Louise C. Showe, Ph.D.

The Showe lab has been a pioneer in the development of cancer biomarkers from blood. In 2009, they published novel findings showing how mononuclear white blood cells (PBMC) from lung cancer patients contain a 29-gene, tumor-relevant gene signature that accurately predicts whether a lung nodule detected by CT scan is benign or malignant. They also demonstrated that information in blood gene expression patterns could predict patient survival and inform further treatments. In moving these studies forward to a clinical application, the lab has adopted a simplified and standardized blood sample collection using commercially available PAXgene RNA stabilizing tubes and successfully moved their assay from the developmental microarray platform to the to the clinically approved Nanostring nCounter platform, (Kossenkov et al, 2019). The technology has been patented and is in development for commercialization.

Ongoing effort: As part of the NCI Early Detection Network, the lab is developing new methods to detect and diagnose cancers early, when they are more easily and successfully treated, and new methods to predict recurrence/survival after treatment. This is a collaborative study with investigators at The University of Pennsylvania, Roswell Park, NYU, Temple University, The Helen F. Graham Cancer Center, NYU Medical Center, Meridian Health, N.J. and the Barzilai Medical Center, Israel.

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of non-Hodgkin lymphomas with characteristics of “skin-homing” T lymphocytes. The most common forms of CTCL are the skin-associated mycosis fungoides (MF) and a more aggressive leukemic form, Sezary Syndrome (SS). SS has been the focus of the laboratory studies. Early interest in this cancer was based on the observation that patients were severely deficient in the production of interleukin 12, a cytokine originally identified and characterized at The Wistar Institute, and on availability of a unique collection of patients being treated at the University of Pennsylvania Department of Dermatology. Based on initial studies, Showe was awarded one of the first National Cancer Institute Director’s Challenge grants to develop molecular diagnostics for CTCL using microarray platforms. This study led to the identification of a small number of genes that could detect SS by microarray or Q-RTPCR. The lab also identified some new specific cellular defects and a signature of poor prognosis that was independent of stage or circulating malignant cell numbers.

Ongoing studies: in collaboration with clinicians at the University of Pennsylvania (Alain Rook and Ellen Kim), Columbia University (Susan Bates) and NCI (Richard Piekarz), present work focuses on understanding mechanisms of therapeutic response both in vitro and in vivo to combined treatments such as toll-receptor agonists and interferon as well as histone deacetylase inhibitors. Combining data from gene and microRNA expression produced using microarrays and next-generation sequencing, the lab is defining parameters that distinguish responders from non-responders and markers of residual disease that can be monitored to detect potential recurrences before they are clinically evident. Using single cell analysis, the team is probing malignant cell heterogeneity and therapeutic response.

Glioblastoma multiforme (GBM) is the most common and severe form of primary malignant brain cancer. GBM is an aggressive cancer with no effective treatments and the median survival time is only 15 months from diagnosis. GBM is a heterogenous tumor having multiple disease subtypes, so it is important for clinicians to understand how these various GBM subtypes respond to emerging therapies that may one day be useful to glioblastoma patients.

Building on collaborative studies initiated with Ramana Davuluri and Donald O’Rourke, the Showe lab is developing a diagnostic platform to help classify GBM tumor subtypes to match to more efficacious treatments.

In a long-term collaboration with the lab of Luis J. Montaner at Wistar, the Showe lab applies functional genomic approaches to understand mechanisms of immune evasion in HIV infections and explore new ways to manage current HIV-1 infections, including the possibility of using immune-mediated control of virus infection upon interrupting drug therapy. Additional studies have focused on developing biomarkers to assess secondary infections, such as tuberculosis, in the presence of an active HIV infection. Showe is a co-Investigator on the BEAT-­HIV Delaney Collaboratory grant to continue these studies.

In collaboration with Cris Constantinescu at The University of Nottingham, UK, the Showe laboratory is examining gene expression profiles in blood and tissue samples from multiple sclerosis patients involved in clinical trials with immuno-modulatory drugs. The aim is to determine whether it is possible to identify gene expression patterns that correlate with responsiveness and non-responsiveness to therapy and to better understand disease initiation and progression.

Studies in collaboration with Hildegund C.J. Ertl at Wistar have examined gene expression changes in young and aged populations as a function of flu vaccination to try to understand the poorer responses to vaccinations in general and in the elderly population in particular. In addition, potential effects of race and timing of repeated vaccination on response were examined. Additional studies using mouse models have explored protocols that increase vaccine response with the potential benefit of improving vaccine efficacy in the growing elderly population.