• Randall S. Carpenter

Remembering Paul S. Frenette (1965-2021)

By Randall S. Carpenter

I was a graduate student in neuroscience at The Ohio State University back in 2014 when I first heard about Paul and his work. At that time I was just getting started in the field of neuroimmunology and became interested in how injury to the nervous system could cause immune system dysfunction, particularly after spinal cord injury (SCI). My thesis committee wanted a basic science question about immune dysfunction after SCI. I remembered reading a paper a few weeks prior that demonstrated the central nervous system, through sympathetic nerve fibers in bone marrow, regulates the function of hematopoietic stem & progenitor cells (HSPCs) in a circadian manner. Since SCI damages supraspinal control of the sympathetic nervous system, I suggested the idea that SCI may impair the generation of immune cells in bone marrow by altering HSPC activity.

That paper by Paul and his lab, published in Nature in 2008, formed the basis of what became my thesis project. But as a neuroimmunologist, I had little to no experience with hematopoietic stem cells or bone marrow! So I jumped into the literature from Paul's lab and began to study hematopoiesis in the context of nervous system injury. I developed standard flow cytometry and methylcellulose culture assays for HSPCs, gathered preliminary data, added a hematologist to my mentoring committee, and wrote an NIH F31 fellowship. But I still felt like an outsider, a hematopoiesis imposter. I looked for upcoming conferences on the subject and found the 2017 Keystone Symposium on Hematopoiesis set for February in Banff, Canada. This was the perfect opportunity to dive into the field, get input from experts on my project, and maybe do a little bit of skiing!

Paul was one of the organizers of that meeting, and I set up a meeting where Paul generously provided his critical eye to my project for over 45 minutes. It was a fantastic discussion, and I left that conference feeling energized by our interaction. A couple of years later I remembered that interaction. How Paul discussed science critically, but with excitement and interest. How he gave credit to his trainees. How the environment he created in his lab fostered creativity and collaboration. I reached out for a postdoc opportunity, and by September 2019 I moved to NYC and started in the lab as a "Frenettocyte".

Dr. Andres Hidalgo defines the term "Frenettocyte" during the Paul S. Frenette Memorial Symposium held on June 2nd, 2022

Paul could be a tough mentor. He would say "Show me the data!" during long lab meetings and often asked the tough questions to really probe the hypothesis. I knew this coming into the lab and was looking to be challenged as a young scientist. But he also cared deeply about his mentees and established a lab environment to foster support and collaboration across the lab. We had some great early scientific discussions related to what eventually would become my postdoctoral project. A project that has since grown to areas of science the lab has not examined before. The whole time Paul was supportive as I ventured into unknown waters.

In December 2020 Paul brought me in on another project to facilitate revision experiments. My first trial experiment failed, and when I discussed the results one day, he pushed me to keep looking and figure out why it may have failed. So I investigated a bit, determined a possible explanation, and re-tested with new parameters. Voila! The experiment worked, Paul was correct, and I was excited to bring him my preliminary results. That was the last time I met with Paul in person. The following week he fell ill and stayed home, but still zoomed in for the lab meeting. That would be our last lab meeting with Paul.

Paul's diagnosis of liver angiosarcoma was devastating for so many people. The lab had just started to get back into projects after navigating the first year of COVID restrictions when he became sick. Yet Paul continued to check in on specific projects and trainees via zoom and phone calls throughout his illness. I remember having a zoom call in May 2020 where he listened to my presentation for an upcoming work-in-progress seminar and provided insight into the project. Paul also called me on a Friday in late July. I was at my bench pipetting, and I had a feeling I should stop and answer the call from an unknown number. Paul asked how the revision experiments were going, and I was happy to tell him that the experiments were working and that we replicated our findings in human cells. He sounded relieved. Even in his final weeks and days he still thought about those of us in the lab. He tried his best to provide a few last moments of mentorship to some of us. On July 26th Paul S. Frenette died.

Attendees gather at the start of the Paul S. Frenette Memorial Symposium on June 2nd, 2022

Paul's death threw all of us still in the lab into a period of grief, mourning, and uncertainty. But Paul, as the inaugural director of the Stem Cell Institute here at Einstein, fostered a supportive and collaborative environment among PIs, trainees, and administration. Within days of Paul's death, many at Einstien offered condolences and support for all of us in the lab. The grants office offered their continued support in providing grant funding for ongoing projects. PIs chipped in to become official mentors to the trainees in the lab and take on responsibilities for the grants that support our work. I am especially thankful for my own scientific advisory committee of Drs. Uli Steidl, Britta Will, and David Fooksman for their continued mentorship and support to this day. I am also thankful for the Frenettocytes; we continue to work together in the same lab space, even though we have "officially" become mentees of other labs/PIs here at Einstein. Lastly, I am thankful for my new mentor Maria, who offered me the opportunity to continue my project under her guidance and in her new lab at Einstein.

On June 2nd, 2022 we held a scientific celebration for Paul here at Albert Einstein College of Medicine. Many attended in person, and many more attended virtually. Speakers included close colleagues and former trainees of Paul, including a presentation by Maria at the end of the day. After lunch, Dr. Uli Steidl announced the winners of the inaugural Paul S. Frenette Scholars Award, set up in Paul's memory, to support six trainees in the Stem Cell Institute. I was honored to receive one of these awards, along with my friend and fellow Frenettocyte Dr. Lidiane Torres and 4 other Stem Cell Institute postdocs. It means a lot to be honored as one of the first awardees.

Dr. Maryanovich presents her science during the Paul Frenette Memorial Symposium held on June 2nd, 2022.

For now, my research on the role of nerves in regulating hematopoiesis continues. I am excited to be part of Maria's new lab and look forward to continuing what has been at times a challenging postdoctoral experience. I also hope to honor Paul by doing what he always asked of us... to expand our understanding of some really cool biology with rigorous experimentation. Being surrounded by some really great people has helped make that easier during such challenging times. We still miss Paul, even a year later. But we continue in his honor, as he would have wanted for all of us.

Members of the Frenette and Maryanovich labs enjoy a special lab meeting lunch in August 2022.


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