About

Patrick John Casey is the James B. Duke Distinguished Professor of Pharmacology and Cancer Biology at Duke University. He holds multiple positions including Professor of Pharmacology and Cancer Biology and is a member of the Duke Cancer Institute. His academic and research focus is within the fields of biochemistry, pharmacology, and cancer biology, contributing to the understanding of these areas through his role at Duke University. His work is associated with the Duke Department of Biochemistry, where he is involved in research and teaching activities.

Research topics

• Biology
• Genetics
• Cell biology
• Medicine
• Gastroenterology
• Pathology
• Immunology
• Internal medicine
• Cancer research

Selected publications

• Gα13 Promotes Clonogenic Growth by Increasing Tolerance to Oxidative Metabolic Stress in Prostate Cancer Cells

  International Journal of Molecular Sciences · 2025-05-20

  articleOpen accessSenior authorCorresponding

  The oncogenic role of the G12 family in many human solid cancers has been extensively studied, primarily through the effects of constitutively active mutants of these proteins on cell migration and invasion. However, these mutations are not seen in cancers, and the biological role of Gα13 in prostate cancer tumorigenesis is largely unexplored. Here, we report that Gα13 promotes anchorage-independent colony formation, spheroid formation, and xenograft tumor growth in human prostate cancer cell lines. Transcriptome analyses suggest that Gα13 modulates genes in the mitochondria and are involved in the oxidative stress response. Silencing of GNA13 increased mitochondrial superoxide levels when prostate cancer cells were cultured in galactose medium and increased the sensitivity to oxidative metabolic stress when the cells were cultured in media containing non-glycolytic metabolites. Furthermore, Gα13 levels impacts the abundance of superoxide dismutase 2 (SOD2) in the mitochondria, as well as SOD2 promoter activity and mRNA expression. Importantly, expression of SOD2 could rescue the effect of Gα13 loss on suppression of anchorage-independent growth. Likewise, stable knockdown of SOD2 decreased anchorage-independent cell growth, which was enhanced by overexpression of Gα13. These results outline a novel biological function of Gα13 mediated via SOD2 in prostate cancer tumorigenesis and highlight it as a potential treatment target.

  PublisherOA PDFDOI

• Exploration Targeting for Pegmatite-hosted Lithium Mineralization in Västernorrland Region, Sweden, by Multivariate Analysis of Till Geochemical Data

  2025-01-01

  article
  PublisherDOI

• Fostering Global Research Collaborations: An Update on Duke-NUS Medical School, the Duke University and National University of Singapore Partnership

  Academic Medicine · 2025-02-26

  articleOpen access

  PROBLEM: Navigating the complexities of international research collaborations is a challenge. This article provides a detailed examination of the international collaboration between Duke University and the National University of Singapore to establish the Duke-NUS Medical School. It explores the evolution and impact of the partnership, focusing on outcomes, knowledge advancement, and the dynamics of international collaborations in academic medicine. APPROACH: The partnership began in 2005 and applies a collaborative approach, including aligning research foci with Singapore's national health priorities, the formation of an academic medical center, faculty exchanges, joint funding for pilot research, and pooling of expertise, diverse and multiethnic data, and samples. OUTCOMES: The collaboration has led to educational and research advancements, including significant contributions to global health, such as the development of the first U.S. Food and Drug Administration-approved SARS-CoV-2 antigen test and a nasal COVID-19 vaccine candidate. Additionally, it has enhanced academic medicine capabilities within Singapore by transforming teaching hospitals into a fully integrated academic medical center. This experience suggests the following toward advancing the partnership: (1) agreement on and revisiting of the shared vision of the partnership by institutional leaders, (2) middle- and end-period reviews within multiyear funding cycles from local ministries, (3) faculty engagement through collaborative resources and spaces, and (4) similar first languages and health systems of the partners. NEXT STEPS: The Duke-NUS Medical School partnership aims to expand its research areas to address more global health challenges, such as the impact of climate change on health and the advancement of precision medicine. This article offers valuable insights for understanding the dynamics, benefits, and challenges of international collaborations in academic medicine.

