Alice in Wonderland may come to mind as you read this issue of LEAP, because we are moving from the large to the small, and back again: A rheumatic disease is big, and its effect can be devastating. However, a disease such as rheumatoid arthritis, scleroderma, or Sjögren’s is, in fact, multiple diseases, each slightly different. Each subgroup has a different trajectory of illness, and may respond better or worse to various forms of treatment. But it gets smaller still. One of our Greene Scholars, Sergi Regot, is studying individual cells that are molecularly and genetically identical; they should all behave in the exact same way, but they don’t. This is because of countless tiny factors that we are now beginning to explore.
I love our cover for this issue, because it perfectly captures our excitement as we are seeing new clues peeking out of tissue samples. They are visible now because we have looked for them in completely new ways.
In Sjögren’s syndrome, because our investigators were intrigued by strange filamentous forms of a protein called IFI-16, found in salivary gland biopsies from patients, we have glimpsed the molecular events that drive the relentless cycle of autoimmunity in this disease. In scleroderma research, Greene Scholar Steven Hsu has pinpointed a molecular mechanism underlying cardiac dysfunction – taking our perspective from large to small and back again. In other work led by Thomas Grader-Beck, we are using new approaches – collecting data from patients and their lives as their disease evolves over time – to build a framework to discover ever-more precise patient subgroups, at scale, and help us refine our care even further. This is precision medicine at its finest: now we can analyze thousands of points of data to find patterns and tailor our diagnosis and treatment for each subgroup – instead of unsuccessfully treating a very heterogenous group of people as if they were all the same.
And then, there is our choir – taking us, on our Alice-in-Wonderland journey, to a much larger scale. My ongoing goal for the Division of Rheumatology is for us all to work together in respect and – well, harmony: in this case, that harmony is soprano, alto, tenor, and bass. We chose a Zulu hymn of peace, called “Ukuthula,” and after many hours of practice, our all-volunteer choir has sung it several times. What an amazing experience! Out of many diverse voices – people from all walks of life, people who didn’t know each other very well, people of different religions and ethnicities, and from different countries of origin – we became one voice. In the process, we learned about each other, we laughed together, and we enjoyed it so much that we have kept on going. As individuals, we have become part of something much bigger. To me, the harmony that we create with our voices is a beautiful representation of the harmony of scale and approach that our Division is pursuing with precision medicine – our patient-reported data, molecular and cell biology – as we work together across all boundaries to accomplish something that is truly unique.
Antony Rosen, M.D.
Director, Division of Rheumatology
Vice Dean for Research