About

Jill Kreiling is a Professor of Molecular Biology, Cell Biology, and Biochemistry with a research focus on aging and chromatin biology. She has held positions at Brown University since 2006, including Associate Professor (Research) at the Brown University School of Medicine and Associate Director of the Brown Center on the Biology of Aging. Her work investigates the molecular mechanisms underlying aging, particularly the regulation of heterochromatin formation and the activity of transposable elements in aging mammalian tissues. Kreiling's research aims to identify biomarkers and understand the epigenetic changes associated with aging, with a specific interest in neural stem cell decline, transposable element activity, and heterochromatin dynamics. She has contributed to advancing knowledge in these areas through her extensive publication record and leadership in funded projects related to aging, stem cells, and epigenetics.

Research topics

• Biology
• Genetics
• Bioinformatics
• Internal medicine
• Medicine
• Computational biology
• Pharmacology
• Neuroscience
• Evolutionary biology
• Psychology
• Cell biology

Selected publications

• RNA transcripts in salivary extracellular vesicle cargo isolated from aged populations

  Frontiers in Aging · 2026-01-12 · 1 citations

  articleOpen accessSenior authorCorresponding

  Introduction: Human saliva contains numerous factors, including DNA, RNA, and protein, that may reflect the health status of the individual. Many of these factors are contained within extracellular vesicles (EVs). The contents of EVs are thought to mirror the cytoplasm of the cell of origin, providing insight into the health of the cell. We investigated the RNA content from EVs isolated from saliva (salEVs) to determine if we could detect transcripts associated with neurodegenerative conditions. Methods: We characterized the RNA cargo of salEVs isolated from individuals over the age of 65 with normal cognition. The salEV RNA content was analyzed by RNA-seq and NanoString miRNA analysis. Results: We found approximately 48.4% of the reads mapped to the human genome, with the remainder mapping to prokaryotic genomes. The transcripts included protein-coding RNA, long non-coding RNA, retrotransposons, and miRNAs. A significant number of the protein-coding transcripts were associated with pathways involved in neurodegenerative conditions. In addition, there was an enrichment of transcripts containing AP-2ε, HEYL, HES4, and TCFL5 transcription factor binding sites. We found that the lncRNA content was similar between samples, with PCBP1-AS1, TEX41, and PVT1 being the top represented transcripts. There were 286 miRNAs found in the salEV samples. The pathways predicted to be affected by the top represented miRNAs include Hippo signaling, TGF-β signaling, Wnt signaling, FoxO signaling, ErbB signaling, axon guidance, and mTOR signaling. We could detect retrotransposon transcripts from LINE, SINE, and LTR elements in salEVs. When compared to blood-derived EVs, salEVs showed greater representation of transcripts associated with neurodegenerative pathways. Discussion: Our results indicate that salEVs contain transcripts that are associated with pathways involved in neurodegeneration. The presence of these transcripts in salEVs suggest that saliva may be used to screen for biomarkers of neurodegenerative diseases.

  PublisherOA PDFDOI

• Associations between Digital Cognitive Assessment and Amyloid Burden in Cognitively Unimpaired Older Adults

