Award: Arthritis and Related Autoimmune Disease Research Grant
Biography: Melanie H. Smith, MD, PhD is an Attending Physician in the Division of Rheumatology at Hospital for Special Surgery (HSS) and an Assistant Professor of Medicine at Weill Cornell Medicine (WCM). She specializes in the treatment of patients with inflammatory arthritis and is the Director of the Inflammatory Arthritis Center at HSS.
Dr. Smith obtained her degrees at the University of California San Francisco where she studied the regulation of misfolded proteins within the cellular microenvironment in the lab of Jonathan Weissman, PhD. She completed her internship and residency in Internal Medicine at NewYork-Presbyterian / WCM and fellowship in Rheumatology at HSS. Her postdoctoral research in immunology with Alexander Rudensky, PhD (Memorial Sloan Kettering) and Laura Donlin, PhD (HSS) explored the implications of interactions between tissue-resident fibroblasts, and infiltrating immune cells in the rheumatoid arthritis joint lining.
Currently, Dr. Smith studies joint-resident stromal cells (fibroblasts and macrophages) in rheumatoid arthritis. By understanding how these cells react to and regulate the influx of immune cells in the specialized environment of the joint, she hopes to identify novel therapeutic targets to improve treatment options in rheumatoid arthritis.
Research Summary: Rheumatoid arthritis (RA) is an autoimmune disease that primarily targets joints resulting in significant pain and swelling. The healthy joint lining, called the synovium, is made up of stromal cells, of which there are two main types: fibroblasts and macrophages. In RA, immune cells are abundant in the synovium and produce inflammatory molecules that change how the stromal cells function. How these cells respond to inflammation likely plays an important role in both the development of RA and treatment response. To develop new treatments that specifically target stromal cells, we first need to better understand how the different stromal cells respond to inflammation. We are particularly interested in studying stromal cells that are found directly adjacent to the joint fluid, which fills with immune cells during active RA. In this proposal, we are testing the hypothesis that the way in which stromal cells respond to inflammation depends on the relative abundance of macrophages and fibroblasts at this fluid interface, how they interact with each other, and specific factors in the synovial fluid. As a practicing rheumatologist and basic scientist with a focus in immunology, I am well prepared to carry out this research. The Hospital for Special Surgery is the ideal place for this research, as we have a large team of scientists and doctors that focus on understanding the human synovium across diseases. Through the research proposed here, we will make discoveries that will hopefully result in new and better treatments for RA.