Circulating Levels of the Pattern Recognition Molecule Pentraxin-3 Rise After Graft Reperfusion and Associate with Ischemia-Reperfusion Injury In Liver Transplantation

Anglt-1: Protocol and Launch of a Randomized, Double-Blind, Placebo-Controlled Pilot Clinical Trial of Angiotensin II as a Second-Line Vasopressor in Liver Transplantation

During his fellowship, Michael Bokoch, MD, PhD, became intrigued by the high incidence of acute kidney injury after liver transplantation and the impact it has on a patient’s recovery. Motivated to discover the answer to this puzzle, he was given an opportunity to start a clinical trial in this area by one of his mentors, Dr. Claus Niemann. This was just the first step on his journey to understand the mechanisms by which liver ischemia-reperfusion leads to injury or failure of other nonhepatic organs, and the role of the vascular endothelium in this process. In 2020, he was recognized for his work on this important topic with an IARS Mentored Research Award for his project, “Endothelial Activation by Liver Reperfusion Injury in Transplantation.” Now an Associate Professor of Clinical Anesthesia and Perioperative Care at UCSF, Dr. Bokoch has continued to make progress towards an answer since receiving the award and presented results from his latest research with two posters on Sunday, April 16 at the IARS 2023 Annual Meeting in Denver. He is hopeful that his investigations into this important topic could lead to advances in personalized vasopressor therapy and other organ protection strategies. Below, he shares how his research may help to develop tools that will lead to a broader understanding of precision medicine, ultimately improving patient care in the future.

1. For this research, you are…

Principal Investigator

2. What drew you to the anesthesiology specialty?

During my undergraduate and PhD training, I was deeply interested in chemistry, molecular pharmacology and drug-receptor interactions. I was fascinated to learn that anesthesiologists use their toolbox of drugs in very precise ways to help patients in stressful situations. Near the end of medical school, I became fully committed to the specialty because it allowed me to focus on one patient at a time and give each my full attention and best possible clinical care.

3. What drew you to this area of research?

During my fellowship, I was particularly puzzled by the high incidence of acute kidney injury after liver transplantation and the impact this has on our patients’ recovery. One of my mentors, Dr. Claus Niemann, gave me the opportunity to help him start a clinical trial in this area.

4. What are the goals you most want to accomplish in your work with this research project (or projects)?

I would like to understand the mechanisms by which liver ischemia-reperfusion leads to injury or failure of other nonhepatic organs and the role of the vascular endothelium in this process. While my major focus is on the kidney, the concept extends to the lung, brain, and hematologic systems as well – perhaps even others. I view my work with vasopressors as complementary, since a better understanding of vasopressor therapy could help us protect these organs.

5. What is the potential impact of your research on the field of anesthesia and patient care?

I believe my work could help advance personalized vasopressor therapy and other organ protection strategies. Precision medicine requires us not only to develop the tools, but also to obtain a better understanding of which patient subsets will benefit the most.

6. What are the benefits of presenting your research during poster sessions at the IARS Annual Meeting?

I have always loved scientific poster sessions because of the opportunity for more in-depth and informal conversations around the research. I’m thrilled that we can all be here in person this year. The IARS is a wonderful, vibrant research community filled with brilliant physicians and scientists. I look forward to the feedback from these poster sessions, because I’m sure it will help me generate new ideas and directions for my research.

7. How did the 2020 IARS Mentored Research Award affect your research and professional trajectory?

The IMRA has been key for my development! Along with generous support from my Department and Chair (Dr. Michael Gropper), the IMRA has allowed me ample protected time for research efforts – including three clinical trials for which I’ve been fortunate to serve as PI or Co-PI. I’ve learned to direct a translational research team, including research coordinators and laboratory staff. Finally, thanks to the IMRA, I’ve been able to complete coursework in statistics and computational methods to make me a better all-around physician-scientist.

8. How is your current research project / projects influenced by your initial 2020 IARS Mentored Research Award research project?

The work I am presenting at the 2023 IARS meeting is all a direct result of the IMRA project. Building on the original project, my mentor (Dr. Judith Hellman) and I believe we have identified an important molecule called pentraxin-3 that is part of a cascade of endothelial activation downstream of liver ischemia-reperfusion injury. My other project, a pilot clinical trial of angiotensin II in liver transplantation, was able to successfully compete for funding from the UCSF Liver Center because of the experience and infrastructure built with the IMRA award.

9. Is there anyone else you wish to acknowledge as part of this research team?

There are so many wonderful people involved in our research effort, I can’t possibly name them all, but here are a few key folks: Dr. Rishi Kothari, now at Thomas Jefferson University, is an informatics genius and runs our innovative clinical database; Dr. Dieter Adelmann is my co-PI in the UCSF Transplant Anesthesia Research Group, he is an incredible partner and we do all of our research together; Dr. Matthieu Legrand is a visionary clinical researcher who I am now lucky to have as a mentor.

10. Outside of your research, what might someone be surprised to learn about you?

I’m learning to ride a skateboard (slowly, with a helmet, on flat surfaces) so that I can keep up with my two wonderful boys, Max (5 years) and Kai (1 year old).