  PublisherDOI

• Identifying marker compounds for elevated storage temperature in orange juice using untargeted LC-Orbitrap analysis

  Food Chemistry Advances · 2025-11-09

  articleOpen access1st authorCorresponding

  • Untargeted LC Orbitrap study of marker compounds in orange juice after 40 °C storage. • Significant increase of flavonoids (Tangeretin and Nobiletin) in all sample types. • Flavonoids offer practical advantages over the established marker compounds. • Flavonoid increase correlated to the % of orange juice concentrate in the beverage. • Results advance the published mechanism for release of flavonoids during heating. In this study Untargeted LC Orbitrap analysis is used to identify marker compounds which can be used to identify when orange juice beverages have been stored at elevated temperature. Orange juice (OJ) products, with varying levels of Concentrate % and Pulp %, were held at 40 °C for one week to replicate the effects of improper storage. Using untargeted analysis, it was found that this temperature results in a significant increase of flavonoids tangeretin and nobiletin in all sample types measured. Further analysis shows that the increase in flavonoid concentration is closely correlated to the % of orange juice concentrate in the beverage. Further discussion details how these results support and enhance previous studies which have proposed a mechanism for the release of phenolic compounds during heating. It is also shown that the flavonoid compounds hesperidin and naringin did not exhibit repeatable changes following 40 °C storage, in comparison to control samples stored at 4 °C. The contrasting behaviour of hesperidin and naringin compared to tangeretin and nobiletin is also discussed. Potential benefits for using tangeretin and nobiletin as analytical markers for elevated storage temperature, along with the effectiveness of LC Orbitrap for untargeted analysis are also discussed.

  PublisherDOI

• Exploring the use of generative AI advice for the academic advancement of faculty

  medRxiv · 2025-05-26

  preprintOpen access

  Abstract The SingHealth Duke–NUS Academic Medical Center manages over 2,800 clinical faculty members and processes over 400 appointments and promotions annually. The current Promotion and Tenure documentation includes over 30 documents, making it difficult and time-consuming for the faculty to locate specific appointment information. We developed “AskADD” in response to requests for clearer academic career development guidance. This study reports initial alpha testing and subsequent beta testing with 35 faculty members using AskADD. AskADD aids the faculty—physician-educators, physician-scientists, physician-innovators, and physician-leaders—in navigating academic career paths while increasing transparency and trust in appointment, promotion, and tenure processes. Our AI-integrated systems, initially tested using low or no-code Microsoft platforms and later developed with a custom GPT, deliver contextualized responses to promotion and tenure queries. The faculty and staff participated in user testing, providing feedback for improvements. Alpha and beta testing conducted with the same group of users indicated that a substantial portion of participants found the tool beneficial; suggestions were given for further refinement. Our experience contributes to the limited literature on AI-driven faculty advancement in academic medical centers and offers a novel paradigm for academic career support.

  PublisherOA PDFDOI

• Concurrent inhibition of ICMT and RAF/MEK suppresses RAC1 ^P29S -driven MAPKi resistance in BRAF ^V600E melanoma by regulating TAZ activity

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-12

  preprintOpen access

  Abstract The RAC1 GTPase hotspot mutation P29S (RAC1 P29S ) is among the top driver oncogenes of cutaneous melanoma, which is known to develop resistance to MAPK pathway inhibitors including those targeting BRAF and MEK. Isoprenylcysteine carboxyl-methyltransferase (ICMT) is the enzyme catalyzing the last step of post-translational prenylation of RAC1, which is among its substrates. We demonstrate that RAC1 P29S/C189S , which lacks C-terminal prenylation site, has lost the ability to induce resistance toward vemurafenib or trametinib in BRAF V600E melanoma cells. Furthermore, the combination of vemurafenib with cysmethynil, a proof-of-concept ICMT inhibitor, showed efficacy in combating RAC1 P29S -driven resistance of BRAF V600E melanoma cells in both in vitro and in vivo settings. Concurrent treatment with cysmethynil and the MAPK pathway inhibitors efficiently inhibited proliferation and tumor formation of RAC1 P29S cells that are resistant to MAPK pathway inhibitor alone. Mechanistically, we found that the combined treatment impaired the nuclear translocation of TAZ, whose transcriptional activity is shown to account for MAPKi resistance in RAC1 P29S melanoma. We further validated the role of TAZ in RAC1 P29S -driven resistance by demonstrating that introducing a constitutively-active TAZ mutant enhanced the MAPKi resistance in native cells, phenocopying the effect of RAC1 P29S . The novel application of MAPKi and cysmethynil combination in RAC1 P29S -driven MAPKi-resistant melanoma cells extends the potential utility of ICMT inhibitors, and also provides a new mechanism for targeting ICMT in cancer.

