The following projects are currently taking place in the NTM Center of Excellence:
Developing rpoB clinical diagnostic sequencing to accurately identify NTM isolates from patients.
Sequencing rpoB gene provides more accurate speciation compared to the current protocol of 16s gene sequencing. Accurate speciation of NTM helps improve the treatment and management of patients at National Jewish Health.
- Accomplishments: The Center of Excellence has completed the initial design, optimization and validation of rpoB sequencing test by sequencing approximately 200 NTM culture isolates.
- Projected Activities: Complete validation of rpoB clinical diagnostic sequencing test and launch it as a diagnostic test for patients from National Jewish Health and all over the United States and world.
Develop clinical diagnostic sequencing test to differentiate M. abscessus, M. massiliense and M. boletti in NTM patients.
Treatment response rates to combination antibiotic therapy including clarithromycin are much higher in patients with M. massiliense than in those with M. abscessus lung disease. Traditional diagnostic methods cannot differentiate M. massiliense from M. abscessus. Hence the need for a more specific molecular diagnostic test using multiple genes.
- Accomplishments: The Center of Excellence has completed the initial design, optimization and validation of multi-gene (rpoB, hsp65, erm41 and secA) sequencing test by sequencing approximately 200 NTM culture isolates.
- Projected Activities: Complete validation of multi-gene clinical diagnostic sequencing test and launch it as a diagnostic test for patients from all over the U.S. and world.
Sequencing entire genome of M. abscessus strains isolated from NTM patients to identify DNA biomarkers of virulence and response to antibiotic therapy.
M. abscessus is resistant to many antibiotics and is very difficult to treat. Traditional diagnostic methods are limited in their ability to guide physicians in stratification of patients in the treatment and management of M. abscessus infections. Sequencing genomes of multiple strains of M. abscessus will help us discover DNA biomarkers of virulence and response to antibiotic therapy.
- Projected Activities: Identify approximately 10-15 clinically challenging strains of M. abscessus and subject them to whole genome sequence.
Correlate M. abscessus genomic information to biochemical, culture, pharmacokinetic and clinical information to help identify DNA biomarkers of virulence and response to antibiotic therapy.
Currently in the process of hiring a post doctoral fellow/bioinformatics specialist trained in wet lab techniques to help analyze the genomic data.
Test Next Step Inc.'s Pharmacogenetics decision support software to study drug to drug interactions and software driven dosing predictions in NTM patients.
Cytochrome P450 family of enzymes in the liver are responsible for metabolizing prescription drugs that are in common use. Drugs administered to patients result in side-effects or are partially efficacious due to inter-patient difference in metabolizing them. These differences are due to common genetic variations that occur in all of us. We believe that applying the latest pharmacogenetics test and analysis software during treatment of NTM patients will help minimize side effects resulting from drug to drug interactions and also in reducing chances of toxic overdose of drugs.
- Projected Activities: Identify a cohort of patients with M. abscessus and analyze DNA polymorphisms using illumina's DMET chip. This genetic information will then be correlated with pharmacokinetic profiles, drug resistance profiles and other clinical information using Next Step Inc.'s Pharmacogenetics decision support software. We hope to identify better ways to treat and manage NTM patients using this personalized medicine approach.
Identify and characterize novel NTM species
NTM is a highly diverse group of mycobacteria and modern diagnostic methods are providing us with the tools to differentiate, categorize and characterize them better.
- Accomplishments: Identified a couple of novel NTM species.
- Projected Activities: To identify and characterize novel NTM species using culture, biochemical and genetic tests.