A conversation with Xiaojun Tian, Mehdi Nikkhah and David Brafman

Biomedical engineering faculty members in the School of Biological and Health Systems Engineering are pushing the boundaries of science and medicine to improve health. Assistant Professor Xiaojun Tian, Associate Professor Mehdi Nikkhah and Assistant Professor David Brafman discuss their work in synthetic biology, microscale modeling and regenerative medicine in the latest episode of the Convergence podcast.

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Podcast guests

Podcast host: Lanelle Strawder, Content and Public Relations Manager, Ira A. Fulton Schools of Engineering 

Transcript

Intro  0:08  

Welcome to the Convergence Podcast brought to you by the Ira A. Fulton Schools of Engineering at ASU.

Lanelle Strawder  0:16  

Welcome back to Convergence, the podcast. I’m your host Lanelle Strawder, the content and PR manager for the Ira A. Fulton Schools of Engineering at Arizona State University, the nation’s largest and most comprehensive engineering school. Today, we’re back to learn more about the research and advancements happening in the School of Biological and Health Systems Engineering, one of six schools in the Fulton Schools of Engineering at ASU. I’m pleased to have joining us again, Marco Santello, the director of the School of Biological and Health Systems Engineering. Along with directing the school, Marco is a professor and an expert in understanding the control of complex movements. Today, he’s going to tell us a little bit more about the biomedical engineering school and its programs, and introduce us to some of the amazing faculty making things happen here at ASU. Welcome, Marco.

Marco Santello  1:15  

Thank you, Lanelle. It’s again a great pleasure to tell you a little bit about our school and Arizona State University. And our mission is to improve human health through research, education and service to the broader community. And the way we do this is by leveraging the highly interdisciplinary expertise of our faculty, and interact with the biomedical industry and clinical community, in the Phoenix area, and in the States as a whole. We have 29 tenure and tenure track faculty, three lecturers and 24 staff, so it’s a very large school and with a very diverse population of students from different backgrounds. And our faculty is also highly interdisciplinary as the discipline is. And in fact, as you will see also from the three faculty I will introduce shortly, you will see that they also come from different backgrounds, but in ways that allows them to really attack similar problems, from very different angles. So just to briefly tell you what our school research thrusts are. We follow the work in the area of bioimaging area of biosensors and bioinstrumentation, molecular, cellular and tissue engineering, neurorehabilitation engineering and synthetic biology and system bioengineering. And the three faculty I’m going to introduce you to shortly work across some of these areas. So I’d like to start with the first faculty, Dr. Xiaojun Tian, who is an assistant professor in the school, and who works across the area of synthetic biology and systems engineering. Xiaojun.

Xiaojun Tian  2:52  

Thanks, Marco and Lanelle. So, currently, my lab is focused on a fundamental problem in the field of synthetic biology and the interactions between the synthetic gene circuit and the host cells. Basically, after the synthetic gene circuits are placed into the host cells, they interact with the host cells in many ways, such as growth, feedback, and other resulting conditions. This is a fundamental problem, but is also a nuisance in the field as synthetic biologists wish to avoid. However, these hidden interactions often force us to go through many rounds of design, build and test cycles to finally get the rest that works, making the whole process very laborious and tedious. And in many cases it led to a high rate of genetic diversity failure. So we really need to find out how the interactions affect our gene circuit. And we need reliable control strategies to manage them. In our first work published in Nature Chemical Biology, we found that interference of the synthetic gene circuit function by the host cell depends on their network typologies. We compared it to a simple gene circuit that’ll work as a memory device, but using different typologies. We found that one circuit quickly lost its memory due to the faster growth of the host cell, but the other was very robust. In another work that is currently under review, we found a winner-take-all phenomenon, in which two modules within one gene circuit competed for the limited resources in the host cell, leading to the activation of only one module in the circuit. So this signify changes in the desired path of multiple cell phase transitions. To solve this problem, we came up with a division of labor strategy instead of putting the whole circuit in one cell, we divided it into two cells, which was really great. And we have many other exciting ongoing research, but I don’t have time today, thanks.

Marco Santello  5:13  

Thank you, Xiaojun. This sounds like really groundbreaking research. So what would you say are the ultimate or desirable kind of skill sets to advance the field of synthetic biology? Because based on your example, there is quite a bit of computational tools that you’re using, of course biology and others of course. So what would you say are the fundamental skills that you need to really make an impact and advance this field?

