About

Bryan A. Wolf, MD, PhD, is an Emeritus Professor of Pathology and Laboratory Medicine at the University of Pennsylvania's Perelman School of Medicine. His research focuses on the signal transduction mechanisms of insulin secretion from the islets of Langerhans, with particular interest in understanding diabetes. He has identified a novel cytokine called PANDER (FAM3B), which is expressed in islets of Langerhans and present in secretory granules. PANDER causes apoptosis of beta-cells and is upregulated by interferon-gamma treatment in beta-cells. His work explores whether PANDER is involved in cytokine-induced destruction of islets and the pathogenesis of type 1 diabetes, as well as its potential role in beta-cell differentiation. His laboratory employs cell biological, biochemical, and molecular biology approaches to elucidate the physiological role of PANDER and its implications in diabetes.

Research topics

• Internal medicine
• Endocrinology
• Biology
• Chemistry
• Cell biology

Selected publications

• Overexpression of Alpha-1 Antitrypsin Increases the Proliferation of Mesenchymal Stem Cells by Upregulation of Cyclin D1

  International Journal of Molecular Sciences · 2024-02-07 · 4 citations

  articleOpen access1st author

  Alpha-1 antitrypsin-overexpressing mesenchymal stromal/stem cells (AAT-MSCs) showed improved innate properties with a faster proliferation rate when studied for their protective effects in mouse models of diseases. Here, we investigated the potential mechanism(s) by which AAT gene insertion increases MSC proliferation. Human bone marrow-derived primary or immortalized MSCs (iMSCs) or AAT-MSCs (iAAT-MSCs) were used in the study. Cell proliferation was measured by cell counting and cell cycle analysis. Possible pathways involved in the pro-proliferation effect of AAT were investigated by measuring mRNA and protein expression of key cell cycle genes. Interval cell counting showed increased proliferation in AAT-MSCs or iAAT-MSCs compared to their corresponding MSC controls. Cell cycle analysis revealed more cells progressing into the S and G2/M phases in iAAT-MSCs, with a notable increase in the cell cycle protein, Cyclin D1. Moreover, treatment with Cyclin D1 inhibitors showed that the increase in proliferation is due to Cyclin D1 and that the AAT protein is upstream and a positive regulator of Cyclin D1. Furthermore, AAT's effect on Cyclin D1 is independent of the Wnt signaling pathway as there were no differences in the expression of regulatory proteins, including GSK3β and β-Catenin in iMSC and iAAT-MSCs. In summary, our results indicate that AAT gene insertion in an immortalized MSC cell line increases cell proliferation and growth by increasing Cyclin D1 expression and consequently causing cells to progress through the cell cycle at a significantly faster rate.

  PublisherOA PDFDOI

• Overexpression of Alpha-1 Antitrypsin Increases the Proliferation of Mesenchymal Stem Cells by Upregulation of Cyclin D1 and is Independent of the Wnt Signaling Pathway

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-10-28 · 1 citations

  preprintOpen access1st author

  Alaph-1 antitrypsin overexpressing mesenchymal stromal/stem cells (AAT-MSCs) showed improved innate properties with a faster proliferation rate when studied for their protective effects in mouse models of diseases. Here, we investigated the potential mechanism(s) by which AAT gene insertion increases MSC proliferation. Human bone marrow-derived primary or immortalized MSCs (iMSCs) or AAT-MSCs (iAAT-MSCs) were used in the study. Cell proliferation was measured by cell counting and cell cycle analysis. Possible pathways involved in the pro-proliferation effect of AAT were investigated by measuring mRNA and protein expression of key cell cycle genes. Interval cell counting showed increased proliferation in AAT-MSCs or iAAT-MSCs compared to their corresponding MSC controls. Cell cycle analysis revealed more cells progressing into the S and G2/M phases in iAAT-MSCs, with a notable increase in the cell cycle protein, Cyclin D1. Moreover, treatment with Cyclin D1 inhibitors showed that the increase in proliferation is due to Cyclin D1 and that the AAT protein is upstream and a positive regulator of Cyclin D1. Furthermore, AAT's effect on Cyclin D1 is independent of the Wnt signaling pathway as there were no differences in the expression of regulatory proteins, including GSK3β and β-Catenin in iMSC and iAAT-MSCs. In summary, our results indicate that AAT gene insertion in an immortalized MSC cell line increases cell proliferation and growth by increasing Cyclin D1 expression and consequently causing cells to progress through the cell cycle at a significantly faster rate.

