About

Anne Frances Buckley is an Associate Professor of Pathology at Duke University and an affiliate of the Duke Regeneration Center. Her role involves teaching and research within the Department of Pathology at Duke University School of Medicine. Specific details about her research focus, background, and key contributions are not provided in the available page text.

Research topics

• Computer Science
• Biology
• Medicine
• Genetics
• Neuroscience
• Virology
• Computational biology
• Environmental science
• Environmental engineering
• Internal medicine
• Physical therapy

Selected publications

• Clinical Reasoning: A 28-Year-Old Man With Seizures and Thalamic Lesions

  Neurology · 2026-05-08

  article

  This case involves a 28-year-old Black man who presented with new-onset seizures and bilateral medial temporal lobe hyperintensities on brain MRI, initially raising concern for viral encephalitis. CSF analysis revealed mild lymphocytic pleocytosis, but extensive infectious testing was negative. One year later, he developed acute right-sided weakness, and an MRI showed an enhancing FLAIR/T2 hyperintense mass-like lesion in the left thalamus. Stereotactic biopsy demonstrated reactive changes and Periodic acid-Schiff diastase (PASD)-positive macrophages, prompting consideration of atypical infectious or inflammatory etiologies. Despite empiric antibiotic treatment, his symptoms recurred 8 months later with new T2/FLAIR hyperintense lesions in the bilateral thalami and internal capsule, accompanied by mucocutaneous findings. He responded well to immunosuppressive therapy, with significant clinical and radiographic improvement. This case highlights the challenges of diagnosing relapsing neurologic syndromes with overlapping infectious, inflammatory, and neoplastic features and underscores the importance of integrating imaging, histopathology, and clinical evolution to reach a definitive diagnosis.

  PublisherDOI

• Podocyte specific knockout ( <scp>KO</scp> ) of the natriuretic peptide clearance receptor ( <scp>NPRC</scp> ) attenuates diabetic kidney disease ( <scp>DKD</scp> )

  Physiological Reports · 2026-05-01

  articleOpen access

  Glomerular podocytes play a key role in the pathogenesis of diabetic kidney disease (DKD). Recent studies suggest that natriuretic peptides (NPs) are podocyte protective. The beneficial effects of NPs are inhibited by the removal of NPs from the circulation by the NP clearance receptor (NPRC). To determine if inhibiting NP clearance by NPRC ameliorated DKD, we deleted NPRC specifically in glomerular podocytes in a mouse model of type 1 diabetes (Akita mice). We found that diabetes induced a significant increase in albuminuria in WT Akita mice, which was significantly reduced by knockout (KO) of NPRC. Histologic damage was mild in both WT and KO Akita mice and limited to a modest increase in mesangial matrix in both groups. In contrast, expression of the fibrotic markers fibronectin and collagen 1 was significantly increased in isolated glomerular preparations, and expression of both fibrotic markers was significantly improved by podocyte-specific KO of NPRC. Taken together, these data suggest that inhibiting NP clearance by glomerular podocytes has beneficial effects in a mouse model of early-stage DKD.

  PublisherDOI

• Podocyte specific knockout of the natriuretic peptide clearance receptor is podocyte protective in focal segmental glomerulosclerosis

  PLoS ONE · 2025-03-10 · 2 citations

  articleOpen accessCorresponding

  Natriuretic peptides (NPs) bind to glomerular podocytes and attenuate glomerular injury. The beneficial effects of NPs are negatively regulated by the NP clearance receptor (NPRC), which is highly expressed in podocytes. To determine if inhibiting NPRC is podocyte protective, we examined the effects of deleting NPRC in both cultured podocytes and in vivo. We found that: 1.Both atrial NP and C-type NP inhibit podocyte apoptosis in cultured podocytes, but these podocyte protective effects are significantly attenuated in cells expressing NPRC, and 2. Atrial NP was significantly more effective than CNP at inhibiting the apoptotic response. Consistent with the protective actions of NPs, podocyte specific knockout of NPRC reduced albuminuria, glomerular sclerosis and tubulointerstitial inflammation in a mouse model of focal segmental glomerulosclerosis. These beneficial actions were associated with: 1. Decreased expression of the myofibroblast marker alpha-smooth muscle actin, 2. Reduced expression of the extracellular matrix proteins collagen 4-alpha-1 and fibronectin, and 3. Preserved expression of the podocyte proteins nephrin and podocin. Inhibiting NP clearance may be a useful therapeutic approach to treat glomerular diseases.

