
Professor
Bioengineering
+1 415 502-0640
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My research uses computational methods to study the dynamic interplay between disease progression, treatment regimen, and drug and biomarker response across relevant scales (molecule, cell, tissue, organ & whole body) to determine causal links underlying variability in (safety and efficacy) clinical outcomes. By integrating multi-scale, and multi-level clinical data, we aim to determine the right dose, schedule, and treatment duration of various therapies, potentially bringing novel, precise and personalized treatment options to patients with unmet need more quickly.
Publications
The kinetics of bedaquiline diffusion in tuberculous cavities open a window for emergence of resistance.
The Journal of infectious diseases
Pharmacokinetics and safety of clofazimine in children with rifampicin-resistant tuberculosis.
The Journal of infectious diseases
Translational Modeling of BTZ-043 to Predict Phase 2A Efficacy and Evaluate Drug-Drug Interactions With Bedaquiline, Pretomanid, and Linezolid in Murine Models.
The Journal of infectious diseases
Author Correction: Risk-stratified treatment for drug-susceptible pulmonary tuberculosis.
Nature communications
Contribution of front-line, standard-of-care drugs to bactericidal responses, resistance emergence, and cure in murine models of easy- or hard-to-treat tuberculosis disease.
Antimicrobial agents and chemotherapy
Percent of lung involved in disease on chest X-ray predicts unfavorable treatment outcome in pulmonary tuberculosis.
medRxiv : the preprint server for health sciences
Selection and prioritization of candidate combination regimens for the treatment of tuberculosis.
Science translational medicine
Linezolid Pharmacokinetic-Anemia Modeling in Children with Rifampicin-Resistant Tuberculosis.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Pyrazinamide Safety, Efficacy, and Dosing for Treating Drug-Susceptible Pulmonary Tuberculosis: A Phase 3, Randomized, Controlled Clinical Trial.
American journal of respiratory and critical care medicine
Risk-stratified treatment for drug-susceptible pulmonary tuberculosis.
Nature communications
Dose optimization of TBI-223 for enhanced therapeutic benefit compared to linezolid in antituberculosis regimen.
Nature communications
Pharmacokinetic-Pharmacodynamic Evidence from a Phase 3 Trial to Support Flat-Dosing of Rifampicin for Tuberculosis.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Pharmacokinetics and Optimal Dosing of Levofloxacin in Children for Drug-Resistant Tuberculosis: An Individual Patient Data Meta-Analysis.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Pharmacokinetics and cardiac safety of clofazimine in children with rifampicin-resistant tuberculosis.
Antimicrobial agents and chemotherapy
Lung microenvironments harbor Mycobacterium tuberculosis phenotypes with distinct treatment responses.
Antimicrobial agents and chemotherapy
Pharmacokinetic analysis across studies to drive knowledge-integration: A tutorial on individual patient data meta-analysis (IPDMA).
CPT: pharmacometrics & systems pharmacology
Effectiveness and pharmacokinetic exposures of first-line drugs used to treat drug-susceptible tuberculosis in children: a systematic review and meta-analysis.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Interplay among malnutrition, chemoprevention, and the risk of malaria in young Ugandan children: Longitudinal pharmacodynamic and growth analysis.
CPT: pharmacometrics & systems pharmacology
A comparison of clinical development pathways to advance tuberculosis regimen development.
BMC infectious diseases
Characterizing HIV-preventive, plasma tenofovir concentrations. A pooled participant-level data analysis from HIV pre-exposure prophylaxis (PrEP) clinical trials.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Pharmacokinetics and Safety of Bedaquiline in HIV-Positive and Negative Older Children and Adolescents with Rifampicin-Resistant Tuberculosis.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Examining nonadherence in the treatment of tuberculosis: The patterns that lead to failure.
British journal of clinical pharmacology
Influence of NAT2 genotype and maturation on isoniazid exposure in low-birth-weight and preterm infants with or without HIV exposure.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Piperaquine induced QTc prolongation decreases with repeated monthly dihydroartemisinin-piperaquine dosing in pregnant Ugandan women.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Prothionamide Dose Optimization Using Population Pharmacokinetics for Multidrug-Resistant Tuberculosis Patients.
Antimicrobial agents and chemotherapy
Pharmacometrics in tuberculosis: progress and opportunities.
International journal of antimicrobial agents
Clinical standards for the dosing and management of TB drugs.
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Proposed Linezolid Dosing Strategies to Minimize Adverse Events for Treatment of Extensively Drug-Resistant Tuberculosis.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Drug concentration at the site of disease in children with pulmonary tuberculosis.
The Journal of antimicrobial chemotherapy
Pharmacokinetics and Safety of Three Months of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention in Pregnant Women.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Moxifloxacin pharmacokinetics, cardiac safety, and dosing for the treatment of rifampicin-resistant tuberculosis in children.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Model-informed drug development of voxelotor in sickle cell disease: Exposure-response analysis to support dosing and confirm mechanism of action.
