About

Stephanie Leiser is a lecturer at the Ford School of Public Policy and serves as the Director of the Center for Local, State, and Urban Policy (CLOSUP) at the University of Michigan. Her general areas of interest include public budgeting, finance, and local government management, with particular expertise in state and local tax policy, business taxation and incentives, and local government fiscal health. She has taught courses in public budgeting and financial management, tax policy, nonprofit financial management, and microeconomics. Leiser holds a PhD in public policy and management from the University of Washington, an MPP from the University of Michigan, and is an alum of both institutions. Her professional background includes working as a tax policy analyst for the Michigan legislature. Her research focuses on public and non-profit management, economics and finance, and budget analysis, contributing to applied academic research that informs local, state, and urban policy issues. She is involved in projects such as the Michigan Public Policy Survey and the Michigan Local Government Fiscal Health Project, which aim to provide data and insights to policymakers, practitioners, and the public.

Research topics

• Biology
• Cell biology
• Genetics
• Neuroscience
• Biochemistry

Selected publications

• eLife Assessment: Hexokinase regulates Mondo-mediated longevity via the PPP and organellar dynamics

  2025-08-11

  peer-reviewOpen access1st authorCorresponding
  PublisherDOI

• fmo-4 promotes longevity and stress resistance via ER to mitochondria calcium regulation in C. elegans

  eLife · 2025-02-14

  articleOpen accessSenior author

  Flavin-containing monooxygenases (FMOs) are a conserved family of xenobiotic enzymes upregulated in multiple longevity interventions, including nematode and mouse models. Previous work supports that C. elegans fmo-2 promotes longevity, stress resistance, and healthspan by rewiring endogenous metabolism. However, there are five C. elegans FMOs and five mammalian FMOs, and it is not known whether promoting longevity and health benefits is a conserved role of this gene family. Here, we report that expression of C. elegans fmo-4 promotes lifespan extension and paraquat stress resistance downstream of both dietary restriction and inhibition of mTOR. We find that overexpression of fmo-4 in just the hypodermis is sufficient for these benefits, and that this expression significantly modifies the transcriptome. By analyzing changes in gene expression, we find that genes related to calcium signaling are significantly altered downstream of fmo-4 expression. Highlighting the importance of calcium homeostasis in this pathway, fmo-4 overexpressing animals are sensitive to thapsigargin, an ER stressor that inhibits calcium flux from the cytosol to the ER lumen. This calcium/ fmo-4 interaction is solidified by data showing that modulating intracellular calcium with either small molecules or genetics can change expression of fmo-4 and/or interact with fmo-4 to affect lifespan and stress resistance. Further analysis supports a pathway where fmo-4 modulates calcium homeostasis downstream of activating transcription factor-6 ( atf-6 ), whose knockdown induces and requires fmo-4 expression. Together, our data identify fmo-4 as a longevity-promoting gene whose actions interact with known longevity pathways and calcium homeostasis.

  PublisherDOI

• End-of-life pathology in UM-HET3 mice treated with 16 α‑hydroxyestradiol or late‑start canagliflozin

  GeroScience · 2025-07-02

  articleOpen access

  Canagliflozin (Cana) started at 16 months of age and 16-hydroxy-estradiol (OH_Est) started at 12 months each led to significant increases in lifespan in male UM-HET3 mice but significant decreases in female lifespan. To seek insights into the basis for these sex-specific effects, we performed end-of-life histopathological analyses of control and treated mice for all three interventions testing program sites. There were no significant drug-induced alterations in inferred cause of death, although statistical power was low for such comparisons. Tabulation of incidental lesions (i.e., combining lethal and non-lethal lesions) revealed a complex set of significant and near-significant changes caused by each of the two agents, in some cases absent, or even opposite in direction, in one of the two sexes. The analysis did not, however, reveal a clear pattern that would explain the selective sex-specific effects of either agent on lifespan. It is plausible that the female-specific harm induced by each of these agents could reflect harmful or toxic effects that are not easily detectable by histopathological examination.

  PublisherOA PDFDOI

• Correction to: Lifespan effects in male UM‑HET3 mice treated with sodium thiosulfate, 16-hydroxyestradiol, and late‑start canagliflozin

  GeroScience · 2025-06-19

  erratumOpen access
  PublisherOA PDFDOI

• The hypoxic response extends lifespan through a bioaminergic and peptidergic neural circuit

  eLife · 2025-08-26

  preprintOpen accessSenior author

  Abstract A coordinated response to stress is crucial for promoting the short- and long-term health of an organism. The perception of stress, frequently through the nervous system, can lead to physiological changes that are fundamental to maintaining homeostasis. Activating the response to low oxygen, or hypoxia, extends healthspan and lifespan in C. elegans. However, despite some positive impacts, negative effects of the hypoxic response in specific tissues prevent translation of their benefits in mammals. Thus, it is imperative to identify which components of this response promote longevity. Here, we interrogate the cell-nonautonomous hypoxic response signaling pathway. We find that HIF-1-mediated signaling in ADF serotonergic neurons is both necessary and sufficient for lifespan extension. Signaling through the serotonin receptor SER-7 in the GABAergic RIS interneurons is necessary in this process. Our findings also highlight the involvement of additional neural signaling molecules, including the neurotransmitters tyramine and GABA, and the neuropeptide NLP-17, in mediating longevity effects. Finally, we demonstrate that oxygen- and carbon-dioxide-sensing neurons act downstream of HIF-1 in this circuit. Together, these insights develop a circuit for how the hypoxic response cell-nonautonomously modulates aging and suggests valuable targets for modulating aging in mammals.