  Alzheimer s & Dementia · 2025-12-01

  articleOpen access

  Abstract Background Digital cognitive screening is poised to improve early detection of Alzheimer's disease and related dementias (ADRD), but existing tools are relatively insensitive to subtle cognitive changes in the preclinical stage of disease. Our digital assessment, the Rhode Island Mobile Cognitive Assessment Tool (RIMCAT), distinguishes cognitively impaired (MCI/early dementia) and unimpaired older adults with high sensitivity and specificity, but it has not yet been examined in the context of AD biomarker status. The goal of this study was to 1) enhance RIMCAT's sensitivity to early/preclinical AD risk by examining four cognitive paradigms sensitive to brain areas affected earliest in the course of disease; and 2) to examine associations between digital assessments and plasma amyloid Ab42/40 levels in cognitively unimpaired older adults. Method Potential participants were cognitively unimpaired older adults currently enrolled in an ongoing longitudinal study of cognitive aging. We invited a random sample ( N = 41) to participate, and 24 individuals ( M age = 73 years, M education = 16 years, 54% male) were enrolled. Plasma samples were analyzed on the PrecivityAD platform to yield an amyloid probability score (APS; based on APOE status and Ab 42‐40 ). Eleven (18% e4 carrier) had an APS < 35, suggesting low amyloid burden, and 13 (92% e4 carrier) had an APS >58, suggesting elevated amyloid burden. Participants completed RIMCAT and four new computerized subtests assessing perceptual discrimination, familiarity memory, feature binding, and response inhibition. Result Participants in the elevated amyloid group performed worse on the RIMCAT and perceptual discrimination, familiarity memory, and feature binding tasks (non‐parametric Mann‐Whitney U tests p 's < .05; medium to large effect sizes, r = .28‐.51) compared to the non‐elevated amyloid group. When examined as a continuous variable across all participants, higher Ab42/40 ratio (less amyloid pathology) was associated with better performance on RIMCAT ( r = .27) and all four new subtests ( r = .23‐.40). Conclusion We demonstrated the preliminary sensitivity of novel digital cognitive screening measures to amyloid burden in cognitively unimpaired older adults. Future research will validate these findings in a larger sample and examine associations with tau and other AD biomarkers.

  PublisherOA PDFDOI

• Investigating Salivary Extracellular Vesicles as Biomarkers for Alzheimer's Disease: ExosomeAD Study Design and Baseline Characteristics

  Alzheimer s & Dementia · 2025-12-01 · 1 citations

  articleOpen access

  Abstract Background Brain‐derived salivary extracellular vesicles (EVs) contain mRNA, miRNA, and protein species which have the potential to be used for molecular characterization of brain health. Prior analysis of salivary EV mRNA identified Alzheimer's disease (AD)‐ and inflammation‐related biomarkers that may be diagnostically useful in this regard, however EV analysis is still in its infancy. The primary objective of this study is to identify a novel biomarker signature for AD using salivary EVs. Method ExosomeAD is a 60‐month longitudinal cohort study enrolling older adults with normal cognition (CN; n = 150) and mild cognitive impairment (MCI; n = 50) at the Rhode Island Hospital Alzheimer's Disease and Memory Disorders Center. Baseline evaluation includes neuropsychological testing, self‐report inventories (mood, subjective cognitive impairment, daily functioning), vital signs, and collection of saliva and blood samples. Salivary EVs are being analyzed for mRNA, miRNA, and protein composition and compared with plasma biomarkers of AD risk assessed by PrecivityAD (C2N Diagnostics) testing (plasma Aß42‐40 ratio, APOE proteotype, and the Amyloid Probability Score (APS)). Participants complete up to 4 annual follow up visits (cognitive testing, surveys, and saliva/blood sample collection). Result Currently, 183 participants (CN=163; MCI=20) have been enrolled. Participants in both groups to‐date are predominately female (CN, n = 115 (71%); MCI, n = 13 (65%). On average, participants with MCI (M age =77.7, standard deviation (SD)=5.6) are older than the CN group (M age =72.1 (5.1)). The group mean Montreal Cognitive Assessment total score in the current sample is lower among those with MCI (M=20.1 (4.1)) vs CN (M=27 (2.2)). MCI participants are more likely to be APOE4 carriers (71.4% vs CN, 31.1%), and have higher median APS (MCI APS =81.5; CN APS =17). More than half of participants endorsed family history positive for dementia (CN=60%; MCI=65%). Conclusion Salivary EVs contain important information about brain health and may be a useful biomarker for AD. However, AD‐specific signatures in EVs have not yet been characterized. If successful, the Exosome Study will be first to demonstrate that salivary EV RNA and protein can be used to detect AD and facilitate the development of an inexpensive and noninvasive screening method for use in specialty and primary care settings.

