Double-strand break repair in Drosophila melanogaster (2015-2016)

PI: Jan LaRocque, Ph.D. (Georgetown University)

Homologous recombination (HR) repair proteins are more highly expressed in older flies.

The frequency of DNA double-strand breaks (DSBs) occurring from stalled replication forks alone is estimated to be ~50 breaks per cell per cell division. Each such event can give rise to large-scale mutation events that must be triaged into a repair pathway or the apoptotic pathway to maintain genomic stability. In this project, we investigated the relationship between DSB repair genes and aging in a fruit fly model, hypothesizing that diminished expression of repair genes might explain the decreased frequency of homologous repair observed in older flies. Contrary to this expectation, we find that the HR pathway is upregulated with advanced age, even in the absence of DNA damage. Read the paper in Aging Cell.

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Predicting failed sternal re-approximation in neonatal cardiac patients (2013-2015)

PI: Catherine Allan, M.D. (Boston Children's Hospital, now at Cleveland Clinic)

Swelling of the heart and lungs is a common, and often dangerous, occurrence in the aftermath of open-heart surgery. Due to their small size, neonates are particularly vulnerable to such swelling and its consequences. Therefore, it is common practice to leave the chest cavity open in the immediate post-operative period to allow swelling to reduce and permit direct monitoring of the heart. However, the consequences of delayed sternal re-approximation on infection and mortality are a matter of debate among specialists. In this study, we performed a retrospective medical chart review to investigate predictors of negative outcomes from this procedure. We find that patients requiring lower levels of mechanical ventilation had significantly lower odds of poor outcome, whereas hemodynamic parameters were not predictive of the outcome.
Read the conference abstract.

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Peripheral nerve regeneration in aging mice (2011)

PI: Clifford Woolf, M.B. B.Ch. Ph.D. (Harvard Medical School)

Injuries to the nervous system are estimated to impact 90,000 people every year. In the peripheral nervous system, the axons of injured neurons undergo a process known as Wallerian degeneration, wherein they lose their myelin sheath and are recycled by macrophages. In this project, we used a mouse model of sciatic nerve injury to ask why axon regeneration declines with advancing age. My summer work demonstrated that incompletely degenerated axons persisted at sites more distal to the injury in two-year-old mice than in eight-week-old mice. In a complementary experiment, I assayed recovery of sensation in the hindpaw following sciatic nerve injury in two transgenic mouse lines with enhanced axon regenerative capacity, finding no improvement in recovery in these two-year-old mice relative to wild-type mice of the same age. Both experiments supported further investigation of the hypothesis that the aging phenotype results from impaired clearance of the injured tissue rather than a decline in regenerative capacity per se.