Sean Manley

Sean Manley

Biography

Sean Manley is a rising sophomore majoring in Chemical Engineering at Howard University, currently conducting research at MIT on microcompartments in gene regulation. His work focuses on how chromatin structure and histone modifications influence microcompartment stability, with the broader goal of advancing biomedical tools for precision medicine. Hailing from Calvert County, Maryland, Sean is deeply committed to improving healthcare for underserved communities—especially Black men, veterans, and those impacted by addiction. His personal experiences have fueled his passion for biomedical innovation that’s grounded in equity, access, and real-world impact. He is particularly interested in artificial organs, advanced prosthetics, and addressing racial disparities in mental health diagnoses. Beyond the lab, Sean mentors youth in his hometown and advocates for representation inSTEM and mental healthcare. With plans to pursue a Ph.D. in Biomedical Engineering, he hopes to bridge scientific discovery with public service to transform care for historically neglected populations.

Abstract

Investigating the Role of Histone Acetylation in Microcompartment Formation

Every cell in the human body contains the same DNA, yet cells differentiate into neurons, skin, or muscle depending on which genes are activated. This process, known as gene expression, is regulated in part by the physical interaction between distant regions of the genome: enhancers and promoters. However, the process of enhancer-promoter interactions (E-PIs) is not fully understood, and the construction and function of microcompartments provide a critical knowledge gap. Microcompartments are nested structures that bring together enhancers and promoters in physical space, potentially making gene expression more efficient. This knowledge gap has consequences both for basic science and industry. Disruptions in genome architecture can lead to improper gene expression and have been linked to diseases like cancer, developmental disorders, and autoimmune conditions. Without a clear understanding of the structural principles that govern these interactions, our ability to design therapies or engineer genes remains limited. Industries focused on gene therapy and synthetic biology depend on accurate models of gene regulation to build effective interventions. Yet, current models often ignore the role of 3D genome organization — especially at the microcompartment scale. Therefore, I propose to use JM8.N4 mouse embryonic stem cells and Region Capture Micro-C (RCMC) to investigate how microcompartments respond to changes in histone H3 acetylation. By using drug treatments (TSA and A485) to increase or decrease H3K27Ac, we can test whether histone acetylation is required for microcompartment formation. High-resolution chromatin contact maps will be generated to visualize the 3D structure of the genome in treated and untreated cells. This will help determine whether changes in acetylation affect microcompartment formation.