McArdle Laboratory for Cancer Research
April 2026 Publications
Abrahams RR, Larsen CIS, Ha R, Majumder K. The interaction between virus-bound KLF4 and host-bound PARP1 directs the localization of wild-type adeno-associated virus type 2 (wtAAV2) to cellular sites of DNA damage. J Virol. 2026 Apr 29:e0030626. doi: 10.1128/jvi.00306-26. PMID: 42053296.
Since adeno-associated viruses (AAVs) are used for gene therapies, it is important to know exactly how the viruses are sustained in the nucleus to maintain their longevity and efficacy. Dr. Kinjal Majumder and his group describe the binding site for AAV2 on the nuclear chromatin. Specifically, they discovered that the virus binds to sites of DNA damage, binding a protein complex that includes KLF4 and PARP1. This information has implications for future AAV vector design. Dr. Majumder is also a member of the Institute of Molecular Virology.
Burns TF, Ammakkanavar NR, Hollebecque A, Lee DH, Koyama T, Cassier PA, Italiano A, Han JY, Singhal N, Takeuchi S, Heist RS, Deming D, Spira A, Chu Q, Sacher A, Fujiwara Y, Chisamore MJ, You AX, McNeely SC, Fink A, Chen A, Oxnard GR, Willard MD, Murciano-Goroff YR, Dragnev KH. Efficacy and Safety of Olomorasib in Combination With Pembrolizumab in Treatment of Patients With KRAS G12C-Mutant Advanced NSCLC. J Thorac Oncol. 2026 Apr;21(4):103528. doi: 10.1016/j.jtho.2025.11.018. Epub 2025 Nov 29. PMID: 41319864.
This paper reports the results of an experimental drug combination of olomorasib and pembrolizumab (Keytruda) in treating advanced KRAS G12C-mutant lung cancer (NSCLC), particularly as a first-line therapy. Dr. Dusty Deming was part of this multi-center trial to improve the safety and efficacy of immunotherapy (pembrolizumab) in combination with the important new mutant Ras inhibitor Olomorasib. The success of this trial has led to a “breakthrough therapy designation”. Dr. Deming is also a faculty member in the Department of Medicine.
den Boon JA, Jaramillo-Mesa H, Horswill M, Jochem A, Bracken M, Zhan H, Ahlquist P. Genetic complementation reveals structure-function links in nodavirus RNA replication complex crowns. PLoS Pathog. 2026 Apr 20;22(4):e1013802. doi: 10.1371/journal.ppat.1013802. PMID: 42008461; PMCID: PMC13094992.
This study from Dr. Ahlquist and his group combines molecular genetics with cryo-electron microscopy to reveal how large protein complexes that replicate viral RNA genomes operate. Multiple copies of a giant, multi-domain viral protein adopt different conformations to each provide distinct replication functions in trans. This cooperative delivery of functions renders replication highly robust. Dr. Ahlquist also directs the Morgridge Institute’s Rowe Center for Virology and is a member of the Institute for Molecular Virology and the Department of Plant Pathology.
Deneuve S, Fervers B, Bruno JS, Bach E, Senkin S, Goldman-Lévy G, Carreira C, Laklouk I, Hu R, Bouaoun L, Pérol O, Chavanel B, Lu L, Lozar T, Gheit T, Lambert PF, Coste I, Renno T, Zavadil J, Virard F. Mutational signature-based classification uncovers emerging oral cancer subtypes with distinct molecular patterns. Int J Oral Sci. 2026 Apr 24;18(1):38. doi: 10.1038/s41368-026-00437-4. PMID: 42031720; PMCID: PMC13109424.
Dr. Lambert, and his postdoc Dr. Taja Lozar collaborated with multiple groups in France to examine the emergence of a human papilloma virus (HPV)-positive oral cavity squamous cell carcinomas arising in never-smokers. These tumors show a tobacco-independent origin of mutations and mechanisms of immune evasion.
Kirchner RE, Pereira ML, Peterson MM, Berres ME, Churpek JE. Long-Read Amplicon Sequencing for the Detection of TERT Promoter Variant Clonal Hematopoiesis in Patients with Telomere Biology Disorders. J Mol Diagn. 2026 Apr;28(4):336-344. doi: 10.1016/j.jmoldx.2026.01.005. PMID: 41654254.
Dr. Churpek and her team developed a long-read sequencing-based protocol, LR-deep AmpSeq, for detecting acquired mutations in the promoter of the telomerase gene. This assay is the first to use long read sequencing for low frequency mutations in this difficult-to-sequence region. It can be used to support a “telomere biology disorder” diagnosis and monitoring of bone marrow function in this patient population. Dr. Churpek is also a faculty member in the Department of Medicine.
Larsen CIS, Abrahams RR, Majumder K. Molecular Mimics: How Viral Genomes Dupe Their Host by Usurping CTCF to Establish Infection. Viruses. 2026 Apr 10;18(4):456. doi: 10.3390/v18040456. PMID: 42043245; PMCID: PMC13120354.
This review from Dr. Majumder, and student lab members examines the many ways that viruses exploit the genome regulation processes of their host cells to regulate their own replication and life cycle.
Shechter D, Huang R, Shah P, Dubois T, Li XM, Parhitko A, Bedford MT, Kuang S, Chen T, Yang Y, Rajyaguru P, Barsyte-Lovejoy D, Zhao X, Xu W, Davies CC, Tikhanovich I, Tran NT, Kako K, Hashimoto M, Luo M, Hevel JM, Fukamizu A, Yu MC. Meeting Report on FASEB Protein Arginine Methylation: Mechanism to Therapeutics. J Biol Chem. 2026 Apr 10:111448. doi: 10.1016/j.jbc.2026.111448. PMID: 41967639.
Leaders in the field of protein arginine methylation, including McArdle faculty member, Dr. Wei Xu, summarize the highlights of a FASEB conference held in January in Japan, pointing out the many roles of this post-translational means of protein regulation in epigenetics, RNA biology, genome stability, immune function and cellular stress responses.