
The word 'pandemic' conjures dystopian images of bodies stacked in the streets and societies on brink collapse. Despite this frightening picture, denialism noncompliance with public health measures are common historical record, for example during 1918 Influenza pandemic or 2015 Ebola epidemic. unique characteristics SARS-CoV-2-its high basic reproduction number (R0), time-limited natural immunity considerable potential asymptomatic spread-exacerbate repercussions interventions (such as...
Abstract Patients with non-small cell lung cancer (NSCLC) who have distant metastases a poor prognosis. To determine which genomic factors of the primary tumor are associated metastasis, we analyzed data from 759 patients originally diagnosed stage I–III NSCLC as part AACR Project GENIE Biopharma Collaborative consortium. We found that TP53 mutations were significantly development new metastases. also more prevalent in history smoking, suggesting these may be at increased risk for...
Abstract As the COVID-19 pandemic continues unabated, many governments and public-health bodies worldwide have ceased to implement concerted measures for limiting viral spread, placing onus instead on individual. In this paper, we examine feasibility of proposition using an agent-based model simulate impact individual shielding behaviors reinfection frequency. We derive estimates heterogeneity in immune protection from a population pharmacokinetic (pop PK) antibody kinetics following...
The development and deployment of several SARS-CoV-2 vaccines in a little over year is an unprecedented achievement modern medicine. high levels efficacy against transmission for some these makes it feasible to use them suppress altogether regions with vaccine acceptance. However, viral variants reduced susceptibility vaccinal natural immunity threaten the utility vaccines, particularly scenarios where return pre-pandemic conditions occurs before suppression transmission. In this work we...
Abstract While the rapid deployment of SARS-CoV-2 vaccines had a significant impact on ongoing COVID-19 pandemic, viral immune evasion and waning neutralizing antibody titers have degraded vaccine efficacy. Nevertheless, manufacturers public health authorities number levers at their disposal to maximize benefits vaccination. Here, we use an agent-based modeling framework coupled with outputs population pharmacokinetic model examine boosting frequency durability vaccinal response Our work...
Contact tracing forms a crucial part of the public-health toolbox in mitigating and understanding emergent pathogens nascent disease outbreaks. United States was conducted during pre-Omicron phase ongoing COVID-19 pandemic. This relied on voluntary reporting responses, often using rapid antigen tests due to lack accessibility PCR tests. These limitations, combined with SARS-CoV-2's propensity for asymptomatic transmission, raise question "how reliable contact States"? We answered this Markov...
The strategy of relying solely on current SARS-CoV-2 vaccines to halt transmission has proven infeasible. In response, many public-health authorities have advocated for using limit mortality while permitting unchecked spread (“learning live with the disease”). feasibility this critically depends infection fatality rate (IFR) SARS-CoV-2. An expectation exists that IFR will decrease due selection against virulence. work, we perform a viral fitness estimation examine basis expectation. Our...
In the face of a long-running pandemic, understanding drivers ongoing SARS-CoV-2 transmission is crucial for rational management COVID-19 disease burden. Keeping schools open has emerged as vital societal imperative during but in-school can contribute to further prolonging pandemic. this context, role in driving acquires critical importance. Here we model from first principles investigate effectiveness layered mitigation strategies on limiting spread. We examined effect masks and air quality...
Individuals in a population often have different fitnesses even when they identical genotypes, but the effect of this variation on evolution through complicated fitness landscapes is unknown. Here, we investigate how populations with non-genetic cross valleys, common barriers to adaptation rugged which must pass deleterious intermediate arrive at final advantageous stage. We develop stochastic computational model describing dynamics an asexually reproducing crossing valley, individuals same...
Abstract The word ‘pandemic’ conjures dystopian images of bodies stacked in the streets and societies on brink collapse. Despite this frightening picture, denialism noncompliance with public health measures are common historical record, for example during 1918 Influenza pandemic or 2015 Ebola epidemic. unique characteristics SARS-CoV-2—its high reproductive number (R 0 ), time-limited natural immunity considerable potential asymptomatic spread—exacerbate repercussions biomedical...
Abstract The rapid emergence of immune-evading viral variants SARS-CoV-2 calls into question the practicality a vaccine-only public health strategy for managing ongoing COVID-19 pandemic. It has been suggested that widespread vaccination is necessary to prevent future mutants. Here we examine proposition using stochastic computational models transmission and mutation. Specifically, look at likelihood immune escape requiring multiple mutations, impact on this process. Our results suggest rate...
ABSTRACT Some cancers originate from a single mutation event in cell. For example, blood known as myeloproliferative neoplasms (MPN) are thought to through the acquisition of driver (most commonly JAK2 -V617F) hematopoietic stem cell (HSC). However, when first occurs individual patients and how it impacts behavior HSCs their native context is not known. Here we quantified impact JAK2- V617F on proliferation dynamics differentiation trajectories progenies MPN patients. We reconstructed...
Abstract The development and deployment of several SARS-CoV-2 vaccines in a little over year is an unprecedented achievement modern medicine. high levels efficacy against transmission for some these makes it feasible to use them suppress altogether regions with vaccine acceptance. However, viral variants reduced susceptibility vaccinal natural immunity threaten the utility vaccines, particularly scenarios where return pre-pandemic conditions occurs before suppression transmission. In this...
Abstract In the face of a long-running pandemic, understanding drivers ongoing SARS-CoV-2 transmission is crucial for rational management COVID-19 disease burden. Keeping schools open has emerged as vital societal imperative during but in-school can contribute to further prolonging pandemic. this context, role in driving acquires critical importance. Here we model from first principles investigate effectiveness layered mitigation strategies on limiting spread. We examine effect masks and air...
Abstract Patient-derived xenografts (PDX) are a powerful assay system for translational prediction of therapeutic potential experimental therapeutics. The primary readout from PDX models is tumor shrinkage, measured by the ratio treated/control volume. This corresponds loosely to Objective Response Rate (ORR) metric used in clinical trials, that it drug effect on sensitive subclones within tumor. In prior work, we have shown there paradoxical relationship between short-term response and...