Valarie Weaver is a professor at University of California San Francisco who describes herself as a ‘Jack of all trades’. Her research group focuses on how cell context regulates cell fate, which involves looking at the interplay between stemness, mechanics and force in tumors and the tissue surrounding them.
Valerie Weaver: I ‘m like a Heinz 57. I’m in the surgery department, the anatomy department, and biology therapeutic sciences.
Pauline Davies: And what is your background? Do you come at this from the biologist standpoint or the physicists, or the chemist, engineering? Or everything?
Valerie Weaver: Okay so my basic degree is in chemistry. And then I did a biochemistry degree after that and my PhD is in biochemistry but the department I was in was a hybrid; it was biochemistry and biophysics. So I think I'm truly a hybrid right from day one and I fell in love with the concept of trying to understand things in context rather than as you do in biochemistry. And so I started doing cell biology, and then I went and trained and a lot of the more hard-core cell biology; but it lacks the kind of rigor that attracted me in the first place to more basics. And that's where I then moved back into something that’s a little bit more of physical sciences and became very much involved, and started doing things that are more like bioengineering. I think I'm really definitely Heinz 57 and a generalist.
Pauline Davies: And you mentioned that you're looking at the material that surrounds cancer cells. Now that’s really quite a change in thinking about cancer. I mean years ago people used to just consider the cell and remove the cell sand they didn't consider what was going on outside the cell; but your focus is on what surrounds the cell, the extracellular matrix, am I correct?
Valerie Weaver: Yes, in principle. What I'm really keen on is how the cells, sort of the whole tension the tissue, and how the cell’s tension is linked to the extracellular matrix tension. And how the cell and the matrix tension are regulated, and regulated by the organization of the tissue; so were really looking at tissue architecture as well. So, it’s very holistic, so you’re correct. It’s really not been very popular to look at the cell in context and I think that it would be remiss to say I’m only looking at extracellular matrix. But I think it's important to look at the whole tissue. And look at the dynamics and the communication and how the tissue is put together. And that encompasses cells, and the extracellular matrix and all the cells that are there. So it’s like a community. I’m trying to understand how the community functions and the overarching theme of the work has distilled down to looking at how that regulates force at the fundamental parameter that regulates tissue behavior in cancer.
Pauline Davies: And is force a very important parameter?
Valerie Weaver: Absolutely. So it’s interesting because when I listen to discussions about genomic landscapes and evolution theories and the atavist theory, I think the most important thing that people forget is that cells, particularly when they actually had to communicate even with their environment and with other cells, that mechanics and force is as fundamental as cell division. It goes way, way back, evolutionarily conserved all the way through and across all basically, the development, all that evolution and right up to us. To ignore it is like trying to ignore gravity, which is would be absurd. I think it's difficult to actually understand how to put this in context and so that's basically what our goal has been; to try to understand and communicate back to our colleagues both within that's small groups that we work with and also with the bigger communities and within the whole scientific community in general and also as an objective towards the cancer group.
Pauline Davies: What cancers are you looking at in particular?
Val Weaver: So we started with breast cancer but in the last three years or four years, we got very involved with pancreatic tumors because they are very rigid and there’s a lot of tension in there. Then in last two years, we've gotten also involved in brain tumors because is that it's a very unique mechanical environment. By actually comparing and contrasting these different tumor types, we’ve actually gotten some very interesting insight. Because each one has an alteration in mechanics but it's done differently. From there we also have outreach to colleagues in terms of skin cancers, squamous cell carcinoma and more lately and recently into liver cancers.
Pauline Davies: Is there in any sense a feeling that by manipulating the forces around the cancer something can be done to treat cancer?
Val Weaver: Absolutely, I think prognosis, diagnosis, and treatment. You know that the real struggle, of course, is actually define what you're looking at and try to understand what drives the forces differently in each different tissue. Then to try to get a handle on how you might go in and manipulate those forces. Some of them are good; some are bad. So, you don't want to just go in uniformly and like destroy that. We have made some progress in that respect and I'm very optimistic that we can and move towards basically exploiting some of these concepts to actually calm the tumor down and begin to actually use this is a way to improve therapy, improve vascularity, enhance the immune function and in some cases prevent metastases.
Pauline Davies: Well that would be wonderful. Are we a long way from that?
