This is unpublished



Blair Armistead, Phd, MD, Post Doctoral Fellow, SCR

The role of inherited maternal cells in infant BCG-specific T cell responses

Year awarded: 2023 

Mycobacterium tuberculosis (Mtb) is a leading cause of illness and death among children worldwide. In Mtb-endemic areas around the world, Bacillus Calmette-Guerin (BCG) vaccine is administered early in life and has been shown to prevent disseminated tuberculosis disease in children. However, efficacy can vary widely, and a more complete understanding of the factors that influence BCG immunogenicity is critical to the development of improved vaccination strategies. 

Aim 1. Evaluate the impact of maternal mycobacterial-specific T cells present at birth to the infant BCG[1]specific CD4+ T cell recall response. 

Aim 2. Assess the relationship between birth MMc, trained immunity, and the BCG-specific CD4+ T cell recall response. 

Blair ARMISTEAD | Postdoctoral fellow | PhD, MPH | Seattle Children’s Research Institute, Seattle | Center for Global Infectious Disease Research | Research profile (


Hassan Eldesouky, PhD, Postdoctoral Research Associate, UW

Chemical biology to eliminate TB persisters

Year awarded: 2023

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains a formidable and enduring threat, resulting in approximately 1.5 million annual fatalities 1-3. The standard TB treatment protocols are known for their extended duration, which leads to prolonged drug exposure, associated 
toxicities, and patient non-compliance 4-8. Even with these demanding treatment regimens, it is estimated that around 5% of TB patients face chronic infection, treatment failure, and relapse 9, 10- a phenomenon attributed to drug-tolerant Mtb subpopulations known as "persisters" 11-14. Further, recent studies have indicated a pivotal role of persisters in the emergence of drug-resistant Mtb strains 11, 15. Despite the 
clinical significance of Mtb persistence, the molecular underpinnings of this phenomenon remain elusive, 
prompting the urgent need to unravel persister biology and develop effective interventions to shorten treatment durations. 

Aim 1: Define the molecular mechanisms underpinning the anti-persister activity of NTP. 

Aim 2: Determine NTP resistance frequency and mechanisms. 

‪Hassan Eldesouky‬ - ‪Google Scholar‬


Engi Attia, PhD, UW

Risk factors, mechanisms and trajectories of post-tuberculosis lung disease in Kenyan children

Year awarded: 2023

Tuberculosis (TB) is a leading infectious cause of morbidity and mortality worldwide. Nearly half of people with pulmonary TB develop post-TB lung disease (PTLD), which is defined broadly as the presence of “chronic respiratory abnormality, with or without symptoms, attributable at least in part to previous [TB].” Modeling studies estimate a high burden of PTLD in children, with the majority in sub-Saharan Africa. But, only two studies have examined aspects of PTLD in children under 5. Little is known about the risk factors, mechanisms or spectrum of lung function abnormalities associated with PTLD, especially in young children in resource-constrained
settings. Establishing a diagnosis of pulmonary TB and subsequent PTLD is challenging in young children given the paucibacillary nature of pediatric TB and difficulties in obtaining respiratory and extrapulmonary samples for culture or nucleic acid amplification (NAA).

Aim 1. Characterize lung function among children <5 years old with and without pulmonary TB, accounting for potentially modifiable risk factors and exposures.

Aim 2. Determine the association of TB disease severity at baseline with lung function and development of PTLD among children <5 with pulmonary TB.

