Riggins Lab Website

Welcome to the Riggins Lab! Our vision is that innovative treatment strategies for breast and brain cancer will be informed by strong basic science grounded in molecular mechanistic studies. Our lab’s mission is to translate our knowledge of the functions of orphan and ligand-regulated nuclear receptors, and other molecules of interest, into actionable therapeutic approaches. We are conscientious, rigorous and collegial members of our scientific communities. We are committed to sharing our data, resources, and expertise to the fullest extent possible, and we are dedicated to ethical and reproducible research.

Please see our Lab Manual for more about who we are and how we work.

Lab logo credit: Sarah Riggins

What we study and why

Glioblastoma (GBM)

Glioblastoma (GBM) is the most commonly diagnosed brain cancer in adults and has an overall survival rate of about one year. Our lab studies the protein estrogen related receptor beta (ERRβ), higher expression of which is associated with significantly longer overall survival in GBM patients. ERRβ has three distinct splice variants: short (βsf), long (β2), and exon 10-deleted (∆10). Two of these – short (βsf) and long (β2) – can have different effects on a cell’s ability to divide into two cancer cells. The long (β2) splice variant appears to be a more effective suppressor of cancer cell division and it localizes to centrosomes, which are essential for proper cell division. We are actively studying the role β2 plays at the centrosome and how it may cooperate with other centrosomal components, like the actin binding protein cortactin, to influence the ability of GBM cells to divide, migrate, and invade.

Invasive Lobular Breast Carcinoma (ILC)

Approximately 70% of breast cancers express estrogen receptor α (ER) and cancers that are ER-positive are often successfully treated with either aromatase inhibitors (AI) or Tamoxifen (TAM). However, approximately half of women treated with these therapies will go on to relapse either on or following therapy, a process defined as endocrine resistance. One way to classify breast cancer is their histology, or the way they look under a microscope. Invasive ductal carcinoma (IDC) is a more common breast cancer that grows as a solid mass while invasive lobular carcinoma (ILC) grows as lines of cells through normal tissue making them more difficult to detect by mammography or palpation. Additionally, recent evidence suggests patients with ILC have increased TAM resistance compared with IDC. Despite apparent differences between IDC and ILC, there are currently no ILC specific treatment options available. We are currently studying how nuclear receptor signaling differs in endocrine resistant ILC, specifically focusing on glutamate signaling and estrogen related receptor gamma (ERRγ).

HER2+/ER+ Breast Cancer

Breast cancers are classified by receptor status, but 50-60% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers also express the estrogen receptor (ER+) and therefore do not fit neatly into this paradigm. Anti-HER2 therapies are less effective in HER2+/ER+ tumors. Combination therapy with HER2- and ER-targeted treatments does not significantly improve outcome, suggesting that a subset of these tumors is also relatively resistant to inhibition of ER. The molecular mechanisms which drive poor treatment response in this ‘double positive’ context are not fully understood. We propose that HER2+/ER+ breast cancer has a distinct tumor biology driven by heterogeneity of estrogen receptor (ER) expression and signaling, and this is directly responsible for resistance to targeted therapies for both receptors.

Triple Negative Breast Cancer (TNBC)

One way breast cancers are classified is whether the tumor expresses certain proteins called receptors, as measured by immunohistochemistry. Triple negative breast cancer (TNBC) is defined by the lack of expression of hormone receptors- estrogen receptor α (ER) and progesterone receptor (PR) - and human epidermal growth factor receptor 2 (HER2), and as a result patients with TNBC do not respond to molecularly tailored therapies that target these receptors. TNBC is the most aggressive subtype of breast cancer, accounting for 12-15% of all cases, with a five-year survival rate that is significantly shorter than receptor-positive breast cancer. TNBC also disproportionately affects African American women. Since systemic chemotherapy is the only course of treatment, there is a great need to develop better, targeted treatments with less toxicity. Preliminary data in our lab suggests that expression of the orphan nuclear receptor, estrogen-related receptor beta (ERRβ), is associated with significantly better overall- and recurrence-free-survival in TNBC. We are currently studying the the function of ERRβ in TNBC, and determining its mechanism of action in normal versus cancer cells.

Who we are

Dr. Riggins received a B.A. in Biochemistry from Hood College, and a Ph.D. in Microbiology from the University of Virginia. Following postdoctoral fellowship training in Tumor Biology at Georgetown University, she joined the Department of Oncology at Georgetown University Medical Center’s Lombardi Comprehensive Cancer Center, where she is an Associate Professor and member of the Breast Cancer Research Program.

Learn more about members of the lab in People!