CHRI Investigator Feature
Dr. Gwenn Skar, Assistant Professor in Pediatric Infectious Diseases (ID), is the inaugural CHRI Scholar awardee. CHRI launched the Scholars Program to catalyze career development of physician scientists who are recently appointed to the faculty and who lead promising research programs in pediatrics fields at Children’s and UNMC. “We are excited to have the opportunity to support our promising early career physician researchers, and are confident that Dr. Skar will represent CHRI and the Scholars Program extremely well as the first of many worthy recipients over the coming years,” states Dr. Ann Anderson-Berry, Interim Executive Director of CHRI.
Dr. Skar embraces the dual tracks of life as a physician-scientist and the synergies that often arise between her clinical and research endeavors. Her ultimate decision to take this professional path was influenced by unexpected encounters and opportunities during college, med school, and training. As a biomedical engineering major at UN-Lincoln, Dr. Skar worked part-time in a microbiology laboratory and enjoyed the rhythms and challenges of lab experimentation. When she entered medical school at UNMC, she thought the research chapter was probably closed. “I felt more interested in pursuing the human, clinical side of things. But then when I was in med school I realized that I actually missed the laboratory. That I actually enjoy pipetting and doing the experimental minutia.”
In the second year of residency training, Dr. Skar found an opportunity to take a one-month rotation in the laboratory of Jessica Snowden, MD, a researcher studying cerebrospinal fluid (CSF) shunt infections through an experimental model in mice. Dr. Skar continued research under Dr. Snowden’s mentorship during her fellowship at UNMC. “During my fellowship I took care of several patients with shunt infections and realized how little we know about those infections, and even making the diagnosis is difficult,” she explained. “We don't have a lot of data to drive the care and management of these infections, so that really cemented my interest in shunt infections. I saw the real need for research to drive better clinical care.” A productive early track record in pursuing this vision led to Dr. Skar’s faculty appointment in 2017, and she is now striving to carve out an independent research portfolio that contributes innovations in the care of hydrocephalus patients who suffer CSF shunt infections.
Current treatment options are rather limited; the shunt must be removed and the patient placed on an extensive course of IV antibiotics until resolution of the infection. Therefore, on the clinical research side, Dr. Skar is engaged with a team of collaborators across Canada and the US in trials aimed at optimizing the dosing and duration for antibiotic therapy in pediatric patients with shunt infections.
On the laboratory and translational side, one major goal is to improve diagnostic tools for shunt infections. The present “gold standard” for diagnostic testing is to culture a pathogen from the CSF specimen by conventional bacteriology methods. At best, this method identifies only 60% of shunt infections. Molecular diagnostics that detect bacterial gene sequences show promise, but Dr. Skar points out that even a positive test result may not nail down the cause of infection. “A lot of the bacterial organisms involved in shunt infections are also skin flora. If you detect the presence of this DNA you don't know if it is from a true infection or if you are picking up contamination from the skin at the time of sampling or during sample handling. So we really need better methods.”
Dr. Skar’s second major experimental goal is to better understand the host-pathogen interactions during these infections and how they affect patient outcomes. She points out, “We know that patients with shunt infections have increased risk of seizures and lower IQs than their peers with shunts who do not have infections. We really don't know why that occurs, so my laboratory is very interested in finding the mechanisms of why those things are happening so that we can ultimately improve care for patients.”
Dr. Skar has laid the groundwork to address these goals partly by establishing an experimental model for shunt infection with Staphylococcus epidermidis in the rat. This is a valuable addition to the mouse model that originated in Dr. Snowden’s lab, partly because rats can supply larger CSF samples for lab analyses. A study they recently published in Infection & Immunity, together with Tammy Kielian, PhD (Department of Pathology & Microbiology), identified protein biomarkers in the CSF that distinguish infected rats from controls with non-infectious CNS inflammation. Bringing it back around to human patients, Dr. Skar was lead author on another recent study showing that CSF of children with shunt infections also have unique cytokine and chemokine biomarker profiles depending on whether the bacterium is gram-positive or gram-negative. Looking ahead, Dr. Skar remarks, “If my efforts could lead to a new test which is reliable and accurate that would be a fantastic step.”
Of the CSF proteins that were increased in rats with experimental shunt infection, a notable number were components of the complement system. Activation of the complement cascade has long been recognized as part of the host’s innate defenses against bacterial infection, but the literature indicates that complement exposure can factor into adverse neurological processes in patients with Alzheimer’s, bacterial meningitis, or traumatic brain injury. Dr. Skar plans to explore the idea that complement activation during childhood shunt infection may contribute to the reported downstream problems like seizures and IQ deficit.
When asked about CHRI’s role in her career thus far as a physician-scientist, Dr. Skar pointed to several positive things. “Investigators being together and being able to collaborate is a great thing. I have enjoyed the writing workshops and monthly seminars. Just hearing about the science that other people are doing can spark an idea for you or potentially identify a collaborator.” Funding support for pilot research in the lab has also been pivotal. “The internal grant program is how I was able to develop the rat model of shunt infection. So these resources have been very instrumental in my career – from me recognizing a clinical problem, analyzing it and having enough preliminary data where I am competitive for federal funding. Without the support of CHRI and the department, I don't think this would have been possible. The support CHRI provides is essential for early stage investigators and I'm very honored to be the first CHRI scholar.”
The CHRI Scholars Program is an institutionally funded competitive 3-year program designed to provide structured mentoring and training resources, combined with funding for research supplies and salary support to ensure a minimum of 0.4 FTE protected research time. Dr. Skar’s faculty mentor is Dr. Tammy Kielian.
by Matthew Sandbulte, CHRI Grant Writer | November 7, 2019