About

Dr. Hai Dang Nguyen is an Assistant Professor in the Department of Pharmacology at the University of Minnesota Medical School. He is an EvansMDS Young Investigator focusing on mechanisms and therapeutic strategies for Myelodysplastic syndrome patients harboring RNA splicing gene mutations. His research involves a multidisciplinary team in the functional genomics of solid tumors, aiming to develop new technologies and models for understanding cancer heterogeneity. Dr. Nguyen received his B.A. degree from The College of Wooster, Ohio, and his Ph.D. from the University of Minnesota in the laboratory of Dr. Anja-Katrin Bielinsky. He completed postdoctoral research training in Dr. Lee Zou's laboratory at Harvard Medical School and Massachusetts General Hospital Cancer Center. His research centers on the DNA damage response, particularly the role of ATR kinase in sensing DNA damage, replication stress, and transcription-related problems such as R-loops, which are major sources of genomic instability. His laboratory investigates how ATR regulates R-loop resolution in cancers and explores targeted therapies by identifying vulnerabilities in cancer cells with splicing factor mutations. The lab is also developing small molecule probes and employing biochemical, cell biological, and genetic approaches to understand R-loop sensing and resolution mechanisms, with the goal of informing new targeted cancer treatments.

Research topics

• Genetics
• Cell biology
• Biochemistry
• Computer Science
• Biology
• Molecular biology
• Stereochemistry
• Endocrinology
• Immunology
• Chemistry
• Organic chemistry

Selected publications

• Radical <i>S</i> -Adenosyl- <scp>l</scp> -Methionine Oxygenase DarE Forms Ether Bond via a Partially Delocalized Tryptophan C _β Radical

  Journal of the American Chemical Society · 2026-01-23

  articleOpen access

  Darobactins are ribosomally synthesized and post-translationally modified peptides (RiPPs) with potent activity against Gram-negative pathogens. Their antibiotic function depends on a distinctive β-strand architecture stabilized by an ether cross-link between two tryptophan residues. Unlike most ether linkages in natural products, which arise from hydroxylated precursors, the darobactin ether bond is formed between two unmodified Trp residues by the radical S-adenosyl-l-methionine (SAM) enzyme DarE. DarE catalyzes both O-insertion and ether bond formation using molecular oxygen as a cosubstrate, but its catalytic mechanism remains largely unexplored. Here, we report detection and characterization of a key radical intermediate at the Cβ position of W3 (W3-Cβ•) using isotopically labeled DarA, kinetic analysis, and spectroscopy methods including EPR, ENDOR, and HYSCORE. Similar radical species were also observed in reactions with W3 variants of DarA. These results provide direct evidence that DarE catalyzes ether cross-link formation through reaction of the W3-Cβ• intermediate with O2, revealing an unprecedented radical-mediated strategy for O-atom incorporation in RiPP biosynthesis.

  PublisherOA PDFDOI

• Supplementary Figure S1 from Germline–Somatic Interactions in BRCA-Associated Cancers: Unique Molecular Profiles and Clinical Outcomes Linking &lt;i&gt;ATM&lt;/i&gt; to &lt;i&gt;TP53&lt;/i&gt; Synthetic Essentiality

  2025-05-01

  preprintOpen access

  &lt;p&gt;Consort like Diagram&lt;/p&gt;

  PublisherDOI

• Supplementary Table S1 from &lt;i&gt;XPO1&lt;/i&gt;&lt;sup&gt;&lt;i&gt;R749Q&lt;/i&gt;&lt;/sup&gt; Mutations Co-occur with &lt;i&gt;POLE&lt;/i&gt; Mutations in Cancer and Can Be Targeted to Overcome Chemoresistance

  2025-09-02

  articleOpen access

  &lt;p&gt;Supplementary Table S1&lt;/p&gt;

  PublisherDOI

• Dissecting the functional differences and clinical features of R-spondin family members in metastatic prostate cancer

  Oncotarget · 2025-07-25 · 1 citations

  articleOpen access

  // Aiden Deacon 1 , 4 , Ava Gustafson 1 , 4 , Allison Makovec 1 , 4 , Ella Boytim 1 , 4 , Gabriella von Dohlen 1 , 4 , David Moline 1 , 4 , Elin Kairies 2 , Sam Kellen 1 , 4 , Khalid Ishani 1 , 4 , Megan L. Ludwig 3 , Emily John 1 , 4 , Alexis Anike 1 , 4 , Hai Dang Nguyen 3 , 4 , Scott M. Dehm 1 , 4 , Justin M. Drake 1 , 3 , Emmanuel S. Antonarakis 1 , 4 and Justin Hwang 1 , 4 1 Department of Medicine, University of Minnesota-Twin Cities, Minneapolis, MN 55455, USA 2 Cornell College, Mount Vernon, IA 52314, USA 3 Department of Pharmacology, University of Minnesota- Twin Cities, Minneapolis, MN 55455, USA 4 Masonic Cancer Center, University of Minnesota-Twin Cities, Minneapolis, MN 55455, USA Correspondence to: Justin Hwang, email: jhwang@umn.edu Keywords: RSPO2; prostate cancer; Wnt signaling; genomics; therapeutics Received: March 18, 2025&emsp;&emsp;&emsp;&emsp; Accepted: July 16, 2025&emsp;&emsp;&emsp;&emsp; Published: July 25, 2025 Copyright: &copy; 2025 Deacon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT This study investigates the R-spondin family of genes ( RSPO1/2/3/4 ), a group of secreted proteins that act as Wnt regulators, and their subsequent role in advanced prostate cancer (PC). When evaluating transcriptomic data from primary and metastatic PC patients, we found that alterations in RSPO2 were more prevalent than in other RSPO family members or Wnt-regulating genes APC and CTNNB1 . Further, we found that RSPO2 alterations in PCs were significantly associated with worse disease-free survival. Through our in silico modeling, RSPO2 exhibited strong positive associations with genes regulating epithelial-mesenchymal transition (EMT) and double-negative prostate cancer (DNPC), but had negative correlations with androgen receptor (AR) and AR-associated genes. Furthermore, 3D modeling of RSPO2 revealed structural differences between itself and other RSPOs. In cell lines, RSPO2 overexpression caused up-regulation of EMT pathways, including EMT-regulatory transcription factors ZEB1, ZEB2, and TWIST1 . Conversely, this was not observed when CTNNB1 was overexpressed in the same models. These findings highlight that, in PC, RSPO2 functions as a unique member of the R-spondin family by promoting genes and signaling pathways associated with aggressive PC, and RSPO2 amplifications are associated with poor outcomes in PC patients.

