Project Name:  Role of Foxa1 Binding Partners in Androgen Regulated Prostate Cancer

 

Transcription factors act as the molecular "engines" that drive cell behavior. In our laboratory, we study how these molecular engines drive prostate and bladder cancer to a lethal stage.

  1. In prostate cancer, we are exploring ways of shutting these engines down to kill tumors and prevent cancer progression and spreading, or metastasis.

    • We will identify exactly how these engines promote cancer growth and spreading.

    • We will test the influence of eliminating these engines on cancer growth and spreading.

    • These aims will be explored through tissue recombination assays and other experiments involving systems which mimic the biology of the prostate organ. Tissue recombination assays involve mixing tissue samples with components whose transcription factors have been altered, growing the tissues in mice, and then analyzing them to see the impact of variously altered tissues on cancer growth and spreading.

  2. In bladder cancer, we are working to find molecular engines which indicate the presence of the deadliest cancers. This is because it is currently difficult for physicians to determine which patients will face the most deadly form of bladder cancer. Identification of these molecular engines may provide us with a new diagnostic test that will help physicians’ better treat, and potentially cure patients.

    • We will explore the correlation between these molecular engines and clinical outcome by staining 300 bladder cancer tissue samples to screen the samples for specific proteins. Because these particular tissue samples are all linked to patient outcome information, we will be able to see the correlation between the presence of these proteins and overall survival and overall disease-free survival. This may lead to the ability to predict which patients are or are not likely to survive longer, and which cancers are or are not likely to recur faster. This information will contribute to the ability to make decisions about the best way to treat future patients whose tumors resemble the ones represented among our 300 samples.

    • We will also work to identify how these molecular engines promote the malignant behavior of bladder cancer through tissue recombination assays (described above).

Summer 2018 Update from Dr. DeGraff: I am an Assistant Professor in the Departments of Pathology, Surgery, and Biochemistry and Director of Urologic Research for the Division of Urology at the Pennsylvania State University College of Medicine in Hershey, PA. The overall research goal of the DeGraff laboratory is to develop an increased understanding of how transcriptional regulation contributes to tissue and molecular heterogeneity, as well as adverse clinical outcomes in bladder cancer. My laboratory has been consistently funded by the American Cancer Society, the National Cancer Institute and the Bladder Cancer Advocacy Network since my arrival at Penn State. Funding support from these entities and others have supported work which is identifying the foundational events for gene expression changes during bladder cancer progression. The short-term goal of these studies is to enhance our ability to identify the most suitable patients for a given therapeutic intervention.

 

Summer 2019 Update from Dr. David DeGraff: Dr. DeGraff continues to serve as Director of Urologic Research within the Department of Surgery at Pennsylvania State University College of Medicine. He has received numerous awards and honors, including the 2018 Best Overall Professor Award from the Penn State College of Medicine Graduate Student Association, as well as the Junior Faculty Teaching Award (Basic Science Educator) from the Penn State Hershey Society of Distinguished Educators. He serves in editorial positions for numerous journals, and serves on several peer review panels, study sections, and Penn State medicine and educational committees. Five current grants support Dr. DeGraff’s research on bladder cancer, with several other grants and clinical trials pending. Dr. Degraff continues to publish articles on his work and to participate in other scientific communications, panel discussions, and conferences.

 

Dr. DeGraff mentors dissertation and rotation students, in addition to his teaching responsibilities.