  PublisherOA PDFDOI

• DOP097 Emulsifier restriction is an effective therapy for active Crohn’s disease: the ADDapt trial - a multi-centre, randomised, double-blind, placebo-controlled, re-supplementation trial in 154 patients

  Journal of Crohn s and Colitis · 2025-01-01 · 13 citations

  article

  Abstract Background Food additive emulsifiers result in bacterial dysbiosis, reduced intestinal mucus thickness, microbiota encroachment and increased permeability resulting in intestinal inflammation in murine models. Dietary intervention trials in inflammatory bowel disease are limited by challenges with blinding, high placebo response rates and because changes to one diet component impact on intake of many others (dietary collinearity). The ADDapt trial aimed to investigate the effects of a low emulsifier diet (LED) compared to control diet for 8-weeks on disease activity in patients with mild/moderately active Crohn’s disease (CD). Methods ADDapt (NCT04046913) was an appropriately powered, randomised, double-blind, placebo-controlled, re-supplementation trial (n=154). Patients with a CD activity index (CDAI) of 150-250 plus objective evidence of inflammation (faecal calprotectin (FCP) ≥150 µg/g or endoscopy/radiology) were randomised to either LED (intervention) or LED plus emulsifier re-supplementation (control). Dietary counselling was provided by a dietitian, plus dietary resources and a mobile app to support shopping. To recreate habitual emulsifier intake in controls, both groups received supermarket deliveries for 25% of foods either containing no emulsifiers (intervention) or similar foods containing emulsifiers (control) and were provided three snacks per day that were either emulsifier-free (intervention) or contained carrageenan, carboxymethylcellulose and polysorbate-80 (control). The primary endpoint was the proportion of patients achieving CDAI response (≥70 reduction) at 8-weeks. Secondary endpoints included CDAI remission and FCP. Regression analyses (adjusting for confounders) assessed the difference between trial arms. Results Patients (n=154, ITT population) were recruited from 19 UK centres with 113 (73%) completing the 8-week trial (PP population). Emulsifier intake reduced from median 30.0 (IQR 33.0) to 2.5 (6.0) in the LED group (p&amp;lt;0.001). In the ITT analysis, the primary outcome of CDAI response was achieved in 39 (49.4%) on LED versus 23 (30.7%) in the control group (p=0.019), with an adjusted relative risk (RR) of response of 3.1 (95% CI 1.5, 6.6, p=0.003), a finding that persisted in the PP analysis. In the ITT analysis, compared to control, patients on a LED were more than twice as likely to experience CDAI remission (Adjusted RR 2.1; 95% CI 1.0, 4.4; p=0.042) and &amp;gt;50% reduction in FCP (Adjusted RR 2.9; 95% CI 1.1, 8.0; p=0.039) (Table 1). There were no serious adverse events. Conclusion A LED is an effective treatment in mild/moderately active CD. Ongoing mechanistic analyses will investigate the impact of the LED on gut microbiota and permeability. Funding The Leona M. and Harry B. Helmsley Charitable Trust

  PublisherDOI

• Reanalysis of <scp>RNA</scp> sequencing data ends diagnostic odyssey and expands the phenotypic spectrum of congenital titinopathy

  American Journal of Medical Genetics Part A · 2024-06-24

  articleOpen access

  Although next-generation sequencing has enabled diagnoses for many patients with Mendelian disorders, the majority remain undiagnosed. Here, we present a sibling pair who were clinically diagnosed with Escobar syndrome, however targeted gene testing was negative. Exome sequencing (ES), and later genome sequencing (GS), revealed compound heterozygous TTN variants in both siblings, a maternally inherited frameshift variant [(NM_133378.4):c.36812del; p.(Asp12271Valfs*10)], and a paternally inherited missense variant [(NM_133378.4):c.12322G > A; p.(Asp4108Asn)]. This result was considered nondiagnostic due to poor clinical fit and limited pathogenicity evidence for the missense variant of uncertain significance (VUS). Following initial nondiagnostic RNA sequencing (RNAseq) on muscle and further pursuit of other variants detected on the ES/GS, a reanalysis of noncanonical splice sites in the muscle transcriptome identified an out-of-frame exon retraction in TTN, near the known VUS. Interim literature included reports of patients with similar TTN variants who had phenotypic concordance with the siblings, and a diagnosis of a congenital titinopathy was given 4 years after the TTN variants had been initially reported. This report highlights the value of reanalysis of RNAseq with a different approach, expands the phenotypic spectrum of congenital titinopathy and also illustrates how a perceived phenotypic mismatch, and failure to consider known variants, can result in a prolongation of the diagnostic journey.

