By Leo Barolo
Most scientists end up leaving their alma mater to do research or complete their studies elsewhere. While they remain Badgers forever, some are lucky enough to come back as faculty and live the other side of the Wisconsin Experience.
Dr. Jessica Lang is doing just that. Having trained at UW-Madison for both her undergraduate and graduate degrees, after seven years away, Dr. Lang has returned to UW-Madison as an Assistant Professor in the Department of Pathology and Laboratory Medicine and as a member of the Center for Human Genomics and Precision Medicine.
Dr. Lang’s translational research is focused on the role of mutations in chromatin modifiers in ovarian cancer. Mutations in the SWI/SNF complex contribute to a substantial number of cancer cases, presumably by remodeling chromatin and, in turn, transcription to drive proliferation and metastasis. Her work is using cutting-edge techniques in epigenetics to understand the etiology of disease and vulnerability to therapeutics in cancer patients. A major goal of her work is to generate new insights that will improve the outcomes for ovarian cancer patients.
As Dr. Lang returns to the place where she received her degrees, we asked the newly appointed Assistant Professor a few questions:
Where are you from originally?
I am from Neenah, WI, which is about 2 hours NNE of Madison.
What is your educational trajectory?
I knew in high school that I wanted to work in cancer research. I went to the University of Wisconsin-Madison as an undergrad and majored in Genetics. I continued at the UW-Madison in the Cancer Biology graduate program, where my thesis work in Dr. Elaine Alarid’s lab focused on the contributions of extracellular signaling from the tumor microenvironment influences breast cancer growth and hormone therapy response. Upon graduating with my PhD, I moved to Phoenix, AZ, where I first worked as a postdoctoral fellow in Dr. Raymond DuBois’s lab at Arizona State University studying inflammation and colorectal cancer, then with Dr. Jeffrey Trent at the Translational Genomics Research Institute (TGen), focusing on the role of SWI/SNF chromatin remodeling defects in a rare form of ovarian cancer.
What is the main topic of your research program?
My research program has a strong translational research focus in ovarian cancer, where we hope to learn more about how mutations to epigenetic regulator genes, such as SWI/SNF chromatin remodeling complex subunits that are inactivated in nearly 20% of all human cancers, lead to altered enhancer and super-enhancer landscapes. We approach this with application of newer technologies, such as ECCITE-seq, to target individual super-enhancer regions directly with a functional readout. We also employ drug treatment models including organoids and PDX models, as well as validate findings from cell lines in clinical specimens. The big picture is that we want to identify key prognostic or diagnostic markers from the epigenetics perspective that might bring more effective and targeted therapies to ovarian cancer patients, who currently lack specific options and face some of the most dismal survival rates.
What led you to get interested in this area?
I studied epigenetics early on as an undergraduate in Dr. David Jarrard’s lab, where I supported projects related to imprinting in prostate cancer. I also developed a strong desire to work in women’s cancers as a graduate student in Dr. Elaine Alarid’s lab. While at TGen under the direction of Dr. Jeff Trent, I led studies on therapeutic vulnerabilities conveyed by SMARCA4 loss in a rare form of ovarian cancer, small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). Dr. Trent’s lab had just discovered the loss of SMARCA4 by biallelic mutation to be the driving event for nearly every patient examined. I became very interested in how the chromatin remodeling defects that resulted, in particular super-enhancer regions, alter the biology of these genetically simple tumors, and how this might extend to more genomically complex subtypes of ovarian cancer.
Is there a single person or experience that most influenced your trajectory to where you are today?
There have been so many influential people along my career–too many to name. My dad had one of the most important influences on me early on. Not only did he generally instill a drive for academics and learning beyond my school requirements, but he really enjoyed working with me on school projects. In fact, he still has my first scientific poster in his basement: a science fair poster from when I was in kindergarten!
How does it feel to come back to UW-Madison? What are you most excited about with your return to UW?
Coming back to UW-Madison really feels like coming home. I’m very excited to work alongside many of the esteemed faculty I looked up to as a student. There are many great resources on campus for my research, including the OB/GYN department and their clinicians, expertise in genetics across campus, and new big data infrastructure. I’m very excited to be part of the new Center for Human Genomics and Precision Medicine in particular. Outside of research and academics, I have missed the beauty of Wisconsin, the seasons (come ask me about that in the winter though), and being closer to family.
Dr. Lang is currently setting up her lab in the WIMR West Wedge building within the Center for Human Genomics and Precision Medicine.