Our research program can be broadly divided into four main projects:
- 1. Circulating Tumor DNA (ctDNA)
We are interested in developing and testing novel methods for detection of circulating tumor DNA in the blood of cancer patients. As tumors grow, a subset of cancer cells die and release some of their genetic material into the blood where it can be non-invasively sampled.
In collaboration with the laboratory of Dr. Ash Alizadeh we have developed a novel method for detecting circulating tumor DNA called CAncer Personalized Profiling by deep Sequencing (CAPP-Seq). CAPP-Seq is extremely sensitive and specific and was designed to apply to the vast majority of patients with a given cancer type, without the requirement for patient-specific optimization. Due to Dr. Diehn’s interest in lung cancer, we initially implemented CAPP-Seq for non-small cell lung cancer (Newman/Bratman et al. Nature Medicine 2014) but have since extended it to a variety of other tumor types.
In ongoing work we are further improving CAPP-Seq and other approaches for detection of ctDNA. Additionally we are working on clinical trials to establish the clinical utility of ctDNA detection in a variety of cancer types. Finally, we are exploring the use of ctDNA for early detection or screening of cancers.
- 2. Normal and Cancer Stem Cells
One of the major focuses of the Diehn lab is cancer stem cell biology and its implications for cancer therapy. We are interested in developing a deeper molecular understanding of cancer stem cells, including identifying pathways and genes important for proliferation and self-renewal. We also study these processes in normal adult stem cells in order to identify differences that could be exploited therapeutically. Additionally, we are interested in analyzing and overcoming resistance mechanisms to radiotherapy and chemotherapy in cancer stem cells. The overarching goal of our studies is the development of novel therapeutic strategies for eliminating cancer stem cells in the clinical setting. Our work in this area is focuses on lung, breast, and gastrointestinal cancers. In order to translate our discoveries into the clinic, we are leading clinical trials testing therapeutic strategies that have been shown to specifically target cancer stem cells in pre-clinical studies.
- 3. Predictive and Prognostic Biomarkers
In addition to our work on circulating tumor DNA we are developing other biomarkers that can either predict response to therapy (i.e. predictive) or patient survival (i.e. prognostic). In this work we employ emerging technologies such as next generation sequencing and single cell gene expression analysis. In addition to molecularly-based biomarkers, we are exploring imaging-based biomarkers using existing or novel imaging modalities.
- 4. Clinical Research
Dr. Diehn leads an active clinical research program with a focus on lung and breast cancer. This includes investigator-initiated prospective trials, population-based comparative effectiveness studies, and retrospective analyses.