  PublisherOA PDFDOI

• Somatic variants in diverse genes leads to a spectrum of focal cortical malformations

  UNC Libraries · 2024-07-17

  articleOpen access

  Post-zygotically acquired genetic variants, or somatic variants, that arise during cortical development have emerged as important causes of focal epilepsies, particularly those due to malformations of cortical development. Pathogenic somatic variants have been identified in many genes within the PI3K-AKT-mTOR-signalling pathway in individuals with hemimegalencephaly and focal cortical dysplasia (type II), and more recently in SLC35A2 in individuals with focal cortical dysplasia (type I) or non-dysplastic epileptic cortex. Given the expanding role of somatic variants across different brain malformations, we sought to delineate the landscape of somatic variants in a large cohort of patients who underwent epilepsy surgery with hemimegalencephaly or focal cortical dysplasia. We evaluated samples from 123 children with hemimegalencephaly (n=16), focal cortical dysplasia type I and related phenotypes (n=48), focal cortical dysplasia type II (n=44), or focal cortical dysplasia type III (n=15). We performed high-depth exome sequencing in brain tissue-derived DNA from each case and identified somatic single nucleotide, indel and large copy number variants. In 75% of individuals with hemimegalencephaly and 29% with focal cortical dysplasia type II, we identified pathogenic variants in PI3K-AKT-mTOR pathway genes. Four of 48 cases with focal cortical dysplasia type I (8%) had a likely pathogenic variant in SLC35A2. While no other gene had multiple disease-causing somatic variants across the focal cortical dysplasia type I cohort, four individuals in this group had a single pathogenic or likely pathogenic somatic variant in CASK, KRAS, NF1 and NIPBL, genes previously associated with neurodevelopmental disorders. No rare pathogenic or likely pathogenic somatic variants in any neurological disease genes like those identified in the focal cortical dysplasia type I cohort were found in 63 neurologically normal controls (P=0.017), suggesting a role for these novel variants. We also identified a somatic loss-of-function variant in the known epilepsy gene, PCDH19, present in a small number of alleles in the dysplastic tissue from a female patient with focal cortical dysplasia IIIa with hippocampal sclerosis. In contrast to focal cortical dysplasia type II, neither focal cortical dysplasia type I nor III had somatic variants in genes that converge on a unifying biological pathway, suggesting greater genetic heterogeneity compared to type II. Importantly, we demonstrate that focal cortical dysplasia types I, II and III are associated with somatic gene variants across a broad range of genes, many associated with epilepsy in clinical syndromes caused by germline variants, as well as including some not previously associated with radiographically evident cortical brain malformations.

  PublisherDOI

• Urethral Mesh Assessment in Cancer Patients

  Cancers · 2023-11-27

  reviewOpen access

  Urethral mesh placement has become a common surgical intervention for the management of stress urinary incontinence. While this procedure offers significant benefits, it is not without potential complications. This review article aims to provide a comprehensive overview of urethral mesh assessment in oncologic patients. The article explores normal magnetic resonance imaging (MRI) and computed tomography (CT) mesh appearances and highlights the pathological aspects associated with urethral mesh complications including both short-term and long-term post-operative complications. By understanding the spectrum of normal findings of urethral mesh and the possible complications, clinicians can improve patient outcomes and make informed decisions regarding urethral mesh management in this patient population.

