# Control of Toxoplasma gondii Growth by the Host Cell Transcription Factor HIF1

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $431,488

## Abstract

The obligate intracellular parasite Toxoplasma gondii is a major opportunistic infection
of AIDS patients. Toxoplasma also causes devastating disease to fetuses and other
immunocompromised patients. While much work has focused on identifying and
characterizing Toxoplasma proteins and pathways important for growth and virulence of
this intracellular pathogen, less is known about which host cell pathways are rate-
limiting for parasite growth. Identification of these host cell processes is important
because if we can inhibit them or the parasite processes dependent on them from
functioning then we can block parasite growth and disease. Modulation of host cell
transcription is a common mechanism to make the host cell’s environment permissive
for pathogen growth. Hypoxia Inducible Factor 1 (HIF-1) is one example of a host cell
transcription that is activated by Toxoplasma infection and is required for parasite
growth. In the previous funding period, we found that HIF-1 is activated by Toxoplasma
triggering the nuclear export and subsequent lysosomal degradation of the PHD2
protein, which is the key negative regulator of HIF-1. Decreases in PHD2 protein is
achieved by the parasite activating a host cell receptor named Activin Like Kinase 4
(ALK4). Finally, we discovered that HIF-1 promotes Toxoplasma growth by
upregulating the host glycolytic hexokinase 2. In this proposal we will establish how
Toxoplasma stimulates PHD2 nuclear export and lysosomal degradation, what ligand
binds to ALK4, and how hexokinase 2 acts to promote parasite growth. These studies
are likely to provide important information regarding the interaction between
Toxoplasma and its host cell.

## Key facts

- **NIH application ID:** 9851313
- **Project number:** 5R01AI069986-15
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Ira J Blader
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $431,488
- **Award type:** 5
- **Project period:** 2006-04-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851313

## Citation

> US National Institutes of Health, RePORTER application 9851313, Control of Toxoplasma gondii Growth by the Host Cell Transcription Factor HIF1 (5R01AI069986-15). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9851313. Licensed CC0.

---

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