  PublisherOA PDFDOI

• Cytosolic DNA crosstalk in senescence: a new axis of inflammatory signaling?

  The EMBO Journal · 2025-08-29 · 7 citations

  articleOpen access

  Cellular senescence is a form of stable growth arrest that contributes to aging and age-related diseases, in part through the senescence-associated secretory phenotype (SASP). Recent studies show that senescent cells accumulate several species of cytosolic DNAs, including mitochondrial DNA (mtDNA), cytoplasmic chromatin fragments (CCFs), and retrotransposable element cDNAs, which collectively activate the cGAS–STING pathway and drive SASP expression. Surprisingly, downregulating any one of these DNA species is often enough to suppress the SASP, raising key questions about their functional interactions. We propose that these cytosolic DNA species do not act in isolation but instead either follow a coordinated sequence or engage in synergistic crosstalk to amplify and sustain inflammatory signaling. While therapeutic approaches directly targeting the cGAS–STING pathway are being developed, we argue that blocking the sources of cytosolic DNA might be a more specific and safer strategy to target the deleterious effects of senescent cells. In particular, this approach should enable reducing chronic inflammation without impairing important immune functions, offering a new direction for therapies aimed at promoting healthy aging.

  PublisherOA PDFDOI

• Combining supervised and unsupervised analyses to quantify behavioral phenotypes and validate therapeutic efficacy in a triple transgenic mouse model of Alzheimer's disease

  Biomedicine & Pharmacotherapy · 2024-12-01 · 2 citations

  articleOpen access

  Behavioral testing is an essential tool for evaluating cognitive function and dysfunction in preclinical research models. This is of special importance in the study of neurological disorders such as Alzheimer’s disease. However, the reproducibility of classic behavioral assays is frequently compromised by interstudy variation, leading to ambiguous conclusions about the behavioral markers characterizing the disease. Here, we identify age- and genotype-driven differences between 3xTg-AD and non-transgenic control mice using a low-cost, highly customizable behavioral assay that requires little human intervention. Through behavioral phenotyping combining both supervised and unsupervised behavioral classification methods, we are able to validate the preventative effects of the immunosuppressant cyclosporine A in a rodent model of Alzheimer’s disease, as well as the partially ameliorating effects of candidate drugs nebivolol and cabozantinib. • Behavioral assays are an important tool to assess cognitive function in pre-clinical neurological disease models. • We combined supervised and unsupervised behavioral classification methods to quantify deficits in female 3xTg-AD mice. • Chronic treatment with cyclosporine, nebivolol, or cabozantinib mitigate behavioral and gait deficits in young and old mice.

  PublisherDOI

• Combining supervised and unsupervised analyses to quantify behavioral phenotypes and validate therapeutic efficacy in a triple transgenic mouse model of Alzheimer’s disease

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-06-08

  preprintOpen access

  Behavioral testing is an essential tool for evaluating cognitive function and dysfunction in preclinical research models. This is of special importance in the study of neurological disorders such as Alzheimer's disease. However, the reproducibility of classic behavioral assays is frequently compromised by interstudy variation, leading to ambiguous conclusions about the behavioral markers characterizing the disease. Here, we identify age- and genotype-driven differences between 3xTg-AD and non-transgenic control mice using a low-cost, highly customizable behavioral assay that requires little human intervention. Through behavioral phenotyping combining both supervised and unsupervised behavioral classification methods, we are able to validate the preventative effects of the immunosuppressant cyclosporine A in a rodent model of Alzheimer's disease, as well as the partially ameliorating effects of candidate drugs nebivolol and cabozantinib.

