# Integrating Transforming Approaches to Identify and Target New Vulnerabilities in Cancer

> **NIH NIH R35** · DANA-FARBER CANCER INST · 2021 · $1,046,441

## Abstract

SUMMARY
The last decade has seen an unparalleled pace of cancer-focused discovery enabled by disruptive
technologies. However, for many malignancies, such as acute myeloid leukemia (AML), survival of the disease
remains unchanged despite a more granular description of its genomic landscape. My research program seeks
to apply new approaches in functional genomics and chemical biology to validate and translate emerging
cancer dependencies in AML and other malignancies defined by simple genomes, particularly pediatric
cancers. In this proposal, I build upon our past success in 1) inventing new approaches to small-molecule
discovery 2) applying state-of-the-art chemical and functional genomic screens to identify new therapeutic
targets in leukemia, Ewing sarcoma, and neuroblastoma, and in 3) translating our discoveries to clinical trials
for patients suffering from these diseases. Primarily focusing on AML, my future research program seeks to 1)
deploy genetic approaches to validate candidate cancer dependencies, 2) discover and test new small-
molecule inhibitors of cancer dependencies, and 3) dissect the mechanisms of each target and its role in AML.
I will begin with the study of targets that have emerged in our research as relevant in high-risk AML subtypes:
the cytoplasmic kinase spleen tyrosine kinase (SYK); a serine-threonine kinase glycogen synthase kinase 3
alpha (GSK-3α), a mitochondrial enzyme involved in folate metabolism, methylenetetrahydrofolate
dehydrogenase 2 (MTHFD2); and a member of the cohesin complex: stromal antigen 2 (STAG2). In some
cases, such as Ewing sarcoma and STAG2, I will extend testing to other disease contexts where the target is
relevant and my laboratory has expertise. With deep expertise in the molecular pathogenesis and care of
patients with AML; experience leading highly multi-disciplinary teams focused on high-throughput screening for
this disease and a rich network of chemistry, biology, and clinical collaborators, I am uniquely positioned to
succeed in the 7 year research plan delineated in this proposal.

## Key facts

- **NIH application ID:** 10225613
- **Project number:** 5R35CA210030-06
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Kimberly Stegmaier
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,046,441
- **Award type:** 5
- **Project period:** 2016-08-09 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225613

## Citation

> US National Institutes of Health, RePORTER application 10225613, Integrating Transforming Approaches to Identify and Target New Vulnerabilities in Cancer (5R35CA210030-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10225613. Licensed CC0.

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