Dr. Daryl Fields "Cerebral spinal fluids serotonin is immediately diagnostic and prognostic for spinal cord injury outcomes." and Dr. Andrew Sayce "The Unfolded Protein Response in Trauma and Sepsis"

Dr. Daryl Fields, MD PhD
Title: Cerebral spinal fluids serotonin is immediately diagnostic and prognostic for spinal cord injury outcomes. 

The National Institutes of Health recognize the need for biomarkers to prognosticate spinal cord injuries (SCI) and guide clinical trial enrollment. Despite a well-appreciated benefit of early interventions for improving SCI outcomes, our current inability to acutely prognosticate long-term SCI outcomes prevents patient stratification necessary for appropriate acute management and clinical trial enrollment. Using machine learning statistics to incorporate a novel molecular biomarker (spinal serotonin levels), electrophysiology, and conventional imaging, we are developing a multi-modality toolset to acutely (<24 hours after injury) diagnose injury severity and prognosticate long-term SCI outcomes.
Mentor: David Okonkwo

Dr. Andrew Sayce, MD DPhil
Title: The Unfolded Protein Response in Trauma and Sepsis

Inflammatory signaling in response to traumatic injury, hemorrhagic shock, and surgical sepsis has been extensively studied. Similarly detailed exploration of the endoplasmic reticulum (ER) stress response has uncovered the mechanisms by which cells recognize and respond to accumulation of unfolded and misfolded proteins, the unfolded protein response (UPR). Trauma and surgical sepsis (i.e., infections requiring surgical management to control the septic source) induce states of profound cellular stress requiring widespread transcriptional and translational reprogramming, and the secretory demands imposed at these times can easily overwhelm the protein processing capacity of the ER and trigger the UPR.

We are currently in the process of investigating the UPR through a systematic approach involving transcriptomic, proteomic, and glycomic techniques. We are defining the transcriptomic ER stress response to surgical sepsis and trauma using existing human clinical datasets from our group and others in comparison to similar murine model datasets. Protein level changes are being evaluated for key components of the UPR across mouse models of trauma and sepsis, and we are working to define the changes in circulating and tissue specific glycans as a consequence of injury and sepsis. We aim to develop a comprehensive understanding of the role of the UPR in inflammatory responses to trauma and sepsis and determine whether modulating the UPR can alter inflammatory responses and improve clinical outcomes.

Mentors: Rosengart, Billiar, Zitzmann