Welcome to the Winn Research Lab

Lung cancer is the leading cause of cancer deaths worldwide with non-small cell lung cancer (NSCLC) attributing to many of the cases diagnosed (90%). Despite advancements in the area of surgery, chemotherapy, and radiotherapy, the five-year survival among lung cancer patients is less than 15%. Smoking has always been at the forefront in the field of lung cancer and more than half of those diagnosed with cancer are former smokers. Despite smoking cessation programs, the increased risk developing lung cancer among this population remains high throughout one's lifetime, emphasizing the need for more effective and novel molecular therapies for this at-risk population.

The Winn Lab goals are to understand the molecular basis of signaling pathways and mechanisms by which oncogenes and tumor suppressors regulate tumor initiation and tumor progression in animal and human models of lung cancer. The studies, using cutting edge techniques, are translational in nature to garner information in hopes to identify novel lung cancer biomarkers to develop new therapeutic treatments. In addition to the basic science, the lab is also interested in racial disparities surrounding lung cancer by defining the genetic, proteomic, and metabolomic differences among various racial/ethnic groups with differing survival outcomes related to lung cancer.

The Winn Lab has been fortunate to have continuous funding through the NIH and Veterans Affairs and fosters many collaborations among various institutions at the national and international level.

The Role of Wnt7A in Lung Cancer

Wnt7AThe dysregulation of the canonical and non-canonical Wnt signaling pathways has been a common theme in many types of cancers, most notably mediated by the stabilization of β-catenin in the canonical pathway to drive tumor progression. Several Wnts have been shown to be upregulated in Non-Small Cell Lung Cancer (NSCLC) tissue and cell lines. However, we were the first to identify that Wnt7A was downregulated in lung cancer and played a critical role in the maintenance of normal epithelial phenotype, independent of β-catenin. It is through a seven-transmembrane receptor, Frizzled-9, that Wnt7A reverses epithelial-mesenchymal-transition and transformed cell growth, re-establishes cellular polarity, and targets downstream tumor suppressor genes such as PPAR-gamma and Sprouty-4. We have also identified that Wnt7A is methylated in a subset of lung tumors and involved in cellular arrest through the targeting of genes involved in the senescence pathway. We continue to expand our research on this novel role of Wnt7A and explore its value as a possible future therapeutic approach for the treatment of lung cancer. Towards this end, we are currently testing the efficacy of Wnt7A in reducing lung cancer progression using the form of a small molecular nanoliposome in our in vivo lung tumor models and lung cancer patient-derived organoids.

The Role of KH-Type Splicing Regulatory Protein (KSRP) in Lung Cancer

KSRPAU-rich elements are found in transcripts encoding proteins that regulate inflammation, transcription, cell proliferation, RNA metabolism, development, and cellular signaling; all of which play important roles in tumorigenesis. KSRP is an AU-rich element RNA binding protein that specifically binds and recruit's RNA decay machinery to ARE-containing transcripts, thereby, targeting them to degradation. Our laboratory was the first to define a novel role for KSRP in lung cancer. It is robustly upregulated in lung cancer patient samples and promotes cell proliferation, migration/invasion, and transformed cell growth in NSCLC cell lines. We have demonstrated that mutations in the KRAS oncogene results in upregulation of KSRP and that deletion of KSRP reduces lung tumor burden in a KRAS mutation-induced lung cancer model. Our goals for this project are: 1) elucidate the mechanisms of KSRP upregulation by mutant KRAS, 2) identify KSRP targets in lung cancer and 3) identify small molecule inhibitors of KSRP. These studies will lead to potential therapeutics for lung cancer patients with KRAS mutations by inhibiting the functions of KSRP.

