About

Susan Ackerman received her Ph.D. from UCLA and was a postdoctoral fellow at the University of Illinois Medical School and the Wistar Institute. Prior to her move to UCSD in 2016, she was a Professor at The Jackson Laboratory in Bar Harbor, Maine, where she was a faculty member for nineteen years. She has been an Investigator of the Howard Hughes Medical Institute since 2005. Her laboratory's goal is to define the molecular pathways necessary to maintain homeostasis in both developing and aging mammalian neurons. To achieve this, her research utilizes forward genetics to identify mutations associated with neuronal loss in the aging mouse brain and to dissect pathways underlying homeostatic disruption and disease. Her work has led to the discovery of disruptions in several novel pathways not previously linked to neuronal function or survival, with particular interest in alterations in translation elongation, translational fidelity, proteostasis, and RNA metabolism in neuronal function.

Research topics

• Computer Science
• Biology
• Neuroscience
• Chemistry
• Cancer research
• Genetics
• Telecommunications
• Psychology
• Cell biology
• Biochemistry

Selected publications

• Polyglycine proteins leave transfer RNAs unglued

  Science · 2025-07-17

  articleSenior author

  Disruption of transfer RNA processing may unite the pathogenesis of CGG repeat expansion disorders.

  PublisherDOI

• The Birth of a Female Child

  2025-09-03

  book-chapter1st authorCorresponding

  Abstract This chapter considers the events that surround a girl child’s birth in ancient Israel and especially the enigmatic passage in Lev 12:5 that decrees that a newly delivered mother is impure for twice as long if she gives birth to a girl child as opposed to a boy. It also examines Ezek 16:4–9, Ezekiel’s metaphorical account of the birth and childhood of Jerusalem, imagined as a girl consonant with the Bible’s general sensibility that cities are gendered as female. In both cases, it is argued that the newborn girl experiences a liminal period of ambiguity within the tripartite structure that Arnold van Gennep described for life-cycle rituals (a transitional time between birth and the child’s full-fledged engagement with her household, family, and the larger community). More crucially, the chapter suggests, in accord with the theoretical model developed in the Introduction, that in both Lev 12:5 and Ezek 16:4–9, the newborn girl’s liminal experience is exacerbated or intensified compared to liminality as manifest in male infants’ birth rituals.

  PublisherDOI

• Nursing and Weaning a Child

  2025-09-03

  book-chapter1st authorCorresponding

  Abstract This chapter begins with a survey of Near Eastern rituals associated with lactation and weaning in order to identify rituals that may have been deployed during the period when an Israelite woman suckled a child. Also surveyed are data from modern medical studies that show both how important it was for a child’s health to sustain breastfeeding and how challenging it might have been for ancient Israelite women to breastfeed successfully—both because of the caloric intake the breastfeeding mother required and because of various causes of lactation failure. Rituals that promoted lactation were thus imperative, including, perhaps, rituals that used the so-called Judean pillar figurines—although the interpretation of these figurines is a matter of scholarly debate. It is much clearer, however, that the point when breastfeeding ends marks a transition from one stage of life to another for the newly weaned child. Yet the suckling’s new identity means the disintegration of the bond that breastfeeding had formed between the child and the mother, as she is no longer the agent on which the child is biologically dependent. Thus, while the mother may have been able to claim at least some measure of elevated status during the breastfeeding period, she returns, at weaning, to the marginal state that the theoretical model developed in the Introduction demonstrates is typical for women in ancient Israel.

  PublisherDOI

• Notch signaling regulates UNC5B to suppress endothelial proliferation, migration, junction activity, and retinal plexus branching

  Scientific Reports · 2024-06-13 · 13 citations

  articleOpen access

  Notch signaling guides vascular development and function by regulating diverse endothelial cell behaviors, including migration, proliferation, vascular density, endothelial junctions, and polarization in response to flow. Notch proteins form transcriptional activation complexes that regulate endothelial gene expression, but few of the downstream effectors that enable these phenotypic changes have been characterized in endothelial cells, limiting our understanding of vascular Notch activities. Using an unbiased screen of translated mRNA rapidly regulated by Notch signaling, we identified novel in vivo targets of Notch signaling in neonatal mouse brain endothelium, including UNC5B, a member of the netrin family of angiogenic-regulatory receptors. Endothelial Notch signaling rapidly upregulates UNC5B in multiple endothelial cell types. Loss or gain of UNC5B recapitulated specific Notch-regulated phenotypes. UNC5B expression inhibited endothelial migration and proliferation and was required for stabilization of endothelial junctions in response to shear stress. Loss of UNC5B partially or wholly blocked the ability of Notch activation to regulate these endothelial cell behaviors. In the developing mouse retina, endothelial-specific loss of UNC5B led to excessive vascularization, including increased vascular outgrowth, density, and branchpoint count. These data indicate that Notch signaling upregulates UNC5B as an effector protein to control specific endothelial cell behaviors and inhibit angiogenic growth.