Engi Attia - PubMed (


E. Chandler Church, MSc, MD, FHCC

A molecular viability assay for detection of dividing MTB in sputum samples

Year awarded: 2023

When treating pulmonary tuberculosis, response to treatment by microbiological methods is a major predictor of treatment success. It is also a determinant of time in isolation and duration of therapy. Current standard of care for patients in the US who are positive on smear microscopy requires patients to clear sputum smear 
microscopy to leave isolation, as well as to complete 14 days of treatment. However, smear microscopy can detect non-viable bacteria as well as actively dividing bacteria, making it an imperfect measurement. Culture, the gold standard, is slow to result, with plates being held 6-8 weeks before being confirmed negative. MTB
PCRs that target DNA have similar limitations to smears, as they can remain positive due to non-viable bacteria. For several years, researchers have been looking for alternative PCR or more rapid methods to monitor treatment response, including targeting mRNA or pre-rRNA which have a much shorter half-life than DNA and would therefore be expected to only detect viable, dividing bacteria. 

Aim 1 Determine if there are baseline patient characteristics that predict persistent smear or culture positivity at 
8 weeks of treatment.

Aim 2 Collect sputum from smear positive patients who have received less than 14 days of therapy for frozen storage with a future aim to examine the specimens using R:S ratio and compare sensitivity relative to smear and culture on same-day sputum collected for clinical monitoring.

E. Chandler Church - PubMed (


Nathan Kieswetter, PhD, UW

Mtb lipid-specific antibodies and B-cells during TB 

 Year awarded: 2023

The role of B cells in TB remains controversial. While key B-cell depletion experiments have failed to induce significant sensitivity to Mycobacterium tuberculosis (PMID: 26883591), several important
studies have shown that low titers of antibodies (Abs) to Mtb glycolipids such as LAM have been associated with increased Mtb dissemination in children (PMID: 1287946), that anti LAM/arabinomannan Abs enhance phagolysosome fusion and inhibit intracellular growth in a titer dependent manner (PMID: 27056953), and that key feature differences in Abs can delineate patients with active Tb from those that are latently infected (PMID: 27667685). Furthermore, recent research indicates that individuals identified as ‘resisters’ display immune reactions characterized by IgM and class-switched IgG antibodies, coupled with non-IFN-γ T cell responses to Mycobacterium tuberculosis (Mtb)-specific proteins ESAT6 and CFP10, providing immunologic evidence of Mtb exposure. In contrast to individuals with conventional latent tuberculosis infection (LTBI), ‘resisters' exhibit increased antibody avidity and distinctive Mtb-specific IgG Fc profiles (PMID: 31110348). Together, these lines of evidence highlight the rationale behind further understanding the role of B-cell and anti-Mtb glycolipid Abs in TB.

Aim 1: Determine the incidence of lipid-specific antibodies in patients exposed to Mtb.

Aim 2: Assess clonal variation of sorted/isolated B-cell and T-cell BRC and TCRs, respectively.

Nathan Kieswetter - PubMed (



Suzanne McDermott, PhD, SCRI

Development of a droplet-based high-throughput single-cell RNA sequencing platform for Mycobacterium tuberculosis

Year awarded: 2023

Mycobacterium tuberculosis (Mtb) generates phenotypically diverse sub-populations during pathogenesis, which is critical for bacterial survival in the face of drug treatments and human immune 
responses, and for bacterial adaptation to different microenvironments in their human hosts. There is a critical need to understand this within-population diversity, which can be tackled via analyses of gene expression in single cells. However, most studies that follow gene expression in Mtb populations have been limited to bulk measurements that ignore heterogeneity between individual bacterial cells. Furthermore, where single cell gene expression has been measured, it has been limited to analysis of a small number of transcripts. The overall objective of this work is to develop a high-throughput single-cell RNA sequencing approach to study 
heterogeneity in Mtb populations. We will initially do so using the attenuated H37Ra strain which will allow us to safely work outside of a BSL-3 containment laboratory, but the approach will be easily adaptable to pathogenic strains and isolates.

Aim 1.1. Fixation, permeabilization and generation of single cell suspensions of Mtb. 

Aim 1.2. High-throughput single-cell RNA sequencing for Mtb.

