Two challenges scientists face in prostate cancer research are distinguishing indolent from aggressive tumors, and effectively treating late stages of the disease. Jindan Yu, MD, PhD, associate professor of Medicine-Hematology/Oncology, takes on these challenges using genomics and bioinformatics to better understand the progression of prostate cancer and to develop diagnostic tools and treatment strategies.
Since joining Northwestern University Feinberg School of Medicine as an assistant professor in 2009, Yu’s lab has published several studies including a recent paper in Nature Communications. She found that protein FOXA1 inhibits the function of androgen receptors and is a tumor suppressor under androgen-depleted conditions. Androgens are a group of hormones that play a role in male traits and reproductive activity.
Last year Yu won the Fifth Annual Early Career Professor Award from Agilent Technologies, a laboratory equipment company, for her outstanding potential for future research.
What are your research interests?
I am interested in understanding the molecular mechanisms underlying oncogenic progression. In particular, our research focuses on genomic and epigenomic regulations of prostate cancer. We work on how transcription factors, such as FOXA1, alter epigenetic modifications and regulate gene expression. A main emphasis is on how these proteins change the transcriptional program mediated by the androgen receptor, a critical driver of prostate cancer progression.
We utilize high-throughput approaches including next-generation sequencing techniques to map the genomic landscapes of transcription factors, histone modifications, DNA methylation or hydroxymethylation, and RNA methylations, and how these are disturbed by oncogenic factors. We are keen to understand how cancer initiation and progression are regulated at the systems level by examining genome-wide profiles. Through these approaches, we aim to pinpoint the most critical genes and pathways. We then use molecular and biochemical approaches to investigate changes in key signal transduction pathways and use functional assays and mouse models to determine how these perturbations lead to tumorigenesis.
What is the ultimate goal of your research?
Our goal is to identify novel cancer-specific events to understand the underlying molecular mechanisms and to translate these research findings from laboratory to the bedside for patient treatment. Through understanding the genomics and epigenomics of prostate cancer, we pursue translational research to define novel diagnostic/prognostic biomarkers by examining gene expression in primary specimens and determining their associations with clinical outcomes. By characterizing the essential oncogenic pathways of cancer, we investigate novel therapeutics strategies for the treatment of late-stage castration-resistant prostate cancer.
What types of collaborations are you engaged in across campus?
The environment at Feinberg and the Robert H. Lurie Comprehensive Cancer Center has cultivated a number of collaborations. I work closely with investigators of the prostate cancer SPORE program including William Catalona, MD, Timothy Kuzel, MD, Ximing Yang, MD, PhD, Sarki Abdulkadir, MD, PhD, Raymond Bergan, MD, Robin Leikin, PhD, and Chung Lee, PhD. These collaborations have already led to several publications and grants. Very recently, we together submitted a SPORE renewal application along with investigators from the University of Chicago and Northshore Health System.
In addition, there are frequent discussions and collaborations with the labs of the Division of Hematology and Oncology, including Jonathan Licht, MD, John Crispino, PhD, Marcus Peter, PhD, and Chonghui Cheng, MD, PhD, and with other investigators sharing common research interests, such as Debabrata Chakravarti, PhD, and Ann Harris, PhD. We also collaborate with Shad Thaxton, MD, PhD, for nanoparticle delivery of siRNA for prostate cancer treatment. Within the Northwestern environment, there are frequent discussions with many other investigators across campus, and new collaborations are continuously being formed, which are essential for the success of our research program.
How is your research funded?
Currently, my laboratory is funded by a National Institutes of Health R01 grant to study the role of tumor suppressor gene NOV in prostate cancer. Our research on androgen receptor and transcriptional regulation is supported by a Research Scholar Award from the American Cancer Society. Our epigenetic projects involving DNA methylation/hydroxymethylation and RNA methylation are funded, respectively, by a Department of Defense Idea Development Award and an Exploration-Hypothesis Development Award. My research is also actively supported by the prostate cancer SPORE grant and an Agilent Early Career Professor Award.
Who are your mentors?
I am very fortunate to have had many great mentors over the years. I did postdoctoral training in the laboratory of Arul Chinnaiyan, MD, PhD, at the University of Michigan, where I learned the skills essential for my work today. I am deeply touched by his passion for translational cancer research and am truly inspired by the way Dr. Chinnaiyan does science, manages his team, and interacts with colleagues. He is my role model and life-time mentor.
I was also extremely fortunate to have Jonathan Licht, MD, as my current mentor. I am always amazed by the broad knowledge and seemingly endless energy Dr. Licht has. His high enthusiasm for science is almost contagious to me. We share common interests in genomic and epigenomic research, and discussions with Dr. Licht have always been constructive and inspiring. It is safe to say that I would not be where I am today without these two critical mentors.