  PublisherOA PDFDOI

• RREB1 regulates neuronal proteostasis and the microtubule network

  Science Advances · 2024-01-10 · 12 citations

  articleOpen accessSenior authorCorresponding

  Transcription factors play vital roles in neuron development; however, little is known about the role of these proteins in maintaining neuronal homeostasis. Here, we show that the transcription factor RREB1 (Ras-responsive element-binding protein 1) is essential for neuron survival in the mammalian brain. A spontaneous mouse mutation causing loss of a nervous system–enriched Rreb1 transcript is associated with progressive loss of cerebellar Purkinje cells and ataxia. Analysis of chromatin immunoprecipitation and sequencing, along with RNA sequencing data revealed dysregulation of RREB1 targets associated with the microtubule cytoskeleton. In agreement with the known role of microtubules in dendritic development, dendritic complexity was disrupted in Rreb1 -deficient neurons. Analysis of sequencing data also suggested that RREB1 plays a role in the endomembrane system. Mutant Purkinje cells had fewer numbers of autophagosomes and lysosomes and contained P62- and ubiquitin-positive inclusions. Together, these studies demonstrate that RREB1 functions to maintain the microtubule network and proteostasis in mammalian neurons.

  PublisherOA PDFDOI

• Cell-type-specific expression of tRNAs in the brain regulates cellular homeostasis

  Neuron · 2024-02-19 · 33 citations

  articleOpen accessSenior authorCorresponding

  Defects in tRNA biogenesis are associated with multiple neurological disorders, yet our understanding of these diseases has been hampered by an inability to determine tRNA expression in individual cell types within a complex tissue. Here, we developed a mouse model in which RNA polymerase III is conditionally epitope tagged in a Cre-dependent manner, allowing us to accurately profile tRNA expression in any cell type in vivo. We investigated tRNA expression in diverse nervous system cell types, revealing dramatic heterogeneity in the expression of tRNA genes between populations. We found that while maintenance of levels of tRNA isoacceptor families is critical for cellular homeostasis, neurons are differentially vulnerable to insults to distinct tRNA isoacceptor families. Cell-type-specific translatome analysis suggests that the balance between tRNA availability and codon demand may underlie such differential resilience. Our work provides a platform for investigating the complexities of mRNA translation and tRNA biology in the brain.

  PublisherOA PDFDOI

• Supplementary Figure 6 from <i>Notch1</i>-Induced Brain Tumor Models the Sonic Hedgehog Subgroup of Human Medulloblastoma

  2023-03-30

  preprintOpen access

  <p>PDF file - 65K, Supplementary Figure 6. A schematic drawing of full length N1ICD in mouse, N1ICD allele analyzed in this study, and the ACTB-Notch1 allele previously published (Yang et al., 2004) and analyzed in Supplementary Figure 6.</p>

  PublisherOA PDFDOI

• Supplementary Figure 1 from <i>Notch1</i>-Induced Brain Tumor Models the Sonic Hedgehog Subgroup of Human Medulloblastoma

  2023-03-30

  preprintOpen access

  <p>PDF file - 158K, Supplementary Figure 1. Reduced p53 dose rescues apoptosis in N1ICD;hGFAP-cre brains.</p>

  PublisherOA PDFDOI

• Supplementary Figure 2 from <i>Notch1</i>-Induced Brain Tumor Models the Sonic Hedgehog Subgroup of Human Medulloblastoma

  2023-03-30

  preprintOpen access

  <p>PDF file - 84K, Supplementary Figure 2. Reduced p53 dose rescues brain sizes in N1ICD;hGFAP-cre transgenic mice.</p>

  PublisherDOI

• Supplementary Figure Legend from <i>Notch1</i>-Induced Brain Tumor Models the Sonic Hedgehog Subgroup of Human Medulloblastoma

  2023-03-30

  preprintOpen access

  <p>PDF file - 89K</p>

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01NS042613

  NIH · $3.1M · 2014

• NIH Grant R21NS096600

  NIH · $439k · 2019

• NIH Grant R01NS094637

  NIH · $1.6M · 2021

• NIH Grant R01AG019358

  NIH · $1.6M · 2009

• NIH Grant R03AG016072

  NIH · $83k · 2000

Frequent coauthors

• Pieter A. Doevendans

  University Medical Center Utrecht

  40 shared

• A. Bertrand

  38 shared

• Vanessa van Empel

  Maastricht University Medical Centre

  38 shared

• Roel van der Nagel

  University Medical Center Utrecht

  38 shared

• Harry J.G.M. Crijns

  Maastricht University Medical Centre

  38 shared

• León J. De Windt

  Maastricht University

  38 shared

• Wim J. Sluiter

  University of Groningen

  38 shared

• Sawa Kostin

  Medizinische Hochschule Brandenburg Theodor Fontane

  36 shared

Labs

• Ackerman Lab at UCSDPI

Education

• Ph.D., Biological Sciences

  University of California Los Angeles

  1987

Awards & honors

• Investigator of the Howard Hughes Medical Institute since 20…