CPT: pharmacometrics & systems pharmacology
Model-informed drug development of voxelotor in sickle cell disease: Population pharmacokinetics in whole blood and plasma.
CPT: pharmacometrics & systems pharmacology
Emerging data on rifampicin pharmacokinetics and approaches to optimal dosing in children with tuberculosis.
Expert review of clinical pharmacology
A rabbit model to study antibiotic penetration at the site of infection for non-tuberculous mycobacterial lung disease: macrolide case study.
Antimicrobial agents and chemotherapy
Model-Based Efficacy and Toxicity Comparisons of Moxifloxacin for Multidrug-Resistant Tuberculosis.
Open forum infectious diseases
Precision-enhancing Risk Stratification Tools for Selecting Optimal Treatment Durations in Tuberculosis Clinical Trials.
American journal of respiratory and critical care medicine
Emerging Therapeutics, Technologies, and Drug Development Strategies to Address Patient Nonadherence and Improve Tuberculosis Treatment.
Annual review of pharmacology and toxicology
A systematic review of endpoint definitions in late phase pulmonary tuberculosis therapeutic trials.
Trials
Is Glycemic Control the Secret to Tuberculosis Control?
American journal of respiratory and critical care medicine
Optimising pyrazinamide for the treatment of tuberculosis.
The European respiratory journal
Lesion penetration and activity limit the utility of second-line injectable agents in pulmonary tuberculosis.
Antimicrobial agents and chemotherapy
A Longitudinal Model-Based Biomarker Analysis of Exposure Response in Adults with Pulmonary Tuberculosis.
Antimicrobial agents and chemotherapy
Pharmacodynamic Correlates of Linezolid Activity and Toxicity in Murine Models of Tuberculosis.
The Journal of infectious diseases
Mycobacterium tuberculosis precursor rRNA as a measure of treatment-shortening activity of drugs and regimens.
Nature communications
Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis.
The New England journal of medicine
Malaria PK/PD and the role pharmacometrics can play in the global health arena: Malaria treatment regimens for vulnerable populations.
Clinical pharmacology and therapeutics
Oxypurinol pharmacokinetics and pharmacodynamics in healthy volunteers: Influence of BCRP Q141K polymorphism and patient characteristics.
Clinical and translational science
COVID-19 pharmacologic treatments for children: research priorities and approach to pediatric studies.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Visualizing the dynamics of tuberculosis pathology using molecular imaging.
The Journal of clinical investigation
Decreased plasma rifapentine concentrations associated with AADAC single nucleotide polymorphism in adults with tuberculosis.
The Journal of antimicrobial chemotherapy
A Mechanistic In Vivo/Ex Vivo Pharmacokinetic-Pharmacodynamic Model of Tenofovir for HIV Prevention.
CPT: pharmacometrics & systems pharmacology
Population Pharmacokinetic Method to Predict Within-Subject Variability Using Single-Period Clinical Data.
Pharmaceuticals (Basel, Switzerland)
Pragmatic global dosing recommendations for the 3-month, once-weekly rifapentine and isoniazid preventive TB regimen in children.
The European respiratory journal
Piperaquine exposure is altered by pregnancy, HIV and nutritional status in Ugandan women.
Antimicrobial agents and chemotherapy
Rifapentine Population Pharmacokinetics and Dosing Recommendations for Latent Tuberculosis Infection.
American journal of respiratory and critical care medicine
Pharmacokinetics and Pharmacological Properties of Chloroquine and Hydroxychloroquine in the Context of COVID-19 Infection.
Clinical pharmacology and therapeutics
Mathematical model and tool to explore shorter multi-drug therapy options for active pulmonary tuberculosis.
PLoS computational biology
Development of New Tuberculosis Drugs: Translation to Regimen Composition for Drug-Sensitive and Multidrug-Resistant Tuberculosis.
Annual review of pharmacology and toxicology
Response to "Quantitative Clinical Pharmacology INPUT to SARS-CoV-2 Therapeutics Should be Based on Robust Data": Data-Driven Dosing Recommendations are Urgently Needed for Hydroxychloroquine in COVID-19 Patients: Response to Letter to the Editor.
Clinical pharmacology and therapeutics
Optimizing Hydroxychloroquine Dosing for Patients With COVID-19: An Integrative Modeling Approach for Effective Drug Repurposing.
Clinical pharmacology and therapeutics
Early Bactericidal Activity Trial of Nitazoxanide for Pulmonary Tuberculosis.
Antimicrobial agents and chemotherapy
Antiretroviral Therapy Concentrations Differ in Gut vs. Lymph Node Tissues and Are Associated With HIV Viral Transcription by a Novel RT-ddPCR Assay.
