2022 Goldberg Fellows
Nao Horio, Ph.D.
Olfaction plays an important role in food seeking, reproductive behavior, territorial aggression, and predator escape. In a complex environment, animals will pay attention only to particular sensory cues, and behavioral attraction can depend on internal physiology. For example, hunger is a powerful motivational state; hungry mice will use olfaction to find and locate food sources needed for survival. Recently, we identified a neuronal mechanism by which hunger selectively promotes attraction to food odors over other olfactory cues in mice (Horio and Liberles, Nature, 2021). My research in Liberles lab focuses on the neural circuitry that enhances food odor preference in fasted mice, and more generally how internal state regulates behavior.
Valentina Rossio, Ph.D.
Ubiquitylation regulates almost every cellular function and therefore deciphering enzyme-substrate relationships in the ubiquitin-proteasome system (UPS) is essential in understanding how cells work. Deubiquitylating enzymes (DUBs) remove ubiquitin from proteins, thereby controlling their stability or activity. Because the UPS is dysregulated in human diseases, DUBs are being explored as potential drug targets. The human genome encodes around 100 DUBs. While some DUBs are well-characterized, others have few known substrates. My research in the King lab aims to understand the mechanisms that govern the specificity of these enzymes. By using a proteomic approach, developed in collaboration with the Gygi lab, we have identified a wide range of DUB substrates that we are using to understand the principles governing DUB specificity.
2021 Goldberg Fellows
Miguel Prado, Ph.D.
My main project in the Finley lab (HMS – Cell Biology Department) seeks to explain how cells transform into highly differentiated states by remodeling their protein and organelle content. This process is exemplified by erythropoiesis, where human hematopoietic stem cells (HSC) differentiate into mature red blood cells (RBC). During this process, the proteome is completely remodeled, from thousands of different proteins expressed in HSC to a simpler proteome in RBC, where a remarkable 98% of the soluble protein content is hemoglobin. Working together with the Gygi (HMS) and Fleming (BCH) labs, we are aiming to move towards a comprehensive understanding of this degradative program by studying how critical components of the ubiquitin-proteasome system triggers this process. One example is UBE2O, an E2/E3 hybrid enzyme that is upregulated during terminal erythroid differentiation. Employing multiple proteomic techniques, we were able to identify UBE2O as a critical component of the machinery in charge of configuring the proteome during erythropoiesis by targeting, among many others, ribosomal proteins for proteasomal degradation (Nguyen*, Prado* at al., Science, 2017). Altogether, we are working to demonstrate that global proteome remodeling is a fundamental new function of the ubiquitin pathway.
Alison Ringel, Ph.D.
Even though cancer incidence increases dramatically with age, very little is known about how aging pathophysiology affects tumorigenesis beyond the increase in mutational burden over time. The immune system is especially vulnerable to functional decline with aging, including CD8+ T cells that can selectively kill tumor cells by recognizing features that differ from normal tissue. Surprisingly little is known about how the aged immune system interacts with developing tumors. My research in the Haigis Lab focuses on the discovery of molecular mechanisms dysregulated within aging tumors that regulate local immune responses and tumor progression.