  PublisherOA PDFDOI

• Supplementary Figure S3 from Germline–Somatic Interactions in BRCA-Associated Cancers: Unique Molecular Profiles and Clinical Outcomes Linking &lt;i&gt;ATM&lt;/i&gt; to &lt;i&gt;TP53&lt;/i&gt; Synthetic Essentiality

  2025-05-01

  preprintOpen access

  &lt;p&gt;Summarized broad trends observed across cancer types&lt;/p&gt;

  PublisherDOI

• Supplementary Figure S3 from &lt;i&gt;XPO1&lt;/i&gt;&lt;sup&gt;&lt;i&gt;R749Q&lt;/i&gt;&lt;/sup&gt; Mutations Co-occur with &lt;i&gt;POLE&lt;/i&gt; Mutations in Cancer and Can Be Targeted to Overcome Chemoresistance

  2025-09-02

  articleOpen access

  &lt;p&gt;Supplementary Figure S3 and legend&lt;/p&gt;

  PublisherOA PDFDOI

• Supplementary Figure S5 from &lt;i&gt;XPO1&lt;/i&gt;&lt;sup&gt;&lt;i&gt;R749Q&lt;/i&gt;&lt;/sup&gt; Mutations Co-occur with &lt;i&gt;POLE&lt;/i&gt; Mutations in Cancer and Can Be Targeted to Overcome Chemoresistance

  2025-09-02

  articleOpen access

  &lt;p&gt;Supplementary Figure S5 and legend&lt;/p&gt;

  PublisherOA PDFDOI

• Contribution of HMGB1 to Keratinocyte Inflammation in Recessive Dystrophic Epidermolysis Bullosa

  JID Innovations · 2025-08-11

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited skin disorder characterized by fragile skin, blistering, and chronic wounds. Keratinocytes, the primary cells in the epidermis, are directly affected by persistent injury in RDEB, contributing to chronic inflammation. High mobility group box 1 (HMGB1) is elevated in the serum of individuals with RDEB. However, its role in keratinocyte inflammation remains unclear. Here, we report an increase in HMGB1 expression in keratinocytes at chronic wound sites compared to matched non-wounded skin from an RDEB individual, suggesting a potential link to local inflammation. Pharmacological inhibition of HMGB1 using inflachromene reduced lipopolysaccharide (LPS)-induced inflammatory responses in a keratinocyte cell line, supporting a role for keratinocyte-specific HMGB1 in inflammation. Surprisingly, deletion of HMGB1 alone or together with its paralogue HMGB2 did not suppress the inflammatory response to LPS. Furthermore, inflachromene still reduced inflammation in these knockout cells. This unexpected discrepancy between genetic deletion and pharmacologic inhibition points to a more complex role for HMGB1 or off-target effects of the compound. These findings suggest that HMGB1 may contribute to inflammation in keratinocytes, but its exact function needs further investigation.

  PublisherDOI

• Supplementary Figure S2 from Germline–Somatic Interactions in BRCA-Associated Cancers: Unique Molecular Profiles and Clinical Outcomes Linking &lt;i&gt;ATM&lt;/i&gt; to &lt;i&gt;TP53&lt;/i&gt; Synthetic Essentiality

  2025-05-01

  preprintOpen access

  &lt;p&gt;Violin plots depicting somatic TMB&lt;/p&gt;

  PublisherDOI

• Supplementary Figure S1 from &lt;i&gt;XPO1&lt;/i&gt;&lt;sup&gt;&lt;i&gt;R749Q&lt;/i&gt;&lt;/sup&gt; Mutations Co-occur with &lt;i&gt;POLE&lt;/i&gt; Mutations in Cancer and Can Be Targeted to Overcome Chemoresistance

  2025-09-02

  articleOpen access

  &lt;p&gt;Supplementary Figure S1 and legend&lt;/p&gt;

  PublisherOA PDFDOI

Frequent coauthors

• Timothy A. Graubert

  57 shared

• Lee Zou

  Harvard University

  55 shared

• Matthew J. Walter

  50 shared

• Maxwell Bannister

  44 shared

• Zhiyan Silvia Liu

  33 shared

• Martina Sarchi

  University of Washington

  31 shared

• Stanley Chun-Wei Lee

  Fred Hutch Cancer Center

  31 shared

• Victor M. Corral

  30 shared

Labs

• Hai Dang Nguyen LabPI

Education

• PhD, Biochemistry, Molecular Biology & Biophysics

  University of Minnesota

  2012

• Biochemistry and Molecular Biology, Chemistry

  College of Wooster

  2006

Awards & honors

• EvansMDS Young Investigator