The goal of this project is to better understand a driver of immune dysregulation in people with Down syndrome, who experience a complex interplay between genetics and immunity, leading to a higher risk of autoimmune diseases. Despite advances in research, the mechanisms driving this heightened susceptibility remain largely unexplored. In the U.S., approximately 1 in every 700 babies are born with Down syndrome each year. Understanding these differences is crucial for developing targeted therapies to improve health outcomes and quality of life. In the Khor lab, we are focused on understanding these mechanisms and how to treat autoimmune diseases common in people with Down syndrome. Preliminary data shows that RNA expression of Duffy, a gene encoding the Duffy antigen receptor for chemokines, is much higher in blood from people with Down syndrome. We want to determine if the protein expression of Duffy follows this same pattern. The Duffy antigen, located on red blood cells, binds chemokines released during inflammation, attracting immune cells to sites of damage. In our experiment, we will use flow cytometry to detect Duffy on RBCs. We expect to find that RBCs from people with Down syndrome express higher levels of the Duffy protein. Our data may reveal a new mechanism of immune dysregulation in Down syndrome and provide insights into how this gene affects the severity of malaria, as the Duffy protein is a receptor for it. This study can serve as a strong foundation for future research on immune dysregulation and infectious diseases like malaria in people with Down syndrome.

In the developing brain of a fruit fly (Drosophila melanogaster), neural stem cells, called neuroblasts, divide to produce new cells that will become neurons. These divisions follow strict biological rules, but because many factors influence how and when neuroblasts divide, predicting their behavior is challenging. While lab experiments provide crucial insights, they are often limited in how many conditions can be tested at once (genetic, physical, or otherwise). To address these limitations, we developed an agent-based computer model that simulates neuroblast divisions and their interactions with neighboring cells. Our model allows exploration of different conditions to predict how neuroblasts behave in complex environments. This work focuses on three key hypotheses about neuroblast behavior: (1) post stem cell division, the larger cells are more likely to remain as stem cells, (2) the cell positioned on top during division will keep its stem cell identity, and (3) clustering of differentiated neural cells on the membrane of a neuroblast suppresses their division. To investigate these hypotheses, we examine emergent behaviors in our model through size-based, location-based, and clustering-based differentiation rules. By adjusting parameters such as cell placement, division timing, and proximity to other neuroblasts, we analyze how these factors influence neuroblast fate. We validate model predictions against experimental data by comparing division patterns observed in simulations to those seen in Drosophila brains through live imaging. By combining computational modeling with experimental data, this work provides a framework for understanding the factors responsible for neural development. Our findings will refine existing models of neural stem cell behavior and help guide future experiments, making it easier to uncover the fundamental rules of brain development.

Down syndrome (DS) is one of the most common genetic conditions and is due to chromosomal anomaly, associated with heightened skin autoimmunity disorders like psoriasis. DS individuals have a significantly altered immune system, often indicated by a higher frequency and severity of infections. A hallmark of this altered immunity is a heightened pro-inflammatory state, characterized by increased signaling by cytokines such as interferon-gamma (IFN-γ). The goal of our project is to investigate the relationship between elevated cytokine signaling and epithelial cell biology, particularly how this dysregulation contributes to inflammation-induced immune responses and dermatological conditions. We hypothesize that elevated signaling of pro-inflammatory cytokines in the serum of individuals with DS alter the biology of epithelial cell function, predisposing them to skin disorders such as psoriasis and vitiligo. To explore this, we are first treating skin samples with serum from individuals with DS to assess its effects on epithelial cells. The serum alone induces a weak transcriptional response, so additional factors may be required to drive significant epithelial cell changes. To better define the impact of IFN-γ, we are treating skin samples with high-dose IFN-γ and comparing the resulting gene expression patterns to known cytokine-induced signatures. This approach will help elucidate the molecular mechanisms underlying epithelial dysfunction in DS. This research may provide insights into targeted anti-inflammatory interventions to preserve normal epithelial function and mitigate skin-related complications like inflammatory skin conditions, barrier dysfunction, slow tissue healing, abnormal cell turnover, and even cancer. Future experimental investigations could  focus on the epithelial microenvironment itself, rather than serum exposure alone, to capture localized skin-specific changes that may provide further mechanistic insights.