Mazhar Adli
Northwestern University, IL·Genetics
Some diseases are driven by specific mutations. Others arise when cells rewire which genes are switched on.
- Fields
Genetics
Biochemistry
Medicine & Clinical Research
- Topics
genome editing
uterine fibroids
leiomyoma
- Grants
- 3 known grants, through May 2030
What they work on
- Create human cell models of uterine fibroids by using CRISPR to engineer specific MED12 mutations, and determine how these mutations drive tumor formation.
- Identify druggable mechanisms that selectively kill MED12-mutant fibroid cells, using the engineered human cell models.
- Determine which transcription factors and combinations reprogram naïve ovarian cancer cells into a platinum-resistant state, using single-cell CRISPR perturbations followed by transcriptome profiling.
- Test a new combinatorial target to achieve synthetic lethality with carboplatin in high-grade serous ovarian cancer, in vitro and in vivo with clinical samples.
- Insert barcoded mini auxin-inducible degrons (mAID), tags that destroy a protein when auxin is added, into 250 essential genes in human induced pluripotent stem cells using CRISPR knock-in.
- Catalog what happens when essential proteins are removed, measuring survival, proliferation, mitosis, differentiation, gene expression and chromatin accessibility in stem cells and derived cell types.
More about the research
A key challenge is building human cell models that show exactly what a given gene or mutation does. Three projects use CRISPR genome editing, a tool for making precise changes to DNA, to tackle this problem. One studies a mutation behind most uterine fibroids. One studies how ovarian cancer cells reprogram their gene activity to resist chemotherapy. One builds a resource for switching off essential human genes on demand.
Why it matters
Human cell models of MED12-mutant uterine fibroids could reveal druggable targets for a condition that seriously affects about a quarter of reproductive-age women. Uncovering how ovarian cancer cells become platinum-resistant, and testing a combination target, could help overcome the main cause of death in high-grade serous ovarian cancer. The barcoded degron resource could help researchers study essential genes tied to human disease and development.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Thomas G Boyer
University of Texas Health Science Center at San Antonio, TX·Biochemistry
Determine how fibroid-causing MED12 mutations destabilize the T-loop of the CDK8 enzyme and reduce its substrate binding and activity, using structural biology and biochemistry.
Yang Yang-Hartwich
Yale University, CT·Genetics
Define how NR2F2, a gene-regulating nuclear receptor, controls the migration and adhesion of ovarian cancer cells that drive spread through the peritoneal cavity.
Analisa DiFeo
University of Michigan, MI·Medicine & Clinical Research
Determine how loss of the microRNA miR-181a affects immune cell infiltration and interferon signaling in patient-derived ovarian tumor organoids, with and without a STING agonist or anti-PD-L1 immunotherapy.
The school
Northwestern University: 71 labs on PI Pages, $1.3B a year on research, 536 research doctorates a year.
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