  PublisherOA PDFDOI

• Correction: The Genomics Research and Innovation Network: creating an interoperable, federated, genomics learning system

  Genetics in Medicine · 2019-11-26

  erratumOpen access

  Correction to: Genetics in Medicine 2019; https://doi.org/10.1038/s41436-019-0646-3, published online 04 September 2019 During the review process the authors added more detail regarding the output of the pilot projects. As such the authors should have updated the authorship with regard to the contributors to the two Pilot Projects discussed in detail (Epilepsy and Short Stature). These authors are Dr. Eric Marsh, Dr. Adda Grimberg and Dr. Colin Hawkes and are now added to this paper, and declare no conflicts of interest. These authors contributed equally: Kenneth D. Mandl, Tracy Glauser and Ian D. Krantz The original article can be found online at https://doi.org/10.1038/s41436-019-0646-3. The Genomics Research and Innovation Network: creating an interoperable, federated, genomics learning systemGenetics in MedicineVol. 22Issue 2PreviewClinicians and researchers must contextualize a patient’s genetic variants against population-based references with detailed phenotyping. We sought to establish globally scalable technology, policy, and procedures for sharing biosamples and associated genomic and phenotypic data on broadly consented cohorts, across sites of care. Full-Text PDF Open Access

  PublisherOA PDFDOI

• The Genomics Research and Innovation Network: creating an interoperable, federated, genomics learning system

  Genetics in Medicine · 2019-09-03 · 46 citations

  articleOpen access

  PURPOSE: Clinicians and researchers must contextualize a patient's genetic variants against population-based references with detailed phenotyping. We sought to establish globally scalable technology, policy, and procedures for sharing biosamples and associated genomic and phenotypic data on broadly consented cohorts, across sites of care. METHODS: Three of the nation's leading children's hospitals launched the Genomic Research and Innovation Network (GRIN), with federated information technology infrastructure, harmonized biobanking protocols, and material transfer agreements. Pilot studies in epilepsy and short stature were completed to design and test the collaboration model. RESULTS: Harmonized, broadly consented institutional review board (IRB) protocols were approved and used for biobank enrollment, creating ever-expanding, compatible biobanks. An open source federated query infrastructure was established over genotype-phenotype databases at the three hospitals. Investigators securely access the GRIN platform for prep to research queries, receiving aggregate counts of patients with particular phenotypes or genotypes in each biobank. With proper approvals, de-identified data is exported to a shared analytic workspace. Investigators at all sites enthusiastically collaborated on the pilot studies, resulting in multiple publications. Investigators have also begun to successfully utilize the infrastructure for grant applications. CONCLUSIONS: The GRIN collaboration establishes the technology, policy, and procedures for a scalable genomic research network.

  PublisherOA PDFDOI

• Art by the Many: London Style Cults of the 1960s

  British Art Studies · 2017-11-30

  articleOpen accessSenior author

  The annals of art history can readily be reduced to a catalogue of names, but salient examples of group effort are never hard to find. In London, the example of the Independent Group (IG) need only be adduced, but its immediate successors are less obvious. Between the dissolution of the IG in 1956 and the founding of Art & Language (A&L) a decade later, there appeared one far less heralded alliance, its subsequent obscurity balanced by its remarkable prescience. Terry Atkinson, later an A&L founder, had earlier been instrumental in creating a collective artistic entity among fellow students at the Slade School of Fine Art—Roger Jeffs, Bernard Jennings, and John Bowstead—who called themselves the Fine-Artz Associates. By the time of the 1964 Young Contemporaries exhibition, the four submitted their work under this name alone, but their ambitions had already expanded beyond the studio into the orbit of radically more extensive collectives.

  PublisherDOI

• Interactive pediatric emergency checklists to the palm of your hand ‐ How the Pedi Crisis App traveled around the world

  Pediatric Anesthesia · 2017-06-07 · 21 citations

  article

  BACKGROUND: Cognitive aids help clinicians manage critical events and have been shown to improve outcomes by providing critical information at the point of care. Critical event guidelines, such as the Society of Pediatric Anesthesia's Critical Events Checklists described in this article, can be distributed globally via interactive smartphone apps. From October 1, 2013 to January 1, 2014, we performed an observational study to determine the global distribution and utilization patterns of the Pedi Crisis cognitive aid app that the Society for Pediatric Anesthesia developed. We analyzed distribution and utilization metrics of individuals using Pedi Crisis on iOS (Apple Inc., Cupertino, CA) devices worldwide. We used Google Analytics software (Google Inc., Mountain View, CA) to monitor users' app activity (eg, screen views, user sessions). METHODS: The primary outcome measurement was the number of user-sessions and geographic locations of Pedi Crisis user sessions. Each user was defined by the use of a unique Apple ID on an iOS device. RESULTS: Google Analytics correlates session activity with geographic location based on local Internet service provider logs. Pedi Crisis had 1 252 active users (both new and returning) and 4 140 sessions across 108 countries during the 3-month study period. Returning users used the app longer and viewed significantly more screens that new users (mean screen views: new users 1.3 [standard deviation +/-1.09, 95% confidence interval 1.22-1.55]; returning users 7.6 [standard deviation +/-4.19, 95% confidence interval 6.73-8.39]P<.01) CONCLUSIONS: Pedi Crisis was used worldwide within days of its release and sustained utilization beyond initial publication. The proliferation of handheld electronic devices provides a unique opportunity for professional societies to improve the worldwide dissemination of guidelines and evidence-based cognitive aids.

