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In-gene-ious

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Hendrickson’s field is DNA repair.  His research has long focused on a pathway called C-NHEJ that is involved in DNA repair. C-NHEJ (classic non-homologous end joining) constitutes the major pathway for repairing double-stranded breaks in DNA.  Double-stranded breaks, in which both the “Watson” and “Crick” strands of DNA are broken, are the most serious kind of DNA damage because there isn’t a strand left to serve as a template for repair. C-NHEJ is a highly evolutionarily conserved mechanism that has been extensively studied in many model systems from bacteria to mice. Unfortunately, while the basic C-NHEJ mechanism has been conserved, the specifics of the process haven’t been and thus many of the observations garnered in these model systems have not proven relevant to human cells. Hendrickson’s use of rAAV to manipulate the C-NHEJ pathway has thus filled an important void in understanding how the C-NHEJ pathway functions specifically in human cells.

His attention is now focused on three areas, all of which involve using rAAV technology:

  • The connection between DNA recombination and immunity in humans.  When immunity is functioning normally, DNA makes site-specific rearrangements to protect the host from bacteria, viruses and tumor cells.  But some people are born without this ability, which makes them extremely vulnerable to opportunistic infections and disease.
  • The repair of double-stranded DNA breaks caused by radiation treatments for cancer patients.  The C-NHEJ gene family repairs double-stranded breaks resulting from the radiation exposures used during cancer therapy. Hendrickson is seeking to understand how C-NHEJ regulates this process and to ultimately use that knowledge to protect cancer patients from side-effects of radiation.
  • How C-NHEJ knows how to skip telomeres.  Telomeres are natural double-stranded breaks that occur at the ends of chromosomes. Paradoxically, C-NHEJ is required for normal telomere maintenance, a process that is critical for genomic stability. How C-NHEJ “knows” that a telomere is a double-strand break that needs to be maintained and not repaired is unknown. Understanding how this discrimination works might help improve or restore DNA repair mechanisms in situations where they are needed.

“I have always considered myself a very basic research scientist and as such I have never really expected to see our research results make their way expeditiously into the clinic or industry,” Hendrickson says. “In the past five years, however, my laboratory has developed a biotechnology component that is almost entrepreneurial in nature. This aspect has been very unexpected, but actually quite rewarding—both for my own laboratory and for the University of Minnesota—and for that I’m exceedingly grateful.”

In short, “life is good” in the Hendrickson lab, thanks to a “truly wimpy” virus that hitchhikes on common cold viruses.

– Peggy Rinard

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