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Axonally synthesized proteins support nerve regeneration through retrograde signaling and local growth mechanisms. RNA binding proteins (RBP) are needed for this and other aspects of post-transcriptional regulation of neuronal mRNAs, but only a limited number of axonal RBPs are known. We used targeted proteomics to profile RBPs in peripheral nerve axons. We detected 76 proteins with reported RNA binding activity in axoplasm, and levels of several change with axon injury and regeneration. RBPs with altered levels include KHSRP that decreases neurite outgrowth in developing CNS neurons. Axonal KHSRP levels rapidly increase after injury remaining elevated up to 28 days post axotomy. Khsrp mRNA localizes into axons and the rapid increase in axonal KHSRP is through local translation of Khsrp mRNA in axons. KHSRP can bind to mRNAs with 3’UTR AU-rich elements and targets those transcripts to the cytoplasmic exosome for degradation. KHSRP knockout mice show increased axonal levels of KHSRP target mRNAs, Gap43, Snap25, and Fubp1, following sciatic nerve injury and these mice show accelerated nerve regeneration in vivo. Together, our data indicate that axonal translation of the RNA binding protein Khsrp mRNA following nerve injury serves to promote decay of other axonal mRNAs and slow axon regeneration.

Objective We describe a multilevel, collaborative research group for trainees and faculty engaging in transplant surgery research within one institution. Design Transplant Research, Education, and Engagement (TREE) was designed to develop trainees’ research skills and foster enthusiasm in transplant surgery along the educational continuum. Our research model intentionally empowers junior researchers, including undergraduates and medical students, to assume active roles on a range of research projects and contribute new ideas within a welcoming research and learning environment. Setting Section of Transplant Surgery, Department of Surgery, Michigan Medicine, Ann Arbor, Michigan. Participants Undergraduate premedical students, first through fourth year medical students, general surgery residents, transplant surgery fellows, and transplant surgery faculty. Results TREE was founded in September 2019 and has grown to include over 30 active members who meet weekly and collaborate virtually on a range of research projects, many of which are led by students. Trainees can assume both mentee and mentor roles and build their research, presentation and writing skills while collaborating academically. Conclusions Our model has increased trainees’ engagement in transplant research projects and fosters early enthusiasm for the field. This model can be feasibly replicated at other institutions and within other subspecialties.

Public Health Service increased risk donor kidneys are discarded 50% more often than nonincreased risk donor kidneys despite equivalent patient and graft survival outcomes. Patient and provider biases as well as challenges in risk interpretation contribute to the underuse of increased risk donor organs. As the ultimate decision to accept or reject an increased risk donor organ results from the patient–provider conversation, there is an opportunity to improve this dialogue. This report introduces the best-case/worst-case communication guide for structuring high-stake conversations on increased risk kidney offers between transplant providers and their patients. Through best case/worst case, providers focus on eliciting patient values and long-term goals. The patient’s unique context can then inform an individualized discussion of “best,” “worst,” and “most likely” outcomes and support the provider’s ultimate recommendation. Transplant providers are encouraged to adopt this communication strategy to enhance shared decision-making and improve patient outcomes.

Proteins generated by localized mRNA translation in axons support nerve regeneration through retrograde injury signaling and localized axon growth mechanisms. RNA binding proteins (RBP) are needed for this and other aspects of post-transcriptional control of localized mRNAs, but only a limited number of axonal RBPs have been reported. We used a targeted mass spectrometry approach to profile the axonal RBPs in naïve, injured and regenerating PNS axons. We detected 76 axonal proteins that are reported to have RNA binding activity, with the levels of several of these axonal RBPs changing with axonal injury and regeneration. These axonal RBPs with altered axoplasm levels include KHSRP that we previously reported decreases neurite outgrowth in developing CNS neurons. We show that KHSRP levels rapidly increase in sciatic nerve axons after crush injury and remain elevated increasing in levels out to 28 days post-sciatic nerve crush injury. Khsrp mRNA localizes into axons and the rapid increase in axonal KHSRP after axotomy is mediated by the local translation of its mRNA. KHSRP binds to mRNAs with a 3’UTR AU-rich element and targets those mRNAs to the cytoplasmic exosome for degradation. KHSRP knockout mice show increased axonal levels of defined KHSRP target mRNAs, Gap43 and Snap25 mRNAs, following sciatic nerve injury and accelerated nerve regeneration in vivo. These data indicate that axonal translation of Khsrp mRNA following nerve injury serves to destabilize other axonal mRNAs and slow axon regeneration.