Journal of acquired immune deficiency syndromes (1999)
Mechanistic Modeling of Mycobacterium tuberculosis Infection in Murine Models for Drug and Vaccine Efficacy Studies.
Antimicrobial agents and chemotherapy
The importance of adherence in tuberculosis treatment clinical trials and its relevance in explanatory and pragmatic trials.
PLoS medicine
Results from a Phase 1 Study of Sodium Selenite in Combination with Palliative Radiation Therapy in Patients with Metastatic Cancer.
Translational oncology
Alternative dosing guidelines to improve outcomes in childhood tuberculosis: a mathematical modelling study.
The Lancet. Child & adolescent health
Accuracy of point-of-care ultrasound by pediatric emergency physicians for testicular torsion.
Journal of pediatric urology
Fluoroquinolone Efficacy against Tuberculosis Is Driven by Penetration into Lesions and Activity against Resident Bacterial Populations.
Antimicrobial agents and chemotherapy
Modeling Prevention of Malaria and Selection of Drug Resistance with Different Dosing Schedules of Dihydroartemisinin-Piperaquine Preventive Therapy during Pregnancy in Uganda.
Antimicrobial agents and chemotherapy
Publisher Correction: A patient-level pooled analysis of treatment-shortening regimens for drug-susceptible pulmonary tuberculosis.
Nature medicine
A patient-level pooled analysis of treatment-shortening regimens for drug-susceptible pulmonary tuberculosis.
Nature medicine
Population Pharmacokinetics and Pharmacodynamics of Disulfiram on Inducing Latent HIV-1 Transcription in a Phase IIb Trial.
Clinical pharmacology and therapeutics
Intermittent Preventive Treatment for Malaria in Pregnancy: Optimization of Target Concentrations of Dihydroartemisinin-Piperaquine.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Impact of immunopathology on the antituberculous activity of pyrazinamide.
The Journal of experimental medicine
Pharmacokinetics of rifapentine and rifampin in a rabbit model of tuberculosis and correlation with clinical trial data.
Science translational medicine
Predicting Optimal Dihydroartemisinin-Piperaquine Regimens to Prevent Malaria During Pregnancy for Human Immunodeficiency Virus-Infected Women Receiving Efavirenz.
The Journal of infectious diseases
Suboptimal Antituberculosis Drug Concentrations and Outcomes in Small and HIV-Coinfected Children in India: Recommendations for Dose Modifications.
Clinical pharmacology and therapeutics
Levofloxacin Population Pharmacokinetics in South African Children Treated for Multidrug-Resistant Tuberculosis.
Antimicrobial agents and chemotherapy
Population Pharmacokinetics of Cladribine in Patients with Multiple Sclerosis.
Clinical pharmacokinetics
Heterogeneous drug penetrance of veliparib and carboplatin measured in triple negative breast tumors.
Breast cancer research : BCR
Tuberculous meningitis.
Nature reviews. Neurology
New Paradigm for Translational Modeling to Predict Long-term Tuberculosis Treatment Response.
Clinical and translational science
Population Pharmacokinetics of Pyrazinamide in Patients with Tuberculosis.
Antimicrobial agents and chemotherapy
Defining the optimal dose of rifapentine for pulmonary tuberculosis: Exposure-response relations from two phase II clinical trials.
Clinical pharmacology and therapeutics
Model Evaluation of Continuous Data Pharmacometric Models: Metrics and Graphics.
CPT: pharmacometrics & systems pharmacology
Importance of Drug Pharmacokinetics at the Site of Action.
Clinical and translational science
Association of busulfan exposure with survival and toxicity after haemopoietic cell transplantation in children and young adults: a multicentre, retrospective cohort analysis.
The Lancet. Haematology
Xpert MTB/RIF Assay Shows Faster Clearance of Mycobacterium tuberculosis DNA with Higher Levels of Rifapentine Exposure.
Journal of clinical microbiology
A Longitudinal HbA1c Model Elucidates Genes Linked to Disease Progression on Metformin.
Clinical pharmacology and therapeutics
The Effect of Famotidine, a MATE1-Selective Inhibitor, on the Pharmacokinetics and Pharmacodynamics of Metformin.
Clinical pharmacokinetics
GeneXpert MTB/Rif to Diagnose Tuberculous Meningitis: Perhaps the First Test but not the Last.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Pharmacokinetic/Pharmacodynamic Relationship of Gabapentin in a CFA-induced Inflammatory Hyperalgesia Rat Model.
Pharmaceutical research
Toward Earlier Inclusion of Pregnant and Postpartum Women in Tuberculosis Drug Trials: Consensus Statements From an International Expert Panel.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study.
The lancet. HIV
Pediatric tuberculous meningitis: Model-based approach to determining optimal doses of the anti-tuberculosis drugs rifampin and levofloxacin for children.
