1. Can proteins that alter the genetic landscapes of B cells cause malignancies?
Yes. AID (activation-induced cytidine deaminase), for example, is a DNA deaminase that catalyzes a process that results in mutations in the B cell genome that is critical to generate a broad array of antibodies. AID can have off target effects that may promote malignancy and cause lymphomagenesis. Unfortunately, we cannot therapeutically target AID because AID is needed for an effective immune response.
2. In your opinion, what has been the most important advancement in the field in the last five years?
Genome editing. The ability to modify the genome, any genome for any given cell, and then go back and deconstruct to see the importance of a particular sequence of a binding site or of a particular region. From using zinc finger protein to using TALEN (Transcription Activator-Like Effector Nucleases) and more recently the CRISPR/Cas9 system to edit genome, I think it has definitely become the way forward.
3. So you see genome editing being used not just to understand biology, but also as a clinical application in the future?
Absolutely. It has been done already at various levels using different approaches, with different levels of success. Basic research is very important, but the holy grail is to be able to cure patients. I think this field is aiming for more from-bench-to-bedside research. The idea is to get cells from a specific patient, identify the deficiency of that patient compared to a normal healthy person, modify the patient's genome and make sure you can rescue whatever the deficiency is in the patient's cells. Once you do that then clearly the next step is putting those modified cells back into the patient to see if you can help the patient. That is the ultimate.
4. What are the technical challenges currently facing the B cell biology field?
Modifying the genome in such a way that gives you a permanent output is very technically challenging, but the main challenge for a lot of biology research is being able to replicate in vitro some natural events observed in vivo. For example, there may be a particular cancer that you recover from a patient, but then to be able to replicate that in vitro, to get the cells to behave the same way in the lab can be challenging. These technical challenges are especially true in the B cell biology field.