Summer 2024 Gina M. Finzi Fellows

The Lupus Foundation of America awarded six individuals to receive the 2024 Gina M. Finzi Memorial Student Summer Fellowship Award.

The Finzi Fellows are spending their summer conducting research in areas that are critical to moving the lupus research field forward. The Finzi Fellows are mentored by an established lupus investigator throughout the duration of their research. The results of research by the awardees will contribute to new therapies, prevention strategies and educational interventions to better understand, detect and treat people with lupus.

The 2024 Gina M. Finzi Memorial Student Summer fellows are:

Jafar Al Souz 

Mentor: Joseph Craft, MD

Institution: Yale School of Medicine 

Project Title: Lymphoid and Kidney-infiltrating CD8 T Cells in Lupus Nephritis

Project Summary: Lupus nephritis is a major complication of lupus that results in kidney damage and failure, caused by immune cells that attack and damage the body. CD8 T cells are a type of immune cell that can directly kill other cells, including in infection, cancer, and autoimmune disease. 

Despite being found in kidney biopsies from patients with lupus nephritis, whether CD8 T cells are directly causing damage and driving disease is not clear. By using mouse models of lupus nephritis, I will carefully characterize CD8 T cells from both kidneys and other immune tissues, including the renal lymph node and spleen. The proposed work will include a bioinformatics approach, which will allow for interrogation of cells at a single cell level, as well as a functional approach, which would directly test the contribution of CD8 T cells to kidney injury. Understanding where pathological CD8 T cells arise, whether they are protective or harmful, and whether they can be selectively targeted will facilitate better understanding of both lupus nephritis as well as lupus as a whole.

Kierra Franklin 

Mentor: Karmella Haynes, PhD

Institution: Emory University & Georgia Tech Wallace H. Coulter Department of Biomedical Engineering 

Project Title: Determining the Impact of MeCP2/DNMT1 Imbalance in Epigenetic Dysregulation 

Project Summary: Systemic lupus erythematosus (SLE) is an autoimmune disease where the immune system is hyperactive and mistakenly attacks its own cells and tissue. Affecting primarily women, SLE is a difficult disease to study, diagnose and treat because of its unpredictable symptoms and complicated biology. Epigenetics, which explores how environmental factors affect how genes work without altering the DNA itself, is crucial in understanding SLE disease onset. 

A key epigenetic process known as DNA methylation controls which genes are turned on and off by adding inhibitory molecules to DNA. Scientists have found that helper T cells in SLE show altered DNA methylation, causing inflammatory genes to be turned on and regulatory genes to be turned off. However, we still do not know the source of these changes. To address this, we will look at the role and interactions of key DNA methylation regulators, DNA methyltransferase 1 (DNMT1) and Methyl-CpG Binding Protein 2 (MeCP2). We will alter MeCP2 and DNMT1 levels and evaluate the effect of dysregulated MeCP2/DNMT1 on helper T cell gene expression and function. The findings from these studies will establish a link between MeCP2/DNMT1 and T cell dysfunction and reveal epigenetic events that precede disease onset. Investigating the role epigenetic modifications play in autoimmunity will help us to understand SLE flares and develop better therapeutic options. 

Chun-Chen Lin

Mentor: Dominique Kinnett-Hopkins, PhD 

Institution: The Regents of the University of Michigan 

Project Title:Improving Measurement and Identifying Predictors of Activity and Function 

Project Summary: Systemic lupus erythematosus (SLE) is a long-term condition where the immune system attacks healthy organ systems. Being physically active can help manage these symptoms, but most people with SLE do not engage in sufficient levels of physical activity, often because they worry it might make their symptoms worse. Studies have shown that less physical activity is linked to lower self-reported physical function and quality of life. However, these studies rely on self-report questionnaires. Self-reports are easily administered and do not rely on extensive training or equipment, but the results might not accurately capture the full picture due to potential recall bias and not accounting for the variation of symptoms within-day and between days. 

To better understand the connection between physical activity and physical function in SLE, we plan to: 

1. Examine how people with SLE perceive their physical function compared to objective measures of balance and walking speed, and assess how these measurements relate to daily accelerometer-measured physical activity behavior over a two week period, and
2. Determine which modifiable factors (i.e., sleep, fatigue, pain, stress, and mood) can predict changes in physical function and physical activity over a short period. 

