Yevgeniya Gartshteyn, MD
2022 Recipient of the Gary S. Gilkeson Career Development Award
Title of Project: Elucidating the role of T-cell co-receptor SLAMF6/SAP signaling in SLE pathogenesis.
Mentor: Adam Mor, MD, PhD and Anca Askanase, MD
About the Researcher
My family and I immigrated to the United States from Ukraine when I was eight years old. I did not speak English and I remember those early days as trying and lonely. Despite a difficult start, I exceled in my education. I received my M.D degree and did my residency at the NYU School of Medicine. After residency, I worked as a general hospitalist at Columbia University Medical Center. It was my encounters with lupus patients admitted for disease flares and/or cardiovascular comorbidities that shaped my future. These encounters with the cardiovascular complication of SLE led to a first publication on the increased prevalence of ECG abnormalities, and a subsequent paper on coronary artery calcium scores (a proxy for atherosclerosis) in patients with systemic lupus. In 2017 I started my formal training in rheumatology and lupus atthe Columbia University Division of Rheumatology
Under the mentorship of Dr. Anca Askanase, I continued my work in SLE and cardiovascular disease and after completing the rheumatology fellowship, I received a TL1 NIH award as well as a grant from the American Philosophical Society to study how the immune dysfunction in SLE affects platelets resulting in increased risk of blood clots and early atherosclerosis. This was an amazing opportunity for me to further my study of lupus while starting to learn basic laboratory research techniques. Next, I joined the lab of Dr. Adam Mor at the Columbia Center for Translation Immunology to gain additional experience in basic immunology.
The transition to the bench was challenging yet rewarding, it became clear that these skills are essential tools for the translational lupus research I would like to do in the future; I hope to be able to seamlessly connect the patient’s bedside to laboratory findings. My long-term goal is to devote my career to improving the health of people with lupus.
Under the mentorship of Dr. Adam Mor, I studied the lymphocyte signaling pathways, in particular SLAMF6, a T cell co-receptor associated with lupus genetic risk in both animal models andlupus patients. A manuscript from this work is being submitted for peer-reviewed publication (and is available for your review upon request). Subsequently, working directly with blood samples collected from my own lupus patients, I showed that SLAMF6 signaling is increased in human lupus T-cells, particularly in activated CD4 follicular helper T-cells that are responsible for B-cell maturation and autoantibody production in lupus. We presented this work at the ACR Annual Meeting in 2021, with additional preliminary data included in the proposal in this application.
I have been fortunate to have a mentoring team that includes both a clinical and a bench scientist mentor and as such was able to put together an application that draws from both areas of expertise.
In parallel with this work, in May 2021 I completed a Master of Science (M.S) degree at the Columbia Mailman School of Public Health. This training provided me with biostatistics and epidemiology skills to accurately design my studies and analyze the research data.
The Gary S. Gilkeson Career Development Award, allows me to extend my work in understanding T-cells’ role in in lupus. I am grateful for the opportunity to become an accomplished independent lupus investigator.
Systemic Lupus Erythematosus is an autoimmune disease in which cells of the immune system become hyper-active and start to attack one’s own organs. T-cells are part of the immune system that normally help fight infection. T-cells are like generals responsible for directing the soldiers of the immune system to respond to infection, but in lupus the T-cell function is dysregulated to react against the self. Many of our current treatments target T-cells, but they are not specific in their function and result in unwanted side effects. In reality, there are different subtypes of T-cells: some protect from inflammation and others make it worse. We need to better understand which T-cell subsets are dysregulated and how they work, only then can we design better treatments to target specific pathways to cure lupus. In our preliminary work, we have identified a signaling pathway through a receptor, SLAMF6, and its messenger, SAP, to be increased in T cells from lupus patients as compared to healthy persons. In this application, we propose to evaluate this SLAMF6/SAP unit across different T-cell subsets, revealing the function of this receptor across the different T cells. In completing this work, we will thus define relevant pathways for future SLAMF6 targeted treatments. Additionally, we will test the theory that higher SAP levels are associated with more active lupus symptoms. If true, then blood SAP levels can be used as a rapid test to identify inflamed lupus patients with an abnormally elevated SLAMF6/SAP signal, identifying these patients as likely to improve if they receive treatment with SLAMF6-targeted treatments.