  PublisherDOI

• The hypoxic response extends lifespan through a bioaminergic and peptidergic neural circuit

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-09 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Abstract A coordinated response to stress is crucial for promoting the short- and long-term health of an organism. The perception of stress, frequently through the nervous system, can lead to physiological changes that are fundamental to maintaining homeostasis. Activating the response to low oxygen, or hypoxia, extends healthspan and lifespan in C. elegans . However, despite some positive impacts, negative effects of the hypoxic response in specific tissues prevent translation of their benefits in mammals. Thus, it is imperative to identify which components of this response promote longevity. Here, we interrogate the cell-nonautonomous hypoxic response signaling pathway. We find that HIF-1-mediated signaling in ADF serotonergic neurons is both necessary and sufficient for lifespan extension. Signaling through the serotonin receptor SER-7 in the GABAergic RIS interneurons is necessary in this process. Our findings also highlight the involvement of additional neural signaling molecules, including the neurotransmitters tyramine and GABA, and the neuropeptide NLP-17, in mediating longevity effects. Finally, we demonstrate that oxygen- and carbon-dioxide-sensing neurons act downstream of HIF-1 in this circuit. Together, these insights develop a circuit for how the hypoxic response cell-nonautonomously modulates aging and suggests valuable targets for modulating aging in mammals.

  PublisherOA PDFDOI

• Deguelin promotes longevity and healthspan through C. elegans fmo-4

  PubMed · 2025-02-18

  articleOpen accessSenior author

  , suggesting these enzymes may promote longevity in a coordinated fashion.

  PublisherOA PDFDOI

• Metabolic regulation of behavior by the intestinal enzyme FMO-2

  Science Advances · 2025-10-24

  articleOpen accessSenior authorCorresponding

  Many elements of an organism’s behavior are intertwined with the organism’s health. Over a long period of time, health status is also indicative of life span, with improved health correlating with a longer life. However, the relationship between longevity and behavior remains relatively unexplored. Here, we report that modification of a single longevity gene downstream of dietary restriction and hypoxia markedly alters behavior in Caenorhabditis elegans . We found that modified expression of flavin-containing monooxygenase ( fmo-2 ) leads to altered sensory perception and decision-making in a variety of behavioral paradigms. This cell nonautonomous signaling pathway is linked to changes in tryptophan metabolism, where loss of fmo-2 requires the tryptophan metabolite serotonin and overexpressed fmo-2 requires the tryptophan metabolite quinolinic acid to change behavior. These results suggest a unique mechanism for gut metabolism to communicate positive satiety signals and negative depressive signals to the organism by modifying an essential amino acid. They also demonstrate the importance of examining pleiotropic effects in promising longevity interventions.

  PublisherDOI

• findWormz is a user-friendly automated fluorescence quantification method for C. elegans research.

  PubMed · 2025-03-05 · 1 citations

  articleOpen accessSenior author

  fluorescence quantification that is accessible to users able to install the free program R and edit a single line of code described here.

  PublisherOA PDFDOI

• Extension of lifespan by epicatechin, halofuginone and mitoglitazone in male but not female genetically heterogeneous mice

  GeroScience · 2025-09-19 · 4 citations

  articleOpen access

  Mice bred in 2021 were tested by the Interventions Testing Program (ITP) for possible lifespan benefits of 2BAct (2BA), dichloroacetate (DCA), Epicatechin (EPI), Forskolin (FSK), Halofuginone (HAL) and Mitoglitazone (MIT). All agents were administered in the diet ad libitum beginning at 7 months of age. In male mice, EPI increased median lifespan by ~ 5%, and HAL and MIT each increased median lifespan by ~ 9%. EPI and HAL, but not MIT, increased 90% survival. In addition to adding 3 new agents to the list of interventions identified by the ITP that extend lifespan, this report continues the strong male bias in the efficacy of life-extending drugs identified so far.

  PublisherDOI

Recent grants

• NIH Grant K99AG045200

  NIH · $180k · 2016

• Mechanisms of cell non-autonomous signaling through the hypoxic response

  NIH · $1.6M · 2019–2024

• Mechanisms of the cell non-autonomous dietary restriction pathway

  NIH · $1.9M · 2018–2024

• Flavin-containing monooxygenases in endogenous metabolism and aging

  NIH · $2.1M · 2022–2026

• Novel approaches to study emerging roles of xenobiotic enzymes

  NIH · $429k · 2018–2021

Frequent coauthors

• Shijiao Huang

  University of Michigan–Ann Arbor

  28 shared

• Hillary Miller

  University of Michigan–Ann Arbor

  28 shared

• Safa Beydoun

  University of Michigan–Ann Arbor

  24 shared

• Ajay Bhat

  University of Michigan–Ann Arbor

  20 shared

• Marshall Howington

  University of Michigan–Ann Arbor

  17 shared

• Matt Kaeberlein

  University of Washington

  16 shared

• Elizabeth S. Dean

  University of Michigan–Ann Arbor

  13 shared

• Charles R. Evans

  University of Michigan–Ann Arbor

  12 shared

Labs

• Center for Local, State, and Urban Policy (CLOSUP)PI

Education

• Ph.D., Cellular and Molecular Biology

  University of Michigan

  2009