Dr. Troy Torgerson: Understanding Immunodeficiency and Autoimmune Diseases From the Gene Up
Dr. Troy Torgerson
Featured in interaction April 2007 (PDF 1.4MB)
Troy Torgerson, MD, PhD is doing something he loves. When Dr. Torgerson was growing up in Utah, he read about the artificial heart program in the news and found himself fascinated with the blending of medicine, research and engineering — so fascinated that as an undergraduate at the University of Utah he worked in the lab of Dr. Willem Kolff, actually building artificial hearts.
He entered the MD/PhD program at Vanderbilt with a plan to study biomedical engineering, and there he found the path he walks today. “I was interested in applying biomedical engineering tools at the cellular level but needed to learn some molecular biology. To do this, I rotated in an immunology lab and got hooked.”
There was no going back for Dr. Torgerson.
Today, Troy Torgerson studies the role of regulatory T-cells within the context of immunodeficiency and autoimmune diseases.
Dr. Torgerson’s primary research relates to the gene FOXP3. A mutation in the FOXP3 gene causes a disease known as IPEX — Immune Dysregulation Polyendocrinopathy Enteropathy X-linked.
IPEX is a disease where male babies are born with an unregulated immune system, endocrine problems such as Type 1 diabetes, thyroid dysfunction and autoimmune bowel disease. Most affected children will die by age two without aggressive treatment.
Shortly after IPEX was linked to mutations in FOXP3 by studies in the labs of Dr. Hans Ochs and Dr. Phillip Chance, Dr. Torgerson began his work with this disease by simply asking “why?”: Why does IPEX happen and why does a mutation in this one gene cause such an aggressive multisymptomatic disease?
The realization that the FOXP3 gene is required for regulatory T-cells of the immune system to function properly provided some beginning clues for answering this question.
“What we still don’t know is how FOXP3 makes certain T-cells able to regulate other cells,” Dr. Torgerson says.
“To find out, it has been important to define the function of different parts of the FOXP3 protein. This is helping us to understand what it may do in T-cells. We also need to know how a regulatory cell tells another T-cell what to do — what is that interaction? If we can find this out, maybe we can mimic the process and discover a way to treat this autoimmune disease and others.”
These studies begin at the bedside with patients who have symptoms of IPEX.
To confirm the diagnosis, samples are sent from around the world to the Immunodeficiency Molecular Diagnostics (IMD) lab, which Dr. Torgerson co-directs.
Gene sequencing and flow cytometry tests done in the lab confirm the diagnosis and provide invaluable information about the molecular basis of the disease.
“Through samples that we obtain from patients with immunodeficiency diseases, we gain knowledge about naturally occurring defects in these genes. For example, we can take the mutations found in the FOXP3 gene, express them in cells and find out how they function. This allows us to learn what FOXP3 actually does,” Dr. Torgerson explained.
The IMD lab currently sequences 21 different genes involved in some of the most severe primary immunodeficiency disorders.
In addition to providing important clues about how the immune system functions in humans, the IMD lab helps doctors quickly diagnose immunodeficiency and autoimmune diseases.
For example, if a baby is exhibiting symptoms, a sample of its cells can be sent to the IMD lab and genetically sequenced, thereby identifying with certainty the specific disease. As the patients affected are often in their first weeks of life, the diagnosis of disease with the minimal intrusion into their already taxed body is very helpful.
Dr. Torgerson’s research is supported by a United States Immunodeficiency Network (USIDNet) grant. Additional support has come from a Pfizer Fellowship grant and a Child Health Research Center Award as well as fees generated by the gene sequencing of samples in the Immunodeficiency Molecular Diagnostics (IMD) lab.
Dr. Torgerson smiles as he summarizes his work, “It is kind of a bed-to-bench, back-to-bed, then bench again relationship that will hopefully give us insight into a wide range of immunodeficiency and autoimmune diseases, how they function and how we can treat them.”