Published May 3, 2023, on WSU Spokane Research News by Judith Van Dongen
A biochemist by training, assistant research professor Anil Singh has conducted inflammation research that spans a variety of diseases, from diabetes to multiple sclerosis and cancer. Since joining the WSU Department of Pharmaceutical Sciences as a research associate back in 2014, he has been mostly focused on studying inflammation in rheumatoid arthritis, a potentially debilitating disease affecting the joints.
Can you explain to us what your research in rheumatoid arthritis entails?
Rheumatoid arthritis is both an inflammatory and autoimmune disease in which your immune system targets your joint tissues, resulting in loss of joint function, pain, and bone loss. This happens in response to the production of inflammatory cytokines, signaling molecules produced by certain types of cells. If you can shut off those signaling processes, you could halt the course of the disease. I am trying to better understand how these signaling processes work and identify the molecules involved to find a potential therapeutic target that could improve the treatment of rheumatoid arthritis. My findings in this area may also translate to other inflammatory diseases, such as gout, and other autoimmune diseases involving inflammation, such as lupus, multiple sclerosis, and inflammatory bowel disease.
Why is it important to conduct this research?
There is currently no cure for rheumatoid arthritis. Since rheumatoid arthritis is an autoimmune disease, you cannot just replace a worn-down knee or hip, because the body keeps targeting its own cells over and over. So rheumatoid arthritis patients are put on medications that suppress their immune system, which is kind of like being on chemotherapy for life. While those drugs halt the damaging immune response, they also reduce an individual’s ability to fight infections. Plus, they don’t work for everyone and will often stop working as the body learns to outsmart the drug. One alternative to immunosuppressants is monoclonal antibodies, but those need to be administered via IV infusion and are extremely expensive. Having more effective treatments for rheumatoid arthritis would not only help patients but would also provide economic benefits to society since the disease is so debilitating that patients eventually have to leave the workforce.
Why haven’t scientists been able to find a cure for rheumatoid arthritis?
The actual cause of rheumatoid arthritis is unknown. Complex genetic and environmental factors come into play. A major barrier to finding a cure is the need to better understand the basic mechanisms that underlie the disease. That’s why we are dissecting the various mechanisms of inflammation to find molecules that could be effective drug targets, not only to relieve the symptoms experienced by patients but also to potentially cure rheumatoid arthritis.
What is your educational background?
I earned a PhD in biochemistry from the University of Hyderabad, one of the largest and highest-ranking public universities in India, my home country. During my PhD, I researched a protein that was thought to be linked to insulin resistance, which is when the body’s cells don’t respond well to insulin, ultimately leading to type 2 diabetes. Surprisingly, my study found that this protein—named resistin—actually promotes inflammation. Since doing this research, resistin has become a biomarker for many diseases, including rheumatoid arthritis.
How did your journey continue after you earned your PhD?
After my PhD I spent a year working as a postdoctoral research fellow at the University of Maryland Baltimore, where I did research on multiple sclerosis. Then I spent another three years as a postdoctoral researcher at a cancer research lab at The Ohio State University Comprehensive Cancer Center, where I received a fellowship to study protein-protein interactions in breast cancer. In 2014, I came to WSU to join the lab of Salah-Uddin Ahmed, where my research focused on the molecular mechanisms that underlie chronic inflammatory diseases such as rheumatoid arthritis, ostheoarthritis, and gout. I started out as a research associate before becoming a staff scientist in 2017 and an assistant research professor in 2019.
What are some of the projects you have been working on here at WSU?
I spent my first few years at WSU helping Ahmed with a research project on how to use green tea’s anti-inflammatory properties to treat rheumatoid arthritis. Next, we conducted a study that identified a potential new target for the treatment of gout, a type of arthritis that causes episodes of painful and stiff joints. In the past couple of years, I have had the freedom to start working on my own independent projects. This has brought me back to studying Ets2, a cancer-promoting protein that I first worked on as a postdoc at The Ohio State University. With funding from the Arthritis National Research Foundation, I’m looking at the role of Ets2 in rheumatoid arthritis. The thickening of joint tissues in rheumatoid arthritis looks a lot like cancer, so it makes sense that this cancer-promoting protein may be involved in rheumatoid arthritis as well. In a mouse model of arthritis, I showed that if you remove Ets2 from the mice it halts the progression of arthritis. I also found that Ets2 changes the immune landscape of joint cells. I found that interleukin-6, an inflammatory cytokine, engages Ets2 to transform rheumatoid arthritis synovial fibroblasts—diseased cells that line the joints—into a different type of cells that destroy bone tissue. I’m currently doing more work to understand how exactly Ets2 works, how it changes inflammatory processes, and whether it could be a feasible drug target for rheumatoid arthritis and potentially other diseases.
In addition to my own project, I’m also working with Ahmed on two projects to determine the potential value of microRNA replacement therapy in treating rheumatoid arthritis. This work follows earlier research that found that the expression of a family of microRNAs known as miR-17 is significantly reduced in rheumatoid arthritis.
What is your proudest achievement as a researcher so far?
When I worked at The Ohio State University, I was an outsider in this cancer lab with a background in inflammation research. At that time, no one wanted to believe there was a connection between inflammation and Ets2. I feel very proud that I have been able to establish that connection.
What do you do when you are not conducting research?
I’m an avid photographer. I like to travel and take photos that showcase human emotion and art. In the past 10 years, I’ve taken probably 100,000 photos. Many featured pictures can be found at https://www.instagram.com/anilsinghxyz/
This interview has been edited and condensed for clarity.