The Role of Potassium Voltage-Gated Channel Modifier Subfamily F Member 1 (KCNF1) in lung cancer

KCNF1Voltage-gated potassium (Kv) channels regulate cell excitability and cell proliferation. Expression of Kv channels is dysregulated in many types of tumors including lung cancer, leading to the interest of targeting them in cancer patients. Ion channels have been extensively studied in cancer biology where the potassium ion channel family has long been known to have altered expression in lung tumors. However, past attempts of treating cancer with various potassium ion channel-blocking agents have proven to be disappointing, as most of these inhibitors directly or indirectly affect the electrophysiological properties of excitable cells, e.g. myocytes and/or neurons, which are crucial to the functions of the cardiac and nervous systems. Our laboratory discovered an increased expression of a unique “electrically silent” Kv channel, (KCNF1), in lung cancer. We demonstrated that KCNF1 drives transformed cell growth and is important to maintain the basement membrane integrity of NSCLC cells. Our goals for this research are: 1) identify the mechanism of how KCNF1 functions in the lung, 2) identify KCNF1 targets in lung cancer and 3) identify small molecule inhibitors of KCNF1. These studies will lead to potential therapeutics for lung cancer patients by inhibiting the functions of KCNF1.

About Dr. Robert A. Winn

VCUSOM About Dr. Robert A. Winn

About Dr. Robert A. Winn

Dr. Winn is an accomplished physician-scientist and a champion of the “bench to community” model in underserved communities. For over a decade, Dr Winn has worked tirelessly to bridge the gap between basic science and community-based health care. He has received national and international acclaim for his efforts to empower underserved patient populations, improve health care delivery, and ensure equal access to cutting-edge medical treatments for all. His basic science research, which has been supported by multiple NIH and VA Merit awards, focuses on the translational aspects of the Wnt Pathway, RNA-binding proteins, and electrically silent-ion channels in lung cancer. As a result of his scientific efforts, Dr. Winn has published over 60 manuscripts and 5 book chapters. His expertise in the field of lung cancer has landed him a seat on several scientific review committees, including Molecular Oncogenesis and Cancer Molecular Pathobiology study sections at the NIH.  (read more)

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Ching-Yi Chen, PhD

Ching-Yi Chen, PhD

Associate Professor

Ching-Yi Chen, PhD

Ching-Yi Chen, PhD

Associate Professor

Massey Cancer Center

Email: chingyi.chen@vcuhealth.org

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Michelle Van Scoyk

Michelle Van Scoyk

Lab Manager/Senior Lab Technician

Michelle Van Scoyk

Michelle Van Scoyk

Lab Manager/Senior Lab Technician

Massey Cancer Center

Email: michelle.vanscoyk@vcuhealth.org

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Priyadarshan Damle, PhD

Priyadarshan Damle, PhD

Instructor

Priyadarshan Damle, PhD

Priyadarshan Damle, PhD

Instructor

Massey Cancer Center

Email: priyadarshan.damle@vcuhealth.org

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Chu-Fang (Herman) Chou, PhD

Chu-Fang (Herman) Chou, PhD

Senior Research Scientist

Chu-Fang (Herman) Chou, PhD

Chu-Fang (Herman) Chou, PhD

Senior Research Scientist

Massey Cancer Center

Email: chufang.chou@vcuhealth.org

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Pei-Ying (Maggie) Wu

Pei-Ying (Maggie) Wu

Senior Lab Technician

Pei-Ying (Maggie) Wu

Pei-Ying (Maggie) Wu

Senior Lab Technician

Massey Cancer Center

Email: peiying.wu@vcuhealth.org

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Stephanie Simko

Stephanie Simko

Lab Specialist (In-vivo models)

Stephanie Simko

Stephanie Simko

Lab Specialist (In-vivo models)

Massey Cancer Center

Email: simkos@vcu.edu

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Dr. Winn’s complete bibliography at MyNCBI:

https://www.ncbi.nlm.nih.gov/myncbi/robert.winn.1/bibliography/public/

Michelle Van Scoyk
Lab Manager/Senior Research Scientist
Massey Cancer Center
Phone:  (804) 827-1158
Email:  michelle.vanscoyk@vcuhealth.org

Lindsey Paisley
Executive Assistant
Phone:  (804) 628-1897
Email:  lindsey.paisley@vcuhealth.org