Dirk Hockemeyer
University of California-Berkeley, CA·Genetics
Human chromosomes end in protective caps called telomeres: long runs of the repeated DNA sequence TTAGGG. Telomeres slowly wear down each time a cell copies its DNA.
- Fields
Genetics
Biochemistry
Biology
- Topics
telomeres
telomerase
shelterin complex
- Grants
- 1 known grant, through Aug 2027
What they work on
- Use deep scanning mutagenesis of TPP1, a shelterin protein that recruits telomerase, to measure how many variants of uncertain significance from ClinVar change telomere length.
- Carry out a structure-function analysis of TPP1 to identify which regions and mutations drive telomere shortening, linked to bone marrow failure, or elongation, linked to cancer.
- Identify separation-of-function TPP1 mutations that change how much TPP1 sits at telomeres without exposing chromosome ends, to study how telomerase decides which telomeres to extend.
- Test the hypothesis that TPP1 density switches telomeres between extendible and non-extendible states, setting the normal telomere length in stem cells.
More about the research
An enzyme called telomerase rebuilds them. Their length must stay balanced. Telomeres that are too short cause dyskeratosis congenita, a bone marrow failure syndrome. Telomeres that are too long have recently been linked to cancer. How cells set the right length, and how to tell which patient mutations push it one way or the other, are open questions.
Why it matters
Patients and families carrying TPP1 mutations often cannot learn whether their variant raises the risk of bone marrow failure, cancer, or neither. A full map of how hundreds of TPP1 variants affect telomere length could help doctors interpret genetic test results for dyskeratosis congenita and telomere-related cancer risk. It could also clarify how healthy stem cells keep telomere length balanced.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jayakrishnan Nandakumar
University of Michigan, MI·Biochemistry
Reconstitute the shelterin proteins of the worm C. elegans outside the cell and determine their structures, to learn how its simpler version of this chromosome-end-protecting complex binds telomeric DNA.
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.
David Savage
University of California-Berkeley, CA·Biochemistry
Develop experimental methods to systematically map how mutations change the function of biomedically relevant proteins, such as CRISPR-Cas genome editing enzymes.
The school
University of California-Berkeley: 46 labs on PI Pages, $1.1B a year on research, 825 research doctorates a year.
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