Interview with 2021 HSF Danby Grant Recipient Dr. Carmelo Carmona-Rivera, PhD
December 1, 2022
Tell us a little bit about yourself.
I am from the little island of Vieques, Puerto Rico and completed a PhD at the University of Puerto Rico, School of Medicine in biochemistry. I studied a genetic pigmentary condition that is common in Puerto Rico called Hermansky-Pudlak for several years before moving to the National Institutes of Health (NIH), where we discovered a disease-causing gene for Hermansky-Pudlak. I then moved to the field of immunology and started to study rheumatic diseases such as systemic lupus erythematosus before transitioning to rheumatoid arthritis (RA) at the University of Michigan. After that, I moved back to the NIH and joined NIAMS where I now study the role of neutrophils and Neutrophil Extracellular Traps (NETs) in RA, and began studying monogenic conditions that cause rheumatic disease, such as Deficiency of Adenosine Deaminase 2 (DAD2) and Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome. I encountered HS when I met Dr. Ginette Okoye and Dr. Angel Byrd and started collaborating with experts in the field.
What was the goal of the project you proposed for the Danby grant?
We know that interactions between cells can dictate the fate of other cells. What I wanted to accomplish with the Danby Grant was to find disease-causing interactions between cells or between cells and NETs. NETs are web-like structures that are made of DNA with proteins and expelled to the extracellular space upon encounter with pathogens. NETs are powerful structures that can damage the host if there is dysregulation either in the formation or clearance of NETs. We found exuberant amounts of these structures in HS skin lesions and they appear to correlate with disease severity: the more severe the patient’s disease, the more NETs you find in their skin lesion. The exuberant formation of NETs in HS skin lesions is indicative of a possible problem in the clearance of these structures by nucleases and macrophages.
To assess disease-causing interactions between cells or cell to NETs, we used samples from different stages of HS severity. For instance, we know that NETs can trigger epithelial-to-mesenchymal transition (EMT) in cells. EMT is a process that allows a polarized epithelial cell to undergo multiple changes that enable it to assume a mesenchymal cell phenotype. If we see that NETs are in close proximity to keratinocytes, then we can postulate that an interaction is likely to happen and that NETs can somehow affect keratinocyte behavior and fate. We are still working on understanding this, and we hope to uncover the mechanisms leading to the formation of tunnels in HS. Also, the Danby Grant helped us to discover the presence of antibodies to DNase, an enzyme that breaks down DNA, in HS and how these antibodies contribute to the dysregulate NET clearance in HS skin lesions.
What were the main takeaways from your project?
HS is a complex and heterogenous disease. We need to look for ways to better categorize this condition biologically. There are many biological pathways that are connected, in some patients they are more pronounced than in others. This may explain why some people respond to treatment and others may not.
Was there anything you were surprised by that you weren’t expecting to find?
I was surprised to see how heterogenous HS is and that only a few genetic targets are currently known for this condition. I believe that there are many different dysregulated biological pathways in HS, and I think that will explain the heterogeneity we see in this disease.
Any future directions for your research?
There are so many! My goal is to uncover how tunnels are formed in HS, with the ultimate goal of figuring out how we can stop HS disease progression. I want to look at the role of eosinophils in HS, as we know these cells can create extracellular traps called EETs (Eosinophil Extracellular Traps) and they also may be playing a role in HS. EETs are not well known or studied, and it is unknown what EETs can do and their effect on skin cells. We want to know if EETs are part of the DNA found in HS and to elucidate their possible role in HS pathogenesis. I also want to work with fibroblasts in the context of NETs. NETs can activate many cells including keratinocytes, fibroblasts, eosinophils - which are all on the list of things to study.
What advice do you have for young researchers?
My advice is to get to know the condition you are studying. Get to know your patients and connect with them. This is the stimulus that you need to continue doing research, especially when you are met with hurdles in your work! Connect with others who share a common love and passion for what they are doing. Together you can work to accomplish common goals.
Any final words?
Do what you love to do! Science is not work for me – it is a passion. And when you have passion, you work weekends and holidays because it doesn’t feel like working, it feels like having fun and working towards your purpose. Why? Because you empathize with your patients. After meeting with patients throughout the years and seeing how they suffer, and knowing they did not ask to have the condition they are enduring, and seeing that the only thing they want is answers – you find yourself asking How can I do better? How can I make their lives better? In my case, I can contribute from the laboratory bench. I can try to find answers to the questions that clinicians have that eventually will be translated to treatments for our patients.