2020 IARS Mentored Research Award

Catharina Conrad, MD, PhD
University of California, San Francisco
Postdoctoral Fellow
San Francisco, CA

Dr. Conrad’s Research

Protease Profiling for Rapid Phenotyping and Monitoring of ARDS

Acute respiratory distress syndrome (ARDS) is a life-threatening condition of critically ill patients, characterized by excessive lung inflammation and pulmonary edema resulting in lung failure. The Covid19 crisis has exposed a significant weakness of standard care for patients with ARDS, and that is shortcomings in ARDS risk assessment, prevention and treatment. A key to overcome these challenges may be molecular phenotyping to predict prognosis and mortality of ARDS patient subgroups. Several classes of proteases, including serine, cysteine and metalloproteases, are instrumental in the pathogenesis of lung injury and modulate the immune response. This proposal intends to determine real-time protease profiles in lung fluids of ARDS patients as a correlate of inflammation to dynamically track disease progression and develop personalized therapeutic approaches. Our consideration is that the activities of inflammatory mediators predict their biological relevance more precisely than mere expression levels. In Aim 1 of this application we will use fluorescent reporters based on known cleavage sites to detect multiple protease activities (>10) by the change of fluorescence over time. Pilot data suggests that proteolytic signatures of ARDS survivors significantly differ from cleavage patterns of non-survivors within 30 minutes, pointing towards a great potential of protease activities for rapid risk assessment of patients with lung inflammation. In Aim 2 we will attribute the activities to particular proteases derived from specific cell types at different phases of inflammation during the course of ARDS. To validate these proteases as therapeutic targets for ARDS, we will perform genetic and pharmacological in vivo studies to neutralize proteolytic activity in murine models of acute lung injury. In vitro cell-culture models will provide mechanistic insight and complement our mouse studies.

Encourage, stimulate, and fund ongoing anesthesia-related research projects that will enhance and advance the specialty, and to disseminate current, state-of-the-art, basic and clinical research data in all areas of clinical anesthesia, including perioperative medicine, critical care, and pain management. The IARS is focused solely on the advancement and support of education and scientific research related to anesthesiology.

A&A Case Reports

IMRA Awards

This award is intended to support investigations that will further the understanding of clinical practice in anesthesiology and related sciences. Up to four research projects are selected annually, with a maximum award of $175,000 each, payable over two years.

Support IARS

The IARS contributes more than $1 million each year to fund important anesthesia research. Your donation will help support innovative and forward-thinking anesthesia research and education initiatives, all of which are designed to benefit patient care. You can feel good knowing that 100% of your donation is directly allocated to research.