Understanding Scleroderma’s ‘Social Network’ May Lead to New Treatments

Michael Whitfield, PhD, a translational genetics researcher at Dartmouth’s Geisel School of Medicine, has earned a second highly competitive award from the Dr. Ralph and Marian Falk Medical Research Trust for his pioneering work on the rare autoimmune disease systemic scleroderma.

This $1 million Transformational Award follows the $300,000 Falk Catalyst Award that he received in 2014. While the Catalyst Award provides seed funding to help investigators tackle critical scientific and therapeutic roadblocks in rare diseases, the Transformational Award continues that research to open new avenues of treatment.

Dr. Whitfield took a few moments away from his busy lab to discuss their recent discoveries and where his research is headed.

Geisel News Center: Since receiving the Falk Catalyst Award, what progress has your lab made in scleroderma research?

Whitfield: With the Catalyst Award, we were able to develop and build a scleroderma genomic network, which tells us which genes are talking to or interacting with other genes. It’s sort of the equivalent of building a network out of someone’s Facebook page; you see whom they interact with the most and on a regular basis. Here we’re seeing which genes in scleroderma interact with other genes most often and what cells those genes are expressed in, so we can understand what might be driving the disease.

Geisel News Center: So what have you learned?

Whitfield: We found that a common link exists between the fibrosis in different organs affected in scleroderma, specifically skin, lungs, GI tract, and peripheral blood cells. That common link is a certain type of cell of the innate immune system that we think is driving the disease. The innate immune system consists of the immediate responses that the body has to an injury or infection.

What’s important about our discovery is that almost every drug currently used to treat scleroderma targets the adaptive immune system, by targeting T cells and B cells, and not those innate immune cells. So fundamentally, the drugs that are being used to treat scleroderma, in most cases, are probably not targeting these important cells.

Geisel News Center: So what’s next?

Whitfield: The first year of this work funded by the Catalyst Award was about defining the network and figuring out which cells to target. Now, the Transformational Award will allow us to focus on confirming that these cell types are really important and figuring out how to target these cells. We are using the network we built as a drug discovery tool.

Geisel News Center: Can you comment on the important role foundations play in funding research?

Whitfield: Foundation grants are really critical for moving research forward in rare diseases, in part because there’s not as much money at the National Institutes of Health (NIH) compared to what is available for more common diseases. Also, foundation support, such as the Falk grants, allows us to do high-risk–high-reward experiments, rather than the incremental research favored by the NIH.

Geisel News Center:  How many people work in your lab?

Whitfield: Nine plus me. I have three postdocs, four graduate students, and two technicians.

Geisel News Center: Who are you partnering with on this work?

Whitfield: Dr. Nicole Orzechowski, a rheumatologist at Dartmouth-Hitchcock;  Dr. Patricia Pioli, an immunologist at Geisel; Dr. Monique Hinchcliff, a rheumatologist and longtime collaborator of mine at Northwestern; and Celdara Medical, LLC, of Lebanon, NH, a biotech company I’m involved with to advance the more translational aspects of my work.

Geisel News Center: Will this work you’re doing shed light on other diseases?

Whitfield: It should, particularly lung fibrosis and pulmonary arterial hypertension, both of which are also major problems for patients with scleroderma. Many of the things we learn about in scleroderma apply to other autoimmune diseases.

The Falk family, which has a long history of supporting biomedical research, also has two endowments at Geisel—one for operating expenses and one for scholarships. Ralph Falk was a 1942 graduate of Dartmouth College and a former member of the Geisel Board of Overseers.