Pawel K. Mazur
University of Texas MD Anderson Cancer Center, TX·Genetics
Lung cancer causes more cancer deaths than any other cancer worldwide. For several of its forms, including small cell lung cancer and lung squamous cell carcinoma, there are still no targeted drugs.
- Fields
Genetics
Pharmacology
Biochemistry
- Topics
lung cancer
lung adenocarcinoma
lung squamous cell carcinoma
- Grants
- 3 known grants, through Jun 2028
What they work on
- Dissect how the enzyme CARM1 methylates the tumor-promoting transcription factor NFIB and signals through the effector protein TRIM29 in small cell lung cancer, using knock-in mice that carry a non-methylatable NFIB.
- Test whether small-molecule CARM1 inhibitors slow small cell lung cancer, using a range of preclinical mouse models.
- Determine how raising or lowering the histone-modifying enzyme NSD2 affects KRAS G12C-driven lung adenocarcinoma initiation, progression, metastasis and tumor diversity, using a tunable NSD2 mouse model.
- Test a first-in-class NSD2 inhibitor, alone and in combination therapies, against KRAS G12C mouse tumors and patient-derived lung adenocarcinoma xenografts.
- Define NSD3's roles in lung squamous cell carcinoma initiation, maintenance and metastasis, using inducible dual-recombinase mice that switch NSD3 on or off at chosen tumor stages.
- Map the gene programs controlled by NSD3 through the H3K36me2 histone mark, and its effect on cell-to-cell diversity in tumors, using epigenomic and single-cell methods in mouse and human models.
More about the research
This research looks at epigenetic regulators as possible drug targets. These are enzymes that chemically tag proteins to control which genes are switched on. The lab's projects focus on methyltransferases, enzymes that attach small methyl groups to histones (the spool proteins that package DNA) or to transcription factors (proteins that turn genes on). Each project combines engineered mouse models of a specific lung cancer, molecular studies of how the enzyme works, and tests of drugs that block it.
Why it matters
Patients with small cell lung cancer and lung squamous cell carcinoma currently have no targeted therapies. Patients with lung adenocarcinoma still see limited gains from existing drugs. By testing CARM1, NSD2 and NSD3 as drug targets, including a first-in-class NSD2 inhibitor and CARM1 inhibitors in preclinical models, this work could support new treatments. Combination therapies that lower the dose of each drug may reduce side effects and slow drug resistance.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Kwok Kin Wong
New York University, NY·Medicine & Clinical Research
Determine how co-mutations such as MYC, KMT2D, STK11 and PTEN change SCLC plasticity (cells' ability to switch identity) and transcriptional subtypes, using new mouse models built on TP53/RB1-mutant SCLC.
Ite Offringa
University of Southern California, CA·Medicine & Clinical Research
Generate a mouse monoclonal antibody that recognizes only isoaspartylated ELAVL4, a damaged protein form on small cell lung cancer cells, by immunizing with a synthetic peptide and optimizing binding speed and strength.
Wantong Yao
University of Texas MD Anderson Cancer Center, TX·Medicine & Clinical Research
Define the molecular pathways through which a newly identified stress-response regulator helps pancreatic ductal adenocarcinoma (PDAC) cells survive nutrient shortage, low oxygen and oxidative stress, and evade the immune system.
The school
University of Texas MD Anderson Cancer Center: 23 labs on PI Pages, $1.4B a year on research.
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