# Mycobacterial determinants of escape from pathogen-specific immunity

> **NIH NIH K08** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $201,160

## Abstract

PROJECT SUMMARY/ABSTRACT
 This proposal presents a 5-year research and career development plan in the study of Mycobacterium
tuberculosis. The candidate, Allison Carey, MD, PhD, is currently a clinical fellow in Pathology at the
Massachusetts General Hospital who has begun postdoctoral research under the mentorship of Dr. Sarah
Fortune at the Harvard T.H. Chan School of Public Health. The proposed career development plan includes a
structured training program to provide Dr. Carey with the skills to become an independent investigator at an
academic medical center with a research focus on Mycobacterium tuberculosis (Mtb) the causative agent of
the globally significant disease, tuberculosis (TB). She will achieve this career goal through the guidance of her
mentor, a scientific advisory committee, formal coursework, seminars, and hands-on training in advanced
laboratory techniques. Her mentor, Dr. Sarah Fortune, is an established leader in TB research with a history of
training successful young scientists, and the members of the scientific advisory committee provide expertise in
each facet of the proposed research project. The scientific environment of the Harvard T.H. Chan School of
Public Health is exceptionally strong, and is embedded within the greater Boston scientific community, which
offers myriad scientific and career development resources. The research proposal builds on the candidate's
previous scientific training in classic Drosophila genetics and clinical microbiology, and is focused on the
bacterial determinants of Mtb immune evasion. Despite effective antibiotic regimens, the global burden of TB
remains high in part due to the failure of prior infection with Mtb or vaccination with Bacille Calmette-Guerin
(BCG) to fully protect against subsequent infection or disease, even though a robust immune response is
generated. Little is known about the bacterial features that facilitate survival in the face of the pathogen-specific
immune response. The candidate's initial post-doctoral work has demonstrated how the genetic diversity that
exists among Mtb clinical strains impacts antibiotic susceptibility and the emergence of antibiotic resistance.
Here, the candidate seeks to investigate how bacterial features including strain diversity determine outcomes
when an immunologically primed host is exposed to Mtb. In Aim 1, comparative genomics and candidate gene
approaches will be used to identify bacterial genetic determinants of success during reinfection. Some
epidemiologic studies suggest that Mtb strains from the rapidly expanding “Beijing” sublineage are more likely
to escape the immunity provided by BCG vaccination, a hypothesis that will be experimentally tested in Aim 2.
In Aim 3, a functional genomics approach, TnSeq, will be used to identify the bacterial genes that are essential
for survival and growth in the setting of a primed immune response. The outcome of these aims will answer
fundamental questions in the field, inform the develop...

## Key facts

- **NIH application ID:** 9928357
- **Project number:** 5K08AI139339-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Allison Carey
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $201,160
- **Award type:** 5
- **Project period:** 2018-06-14 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928357

## Citation

> US National Institutes of Health, RePORTER application 9928357, Mycobacterial determinants of escape from pathogen-specific immunity (5K08AI139339-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9928357. Licensed CC0.

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