BBI Faculty Conversations: Dr. Tina Lockwood

BBI Faculty Conversations: A recurring profile of BBI members from our partner institutions: UW Medicine, The Fred Hutchison Cancer Research Center, and Seattle Children's.

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BBI: How has your work and career been guided and impacted by precision medicine?

Dr. Lockwood: I’m fortunate to interact with several different areas of precision medicine. As an academic medical center actively invested in research, UW is always trying to make new discoveries and innovate. Our operations are able to be nimble, with strong partnerships between our cutting-edge research labs and our clinical labs. The space I occupy is focused on that jump, translating research work into clinical practice, and helping those innovations actually reach patients.

Our innovation in non-invasive prenatal screening is a nice example of how our academic medical center is innovating in precision medicine. Cell-free DNA prenatal testing involves using a blood draw from the mother to assess for chromosomal copy number abnormalities in the fetus. The sequencing capabilities for fetal DNA in maternal blood had been fairly well established previously, but we made important advancements on the informatics side. Early in pregnancy, mom doesn’t have very much cell-free DNA coming from the placenta in her blood. We needed to find ways to develop custom methods to make early testing reliably predictive. We developed new algorithms to be able to accurately detect abnormalities in very low fetal fraction samples using low-pass whole genome sequencing. These tests help us non-invasively detect fetal abnormalities, such as Trisomy 21, early in pregnancy.

BBI: Related to your cell-free DNA work, what are the latest updates on your co-leadership of the BBI Cell-free DNA Working Group?

Dr. Lockwood: Aside from continuing to invest in low-pass whole genome sequencing to assess copy number alterations, we are next looking to tests with very high sensitivity for mutation detection. These tests look for very low abundance genetic variants that you can detect in blood plasma. Most people see this area of testing as being of highest utility in cancer diagnosis and treatment by sampling for fragments of tumor-derived DNA in a patient’s blood.

There are many other intriguing possibilities for this line of testing, however. For example, we are working with Dr. Andrew Stacey at Seattle Children’s to identify retinoblastoma, a pediatric cancer, during pregnancy. To illustrate the impressive sensitivity needed for this testing, this test would look for a cancer-causing mutation in a single gene in the fetus, using only small pieces of circulating fetal DNA in a blood draw from the mother.

BBI: How has BBI assisted you in this work?

Dr. Lockwood: For the example I mentioned previously, the BBI Cell-Free DNA Working Group is facilitating the identification and funding of these projects that are continually helping us push the envelope in cell-free DNA research in ways that are often of immediate clinical value to our patients.

More generally, BBI is helping us break down barriers between our research institutions. It not only facilitates us working across institutions, it incentivizes it. This has many downstream effects, because the seed funding that BBI provides for innovative projects helps new ideas to gain leverage for further funding from other sources.

BBI: Given your perspective on the field, where do you see your research, and precision medicine in general, heading in the next 10-20 years?

Dr. Lockwood: Taking cancer as an example, there is no reason molecular technologies should not be able to identify individual cancer predisposition that can direct appropriate health surveillance. Technologies such as cell-free DNA will absolutely be used in the near future for cancer screening, and it will help reduce the number of late-stage cancer diagnoses. Of course, the next step is to further develop gene editing techniques that may one day help us fix the genetic abnormalities once they are identified. I think both lines of research will mature by leaps-and-bounds in the next 10-20 years.

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