Dr. Larkin’s work focuses on regulatory T cells (part of the immune system) and on uncovering their connection to diabetes, lupus, and rheumatoid arthritis.

Dr. Larkin received his bachelor’s degree from the University of Florida in 1996, and stayed in the same lab where he worked as an undergraduate for his Ph.D. work. After completing his Ph.D. in 2000, he was a postdoctoral fellow at the Wistar Institute at the University of Pennsylvania.

Cells receive cues from their external environment, which lead to changes in which genes are expressed (turned on). In many cases, these signals cannot enter the cell. Instead, the surface of the cell is covered with receptors, which span across the cell membrane from the outside to the inside. The external part of the receptor binds a ligand, some kind of signal coming from outside the cell. Once the receptor binds to the ligand, the internal part of the receptor triggers a chain reaction of signals inside the cell — often this starts with a conformational (shape) change of the receptor that can only happen when its bound to a ligand.

One of the most important and well-studied signaling pathways is the JAK/STAT pathway, which is involved in the immune response, as well as cell proliferation and cell death. In this pathway, the ligands are often cytokines (signals given off by immune cells and taken up by neighboring cells), which bind a cytokine receptor. On the inside of the cell, the cytokine receptor is attached to a protein called JAK, which activates other proteins. When the cytokine binds its receptor, the attached JAK is activated and it activates two STAT proteins, which will partner up and enter the nucleus to make changes to RNA transcription.

In a recent paper, Dr. Larkin and colleagues investigated two proteins called SOCS1 and SOCS3. These two proteins are part of a family of 8 closely-related proteins, which can block JAK from interacting with the STAT proteins. The ability to dial back the JAK/STAT pathway has a lot of therapeutic potential for treating autoimmune diseases. However, the SOCS proteins are pretty unstable, so it has been difficult to give them to people as a medication. In their paper, Dr. Larkin and others created a synthetic protein that only contains the JAK-interacting part of SOCS1. When they treated rats with a chronic inflammatory eye disease using eye drops containing this synthetic protein, the rats showed improvement for up to 50 days. The authors were also excited to find that they could achieve this effect with only 1 eye drop per day, which is both non-invasive and reduces the risk of side effects to the immune system elsewhere in the body.