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• Supplemental Figure 2 from Radioprotection of the Brain White Matter by Mn(III) &lt;i&gt;N&lt;/i&gt;-Butoxyethylpyridylporphyrin–Based Superoxide Dismutase Mimic MnTnBuOE-2-PyP&lt;sup&gt;5+&lt;/sup&gt;

  2023-04-03

  preprintOpen access

  &lt;p&gt;Supplemental Figure 2: Neurocognitive analysis of mice by Morris watermaze (A and B), novel object test (C and D), and fear conditioning (E and F). Tests were performed as described (29). (G and H) Distance and velocity during the novel object training and test periods and overall averages.&lt;/p&gt;

  PublisherDOI

• Data from Radioprotection of the Brain White Matter by Mn(III) &lt;i&gt;N&lt;/i&gt;-Butoxyethylpyridylporphyrin–Based Superoxide Dismutase Mimic MnTnBuOE-2-PyP&lt;sup&gt;5+&lt;/sup&gt;

  2023-04-03

  preprintOpen access

  &lt;div&gt;Abstract&lt;p&gt;Cranial irradiation is a standard therapy for primary and metastatic brain tumors. A major drawback of radiotherapy (RT), however, is long-term cognitive loss that affects quality of life. Radiation-induced oxidative stress in normal brain tissue is thought to contribute to cognitive decline. We evaluated the effectiveness of a novel mimic of superoxide dismutase enzyme (SOD), MnTnBuOE-2-PyP&lt;sup&gt;5+&lt;/sup&gt;(Mn(III) meso-tetrakis(&lt;i&gt;N&lt;/i&gt;-n-butoxyethylpyridinium-2-yl)porphyrin), to provide long-term neuroprotection following 8 Gy of whole brain irradiation. Long-term RT damage can only be assessed by brain imaging and neurocognitive studies. C57BL/6J mice were treated with MnTnBuOE-2-PyP&lt;sup&gt;5+&lt;/sup&gt; before and after RT and evaluated three months later. At this time point, drug concentration in the brain was 25 nmol/L. Mice treated with MnTnBuOE-2-PyP&lt;sup&gt;5+&lt;/sup&gt;/RT exhibited MRI evidence for myelin preservation in the corpus callosum compared with saline/RT treatment. Corpus callosum histology demonstrated a significant loss of axons in the saline/RT group that was rescued in the MnTnBuOE-2-PyP&lt;sup&gt;5+&lt;/sup&gt;/RT group. In addition, the saline/RT groups exhibited deficits in motor proficiency as assessed by the rotorod test and running wheel tests. These deficits were ameliorated in groups treated with MnTnBuOE-2-PyP&lt;sup&gt;5+&lt;/sup&gt;/RT. Our data demonstrate that MnTnBuOE-2-PyP&lt;sup&gt;5+&lt;/sup&gt; is neuroprotective for oxidative stress damage caused by radiation exposure. In addition, glioblastoma cells were not protected by MnTnBuOE-2-PyP&lt;sup&gt;5+&lt;/sup&gt; combination with radiation &lt;i&gt;in vitro&lt;/i&gt;. Likewise, the combination of MnTnBuOE-2-PyP&lt;sup&gt;5+&lt;/sup&gt; with radiation inhibited tumor growth more than RT alone in flank tumors. In summary, MnTnBuOE-2-PyP&lt;sup&gt;5+&lt;/sup&gt; has dual activity as a neuroprotector and a tumor radiosensitizer. Thus, it is an attractive candidate for adjuvant therapy with RT in future studies with patients with brain cancer. &lt;i&gt;Mol Cancer Ther; 14(1); 70–79. ©2014 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;

  PublisherDOI

• Supplemental Figure 3 from Radioprotection of the Brain White Matter by Mn(III) &lt;i&gt;N&lt;/i&gt;-Butoxyethylpyridylporphyrin–Based Superoxide Dismutase Mimic MnTnBuOE-2-PyP&lt;sup&gt;5+&lt;/sup&gt;

  2023-04-03

  preprintOpen access

  &lt;p&gt;Supplemental Figure 3: Effects of radiation and MnTnBuOE-2-PyP5+ on tumor cells. (A) LN-18 and (B) LN-229 glioblastoma cell lines treated with or without 50 nM MnTnBuOE-2-PyP5+ in clonogenic survival assays prior to various doses of radiation.&lt;/p&gt;

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Frequent coauthors

• Darell D. Bigner

  Duke University

  43 shared

• Stefan M. Pfister

  University Hospital Heidelberg

  41 shared

• C. Hawkins

  University of Portsmouth

  40 shared

• James T. Rutka

  Hospital for Sick Children

  36 shared

• Diane K. Birks

  35 shared

• Paul A. Northcott

  St. Jude Children's Research Hospital

  31 shared

• D. Picard

  30 shared

• Michael Handler

  UMIT - Private Universität für Gesundheitswissenschaften, Medizinische Informatik und Technik

  30 shared