# Novel Imaging and host-directed therapy in pediatric CNS TB

> **NIH NIH K08** · JOHNS HOPKINS UNIVERSITY · 2021 · $198,720

## Abstract

PROJECT SUMMARY: Central nervous system (CNS) tuberculosis (TB), most often TB meningitis (TBM), is
the most severe form of TB and disproportionately affects children, causing death or neurologic disability in over
half despite treatment. Current treatment is inadequate – it is based on pulmonary TB, is not optimized for CNS
penetration and does not sufficiently ameliorate the neuroinflammation causing neurologic injury. The K08 award
will provide Dr. Tucker, a pediatric intensivist at Johns Hopkins University, the essential time, training, resources
and mentorship to achieve her goals. Her long-term goal is to become an independent clinician scientist to better
understand the host immune response resulting in brain injury in TBM, to inform antimicrobial and adjunctive
therapeutic strategies, and to design therapeutic monitoring tools in order to improve treatment and prognosis of
children with this devastating disease. In the current proposal, Dr. Tucker will use a juvenile TBM rabbit model
to investigate the following aims: (1) optimize dosing of new TB antimicrobial drugs at the site of infection, (2)
determine whether the degree of bacterial burden, inflammation or antimicrobial penetration at the site of
infection correlates most with neurologic outcomes using multi-modality position emission tomography (PET)
imaging, and (3) determine if adjunctive host-directed, anti-oxidative therapy (dendrimer-N-acetyl-L-
cysteine[NAC]) targeted to activated microglia attenuates neuroinflammation and improves neurologic injury. To
achieve her long-term goals and complete her K08 aims, Dr. Tucker has assembled an interdisciplinary
mentorship team of experienced investigators committed to her success. Her mentors are experts in their fields;
Dr. Sujatha Kannan is a Professor of Pediatric Critical Care Medicine, whose research focuses on investigating
the role of neuroinflammation in the developing brain and utilization of nanotherapeutics, and Dr. Sanjay Jain is
a Professor of Pediatric Infectious Disease and Radiology who is an expert in TBM and development of novel
PET imaging tracers. Additionally, her advisory committee strengthens her mentorship with expertise in
nanomedicine, mass spectrometry and pharmacometrics to provide a strong foundation for her training. The five-
year career development plan will provide training in neuropathology, immunology, pharmacology, metabolomics
and biostatistics in order to complete these aims and lead to future R01 applications to investigate therapeutic
strategies that will improve the prognosis of children with TBM. Completion of the proposed research will
significantly advance our knowledge of the dynamic interactions between bacterial burden, host immune
response and antimicrobial penetration at the site of infection and provide new insights into TBM’s pathogenesis.
Additionally, this research will provide a foundation for clinical translation to optimize treatment in CNS infections
with pharmacokinetic modeling...

## Key facts

- **NIH application ID:** 10158397
- **Project number:** 5K08AI139371-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Elizabeth Winans Tucker
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $198,720
- **Award type:** 5
- **Project period:** 2019-06-05 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10158397

## Citation

> US National Institutes of Health, RePORTER application 10158397, Novel Imaging and host-directed therapy in pediatric CNS TB (5K08AI139371-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10158397. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*