A conversation with Professor Sanjay Kumar about the technologies still needed to enable the future of medicine.
This is the first in a series of interviews with faculty members about the hot developments and unmet needs in their fields.
What is the main focus of your lab, and why?
Everything we do in my lab is focused on trying to understand how living systems process physical signals they receive from non-living systems, such as the materials found within tissue or in medical devices.
This is important because if we want to understand and interfere with, for example, how a tumor invades living tissue — which is ultimately what drives the progression of a tumor and kills people — then it’s really critical to understand something about how a tumor cell shapes and is shaped by those tissue surroundings.
What is a major potential application of your research?
We feel that this is an important problem to solve for the development of personalized medicine in cancer treatment. Moving beyond the era of one-size-fits-all therapy, not just in cancer but in a lot of other diseases as well, is at the heart of personalized medicine. It will mean trying to develop therapies that fit the person. The notion that every tumor is exactly the same is now widely regarded as incorrect, and even within a tumor there is quite a lot of heterogeneity.
In cancer especially, where heterogeneity within and between patients is a huge part of the problem, we’d like to take tumor cells from a patient, learn something about it in culture — what it responds to, what drugs kill it, what halts invasion — and then use that information to design rational therapies that we can deploy in patients. To do all of that we need to know how to design culture systems so that what we see in the laboratory has predictive value for what will happen in the body.
Is there a specific need you’re trying to fill?
There is an enormous unmet need for scalable culture technology that allows you to go from a patient sample to a patient therapy. I would argue that a critical stepping stone in the development of this technology is having culture platforms that can accurately capture defining structural and mechanical features of tissue.
Right now the standard for culturing cells is still to use flat, two-dimensional cell substrates. You put cells on pieces of plastic that are relatively stiff and bathed in soluble factors at very high concentrations, which is not what tissue actually looks like. Tissue is three dimensional, often with a consistency close to soft rubber or Jell-o, and it’s a living system. It can be remodeled by the cells: they can chew it up, they can change it. In fact, even the signals we think of as freely soluble, like growth factors, are anchored to scaffolds within tissue. None of that can happen on plastic.
I think this is an idea that a lot of people recognize but are only beginning to put into practice. So an important goal of ours is to put tools into place that will accelerate the translational process.
What does your solution look like?
We are trying to develop scalable systems that allow us to model processes such as growth, invasion, and differentiation in vitro. We’re using systems like biopolymer hydrogels whose composition, structure, and mechanics are much closer to brain tissue, and seeing if we can re-create the invasion of brain tumors in a dish. We’d like to use systems like this as platforms for drug screening and various kinds of molecular analysis. Similarly, we’re using tools from the microfabrication toolbox to make channel arrays that simulate what tumor cells might see as they invade along a blood vessel.
Right now we’re taking the most tumorigenic cells from primary tumors, putting them in our next-generation culture platforms, and interrogating them to see what we can learn. Later we’ll want to ask if the information we’ve learned from such studies is useful for management of that tumor.
Are you working with other members of the Bioengineering Graduate Program?
Most of these efforts involve collaborations with faculty with expertise in other areas, and fostering those interdisciplinary opportunities is where our graduate program really excels.
We have a Keck Foundation grant with Professor Niren Murthy that focuses on developing proteomic fingerprints for cancer. Niren’s lab is very interested in ultra-sensitive proteomic reagents that can detect low quantities of specific proteins. So the idea is that maybe we can combine our culture platform with his detection methods to figure out, in these very rare populations of cells, what proteins they express that make them different. What predictions can we make about how those cells will respond to therapy based on those fingerprints?
On the microfluidics side, we have an NCI grant with Professor Amy Herr’s lab, in which we’re trying to combine our culture platform with her team’s high-end proteomic tools, like single cell western blotting and related technologies. The goal here, if all goes well, is to gain insight into why some tumor cells invade more aggressively than others, as a first step towards specifically targeting those systems.
We’re also fortunate to have great collaborators in other areas we’re working in, especially stem cell engineering, where we’ve been partnering with Professor David Schaffer’s lab for nearly a decade. More recently we’ve been working with Associate Professor Tamara Alliston at UCSF on developing material platforms for controlling stem cell differentiation in cartilage replacement.
How is this a unique experience for students?
Our students really embrace the cross-disciplinary nature of our work, whether their research is focused within our lab or crosses over to these collaborations. One thing I’ve been excited to see in the trainees at all levels — undergraduate, masters, and doctoral — is that they are finding ways to engage with clinical medicine and/or the biotechnology industry while they’re here and after they graduate.
An important and unique mission of the bioengineering program is to train people to interface between traditional engineering and biology and medicine. One hopes that these students are going on to populate not only traditional engineering jobs but also positions embedded within clinical settings, in the biotechnology sector, and in biomedical device development. So far I think we’re doing a great job of that.
What do you predict for the impact and prospects of this area in the future?
This is a very exciting time to be working at the interface of biomechanics, biomaterials, and cell biology, because the scientific principles are really coming into focus and the field is now pivoting towards translational applications. People sometimes think that developing new therapies is the only way to make clinical contributions, but the reality is that platforms for discovery, diagnosis, and prognosis can make an enormous impact on human health. The same is true of support technologies that may never directly see the patient, such as new culture systems that may make existing “biological” therapies more scalable or promote good manufacturing practices. Bioengineers can and should contribute in all of these areas.