  PublisherOA PDFDOI

• Drug repurposing for neurodegenerative diseases using Zebrafish behavioral profiles

  Biomedicine & Pharmacotherapy · 2024-01-06 · 16 citations

  articleOpen access

  Drug repurposing can accelerate drug development while reducing the cost and risk of toxicity typically associated with de novo drug design. Several disorders lacking pharmacological solutions and exhibiting poor results in clinical trials - such as Alzheimer's disease (AD) - could benefit from a cost-effective approach to finding new therapeutics. We previously developed a neural network model, Z-LaP Tracker, capable of quantifying behaviors in zebrafish larvae relevant to cognitive function, including activity, reactivity, swimming patterns, and optomotor response in the presence of visual and acoustic stimuli. Using this model, we performed a high-throughput screening of FDA-approved drugs to identify compounds that affect zebrafish larval behavior in a manner consistent with the distinct behavior induced by calcineurin inhibitors. Cyclosporine (CsA) and other calcineurin inhibitors have garnered interest for their potential role in the prevention of AD. We generated behavioral profiles suitable for cluster analysis, through which we identified 64 candidate therapeutics for neurodegenerative disorders.

  PublisherDOI

• Loss of epigenetic information as a cause of mammalian aging

  Cell · 2024-02-01 · 38 citations

  erratumOpen access
  PublisherOA PDFDOI

• Dysregulation of endogenous retroviruses triggers aging and senescence

  Nature Aging · 2024-11-20 · 4 citations

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

• TRAIL pathway suppression of cancer cell growth and immune cell-mediated tumor cell-killing in a senescent fibroblast-constructed tumor microenvironment

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-12-01

  preprintOpen access

  Abstract Cellular senescence and the associated secretory phenotype (SASP) promote cancer in the aging population. During aging or upon chemotherapy exposure, cellular and molecular changes occur in non-cancerous cells and alter responses to cancer therapy, primarily via modifications in the tumor microenvironment (TME) and immune response. Targeting senescent cells through removal, modulation of the SASP, or cellular reprogramming represent promising therapeutic avenues for treating cancer. We elucidate an interplay between cancer cells, immune cells, and senescent fibroblasts and describe the impact of fibroblast senescence on tumor growth and response to cancer therapy. Cytokine profiling reveals dynamic changes in SASP production during etoposide-induced senescence in IMR90 fibroblasts. We show that SASP is partially regulated by p21 (WAF1; CDKN1A), leading to the downregulation of anti-tumorigenic cytokines and upregulation of pro-tumorigenic cytokines. Senescent fibroblasts promote bystander cancer cell growth via a p21-driven SASP. These results provide strategies to target the p21-driven SASP in the TME during cancer therapy. Treatment with TRAIL or TRAIL-inducing Dordaviprone (TIC10/ONC201) reduces cell viability of tumor cells co-cultured with senescent or proliferating fibroblasts and promotes immune-mediated tumor cell-killing in co-culture with senescent IMR90 fibroblasts. ONC201 combined with senolytic drugs (e.g., Navitoclax, Lamivudine) synergizes towards tumor suppression. These results indicate that senolytic therapies may be combined with cancer therapies to target senescence-associated changes in the TME including for modulation of the senescent cytokine landscape.

  PublisherOA PDFDOI

Recent grants

• Salivary Extracellular Vesicles as Biomarkers for Alzheimer's Disease and Related Disorders

  NIH · $3.9M · 2022–2027

• NIH Grant K01AG039410

  NIH · $582k · 2017

• Regulation of Neural Stem Cell Quiescence by FOXO3 During Aging

  NIH · $20.4M · 2020–2024

Frequent coauthors

• John M. Sedivy

  Brown University

  52 shared

• Robbert Créton

  Providence College

  45 shared

• Sayali V. Gore

  Providence College

  25 shared

• Thaís Del Rosario Hernández

  Brown University

  25 shared

• Bianca Kun

  Brown University

  22 shared

• Nicola Neretti

  Providence College

  20 shared

• Steven W. Criscione

  AstraZeneca (United States)

  20 shared

• Abigail L. Peterson

  Providence College

  20 shared

Labs

• Kreiling, JillPI

Education

• Ph.D.

  Brown University School of Medicine

• M.D.

  Brown University School of Medicine

• B.A.

  Brown University