One of the key challenges in infectious diseases control is unavailability of rapid and low-cost diagnostics with high specificities and sensitivities. I am a Molecular-microbiologist currently working with Dr. Jason Andrews at the Division of Infectious Diseases. My research primarily focuses on applying novel strategies to detect Mycobacterium tuberculosis and SARS-CoV-2 in various sample types and environments for treatment and control of TB and COVID-19.
i)Development and validation of molecular viability assays for detection and quantification of novel SARS-CoV-2 virus in COVID-19 patients
ii)Development and validation of a novel aerosol capture tool for the detection of SARS-CoV-2 in exhaled breath from COVID-19 patients with mild and severe symptoms
iii)Development of a rapid pharmacogenomic assay to detect NAT2 polymorphisms and predict INH acetylation to guide dosing for tuberculosis treatment
iv)Detection of M. tuberculosis in the environment as a novel tool for identifying high-risk locations for tuberculosis transmission
v)Analyzing host serum biomarkers in latent and active Tuberculosis using ELISA assays in patients as a measure of disease severity.
Honors & Awards
Life Science National eligibility test (NET) award, Council of Scientific and Industrial Research (CSIR) Govt. of India (Jun 2011)
National Senior Research PhD Fellowship, Council of Scientific and Industrial Research (CSIR)- University grants commission (UGC) (Jan 2015-Dec 2016)
National Junior Research PhD fellowship, Council of Scientific and Industrial Research (CSIR)- University grants commission (UGC) (Jan 2012-Dec 2014)
All-India Graduate Aptitude Test in Engineering -GATE Fellowship in Biotechnology, Indian Institute of Science (IISc) (April 2011)
BCIL (Biotech Consortium India Limited) Industrial training Fellowship, Department of Biotechnology (DBT), Govt. of India (2010)
Contingency grant for MSc. dissertation at HCG Hospitals Bangalore, Department of Biotechnology, Govt. of India (2010)
DBT Fellowship for MSc Biotechnology, Department of Biotechnology (DBT), Govt. of India (2008-2010)
Doctor of Philosophy, Institute of Bioinformatics, Bangalore, India (2017)
Master of Science, University Of Mysore (2011)
Bachelor of Science, Bangalore University (2008)
Blood-based host biomarker diagnostics in active case finding for pulmonary tuberculosis:
EClinicalMedicine, published by The Lancet
View details for DOI 10.1016/j.eclinm.2021.100776
A Rapid Pharmacogenomic Assay to Detect NAT2 Polymorphisms and Guide Isoniazid Dosing for Tuberculosis Treatment.
American journal of respiratory and critical care medicine
Standardized dosing of anti-tubercular drugs contributes to a substantial incidence of toxicities, inadequate treatment response, and relapse, in part due to variable drug levels achieved. Single nucleotide polymorphisms (SNPs) in the N-acetyltransferase-2 (NAT2) gene explain the majority of interindividual pharmacokinetic variability of isoniazid (INH). However, an obstacle to implementing pharmacogenomic-guided dosing is the lack of a point-of-care assay.To develop and test a NAT2 classification algorithm, validate its performance in predicting isoniazid clearance, and develop a prototype pharmacogenomic assay.We trained random forest models to predict NAT2 acetylation genotype from unphased SNP data using a global collection of 8,561 phased genomes. We enrolled 48 pulmonary TB patients, performed sparse pharmacokinetic sampling, and tested the acetylator prediction algorithm accuracy against estimated INH clearance. We then developed a cartridge-based multiplex qPCR assay on the GeneXpert platform and assessed its analytical sensitivity on whole blood samples from healthy individuals.With a 5-SNP model trained on two-thirds of the data (n=5,738), out-of-sample acetylation genotype prediction accuracy on the remaining third (n=2,823) was 100%. Among the 48 TB patients, predicted acetylator types were: 27 (56.2%) slow, 16 (33.3%) intermediate and 5 (10.4%) rapid. INH clearance rates were lowest in predicted slow acetylators (median 14.5 L/hr), moderate in intermediate acetylators (median 40.3 L/hr) and highest in fast acetylators (median 53.0 L/hr). The cartridge-based assay accurately detected all allele patterns directly from 25 ul of whole blood.An automated pharmacogenomic assay on a platform widely used globally for tuberculosis diagnosis could enable personalized dosing of isoniazid.
View details for DOI 10.1164/rccm.202103-0564OC
View details for PubMedID 34375564
SARS-CoV-2 subgenomic RNA kinetics in longitudinal clinical samples
Open Forum Infectious Diseases
View details for DOI 10.1093/ofid/ofab310
- Detection, survival and infectious potential of Mycobacterium tuberculosis in the environment: a review of the evidence and epidemiological implications EUROPEAN RESPIRATORY JOURNAL 2019; 53 (6)
Whole Genome Sequencing of Mycobacterium tuberculosis Clinical Isolates From India Reveals Genetic Heterogeneity and Region-Specific Variations That Might Affect Drug Susceptibility
FRONTIERS IN MICROBIOLOGY
View details for DOI 10.3389/fmicb.2019.00309
Rise of Clinical Microbial Proteogenomics: A Multiomics Approach to Nontuberculous Mycobacterium-The Case of Mycobacterium abscessus UC22.