  PublisherDOI

• Lateral acetabular labral length is inversely related to acetabular coverage as measured by lateral center edge angle of Wiberg

  Journal of Hip Preservation Surgery · 2016-02-29 · 36 citations

  articleOpen access

  Patients with developmental dysplasia of the hip often have compensatory labral hypertrophy, which presumably lends stability to an unstable joint. Conversely, patients with acetabular overcoverage may have small or ossified labra. The purpose of this study is to explore the interaction of labral length with the degree of acetabular hip coverage. A retrospective cohort of patients with hip pain presenting to a hip preservation center, who had undergone hip magnetic resonance imaging and AP pelvis radiographs were studied. General linear multivariate models were used to assess the association between three measures of labral length (lateral, anterior and anterior inferior locations along the acetabular rim) and the X-ray derived lateral center edge angle (LCEA) of Wiberg. Of the three acetabular labral locations measured, only the lateral labrum was associated with LCEA Wiberg (P = 0.0008). Lateral labral length increases as LCEA of Wiberg decreases. The anterior and anterior inferior labral locations did not show a predictable increase in labral length as LCEA Wiberg decreased.

  PublisherOA PDFDOI

• PEDSnet: a National Pediatric Learning Health System

  Journal of the American Medical Informatics Association · 2014-05-13 · 239 citations

  articleOpen access

  A learning health system (LHS) integrates research done in routine care settings, structured data capture during every encounter, and quality improvement processes to rapidly implement advances in new knowledge, all with active and meaningful patient participation. While disease-specific pediatric LHSs have shown tremendous impact on improved clinical outcomes, a national digital architecture to rapidly implement LHSs across multiple pediatric conditions does not exist. PEDSnet is a clinical data research network that provides the infrastructure to support a national pediatric LHS. A consortium consisting of PEDSnet, which includes eight academic medical centers, two existing disease-specific pediatric networks, and two national data partners form the initial partners in the National Pediatric Learning Health System (NPLHS). PEDSnet is implementing a flexible dual data architecture that incorporates two widely used data models and national terminology standards to support multi-institutional data integration, cohort discovery, and advanced analytics that enable rapid learning.

  PublisherOA PDFDOI

• Martin Puryear, Desire

  Conversations An Online Journal of the Center for the Study of Material and Visual Cultures of Religion · 2014-01-01

  article1st authorCorresponding

  There is very little at first glance in Martin Puryear’s Desire, 1981, that suggests either religion or the sacred. The sculpture—an awkward, oversized wooden wheel joined to an inverted basket—is constructed from vernacular materials (pine, red cedar, poplar and Sitka spruce) rather than rare or exotic woods. The wheel stands twice the height of its viewers and the basket reaches up eight feet towards the ceiling. Each possesses a fantastical quality that places it in an oversized, surreal world of familiar objects rendered uncanny. But that is our first clue: the uncanny quality of Desire. Puryear alludes to the realm of everyday objects even as he estranges us from it by exaggerating sizes, simplifying forms, and rendering his shapes conspicuously non-functional. The world of handmade objects and manual labor turns strange in this work, and in this way, the ordinary becomes—here is list of options, choose one—estranged, uncanny, defamiliarized.

  PublisherDOI

• Talbot-Wang - Brain Insulin Resistance in AD Suppl Data 4-2-12

  2013-01-01

  article
  Publisher

Recent grants

• NIH Grant K04DK002217

  NIH · $357k · 1998

• NIH Grant R01DK043354

  NIH · $1.1M · 2001

• NIH Grant P01DK049814

  NIH · $8.5M · 2006

Frequent coauthors

• Zhiyong Gao

  Henan Normal University

  65 shared

• Michael L. McDaniel

  36 shared

• Robert Young

  University of Pennsylvania

  34 shared

• John Turk

  Washington University in St. Louis

  33 shared

• Jianmei Wu

  Anhui Agricultural University

  31 shared

• Scott R. Greene

  University of Pennsylvania

  27 shared

• Jichun Yang

  Peking University

  25 shared

• Brant Burkhardt

  22 shared

Labs

• Pathology and Laboratory MedicinePI