Hossein Firouznia, Ph.D, Flatiron Research Fellow, Biophysical Modeling
Leakage and Recovery During Nuclear Envelope Rupture : The nuclear envelope (NE) is a highly organized composite membrane structure that encloses the genome and separates the nucleus from the cytoplasm in eukaryotic cells. It comprises two lipid bilayers joined at nuclear pores and reinforced by a filamentous protein meshwork—the nuclear lamina—anchored to the inner membrane. Although NE rupture can occur under normal physiological conditions, it becomes particularly prominent and consequential in diseases such as cancer and certain genetic disorders. In cancer, for example, enhanced cell migration imposes high mechanical loads on the nucleus, while in certain genetic disorders, mutations compromise the mechanical integrity of the nuclear lamina. Rupture of the NE exposes chromatin to the cytoplasm, risking genomic damage and cell death. To recover from NE rupture, cells have a robust repair mechanism that includes recovering the leaked chromatin and re-sealing the rupture site. A key component of this process is the protein Barrier-to-Autointegration Factor (BAF), which crosslinks chromatin to itself and to the nuclear lamina, promoting chromatin compaction and facilitating its retrieval. Motivated by experiments in which NE rupture is induced via mechanical compression or laser ablation, we develop a coarse-grained model for the transport and interaction of BAF and chromatin. Our model captures the dynamics of chromatin leakage and recovery, reproducing key experimental observations and highlighting the essential role of BAF. Furthermore, we show that severe rupture events can lead to global nuclear contraction, resulting in wrinkling of the nuclear envelope.
Christopher Park, Ph.D, Research Scientist, Genomics Project Lead, RNA Regulation
Hormonal Regulation and Pituitary Adaptation in Obesity: Understanding the impact of hormonal regulation on human health and disease remains a significant challenge. In this talk, I will delve into my efforts to uncover the genetic and cellular foundations of hormonal regulation by focusing on the pituitary gland, a key central endocrine organ. I will provide an overview of the hormonal circuits governed by the pituitary and present new findings on how metabolic state, particularly obesity, affects pituitary function. These observations reveal a novel link between metabolic dysregulation and endocrine adaptation, offering insights into the mechanisms by which obesity may contribute to hormonal imbalance and disease risk.