Suzanne M McDermott - ORCID


Nuttada Panpradist, PhD, Postdoctoral Fellow, UW

Laboratory-developed assay for tuberculosis drug resistance detection in Kenya

Year awarded: 2022

Antimicrobial resistance remains a formidable obstacle to tuberculosis (TB) control, especially in low-to-middle countries (LMICs), including Kenya. Screening of rifampin (RIF) resistant TB via GeneXpert® provides limited information for the detection of multi-drug-resistant TB (MDR-TB) or extreme-drugresistant TB (XDR-TB).

AIM 1: Develop probes to detect mutations associated with resistance to the 1st-line regimen (MDR-TB).

AIM 1: Develop probes to detect mutations associated with resistance to the 1st-line regimen (MDR-TB).

Innovation | Nuttada Panpradist


Vishant Boradia, PhD, Fellow PhD, SCRI

Calcium (Ca2+) signaling in Mycobacterium tuberculosi

Year awarded: 2022

Calcium (Ca2+) and phosphate are the major signaling currencies in eukaryotic cells. While protein phosphorylation as a signaling mechanism is also well established in bacteria, Ca2+ signaling is not. The basis for Ca2+ signaling is a Ca2+ gradient between the outside and inside of cells, which has also been shown to be maintained by some bacteria. In addition, some bacterial Ca2+
-binding proteins and putative transporters have been identified, suggesting the presence of a bacterial Ca2+ signaling system analogous to that in eukaryotes. However, many fundamental questions about bacterial Ca2+signaling remain unexplored, from Ca2+ transport, Ca2+ binding proteins, Ca2+ storage, and finally the effects of Ca2+ on bacterial physiology and pathogenesis. 

Aim 1: Determine the triggers for Ca2+ influx and efflux in Mtb.

Aim 2: Identify the Ca2+-binding proteins in Mtb. 

Vishant BORADIA | Post-Doctoral Scientist | PhD | Center for Infectious Disease Research, Seattle | Research profile (


Benjamin Gern, MD, Acting Assistant Professor, SCRI

Dissecting the stromal determinants of granuloma morphology

Year awarded: 2022

Effective strategies to prevent and treat tuberculosis (TB) are urgently needed, but our failure to adequately understand TB pathogenesis and immunity is a roadblock to developing them. Our current understanding of TB is largely driven by detailed mechanistic studies in immune cells. The contribution of stromal cells, which make up the majority of cells within the granuloma at early timepoints and have the capacity to induce major changes in immune microenvironments, is underappreciated. Thus, it is crucial to develop a better understanding of the mechanistic contribution of stromal cells on the generation of granuloma structures in order to drive the development of new strategies to combat this deadly disease.

Aim 1. Characterize stromal signaling environment in granulomas during their formation.

Aim 2: Validate protein expression of potential pathways and characterize effects on immune microenvironments.

Gern Lab Team - Center for Global Infectious Disease Research (


Karolina Maciag, MD, PhD, Senior Fellow, UW

IFNγ-independent modulation of of lung macrophages by T cells during Mycobacterium tuberculosis infection

Year awarded: 2022

An effective vaccine for Mycobacterium tuberculosis (Mtb) is urgently needed, yet its development has been hampered 
by incomplete understanding of immunity to Mtb. While vaccine candidates are routinely assessed by their ability to induce CD4+ T cell-derived interferon gamma (IFNγ), this marker has been unreliable in predicting vaccine protection against tuberculosis (TB) disease1–7. Studies in mice have shown that T cell-derived IFNγ is only part of a multi-modal CD4+ T cell immune response to Mtb8–10. However, the identity of the alternative CD4+ T cell responses, and the cellular mechanisms they induce in infected cells, remain largely unknown.

Aim 1: Identify candidate protective IFNγ-independent mechanisms induced by T cells in pulmonary macrophages during Mtb infection in mice in vivo

Aim 2: Validate the expression of candidate T cell-induced IFNγ-independent mechanisms in lung MDMs of Mtb-infected mice in the setting of naïve or vaccination-induced partial immunity 

Karolina Maciag, PhD | Department of Immunology (