Meet the Scientist

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Copy, Paste, Repeat: Virologist Studying the Secret Life of Retroelements

Dr. Siddharth ‘Sidd’ Krishnamurthy is a virologist on the CU Anschutz medical campus investigating retroelements, which are parts of our DNA that can copy themselves and move around within our genome. Just like the copy-and-paste function we use to duplicate text and move it to a new spot in a document, these genetic elements make copies of themselves and insert the copies into new and different places within our DNA genome.

While retroelements are a normal part of our biology and play important roles in things like brain function, immune system development, and tissue repair, they can sometimes trigger the immune system in ways that cause disease.

Copy, Paste, and Consequences: Retroelements, the Immune System and Disease

Because retroelements behave a bit like viruses, our immune system can sometimes mistake them for invaders. Under normal conditions, our cells keep retroelements in check to prevent problems. But when these elements become overly active or escape regulation, they can contribute to disease. To avoid triggering immune responses, cells rely on specialized enzymes to clear leftover genetic material from retroelements. If these enzymes malfunction, often due to genetic mutations, the immune system may overreact, leading to chronic inflammation and disease. One example is that cancer cells can sometimes use retroelements to survive through becoming more unstable and adaptable. Other examples include autoimmune diseases like systemic lupus erythematosus (aka ‘lupus’) or inflammatory conditions like Aicardi-Goutieres Syndrome (AGS).

The Questions Driving Discovery

Sidd and his research team are exploring which cells are most responsible for detecting retroelements. Do innate immune cells, like macrophages and dendritic cells detect retroelements, or are other non-immune cell types, such as epithelial or stromal cells, playing a significant role in detection? Understanding which cells play a role in detection will help us understand how the body mounts antiviral defenses when retroelements become active.

Another important question under investigation is which types of retroelements are triggering immune responses? Are certain elements more likely to stimulate an immune response? If so, what characteristics or features make them more immunostimulatory? Other questions revolve around understanding regulatory mechanisms. How do immune cells and their associated proteins control the detection of retroelements? Do these pathways differ between cell types, and how do they balance antiviral defense with preventing autoimmunity?

Studies in mice show that mutations in these enzymes can cause very different outcomes depending on which gene is affected and which cells are involved. For example, some mice die before birth unless the mutation is corrected in specific cells. In other cases, some mice develop heart inflammation while others show no obvious symptoms but still have signs of immune activation. Taken together, these findings in mice suggest that we have a lot more to learn about retroelements!

Unlocking the Secrets of Retroelements and the Impact on Health

Scientists like Sidd are working to uncover why certain retroelements activate the immune system. While retroelements are a normal part of our biology, they can sometimes trigger the immune system in ways that cause disease. One such disease is Aicardi-Goutieres Syndrome (AGS), where the immune system is constantly activated as if fighting a virus even though there’s no infection. This happens because the body mistakenly reacts to retroelements as if they were harmful. By understanding these triggers, researchers hope to harness retroelements to support healthy immune function without directly interfering with the immune system’s sensors.

The discoveries from the Krishnamurthy lab at CU Anschutz will deepen our understanding of how genomic elements interact with immune surveillance, with far-reaching implications for infection, cancer, and autoimmune disease. For example, if retroelements play a role in conditions like rheumatoid arthritis, future therapies could target the problematic elements themselves rather than broadly suppressing the immune system.

If you want to learn more about the scientist, please go to their official CU webpage 

If you want to learn more about the research, please go to the lab website