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Wenrui Duan, PhD

Associate Professor

Human & Molecular Genetics


Office: AHC4 316

Phone: 305-348-9135

Email: wduan@fiu.edu

Lab: AHC4 342

Wenrui Duan joined HWCOM in October of 2016 and leads the Duan Lab. He was previously a research scientist at the Comprehensive Cancer Center of the Ohio State University (OSUCCC), and a research oriented assistant professor in the Division of Medical Oncology, College of Medicine at Ohio State University. 

Education

PhD, Molecular Genetics, The Ohio State University  
MS, Zoology, The Ohio State University
BS, Biology, Inner Mongolia University

Research Interests

Duan’s research interests include cancer genetics, the development of cell and animal 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. Duan has been involved in several universities, foundations, States, and NIH-funded research projects as both a principal investigator and co-investigator.

Area of Interest/Specialization

  1. 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 tumors harbors somatic genetic or epigenetic alterations resulting in defective FA homologous recombination repair.  We are performing genomic 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. 

  1. 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.  The KRAS 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. Mutations in TP53 and KRAS are common and oncogenic.  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 malignancies.  We investigated the PRIMA-1 in 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.   

KRAS G12C inhibitor AMG 510 (sotorasib) or MRTX849 (adagrasib) selectively reduced cell survival in lung cancer cells containing mutant KRAS G12C. Although it was reported the success in the treatment of lung cancer containing KRAS G12C mutation with these inhibitors, researchers have also observed that single agent of KRAS 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. 

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 lung specific transgenic 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 the 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 lung cancers, 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. 

Selected publications 

  1. Duan W*, Tang S, Gao L, Dotts K, Fink A,KalvalaA, Aguila B, Wang QE, Villalona-Calero MA. MiRNA-200C expression in Fanconi anemia pathway functionally deficient lung cancers. Sci Rep. 11(1):4420, 2021. PMID: 33627769 
  2. RamelowJ, Brooks C, Gao L,Almiman AA, Williams TM, Villalona-Calero MA, Duan W*. The oncogenic potential of a mutant TP53 gene explored in two spontaneous lung cancer mice models, BMC Cancer. 20(1):738, 2020. PMID: 32770960 
  3. Wesolowski R, Stover DG, Lustberg MB,ShobenA, Zhao M, Mrozek E, Layman RM, Macrae E, Duan W, Zhang J, Hall N, Wright CL, Gillespie S, Berger M, Chalmers JJ, Carey A, Balasubramanian P, Miller BL, Amaya P, Andreopoulou E, Sparano J, Shapiro CL, Villalona-Calero MA, Geyer S, Chen A, Grever MR, Knopp MV, Ramaswamy B. Phase I Study of Veliparib on an Intermittent and Continuous Schedule in Combination with Carboplatin in Metastatic Breast Cancer: A Safety and [18F]-Fluorothymidine Positron Emission Tomography Biomarker Study. Oncologist. 25(8):e1158-69.  2020. PMID: 32452601 
  4. Duan W*, Gao L,KalvalaA, Aguila B, Brooks C, Mo X, Ding H, Shilo K, Otterson GA, Villalona-Calero MA. Type of TP53 mutation influences oncogenic potential and spectrum of associated K-ras mutations in lung-specific transgenic mice. Int J Cancer. 145(9):2418-26. 2019. PMID: 30873587. 
  5. ArasadaRR, Shilo K, Yamada T, Zhang J, Yano S, Ghanem R, Wang W, Takeuchi S, Fukuda K,Katakami N, Tomii K, Ogushi F, Nishioka Y, Talabere T, Misra S, Duan W, Fadda P, Rahman MA, Nana-Sinkam P, Evans J, Amann J, Tchekneva EE, Dikov MM, Carbone DP.  Notch3-dependent β-catenin signaling mediates EGFR TKI drug persistence in EGFR mutant NSCLC. Nat Commun. 9(1):3198. 2018. PMID: 30097569. 

Complete List of Published Work