Project 1: Protein Engineering and Development of Antigen Specific Therapeutics and Novel Therapeutic Approaches of Autoimmune Disorders
Autoimmune diseases impact at least 23.5 million Americans, making them the second leading cause of long-term chronic illness. These conditions arise when the immune system mistakenly attacks healthy cells in the body. Unfortunately, current treatments often rely on non-specific drugs that suppress the entire immune system, leaving patients vulnerable to infections and diminishing their ability to combat them effectively.
Our research aims to revolutionize this approach by developing targeted therapeutic strategies that selectively inhibit only the dysfunctional components of the immune system. In this project, we are engineering innovative proteins that can serve as diagnostic agents, enhance our understanding of the key proteins involved in autoimmune disorders, and prevent the immune system from harming healthy cells.
At the MIR lab, we are currently dedicated to creating advanced therapeutics for primary membranous nephropathy (PMN) and systemic lupus erythematosus, paving the way for more effective and safer treatment options for those affected by these challenging conditions.
Project 2: Modeling and Investigation of Structure and Function Relationships of Unsolved Protein Structures
Gaining insight into the protein structures linked to autoimmune disorders, cancer, and neurological conditions is crucial for the advancement of more effective therapeutics. Many of the proteins central to these diseases remain uncharacterized, presenting a significant challenge. To address this, our lab is dedicated to creating 3D models of protein structures associated with cancer and the protein antigens implicated in autoimmune disorders.
We achieved a significant milestone by successfully developing a homology model of the 250kDa thrombospondin type-1 domain 7A antigen, which plays a role in the autoimmune disorder primary membranous nephropathy (PMN). Our current focus is on leveraging these models to unravel the biological functions of this antigen and other related proteins within this expansive super protein family. By deepening our understanding of these structures, we aim to pave the way for innovative therapeutic strategies that can transform patient care.
Project 3: Design, Synthesis, and Biological Testing of Novel Therapeutic Compounds for Immune-Mediated Diseases and Neurological Disorders.
Cancer is the second leading cause of death in the United States, driving our efforts at the MIR lab to develop innovative compounds for various cancer types. We focus on targeting a family of 18 histone deacetylases (HDACs), which are crucial for gene regulation and vary in expression across different cancers, making them promising therapeutic targets.
Our project aims to create both potent and selective HDAC inhibitors, particularly for neuroblastoma, a challenging pediatric cancer characterized by the overexpression of HDAC8. We are actively developing selective HDAC8 inhibitors to improve treatment outcomes.
Additionally, we are exploring the role of histone deacetylase 4 (HDAC4) in neurological disorders like Huntington’s disease and glioblastoma. We have identified novel HDAC4 inhibitors and are currently focused on synthesizing and evaluating these compounds to provide new therapeutic options for these conditions. Through our research, we aim to make a significant impact on patient care.
Project 4: Development of Broad-Spectrum Coronavirus Antivirals
Coronaviruses have caused one epidemic and two pandemics in the last two decades, with the COVID-19 pandemic being the most significant threat to billions worldwide. In response to this urgent challenge, the MIR lab is focused on understanding the coronavirus main proteases (Mpro), the receptor binding domain, the HR1 and HR2 domains, and the nucleocapsid domain, which are all crucial for the virus's life cycle.
Our research aims to define the substrate preferences of these proteases to develop targeted antiviral therapies. By integrating computational chemistry, synthesis, and biological evaluation, we are creating novel antiviral compounds that specifically inhibit Mpro, disrupting the viral replication process.
Additionally, we are developing innovative proteins that bind to the coronavirus crown, preventing it from entering host cells and blocking the initial stages of infection. Through these efforts, we aim to contribute to the fight against coronavirus-related diseases and enhance global health security, preparing for future viral outbreaks with effective therapeutic solutions.