  PublisherOA PDFDOI

• 12234 Gα13 Promotes Clonogenic Growth By Increasing Tolerance To Oxidative Metabolic Stress In Prostate Cancer Cells

  Journal of the Endocrine Society · 2024-10-01 · 1 citations

  articleOpen accessSenior author

  Abstract Disclosure: D. Wu: None. W. Lim: None. X. Chai: None. V.P. Seshachalam: None. S.A. Rasheed: None. S. Ghosh: None. P.J. Casey: None. Gα13 and Gα12 are members of the G12 family of Gα proteins that, along with their associated Gβγ subunits, mediate signaling from specific G protein-coupled receptors. Analyses of tumor specimens indicate that Gα13 expression correlates with patient survival in several solid cancers. We previously reported a role for Gα13 in cell migration and invasion in prostate cancer cell lines. Interestingly, patient data supports the notion that mitochondrial superoxide dismutase 2 (SOD2) correlates with prostate cancer risk and prognostic Gleason scores. Gα13 lower-expressing LNCaP cells also have lower SOD2 protein levels compared to the Gα13 higher-expressing PC3 cells. Hence, we explored the role of Gα13 in prostate tumorigenesis, and its effect on cellular processes such as cell survival and mitochondrial metabolism, in human prostate cancer cell lines PC3 and LNCaP. We stably knocked-down GNA13 expression in PC3 cells and overexpressed GNA13 in LNCaP cells. We found that Gα13 promoted anchorage-independent cell growth in PC3 and LNCaP cell lines, as assessed by soft agar colony formation, spheroid formation, and xenograft tumor growth. Whole-genome transcriptome analyses suggested that Gα13-regulated genes are functionally enriched in the mitochondria compartment and that GNA13 expression positively correlated to SOD2 transcript levels in PC3 cells. We found that silencing GNA13 sensitized PC3 cells to long-term oxidative metabolic stress when cultured in media containing non-glycolytic metabolites, namely galactose, glutamate plus malate, and succinate. Furthermore, Gα13 levels impacted the abundance of SOD2 protein in the mitochondria, as well as SOD2 promoter activity and mRNA expression. In addition, silencing GNA13 increased mitochondrial superoxide levels in PC3 cells when cultured in galactose medium, as assessed by MitoSOX staining and flow cytometry. Moreover, overexpression of SOD2 could rescue the effect of Gα13 loss on suppression of anchorage-independent cell growth in PC3 cells. Importantly, anchorage-independent cell growth was not rescued when a catalytically-inactive SOD2(Q167A) mutant was expressed. Likewise, stable knockdown of SOD2 suppressed the effect of overexpression of Gα13 on anchorage-independent cell growth in LNCaP cells. We propose a novel biological route of Gα13-mediated anchorage-independent growth and response to oxidative metabolic stress through regulation of SOD2 expression in prostate cancer cells. Given that SOD2 protein levels correlate with prostate cancer Gleason grade, identifying the upregulated GPCRs that signal through Gα13 in prostate cancer could lead to novel preventive or therapeutic strategies. Presentation: 6/1/2024

  PublisherOA PDFDOI

• Targeting RAS membrane association

  Elsevier eBooks · 2024-10-18 · 1 citations

  book-chapter
  PublisherDOI

• Retroperitoneal Approach for Ilio-Superior Mesenteric Artery Bypass

  Journal of Vascular Surgery · 2024-05-20

  articleOpen access
  PublisherOA PDFDOI

• Contributors

  Elsevier eBooks · 2024-10-18

  book-chapterOpen access
  PublisherDOI

Recent grants

• NIH Grant R01CA100869

  NIH · $1.4M · 2009

• NIH Grant F32GM011982

  NIH · $45k

• NIH Grant R55GM055717

  NIH · $100k · 1999

• NIH Grant R01DK076488

  NIH · $1.1M · 2010

• NIH Grant R21CA091159

  NIH · $308k · 2004

Frequent coauthors

• Stephen G. Young

  University of California, Los Angeles

  74 shared

• Mei Wang

  56 shared

• Martin O. Bergö

  Karolinska Institutet

  55 shared

• Patrick Kelly

  Novo Nordisk (United States)

  52 shared

• L.S. Beese

  Duke University Hospital

  50 shared

• Thomas E. Meigs

  49 shared

• Carolyn Weinbaum

  Weill Cornell Medicine

  45 shared

• Christopher B. Newgard

  Duke Medical Center

  43 shared

Education

• Ph.D., Biochemistry

  Brandeis University

  1986