Interview with Bodhour Salhia, PhD, Assistant Professor of Translational Genomics, Keck School of Medicine of USC

Q: How did you find out about the Komen Tissue Bank, and why did it interest you?

Honestly, I leaned of the KTB from performing a google search while I was looking for plasma samples.

Q: What types of samples have you obtained from the Komen Tissue Bank?

We obtained a unique set of samples from the KTB. We were specifically interested in plasma to perform a study that would allow us to identify circulating DNA methylation biomarkers of breast cancer recurrence. Our cohort of 120 plasma samples from women who were healthy, who had a history of breast cancer but were in remission or who had stage IV breast cancer.

Q: What do you hope to discover/have you discovered in your research? (Reader, please note: a “layman’s explanation” can be found later in the interview, if you find this response too technical to easily comprehend)

Metastatic breast cancer (MBC) is an incurable disease, affecting 10-15% of breast cancer patients, and is often refractory to therapy. Since tumor tissue is not always available after therapy is complete, there is a need for biomarkers that can be monitored noninvasively such as from blood to measure risk of recurrence due to microscopic metastatic residual disease. Numerous studies suggest that DNA methylation could be a useful biomarker for improving the clinical management of disease. Recently circulating cell-free (cf) DNA has attracted attention for clinical use in the context of risk prediction, prognostication and prediction of response to chemotherapy in human cancer and several groups have now reported the detection of tumor-associated DNA methylation patterns in plasma or serum. We identified by whole genome bisulfite sequencing hypermethylation of 21 CpG islands (CGI) in plasma of MBC compared with disease free survivors or healthy cases. Our hypothesis is that a 21-gene DNA hypermethylation signature involving rationally selected hotspots detectable in circulation can be used to detect micrometastatic disease at the end of therapy in patients with early stage breast cancer. We are working hard to validate these findings and to making this a test that doctors can use to manage care for breast cancer patients.

Please see the link to our paper we published for more details: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573288/

Q: How will the Komen Tissue Bank samples help with your research? What value do they add?

The samples we obtained for KTB were essential to our study and goal of identifying predictive biomarkers of breast cancer recurrence. Without them we wouldn’t have been able to complete this study in the time we did because of how difficult these samples would have been to obtain if we had to collect them prospectively. This is especially true since when I started this work I was not affiliated to a medical center. So we are most grateful to the KTB for these important samples that made our study possible.

Q: Please explain in lay terms how your research might impact treatment options for BC patients in the future?

Metastatic breast cancer (MBC) is an incurable disease, affecting 10-15% of breast cancer patients, and is often refractory to therapy. Current risk assessment criteria are still unable to define which patients will have a recurrence at the end of the most effective therapies. A blood test to detect mircometastatic disease would be advantageous at the time of surgery and/or after the completion of chemotherapy to indicate patients with residual metastatic disease who are likely to recur and could benefit from additional therapy. We used KTB plasma samples to make initial discoveries for non-invasive approaches for detecting recurrence before it happens.

Q: Our readers would love to know some personal information about you. What would you like to tell us?

I love to travel. A great perk about being a scientist is that it allows you to travel for meetings and conferences. Among some of the most exotic and favorite places that I have visited are Egypt, South Africa, Hawaii, Scotland and India. I have a little girl who will be turning five in May. She loves dinosaurs but I am already teaching her human anatomy! I have a fear of falling and downward acceleration but I don’t have a fear of heights. So I am deadly afraid of skiing but I got my glider pilot’s license when I was 16. Actually…I’m also afraid of skating as well as skiing, so maybe that’s a phobia about gliding on my feet??!

Interview with Michael Wendt, PhD, Assistant Professor Medicinal Chemistry and Molecular Pharmacology, Purdue University College of Pharmacy

Q: How did you find  out about the Komen Tissue Bank, and why did it interest you?

I was made aware of the KTB through the Indiana Clinical and Translational Science Initiative (CTSI) annual retreat several years ago.

Q: What types of samples have you obtained from the Komen Tissue Bank?

We have obtained breast biopsies and plasma samples through the KTB.

Q: What do you hope to discover/have you discovered in your research? 

Our lab is working to the development of Fibroblast Growth Factor Receptor (FGFR) as a novel target for breast cancer therapy. While several excellent drugs have been developed to inhibit the activity of this receptor, it is unclear which breast cancer patients would most benefit from this therapy. We are investigating the function of a specific versions or isoforms of the receptor called FGFR1-a and FGFR1-b . This is important because while FGFR1-b supports tumor growth FGFR1-a may actually be a tumor inhibitor. By obtaining 100 normal breast samples we have been able to establish that expression levels of FGFR1-b increase with age. This is variable that we now know to consider when developing FGFR1-b as a diagnostic for the application of inhibitor therapies.

Q: How will the Komen Tissue Bank samples help with your research? What value do they add?

Normal samples are critical in our study and other studies to set baseline control levels of factors being evaluated. This is often a major hurdle in biomarker or diagnostic development. Furthermore, as described above the annotated data that comes along with KTB tissue samples allows us to make demographic insights that are not possible through laboratory studies or with other tumor tissue banks.

Q: Please explain in lay terms how your research might impact treatment options for BC patients in the future?

As anticancer drugs become more and more specific we are avoiding the toxic side effects of general chemotherapy. However, with the increased specificity of these drugs we need to understand more about which specific patients are most likely to benefit from them. We are working to establish biomarkers that will predict patient response to a developing class of drugs that target a specific growth factor. To do this it is imparitive that we first understand the expression levels of these biomarkers in normal patients.

Q: Our readers would love to know some personal information about you. What would you like to tell us?

I grew up in Wisconsin where I developed an inherent interest in figuring out how things around me worked, which ended up in several dismantled bikes, radios and car parts. In college, I melded these interests into my curiosity for the natural world graduating with a bachelors degree in biology from St. Norbert College in 2002. After completing my graduate studies in Molecular genetics at the Medical College of Wisconsin in 2008, I became an American Cancer Society fellow with Dr. William Schiemann at the University of Colorado Cancer Center. In 2010 I moved with the Schiemann lab to Case Western Reserve University Cancer Center where I received a K99/R00 faculty transition award from the National Cancer Institute. I joined the faculty of Purdue University as an Assistant Professor in 2014,  and my work is currently supported by a Research Scholar grant from the American Cancer Society and an R01 from the Nation Cancer Institute. When I’m not in the lab I enjoy spending time with my wife, Becky, and our two children Maya and Isaac. I try to stay active by gardening and playing softball and basketball in local recreational leagues. I also indulges my creative side through music by playing the guitar and the banjo.