Andrew Ludlow
University of Michigan, MI·Physiology
Aging is the biggest risk factor for cardiovascular disease and for cancer. Both diseases share common drivers: failing mitochondria (the cell's power plants), damage from reactive oxygen species, unstable DNA and chronic inflammation.
- Fields
Physiology
Genetics
Biology
- Topics
telomerase
alternative splicing
splice variants
- Grants
- 1 known grant, through Apr 2027
What they work on
- Generate transgenic rats expressing full-length TERT or the catalytically inactive β-del-TERT splice variant to test whether TERT's mitochondrial functions protect tissues independent of telomere lengthening.
- Compare the new transgenic rats with wild-type and TERT knockout rats for mitochondrial function, DNA damage, telomere-associated damage foci and senescence markers in liver, intestine, muscle, heart and brain.
- Test whether β-del-TERT is sufficient to cause mitochondrial dysfunction that impairs endothelial cell dilation in blood vessels and accelerates cardiovascular disease progression.
- Determine whether β-del-TERT shifts the blood-forming (hematopoietic) system toward myeloid cells, altering macrophage polarization and increasing inflammatory stress.
More about the research
Telomerase reverse transcriptase (TERT) is best known for lengthening telomeres, the protective caps on chromosome ends. TERT also works in mitochondria, where it can protect cells from stress. Cells make several versions of TERT through alternative splicing, which cuts and joins the gene's message in different ways. No animal model yet exists to study what these versions do in the body.
Why it matters
Cardiovascular disease and cancer both rise sharply with age. By testing whether TERT's protective work in mitochondria slows aging-related damage, this work could point to molecular or drug strategies that restore TERT's protective functions. It also offers a rat model that other researchers could use to study TERT splice variants in aging and disease.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Charles Reynolds
Texas Tech University Health Sciences Center, TX·Medicine & Clinical Research
Test whether telomere dysfunction drives high ATM kinase activation, a DNA-damage alarm signal, across ALT+ cancers of many types, using patient-derived cell lines and mouse xenografts compared with telomerase+ models.
Aditi Gurkar
University of Pittsburgh, PA·Medicine & Clinical Research
Map how oxidative 8-oxoguanine damage at telomeres signals to mitochondria to drive senescence in human iPSC-derived cardiomyocytes and cardiac fibroblasts, using a light-activated chemoptogenetic tool that damages only telomeres.
Mary Armanios
Johns Hopkins University, MD·Genetics
Identify additional large-effect inherited variants that cause long telomere syndromes in cancer-prone families, extending beyond the POT1 mutations and the two other telomere genes already found to phenocopy them.
The school
University of Michigan: 124 labs on PI Pages, $2.1B a year on research, 963 research doctorates a year.
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