Rosalie Lawrence, Ph.D.

Faculty Member

Assistant Professor
Department of Biological Chemistry
David Geffen School of Medicine
University of California, Los Angeles

Personal Statement

I am a cell biologist fascinated by how stress remodels cellular metabolism. Cellular metabolism is not static: the cell can profoundly remodel metabolic networks in response to changing environmental cues including biological stressors. This remodeling process can enable cellular survival in response to acute stress, but can become maladaptive when the new metabolic state becomes chronic and impairs cellular function. This is especially true in the brain, a highly metabolically active organ composed of highly specialized cell types. Dysregulation of cellular stress responses and metabolism in the brain is a hallmark of age-related neurodegenerative disease.

 As a graduate student, I received excellent training in cell biological approaches to studying nutrient sensing and metabolism in the laboratory of Roberto Zoncu. I used live imaging to define mechanisms of amino acid-dependent mTORC1 recruitment to the lysosome and biochemical and structural approaches to discover the Lysosomal Folliculin Complex, which enables mTORC1 to distinguish between its many substrates in a nutrient-dependent manner. In my postdoc in the Peter Walter lab, I built expertise in diverse structural approaches and discovered the allosteric mechanism that activates the Integrated Stress Response. In my own lab, I am leveraging new structural and biochemical insights into mechanisms of Integrated Stress Response (ISR) signaling. Specifically, we model chronic ISR signaling states, which are associated with a wide variety of neurodegenerative diseases, from genetic gliopathies such as Vanishing White Matter Disease to complex neuropathologies such as down sydrome. We have used structure-guided engineering to generate chronic-ISR iPSCs which can be differentiated into disease-associated cell types, including white matter astrocytes and dopaminergic neurons.

 I am excited to join the Brain Research Institute in order to interface with a diverse range of researchers and build collaborations to define mechanisms via which disordered stress signaling contributes to neurodegenerative diseases.