Nuclear-endoplasmic reticulum communication during normal remodeling and pathological alteration of these organelles

Katharine Ullman and Maho Niwa are leading a research project to investigate the interactions between the nucleus and one of its neighboring organelles, the endoplasmic reticulum. These two cellular structures are joined at the hip — together, their outer borders form one continuous, folding membrane. Despite their close connections, these structures are often studied independently, and their influences on each other beyond transcription remain poorly understood. Ullman and Niwa plan to study their interactions by inducing stress on either the nucleus’s border, also known as the nuclear envelope, or the endoplasmic reticulum and observing the effects of that stress on the other organelle. They will also ask how interactions between the nucleus and endoplasmic reticulum affect cell division, during which these organelles undergo major structural changes. Their findings could shed light on basic cell biology and diseases like cancer where alterations to nuclear structure and demands on endoplasmic reticulum function place heightened pressure on their crosstalk.  

Affiliated Investigators

Katharine Ullman, Ph.D.

University of Utah

Katharine Ullman, Ph.D., is a Professor of Oncological Sciences and Huntsman Cancer Institute Investigator at the University of Utah.  She studied biochemistry, molecular biology and cell biology at Northwestern University, graduating with a B.A. in 1986 and then attended Stanford University for graduate school, where she earned her doctoral degree working with Dr. Gerald Crabtree. She did postdoctoral training in the lab of Dr. Douglass Forbes at the University California San Diego before joining the faculty at the University of Utah in 1998. Ullman served several years as a Cancer Center Program leader and currently is the associate dean of the University of Utah Graduate School. Past honors include a Burroughs Wellcome Career Award and a Leukemia and Lymphoma Scholar Award.  Her lab focuses on elucidating molecular steps of nuclear assembly and their coordination with disassembly of the mitotic spindle apparatus, as well as building further on the novel connection her lab discovered between the function of particular nuclear pore proteins and the regulation of cytokinesis. Collaborating with Dr. Maho Niwa opens exciting new opportunities to study how the architecture and function of the nucleus and another major cellular organelle, the endoplasmic reticulum, are interconnected.  

Maho Niwa, Ph.D.

University of California San Diego.

Maho Niwa, Ph.D., is a Professor of Molecular Biology in the Division of Biological Sciences at the University of California San Diego. Dr. Niwa received her Ph.D. from Baylor College of Medicine with Dr. Susan Berget, pioneering how exons are molecularly chosen from the sea of intron sequences present in each human gene. Dr. Niwa joined Dr. Peter Walter’s laboratory at the University of California, San Francisco, where she received postdoctoral training, supported by a Jane Coffin Childs postdoctoral fellowship. Dr. Niwa started her own laboratory at UCSD in 2002. Her past honors include a Searle Foundation Faculty Scholar award, and two American Cancer Society Faculty Scholar awards. Research in Dr. Niwa’s laboratory focuses on understanding how the endoplasmic reticulum (ER), the gateway to the secretory pathway and source of most lipids and approximately one-third of all cellular proteins, regulates these functional demands in response to distinct environmental, developmental, or disease cues. This is achieved by studying a stress signaling pathway called the Unfolded Protein Response (UPR). Dr. Niwa studies how mis-regulation of the UPR leads to human diseases, ranging from asthma to cancer. Her lab also discovered a cell cycle checkpoint in yeast that ensures that all dividing cells receive both functionally correct and spatially sufficient ER during the cell cycle. This was one of the first cell cycle checkpoints found to regulate the inheritance of the cytoplasmic components and is known as the ER stress surveillance (ERSU) checkpoint. In yeast, ERSU halts ER inheritance, leading to a block of cell division until the ER can be repaired. Recently, the Niwa lab made seminal discoveries in both yeast and mammals that ER stress induces specific sphingolipids and these in turn act as key inducers for the ER cell cycle checkpoint. In collaboration with Dr. Katherine Ullman (Huntsman Cancer Institute, U. Utah), she plans to investigate how the ER communicates with the architecture and function of the nucleus, unleashing a new exciting area of cell biology.