OMICS, journal of Integrative biology
View details for DOI 10.1089/omi.2018.0116
Integrated Multi-Omic Analysis of Mycobacterium tuberculosis H37Ra Redefines Virulence Attributes.
Frontiers in microbiology
View details for DOI 10.3389/fmicb.2018.01314
Quantitative Proteomic and Phosphoproteomic Analysis of H37Ra and H37Rv Strains of Mycobacterium tuberculosis
JOURNAL OF PROTEOME RESEARCH
2017; 16 (4): 1632-1645
Mycobacterium tuberculosis, the causative agent of tuberculosis, accounts for 1.5 million human deaths annually worldwide. Despite efforts to eradicate tuberculosis, it still remains a deadly disease. The two best characterized strains of M. tuberculosis, virulent H37Rv and avirulent H37Ra, provide a unique platform to investigate biochemical and signaling pathways associated with pathogenicity. To delineate the biomolecular dynamics that may account for pathogenicity and attenuation of virulence in M. tuberculosis, we compared the proteome and phosphoproteome profiles of H37Rv and H37Ra strains. Quantitative phosphoproteomic analysis was performed using high-resolution Fourier transform mass spectrometry. Analysis of exponential and stationary phases of these strains resulted in identification and quantitation of 2709 proteins along with 512 phosphorylation sites derived from 257 proteins. In addition to confirming the presence of previously described M. tuberculosis phosphorylated proteins, we identified 265 novel phosphorylation sites. Quantitative proteomic analysis revealed more than five-fold upregulation of proteins belonging to virulence associated type VII bacterial secretion system in H37Rv when compared to those in H37Ra. We also identified 84 proteins, which exhibited changes in phosphorylation levels between the virulent and avirulent strains. Bioinformatics analysis of the proteins altered in their level of expression or phosphorylation revealed enrichment of pathways involved in fatty acid biosynthesis and two-component regulatory system. Our data provides a resource for further exploration of functional differences at molecular level between H37Rv and H37Ra, which will ultimately explain the molecular underpinnings that determine virulence in tuberculosis.
View details for DOI 10.1021/acs.jproteome.6b00983
View details for Web of Science ID 000398985700023
View details for PubMedID 28241730
Whole Genome Sequencing of Mycobacterium tuberculosis Isolates From Extrapulmonary Sites.
Omics : a journal of integrative biology
View details for DOI 10.1089/omi.2017.0070
A network map of Interleukin-10 signaling pathway
JOURNAL OF CELL COMMUNICATION AND SIGNALING
2016; 10 (1): 61-67
Interleukin-10 (IL-10) is an anti-inflammatory cytokine with important immunoregulatory functions. It is primarily secreted by antigen-presenting cells such as activated T-cells, monocytes, B-cells and macrophages. In biologically functional form, it exists as a homodimer that binds to tetrameric heterodimer IL-10 receptor and induces downstream signaling. IL-10 is associated with survival, proliferation and anti-apoptotic activities of various cancers such as Burkitt lymphoma, non-Hodgkins lymphoma and non-small scell lung cancer. In addition, it plays a central role in survival and persistence of intracellular pathogens such as Leishmania donovani, Mycobacterium tuberculosis and Trypanosoma cruzi inside the host. The signaling mechanisms of IL-10 cytokine are not well explored and a well annotated pathway map has been lacking. To this end, we developed a pathway resource by manually annotating the IL-10 induced signaling molecules derived from literature. The reactions were categorized under molecular associations, activation/inhibition, catalysis, transport and gene regulation. In all, 37 molecules and 76 reactions were annotated. The IL-10 signaling pathway can be freely accessed through NetPath, a resource of signal transduction pathways previously developed by our group.
View details for DOI 10.1007/s12079-015-0302-x
View details for Web of Science ID 000377699100008
View details for PubMedID 26253919
View details for PubMedCentralID PMC4850137
Data on whole genome sequencing of extrapulmonary tuberculosis clinical isolates from India.
Data on whole genome sequencing of extrapulmonary tuberculosis clinical isolates from India.
View details for DOI 10.1016/j.dib.2018.08.048.