Clinical pharmacology and therapeutics
Host-Mediated Bioactivation of Pyrazinamide: Implications for Efficacy, Resistance, and Therapeutic Alternatives.
ACS infectious diseases
Population pharmacokinetics of busulfan in pediatric and young adult patients undergoing hematopoietic cell transplant: a model-based dosing algorithm for personalized therapy and implementation into routine clinical use.
Therapeutic drug monitoring
Novel dosing strategies increase exposures of the potent antituberculosis drug rifapentine but are poorly tolerated in healthy volunteers.
Antimicrobial agents and chemotherapy
The effect of malnutrition on the pharmacokinetics and virologic outcomes of lopinavir, efavirenz and nevirapine in food insecure HIV-infected children in Tororo, Uganda.
The Pediatric infectious disease journal
Daily rifapentine for treatment of pulmonary tuberculosis. A randomized, dose-ranging trial.
American journal of respiratory and critical care medicine
Designing drug trials: considerations for pregnant women.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Impact of adherence and anthropometric characteristics on nevirapine pharmacokinetics and exposure among HIV-infected Kenyan children.
Journal of acquired immune deficiency syndromes (1999)
Phase I safety, pharmacokinetics, and pharmacogenetics study of the antituberculosis drug PA-824 with concomitant lopinavir-ritonavir, efavirenz, or rifampin.
Antimicrobial agents and chemotherapy
Genetic variants in transcription factors are associated with the pharmacokinetics and pharmacodynamics of metformin.
Clinical pharmacology and therapeutics
Population pharmacokinetics of rifapentine and desacetyl rifapentine in healthy volunteers: nonlinearities in clearance and bioavailability.
Antimicrobial agents and chemotherapy
Rifapentine Pharmacokinetics and Tolerability in Children and Adults Treated Once Weekly With Rifapentine and Isoniazid for Latent Tuberculosis Infection.
Journal of the Pediatric Infectious Diseases Society
Pharmacokinetics of lopinavir/ritonavir and efavirenz in food insecure HIV-infected pregnant and breastfeeding women in Tororo, Uganda.
Journal of clinical pharmacology
Effect of weight and maturation on busulfan clearance in infants and small children undergoing hematopoietic cell transplantation.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
Reduced renal clearance of cefotaxime in asians with a low-frequency polymorphism of OAT3 (SLC22A8).
Journal of pharmaceutical sciences
Effect of adherence as measured by MEMS, ritonavir boosting, and CYP3A5 genotype on atazanavir pharmacokinetics in treatment-naive HIV-infected patients.
Clinical pharmacology and therapeutics
The pharmacokinetics of oxypurinol in people with gout.
British journal of clinical pharmacology
Optimising the manufacture, formulation, and dose of antiretroviral drugs for more cost-efficient delivery in resource-limited settings: a consensus statement.
The Lancet. Infectious diseases
Analysis of exposure-response of CI-945 in patients with epilepsy: application of novel mixed hidden Markov modeling methodology.
Journal of pharmacokinetics and pharmacodynamics
Standard Error of Empirical Bayes Estimate in NONMEM® VI.
The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology
Two bootstrapping routines for obtaining imprecision estimates for nonparametric parameter distributions in nonlinear mixed effects models.
Journal of pharmacokinetics and pharmacodynamics
Implementation and evaluation of the SAEM algorithm for longitudinal ordered categorical data with an illustration in pharmacokinetics-pharmacodynamics.
The AAPS journal
Evaluation of an extended grid method for estimation using nonparametric distributions.
The AAPS journal
Performance in population models for count data, part II: a new SAEM algorithm.
Journal of pharmacokinetics and pharmacodynamics
Importance of shrinkage in empirical bayes estimates for diagnostics: problems and solutions.
The AAPS journal
Evaluation of the nonparametric estimation method in NONMEM VI: application to real data.
Journal of pharmacokinetics and pharmacodynamics
Semiparametric distributions with estimated shape parameters.
Pharmaceutical research
Evaluation of the nonparametric estimation method in NONMEM VI.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
Population pharmacokinetics of rifampin in pulmonary tuberculosis patients, including a semimechanistic model to describe variable absorption.
Antimicrobial agents and chemotherapy
Implementation of a transit compartment model for describing drug absorption in pharmacokinetic studies.
Journal of pharmacokinetics and pharmacodynamics
Diagnosing model diagnostics.
Clinical pharmacology and therapeutics
Population Pharmacokinetic Analysis of the Oral Absorption Process of Tacrolimus in Healthy Volunteers
Kor J Clin Pharmacol Ther
Pharmacokinetics of desmopressin administrated as an oral lyophilisate dosage form in children with primary nocturnal enuresis and healthy adults.
Journal of clinical pharmacology
Application of population pharmacokinetics to cladribine.
BMC pharmacology