Written by Katherine Tran
Lupus is among the most perplexing autoimmune diseases. It can be debilitating when not regulated, with symptoms ranging from butterfly-shaped rashes across the face to fatigue, fever, joint inflammation, and more severe complications like kidney failure and heart attack. Approximately 1.5 million people in the US suffer from lupus, so effective research is key to better understanding the disease.
May is Lupus Awareness Month with May 10th as World Lupus Day. This year marks a milestone for lupus awareness with the establishment of the Lupus Accelerating Breakthroughs Consortium. Powered by the FDA and Lupus Research Alliance, the consortium will bring together industry representatives, which can yield partnerships and strategies to accelerate lupus treatment for patients.
Increased emphasis on lupus research is not only through large-scale initiatives but also because of individuals like Katherine Tran, SCIEX Senior Global Market Development & Marketing Manager of the Proteomics Division. She took a personal interest because of her own experience with the disease. The difficulty of her diagnosis made her realize that lupus manifested in various ways, and currently identified biomarkers and clinical symptoms were not enough to cover the complex patient profile. Recently, Tran became associated with a collaboration with Aalborg University to elicit patient profiles, identify biomarkers for different patient types, and predict treatment outcomes.
Experiencing Lupus for the First Time
Tran has a long-running history of interest in disease pathology from her time as a research assistant at Health Canada and the University of Waterloo. Her intrigue deepened through personal encounters with two autoimmune diseases.
Between 2010 and 2016, she was hospitalized five times—one of which involved a severe lung collapse due to necrotizing pneumonia. It put her in the ICU for a month. It was not until a doctor noticed a pattern of abnormally low white blood cell counts during her hospitalization in 2016 that prompted further investigation. Because she didn’t show physical symptoms of lupus, the initial guess was leukemia due to her neutropenic state (neutrophil count as low as <500/µL). It was only after a bone marrow autopsy that she was diagnosed with systemic lupus erythematosus (SLE) and Sjögren’s syndrome—the latter often differentiated by dry eyes and mouth.
Daily use of Plaquenil (hydroxychloroquine) helped alleviate most of Tran’s SLE symptoms by suppressing her body’s immune system. She has not had any serious episodes caused by SLE since then. But that doesn’t mean her disease vanished. Even something as simple as a paper cut or using a public restroom may lead to an infection, which can be exacerbated because of the diseases and the negatively affected immune system. She is still advised to take antibiotics before surgery (including minor operations). What’s more, Tran’s medical profile recommends the use of Neupogen (filgrastim), a bone marrow stimulant to promote growth of white blood cells, whenever she is admitted to the hospital with signs of infection.
Personal Experience to Motivate Efforts for Biomarker Research
As an integral part of the Proteomics Division at SCIEX, Tran raises awareness about state-of-the-art mass spectrometry (MS) technologies and how they can be used to elevate biomarker research. Part of her strong passion for this is due to the lack of knowledge about the cause of lupus. Researchers still have yet to discover what may trigger or lead to this and other autoimmune diseases.
Throughout her work in proteomics, she happened to cross paths with Dr. Allan Stensballe, an associate professor in the Department of Health Science and Technology at Aalborg University in Denmark. His Ph.D. in protein science and postdoctoral work at Ludwig Institute for Cancer Research granted him a strong skill set in Omics-driven precision medicine. His research group focuses on understanding disease pathophysiology related to autoimmune diseases. By applying proteomics to multi-omics-based profiling of patient samples, they can predict treatment outcomes and gain a deeper understanding of autoimmune diseases.
Currently, Dr. Stensballe has been leading a precision medicine project to utilize omics-based methods to investigate SLE.
“Our lupus research focuses on finding biomarkers for patient subtyping and prediction of disease severity,” wrote Dr. Stensballe. “We apply mass spectrometry-based proteomics as well as protein array-based technologies combined with data-mining.”
Mass Spectrometry: Taking Lupus Research to a New Level
Mass spectrometry (MS) is integral to Dr. Stensballe’s research for identifying lupus biomarkers in patient samples, requiring high-throughput and standardized proteomics.
Rapid advances in proteomic technology have led to the identification of several novel protein biomarkers related to both SLE and lupus nephritis (LN), including monocyte chemoattractant protein-1 (MCP-1), the tumor necrosis factor-like weak inducer (TWEAK), transferrin, and various interleukins and TNF-α related proteins. However, these organ-specific biomarkers do not serve only as markers of lupus and of primary organ participation in lupus. Despite tremendous basic and clinical research progress regarding biomarkers discovery, SLE remains an unsolved puzzle due to a lack of appropriate disease monitoring and the absence of predictive/diagnostic biomarkers. The quest for such markers continues—this time with MS at the forefront. MS technologies have become a significant approach in clinical proteomics, which allows the exploration in depth of an illness and its underlying mechanisms.
In 2021, SCIEX announced a comarketing partnership with Evosep Biosystems, a Denmark-based biotechnology company providing leading high-throughput liquid chromatography (LC) separation technologies to further innovate how drug discovery and clinical diagnostics are performed. Evosep Biosystems has recently received a $40M strategic investment, allowing the company to establish Centers of Excellence in Clinical Proteomics located in Odense, Denmark and Boston, USA.
Recently, Tran worked with Evosep to present some of Dr. Stensballe’s current research at the 21st Human Proteome Organization (HUPO) congress in Cancun, Mexico. The data was acquired with the SCIEX ZenoTOF 7600 system in concert with the Evosep One’s 500 samples per day (SPD) workflow to achieve remarkable, high-throughput performance while exemplifying sensitivity and proteomic depth. The synergy between the robust and efficient chromatographic separation methods of the Evosep One and the unique features of the ZenoTOF 7600 system enables the pair to be a powerful workhorse to advance biomarker research. First, the ZenoTOF 7600 system offers very fast acquisition speeds to facilitate large cohort projects, thus allowing researchers to analyze proteins faster than previously possible with former mass spectrometer systems. In a recent podcast with Dr. Stensballe, he explains that mass spectrometry-based proteomics workflows that would previously take up to 2 hours now only takes 5 minutes to generate a dataset useful for diagnostic purposes using the ZenoTOF 7600 system. In addition, the unique Zeno trap technology greatly improves the mass spectrometer’s duty cycle, leading to the identification of 40% more proteins than previously used systems, even with very low sample amounts.
For future considerations, Dr. Stensballe’s team may be able to gain further insights from the samples by also utilizing the ZenoTOF 7600 system’s electron activated dissociation (EAD) fragmentation method. The range of electron-based fragmentation mechanisms provided by EAD offers alternative perspectives in MS data and facilitates the analysis of labile post-translational modifications (PTMs), such as phosphorylation and glycosylation, which are very important in biological processes.
Dr. Stensballe’s research group currently runs cohort studies with volunteering patients, who support his research to generate new knowledge on their illnesses. They also collaborate with medical research groups on a national and international scale, broadening the scope of the information they gain. Such discoveries can reveal the main risk factors of lupus, accelerating and tailoring healthcare efforts to alleviate symptoms and find more effective treatments.
Through her efforts to facilitate collaborations and promote new technological advancements in research, Katherine Tran hopes to improve the quality of life for lupus patients, including herself. The road of autoimmune disease research is long, but innovative solutions can help lead the way.
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