Val Weaver: I don’t think so. Some of the work we’re doing now, there are drugs that are already in existence. We have some proposals pending and we are going to do this anyways, where these drugs are already out there that may be used for things like cardio vascular disease, cholesterol treatment, and they seem to have some effects that would be consistent with reducing tissue tension. So, we’re going to be starting those studies in a couple of different model systems. And because they've already been approved by FDA and they’re very inexpensive, they would have very rapid transition into the clinic. So, we’re very optimistic. Not saying this could cure cancer; my goals are not so lofty but it would be lovely if I could. But certainly I think that you can make a huge difference with baby steps and so that’s where we’re heading.
Pauline Davies: And are those drugs the statins and the aspirins?
Val Weaver: Yes, it's like that lipophilic statins and some of the ibuprofens,some of the some of the other inhibitors that are actually out there for treating cardiovascular disease and what have you. So I think we're trying with those until such time as we can alternative approaches, but I think it you have to start with something.
Pauline Davies: What do you think about the PS-OC concepts?
Val Weaver: I honestly, I’m one hundred percent for it. I think that it's still in its infancy. I think that it would be a terrible shame and very shortsighted to stop it at this point. I think it's just now catching its stride, I think it’s just now that the ideas are really nucleating and new things are happening. I think that it takes a while to educate physical scientists and really bring them into the fold. I think it takes time to educate in a classic cancer biologist and biochemists and other people. It's really about the grassroots and so it's our trainees that are really with the ones that are moving us forward and I think it would be just a real shame particularly considering the actual overwhelming and looming horrible healthcare costs that are facing this country to actually to stop something like this because I really do think that this could actually make a big difference.
Pauline Davies: What are the challenges?
Val Weaver: Okay, so if aside from the obvious challenges regarding funding and what have you; I think that the way I look at this is that there is this huge group of very, very talented cancer biologist that are out there and they genuinely want to do something that makes a difference. Then there are clinicians and what have you in that group. And I think that the challenge for the PS-OC and the challenge for this particular community that I'm working with and the folks that are dedicated to interdisciplinary work, is to engage that community. It is to bring this community into the fold. Because then you will actually make progress, because it's not really about us moving ourselves for greater aggrandizement of ourselves. It’s really to make a difference. And to do that, I think we need to actually think about ways to use their form of communication, to come down to their level and try to understand what actually resonates with them and not hold itself aloof from that. So, if we need to provide models whether they be experimental models, animal or culture models or theories and models that they can use, but to actually work and I would say tread gently because you want to engage people. They are going to be critical to making this last.
Pauline Davies: You, yourself, describe yourself as the 57 varieties so I guess it’s easy for you to be cross-disciplinary. Have you found that your colleagues are equally supportive of the PS-OC?
Val Weaver: Uh, No. So the general community, I’ve had mixed responses. There is always going to be a core of individuals that will be very skeptical but there are also those individuals that are very excited by some of the ideas. Again, they need to actually see tractable, pragmatic, realistic ways for them to understand. I would say that we have to understand also that a lot of these guys, and it sounds terrible to say this but it’s true, a lot of them are mathphobes or they don't understand the concepts and so it becomes very difficult and so the first response is to just put their hand up and go no. So, we don't want that we want to do is open it up to them. So, yes I actually a have a probably unique background and training that I been sensitized, if you will, to this sort of idea and this thinking. And I see myself as one of the vanguard of individuals that's really going to try to make a difference that way. I may not have like a said a major impact on, you know, basically solving cancer or curing cancer, but I put myself out there to be one of the individuals to actually link you know, between these two communities to really try to make a difference and engage them. I think to do that, you know, it's can take a while but it's starting to happen, and the key is to actually get a couple of the really big players on board and are starting to. That’s giving me a lot of encouragement, but first this is just in my small area, which is mechanics. And course to bring in evolutionary theory and other things, you need to engage another group and community. And that requires, I think, another in a group of people that will have a real dedication to engaging the main scientific community, the main cancer community. The engineers buy all of this, the physicists are on board with all of this, or at least a group of them are. I’m talking about your card-carrying a cancer community. I'm still trying to even get the PS-OC or physical sciences kind of approaches brought into a formal session in the American Cancer Association meetings, but there are other meetings where they are now entertaining this. Certainly the fact I get invited around to all these places, as being other but they seem to be opening up to that and I have lots of good responses and there are a few other people that are now being invited, suggests that they are starting to listen.