Integrating transcriptomic and proteomic data for accurate assembly and annotation of genomes
2017; 27 (1): 133-144
Complementing genome sequence with deep transcriptome and proteome data could enable more accurate assembly and annotation of newly sequenced genomes. Here, we provide a proof-of-concept of an integrated approach for analysis of the genome and proteome of Anopheles stephensi, which is one of the most important vectors of the malaria parasite. To achieve broad coverage of genes, we carried out transcriptome sequencing and deep proteome profiling of multiple anatomically distinct sites. Based on transcriptomic data alone, we identified and corrected 535 events of incomplete genome assembly involving 1196 scaffolds and 868 protein-coding gene models. This proteogenomic approach enabled us to add 365 genes that were missed during genome annotation and identify 917 gene correction events through discovery of 151 novel exons, 297 protein extensions, 231 exon extensions, 192 novel protein start sites, 19 novel translational frames, 28 events of joining of exons, and 76 events of joining of adjacent genes as a single gene. Incorporation of proteomic evidence allowed us to change the designation of more than 87 predicted "noncoding RNAs" to conventional mRNAs coded by protein-coding genes. Importantly, extension of the newly corrected genome assemblies and gene models to 15 other newly assembled Anopheline genomes led to the discovery of a large number of apparent discrepancies in assembly and annotation of these genomes. Our data provide a framework for how future genome sequencing efforts should incorporate transcriptomic and proteomic analysis in combination with simultaneous manual curation to achieve near complete assembly and accurate annotation of genomes.
View details for DOI 10.1101/gr.201368.115
View details for Web of Science ID 000391906500012
View details for PubMedID 28003436
View details for PubMedCentralID PMC5204337
- A network map of BDNF/TRKB and BDNF/p75NTR signaling system. Journal of cell communication and signaling 2013; 7 (4): 301-307
A multilectin affinity approach for comparative glycoprotein profiling of rheumatoid arthritis and spondyloarthropathy.
2013; 10 (1): 11-?
Arthritis refers to inflammation of joints and includes common disorders such as rheumatoid arthritis (RA) and spondyloarthropathies (SpAs). These diseases differ mainly in terms of their clinical manifestations and the underlying pathogenesis. Glycoproteins in synovial fluid might reflect the disease activity status in the joints affected by arthritis; yet they have not been systematically studied previously. Although markers have been described for assisting in the diagnosis of RA, there are currently no known biomarkers for SpA.We sought to determine the relative abundance of glycoproteins in RA and SpA by lectin affinity chromatography coupled to iTRAQ labeling and LC-MS/MS analysis. We also used ELISA to validate the overexpression of VCAM-1, one of the candidate proteins identified in this study, in synovial fluid from RA patients.We identified proteins that were previously reported to be overexpressed in RA including metalloproteinase inhibitor 1 (TIMP1), myeloperoxidase (MPO) and several S100 proteins. In addition, we discovered several novel candidates that were overexpressed in SpA including Apolipoproteins C-II and C-III and the SUN domain-containing protein 3 (SUN3). Novel molecules found overexpressed in RA included extracellular matrix protein 1 (ECM1) and lumican (LUM). We validated one of the candidate biomarkers, vascular cell adhesion molecule 1 (VCAM1), in 20 RA and SpA samples using ELISA and confirmed its overexpression in RA (p-value <0.01). Our quantitative glycoproteomic approach to study arthritic disorders should open up new avenues for additional proteomics-based discovery studies in rheumatological disorders.
View details for DOI 10.1186/1559-0275-10-11
View details for PubMedID 24010407
View details for PubMedCentralID PMC3846907
Proteomic analysis of purified protein derivative of Mycobacterium tuberculosis.
2013; 10 (1): 8-?
Purified protein derivative (PPD) has been used for more than half a century as an antigen for the diagnosis of tuberculosis infection based on delayed type hypersensitivity. Although designated as "purified," in reality, the composition of PPD is highly complex and remains ill-defined. In this report, high resolution mass spectrometry was applied to understand the complexity of its constituent components. A comparative proteomic analysis of various PPD preparations and their functional characterization is likely to help in short-listing the relevant antigens required to prepare a less complex and more potent reagent for diagnostic purposes.Proteomic analysis of Connaught Tuberculin 68 (PPD-CT68), a tuberculin preparation generated from M. tuberculosis, was carried out in this study. PPD-CT68 is the protein component of a commercially available tuberculin preparation, Tubersol, which is used for tuberculin skin testing. Using a high resolution LTQ-Orbitrap Velos mass spectrometer, we identified 265 different proteins. The identified proteins were compared with those identified from PPD M. bovis, PPD M. avium and PPD-S2 from previous mass spectrometry-based studies. In all, 142 proteins were found to be shared between PPD-CT68 and PPD-S2 preparations. Out of the 354 proteins from M. tuberculosis-derived PPDs (i.e. proteins in either PPD-CT68 or PPD-S2), 37 proteins were found to be shared with M. avium PPD and 80 were shared with M. bovis PPD. Alignment of PPD-CT68 proteins with proteins encoded by 24 lung infecting bacteria revealed a number of similar proteins (206 bacterial proteins shared epitopes with 47 PPD-CT68 proteins), which could potentially be involved in causing cross-reactivity. The data have been deposited to the ProteomeXchange with identifier PXD000377.Proteomic and bioinformatics analysis of different PPD preparations revealed commonly and differentially represented proteins. This information could help in delineating the relevant antigens represented in various PPDs, which could further lead to development of a lesser complex and better defined skin test antigen with a higher specificity and sensitivity.
View details for DOI 10.1186/1559-0275-10-8
View details for PubMedID 23870090
View details for PubMedCentralID PMC3729367