We will analyze the data from an ongoing observational study that uses technology-assisted assessment techniques to track daily experiences and function. By using new assessment techniques, we hope to get a clearer picture of physical function and find ways to help people with SLE be more active and healthier overall. This study will enhance our understanding of what affects the ability to move, helping us to further develop tailored specific interventions to promote physical activity engagement and enhance overall health and well-being in people with SLE.

Alberto Nordmann-Gomes

Mentor: Juan M. Mejia-Vilet, MD, MSc, PhD

Institution: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Project Title:Lupus Nephritis Guidelines: Evidence Gaps and Underrepresented Groups 

Project Summary: Guidelines for the management of diseases are a useful tool for clinical practice in several diseases. The
recommendations included in these guidelines proceed from clinical studies of the different medications and
interventions that may serve in a specific disease. In the last year, new guidelines for the management of lupus nephritis were published, including at least four different medication schemes. 

However, studies are usually limited to certain populations, and therefore, the findings may not apply to all populations. For example, the studies supporting the efficacy of tacrolimus, a medication now recommended as first- line therapy in a combined scheme, were only performed in Asia, in specific patients who had no established damage in their kidneys. This may limit the applicability of this recommendation to patients in other locations (e.g. Europe or America) and with other disease characteristics as established chronic damage in their kidneys. In this study, we propose to perform a systematic review of all clinical studies of medications used in lupus nephritis, to summarize the characteristics of the populations studied for each medication, and to identify underrepresented groups in these studies. The study plans to carefully collect all details regarding the study design, the population studied, and the results obtained. Later, the results will be reported by each studied medication, to discuss which populations benefit from each medication recommended in current guidelines. We expect this study will help identify the populations that may benefit from each medication recommended in the guidelines, but also populations where information is lacking and guidelines may not apply, and thus clinical research needs to generate more information.

Ganesh Ramanathan 

Mentor: Andrea Knight, MD, MSCE 

Institution: Hospital for Sick Children, Toronto

Project Title:  Brain Injury and Inflammation in Childhood-onset Systemic Lupus Erythematosus 

Project Summary: Systemic lupus erythematosus (lupus) is a chronic autoimmune disease. Inflammation due to lupus affects multiple organs in the body, and can affect the brain. About 20% of people with lupus have childhood-onset lupus. These patients usually develop the disease during adolescence, an important time for brain development. Brain inflammation can cause cognitive changes (problems with thinking) interfering with school, daily activities, and quality of life. Current medical tests are limited, and it is often difficult to diagnose brain inflammation in children with lupus. Delays in treatment can results in worse patient outcomes. Blood markers related to brain injury may be a useful tool to help detect brain inflammation in children with lupus. The goal of this study is to understand how childhood-onset lupus affects the developing brain. Blood samples will be analyzed from children with lupus and healthy peers. The study has two aims:

1. To look at blood markers of brain injury, comparing levels in patients with lupus to their peers.
2. To look at the relationship between blood markers of brain injury and lupus disease characteristics. We will also look at how blood markers of brain injury relate to blood markers of inflammation.

We expect that the results of the study will help us to better identify young patients at risk for brain involvement due to lupus. The hope is that early identification and treatment will help prevent progression to impairment. Our research strives to improve quality of life and outcomes for patients with lupus.

Andrew Van Horn 

Mentor: Ruth Napier, PhD

Institution: Oregon Health & Science University

Project Title:  Defining the Role of NOD2 in Autoimmunity and Renal Candida Resistance 

Project Summary: Many patients with systemic lupus erythematosus (SLE) will eventually develop lupus-associated kidney disease. Among SLE patients who have kidney disease, fungal infection is common and often lethal. We recently discovered that deletion of the immune sensor protein nucleotide oligomerization domain 2 (Nod2) protects mice against lethal fungal infection due to antifungal activities of resident kidney cells. However, we have seen mice lacking Nod2 develop severe autoimmune disease that has been associated with the immune signaling molecule interleukin-17A (IL-17A) and elevated immune marker C3. This is consistent with humans who have mutations in Nod2 often suffering from autoinflammatory disorders, including lupus-associated kidney disease. Our project aims to discover the mechanisms by which Nod2 (i.e. elevated IL-17A and C3) affect antifungal immunity in the kidney and trigger autoinflammation. Therefore, our work represents a great opportunity to discover novel drug targets that clinicians could use for treating kidney disease and fungal infections in SLE patients.