Joshua T Mendell
University of Texas Southwestern Medical Center, TX·Biochemistry
Kidney cancer, particularly renal cell carcinoma (RCC), is deadly once it spreads, and treatment options are limited. These projects ask how RNA molecules that do not code for proteins help cancer cells grow and spread.
- Fields
Biochemistry
Genetics
Medicine & Clinical Research
- Topics
renal cell carcinoma
ccRCC
kidney cancer
- Grants
- 2 known grants, through Jul 2030
What they work on
- Determine how altering dihydrouridine synthase (DUS) activity changes D modifications on tRNAs, overall tRNA metabolism and the PTMD mRNA-decay pathway in human and mouse ccRCC cells.
- Test whether gain or loss of DUS activity, or CNOT3 mutations that impair PTMD, change mitochondrial activity and metastasis in ccRCC models.
- Use cryo-EM to reveal how extra dihydrouridine modification alters tRNA structure and its ability to recruit the CCR4-NOT mRNA-degrading complex.
- Dissect the molecular function of the lncRNA CRNDE, building on a critical region essential for RCC cell growth and the proteins that bind it.
- Define the role of Crnde in normal physiology and in RCC development in vivo using engineered mice with whole-body or conditional deletion of critical Crnde sequences.
More about the research
One project focuses on chemical tags on transfer RNAs (tRNAs), the adaptors that read genetic code during protein synthesis. The other focuses on a long noncoding RNA (lncRNA), an RNA over 200 nucleotides long that makes no protein. Together they connect basic RNA regulation to kidney tumor biology.
Why it matters
Metastatic kidney cancer has few effective treatments. By uncovering how tRNA modifications fuel mitochondrial activity and metastasis in ccRCC, and how the lncRNA CRNDE supports RCC growth, this work could reveal new therapeutic vulnerabilities and drug targets. These include the DUS enzymes, CRNDE or the pathways they control, which may benefit patients with aggressive renal cell carcinoma.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Yin Xi
University of Texas Southwestern Medical Center, TX·Medicine & Clinical Research
Measure blood flow in clear cell renal cell carcinoma with arterial spin labeling (ASL) MRI and test whether it matches tumor regions with molecular changes that drive new blood vessel growth, such as HIF and VEGF activity.
Jeffery Coller
Johns Hopkins University, MD·Biochemistry
Determine how the mRNA degradation complex senses ribosome speed as it changes with codon optimality.
Eleonora Dondossola
University of Texas MD Anderson Cancer Center, TX·Medicine & Clinical Research
Define the cell types, gene activity states and real-time behavior of the ccRCC bone metastasis environment in mice, combining multiphoton microscopy in living animals and removed tissue with single-cell RNA sequencing.
The school
University of Texas Southwestern Medical Center: 40 labs on PI Pages, $869M a year on research, 86 research doctorates a year.
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