2024 Annual Symposium Keynote Speaker – Dr. David Fajgenbaum

May 16, 2024

Dr David Fajgenbaum was the Keynote Speaker at the Jane Coffin Childs Fund for Medical Research 2024 Annual Symposium. Dr. Fajgenbaum is an Associate Professor of Medicine at the University of Pennsylvania, where he is also the Founding Director of the Center for Cytokine Storm Treatment & Laboratory and Associate Director of Patient Impact at the Penn Orphan Disease Center. Fajgenbaum shared with the JCC Fellows his experience as a patient with a rare disease, and how that influenced his research and vocational trajectory.


Dr. David Fajgenbaum gives the keynote address to JCC Fellows.

Diagnosed with Castleman’s Disease

During Fajgenbaum’s 3rd year of medical school he became very sick and fatigued. It took quite some time for Fajgenbaum to be diagnosed with Castleman’s Disease, after his doctors originally thought that he had lymphoma. Castleman’s Disease is a rare immune dysregulation where a hyperactivated immune system attacks the patient’s own body.

Given the role of the immune system, Interleukin-6 antagonists are used as a front therapy. Siltuximab is an antibody that binds to Interleukin-6 (IL-6) and prevents IL-6 from binding to IL-6 receptors. This antibody is used to treat Castleman’s Disease, and about one-third of people recover and get back to their full lives as long as they continue to receive infusions every couple of weeks.

Unfortunately, Fajgenbaum was among the two-thirds of Castleman’s patients that don’t respond to IL-6 inhibition. When it became clear that siltuximab wasn’t working for Fajgenbaum he started a chemotherapy cocktail instead. While most people feel terrible on chemotherapy, Fajgenbaum actually felt much better since it was tamping down his hyperactive immune system that had been wreaking havoc on his organs.

This initial episode of Castleman’s kept Fajgenbaum in the hospital for around 6 months, during which his father never left his side. Through these difficulties, Fajgenbaum learned to find humor in the most difficult of life’s challenges. He submits that going from a college football player to a Castleman’s patient has to be the worst before and after pictures ever. Fajgenbaum also remembers when an emergency room drunk mistook him for his father’s pregnant wife due to the severe swelling in his abdomen. He and his father couldn’t stop laughing when this acquaintance wished them the best of luck with their new baby!

Into Action

Reflecting on that time, Fajgenbaum sees himself as a naïve medical student who trusted that there was set criteria for diagnosing and treating most diseases. He imagined that medical doctors and researchers seamlessly work together to find cures for diseases.

Through his first-hand experience as a patient he learned that this is often not the case, especially for rare diseases such as Castleman’s. This reflection taught Fagjenbaum that hope is not be a passive concept – rather, it’s a choice and a force. Is short, hope must be transformed into action.

Over the coming years Fajgenbaum launched into action doing research, launching collaborative networks, and starting his own lab and later a nonprofit dedicated to rare disease research and drug repurposing.

Feeling better after chemotherapy, Fajgenbaum started on the IL-6 antagonist. Although siltuximab didn’t work in the acute phase of his disease, the thought was perhaps it would help keep him in remission.

During this time Fajgenbaum returned to medical school and finished his 3rd year. In his spare time Fajgenbaum initiated lab experiments to try to discover more about Castleman’s, and how it could be treated. Through this work, Fajgenbaum developed an official criteria for diagnosing Castleman’s Disease.

Siltuximab kept Castleman’s at bay for only so long, however, and eventually Fajgenbaum’s disease returned. He spent another month in the ICU, and describes this period as more psychologically difficult than the initial bout, as this time the doctors told him there was nothing left to do. At that point, Fajgenbaum decided to dedicate his life, however much time he had left, to finding a cure for Castleman’s.

Castleman Disease Collaborative Network

Continuing his research at Penn, Fajgenbaum realized that there was only so much progress that he was going to make on his own at the bench, and decided he needed to also take a team approach to tackling Castleman’s Disease.

In disease-focused research funding, the typical scenario is that a group will raise money, solicit applications, and then decide whom to fund. Fajgenbaum says this approach works well for diseases with a lot of patients and recognition – think of the American Cancer Society, for example.

However, for rare diseases such as Castleman’s there are only a few researchers submitting applications. Fajgenbaum rhetorically asked what are the chances that these few researchers, out of everyone in the world, have the best ideas that are going to move treatment forward?

So Fajgenbaum next started the Castleman Disease Collaborative Network to build a new funding paradigm and connect physicians, researchers, and patients to figure out what research, if successful, would actually improve the diagnosis and treatment of Castleman’s. They prioritize the best research ideas, then seek out the researchers best suited to conduct the research and offer them funding to lend their technical expertise to Castleman’s Research.

Currently the Castleman’s Disease Collaborative Network includes over eight hundred researchers and physicians and has raised over one million dollars for research.

Third Relapse

In the midst of all of this tremendous progress Fajgenbaum was pushing forward on Castleman’s Disease, he suffered a third relapse in 2013. At this point Fajgenbaum was engaged to be married to his long-term girlfriend Caitlin who had been through his side during this entire battle with Castleman’s. He was determined to do whatever it took to make it to their wedding day.

This time Fajgenbaum had protocols in place and had been routinely drawing his own blood samples, so he had a crucial time course of samples leading up to his relapse. He was also able to convince his doctor to take out a few lymph nodes for additional samples.

These resources helped Fajgenbaum determine that there was TOR pathway activation in T cells. Based on these findings Fajgenbaum convinced his doctor to start him on rapamycin, a TOR inhibitor that had been discovered nearly forty years earlier on Easter Island. To date, Fajgenbaum’s disease has been in remission for 10 years and counting on rapamycin.

So – as you probably guessed – he made it to his wedding date and Fajgenbaum and his wife now have two kids. Also during that time Fajgenbaum has joined the faculty at Penn where, based on his own experience, he is passionately chasing down repurposing of FDA-approved drugs for rare diseases.

Repurposing FDA-approved drugs

There are currently a little over three thousand drugs approved to treat about three thousand diseases. However, there are another nine thousand diseases with no approved therapy. Patients such as Fajgenbaum don’t have a decade to wait for a new drug to be developed. However, Fajgenbaum believes that many more approved drugs can be repurposed, like rapamycin in Castleman’s, to treat as many different diseases as possible.

Towards this goal Fajgenbaum cofounded Every Cure – a nonprofit using machine learning to unleash the potential of approved drugs to treat as many diseases and patients as possible. This is still a work in progress, but Fajgenbaum says to stay tuned for a RoadMap which will soon be publicly available.

Engaging JCC Fellows

Fajgenbaum closed with three main takeaway points for JCC Fellows:

  • Turn hope into action.
  • Find humor in all of life’s challenges.
  • Solutions are hiding in plain sight – it is our responsibility to find them.


Additionally, Fajgenbaum called for their help with:


A robust Q&A session followed, and it was clear that Fajgenbaum’s story had sparked broad interest. Of note – the collection of FDA-approved drugs is available from The Broad Institute for anyone who has a disease model that they would like to screen this collection against.

Thank you, Dr. Fajgenbaum, for sharing your inspiring journey with the Jane Coffin Childs Fund for Medical Research Annual Symposium!