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Dr. Wenrui Duan's research interests include cancer genetics, development of cell and animal models, patient-derived tumor xenograft (PDX) models for targeted therapy in cancers. He is also interested in the development of novel biomarkers for the identification of subgroups of patients who are most likely to respond to treatment of novel anticancer agents. Dr. Duan is also interested in the investigation of the interaction between environmental carcinogen and genetic alterations in cancer initiation and development.

The Duan lab is led by Wenrui Duan, Ph.D., an Associate Professor in the Department of Human & Molecular Genetics, Herbert Wertheim College of Medicine at Florida International University (FIU). The lab is located on the 3rd floor of the Academic Health Center 4. 


  • Fanconi Anemia (FA)/BRCA pathway as a biomarker for cancer treatment

    A major mechanism of DNA repair-related to homologous recombination is the Fanconi Anemia (FA) pathway.  FA genes collaborate with other genes to form foci of DNA repair on chromatin following DNA damage or during S phase of the cell cycle. Lack of repair foci and BRCA gene (BRCA1 or BRCA2) deficiency have been identified as predictors of the cytotoxicity of DNA breaking agents, PARP inhibitors, respectively.

    We have recently developed a FA triple staining immunofluorescence based method (FATSI) to evaluate FANCD2 foci formation, which is capable of evaluating the presence or absence of FANCD2 foci using formalin-fixed paraffin-embedded (FFPE) tumor samples, and have generated preliminary data showing somatic deficiency of this pathway in tumors across several organ sites. However, the specific genetic and epigenetic alterations that lead to the inactivation of FA pathway in these sporadic tumors and the potential implication of these changes related to treatment are still unknown.

    We hypothesize that a substantial proportion of solid tumor harbors somatic genetic or epigenetic alterations resulting in defective FA homologous recombination repair. We are performing genomics analysis of FANCD2 foci defective tumors and adjacent non-tumor tissues, using next generation sequencing. In addition, we also investigate promoter methylation of FA genes in FANCD2 foci defective tumors. Currently, this study is supported by the Florida Department of Health, James and Esther King Biomedical Research Program.

  • Modeling and targeting mutant TP53 and KRAS in lung cancer

    TP53 and KRAS mutations are among the most common genetic events in lung cancer. TP53 mutations are present in 50-60% of non-small cell lung cancers and in 90% of small cell lung tumors.  KRAS mutations occur in 20% to 30% of human non-small cell lung cancers.

    TP53 mediates tumor suppression by activating the transcription of multiple genes specifically involved in cell cycle regulation, apoptosis, and genomic stability.  TP53 mutations can be classified in two major groups with distinct biological and functional properties.  Type I mutations occur in the DNA binding surface and disrupt the protein DNA contact points (contact mutations), whereas type II mutations occur in areas important for the conformational stability of TP53 (conformational mutations). Type II mutations have been shown to be more oncogenic than type I mutations in cancer cell lines. Furthermore, type II mutants are more resistant to etoposide-induced apoptosis. However, these differences have not been evaluated in spontaneous lung cancer models.

    The K-ras protein is a GTPase, which acts as a molecular switch to converts GTP into GDP, plays an important role in cell cycle regulation and apoptosis. Mutant KRAS is common and oncogenic in lung cancers.  Despite the frequency and good mechanistic characterization of these mutations, therapeutic strategies based on TP53 and KRAS abnormalities are limited in the clinic.

    The novel small molecule PRIMA-1 (TP53-dependent reactivation and induction of massive apoptosis) has been shown to induce apoptosis in human tumor cell lines containing mutant TP53 by restoration of the tumor suppressor function of TP53. Clinical trials testing safety and efficacy of methylated analog of PRIMA-1 (APR-246) agent have recently been initiated in hematologic and ovarian malignancies.  We investigated the PRIMA-1 several human lung cancer cell lines containing null, wild and mutant TP53, and found that this agent selectively induced apoptosis in lung cancer cells containing mutant TP53 but was less toxic to the cells containing wild type TP53.  In addition, we found the PRIMA-1 up-regulates microRNAs to promote apoptosis in the lung cancer cells containing mutant TP53.  Although it was reported the success in treatment of lung cancer containing KRAS G12C mutation, researchers have also observed that single agent of KRAS G12C inhibitor was not efficacious in clinical studies.

    Our preliminary results showed that the combination of APR-246 and KRAS G12C inhibitor AMG 510 (sotorasib) or MRTX849 (adagrasib) selectively reduced cell survival in lung cancer cells containing both mutant TP53 and KRAS, but was less toxic to cells containing mutant KRAS in a wild-type TP53 background. 

    We have developed two lines of transgenic mice in which either type I (SPC-TP53-273H) or type II (SPC-TP53-175H) TP53 mutant are expressed in a lung specific manner through the control of the surfactant C (SPC) promoter.  These type I and II mice develop lung tumors with typical histological characteristics of human adenocarcinomas. Overall, 42% of the murine lung tumor contained KRAS mutations.  We are currently investigating the role of PRIMA-1Met in combination with KRAS inhibitors in induction of apoptosis using human lung cancer cell lines and murine lung cancer models.

    In recent years, another modality of therapy, inhibition of immune checkpoints such as programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) has been also shown to benefit patients with lung cancer. However, despite the significant survival benefit for some patients with advanced NSCLC, the objective response rates (ORRs) remain relatively low with a large proportion of patients demonstrating primary resistance. We are also interested in the combination treatment of PRIMA-1Met and Immune checkpoint inhibitors with murine lung cancer models.