She studies a population of immune system cells called T-cells. They are the cells that go on to destroy the insulin-producing beta cells that lead to the insulin deficiency seen in type 1 diabetes (T1D). But it is how graduate student Rachel Madley studies these T-cells that is interesting. She works on what is called a Personalized Immune Mouse model, or PIM, to try and look at the genetic factors that underlie T1D.
“Essentially in this mouse we can generate a human’s immune system, to study it,” explained Rachel, who works in the laboratory of the scientist who pioneered the PIM, Megan Sykes, MD, the Michael J. Friedlander Professor of Medicine at Columbia. “So we can generate in a mouse, an immune system from a T1D patient and we can generate in another mouse the immune system of a healthy person and then compare the two to each other. We can then look at any differences that are caused by genes within a person with T1D.”
Specifically, Rachel is using the PIM model to explore what might be going wrong during the development of these T-cells (normally, she says, T-cells are supposed to eliminate invading bacteria and infected cells to keep a person healthy) that makes them destroy beta cells in a type 1 diabetic. “I’m trying to see how these T-cells are allowed to develop and cause this autoimmunity,” said Rachel. “If we can figure out how that happens and what genetic factors underlie that, it would then open the door to start thinking of ways to create a preventative therapy or just a normal therapy to stop these T-cells from existing in a person with T1D.”
The PIM model is giving researchers an unprecedented look, among other things, at T-cells, which are very hard to study, if not for PIMs. Think about it she said. “If you take just a blood sample from a human donor—that’s very helpful, but those T-cells have already developed. So there’s no way for us to look at a microscopic level how T-cells are developing and what’s going wrong. The mice are an extremely important tool—and the human donor stem cells that we get (from patients at the Berrie Center), without them our work would be impossible.”
Rachel, born and raised in New Jersey, graduated with distinction from the University of Michigan with a degree in cellular and molecular biology in 2016. She is 23 years old and has been motivated to study the immunology of T1D since she fell in love with biology as a teenager in high school.
She was also diagnosed with T1D when she was 14. “I had a great endocrinologist growing up who was really good at explaining what was going on in T1D in the human body from a scientific point of view. That just really caught my interest. I also like to think my diabetes pushed me into the field, so that way, it’s not all bad.”
Even as a teenager, when it came to her own T1D, “I was always thinking, if we know what’s going wrong, we can start thinking of ways to fix it,” said Rachel who considered becoming a physician, but her interests were primarily, as she put it “in finding new treatments for a disease rather than treating patients. When I would learn about a disease in college my mind would always go to, ‘how can we intervene to make the symptoms less painful, how can we stop it from progressing, how can we cure it?’ That’s how I knew I wanted to be in the research field.”
When she was looking at graduate schools online, she boiled down her professional goals to two words and googled “translational immunology”. Then, up came Dr. Megan Sykes who is also the director of Columbia’s Center for Translational Immunology. “I knew right then exactly the part of science I wanted to study.”