Xiaojun Tian  5:40  

Our research strategy I mean, when we designed the gene circuit, right. So, we needed to consider these hidden centrally host interactions, especially when we design a larger gene circuit, and we want to use them to use a real life environment. For example, we are also working on designing gene circuit for cancer cell. However, we all know that as a cancer, macro environment is very highly dynamic and homogeneous. So it is very challenging to make robust gene circuit under this context. But I believe that as a design principle and as a control strategy, we have learned can be practically applied here.

Marco Santello  6:26  

Okay. Thank you very much, Xiaojun. So your answer, Xiaojun really introduces very well also the work of the next two faculty I’m about to introduce which is the general theme of this podcast is really how biomedical engineering and advance cancer research and also research for other diseases. And so it’s my pleasure also to introduce the next faculty is an associate professional in our school, Dr. Mehdi Nikkhah. Mehdi.

Mehdi Nikkhah  6:52  

Hello, thank you very much for this opportunity to discuss our research. So the research in my lab at ASU biomedical engineering is focused at the interface of micro and nanoscale technologies, biomaterials and in biology, to better understand the mechanism of disease progression in humans. So one of the specific diseases that we have been focused on is basically cancer. And as you know, cancer is one of the leading cause of death across the U.S. and in the globe. And across different types of cancer, our interest has been on breast cancer and brain cancer, and recently on prostate cancer. So what we do in our lab, we develop micro scale devices. And by micro what I mean is the devices that are all in the order of a single cell. And then with these tiny devices, we can do precise analysis on the behavior of cancer cells, and to see the process of metastasis of cancer cells in the body. So the process of drug development in the pharmaceutical industry, for patients who are suffering from cancer is a very, very long process. And it requires a lot of expenses. And approximately development of one drug, including anti-cancer drugs cost about one billion dollars. And the process is about ten years. But now most of the cancer assays and drug screening assays are used based on animal models, which are not human first, and they’re actually physiologically different. And the findings of animal studies does not translate necessarily to clinical studies in humans. So our micro-engineered chips are going to help do that and to better understand the biology of the disease, specifically cancer and to better design drug compounds. So what we have done, for instance, in the area of breast cancer, we have isolated patient tumor cells from our collaborators at Mayo Clinic of Arizona, we bring them to our lab we isolate cancer cells and stromal cells, and then we put them in our micro-engineered chips. And as I mentioned, these are very tiny devices or small devices. And you can precisely see how similar environment in the mammary tissue or breast tissue signal to tumor cells, which lead them to invade through the tissue. So in one of our recent findings, which was published in Cancer Research in 2019, for instance, using our tumor model, micro-engineered breast tumor model, we identified novel gene called glyco protein nonmetastatic B gene, which was promoted in tumor cells because of presence of cancer associated fibroblasts. And interestingly, when we knocked down the gene, we were able to kind of inhibit the invasion of cancer cells. And that was a significant finding. And now that was a patient specific tumor for breast cancer patients. Now we are working with other clinical collaborators such as Barrow Neurological Institute to develop brain cancer on a chip. Now we receive a brain tumor cells we culture them on our chip, and then basically we assess the response of brain tumor cells to drugs and we are actually extending our collaboration toward prostate cancer, and then other types of cancer because it has actually generated a lot of interest in the community to develop these disease tissue models on a chip. So thank you very much. I’ll stop here.

Marco Santello  10:14  

Thank you very much, Mehdi this is very fascinating. So what do you see the next step or the biggest obstacle to make the final translational step? Meaning, you know, clearly it is going to be an accelerator for drug development, right the way you described it. So where do you see the biggest obstacles to make that happen right now from where you are right now to what you want to see deployed?

Mehdi Nikkhah  10:37  

So that’s a very good question. So in our recent tumor on chip, for instance, we isolated fibroblasts, as I mentioned, from patient tumor biopsy samples from three types of subtypes of cancer at Mayo Clinic of Arizona. So the patient, for instance, was in the surgery room, they were doing mastectomy, we’re isolating the tumor then fibroblasts. But now the the challenge right now we are facing and we want to actually accomplish that goal, hopefully, if we are successful is to isolate all the tumor cells, immune cells, and connective tissue cells, such as fibroblasts, basically, to develop a fully patient derived tumor on these chip technologies that mimics the native tumor microenvironment. And then we can validate that by isolation of the cells and putting them in our chip, we do not make any molecular changes or genetic changes in the cancers, and we have the same physiological relevance as the patient. So that ensures the validity of drug screening. So that’s a big challenge right now. So we are working toward that set to make it a fully patient specific tumor.

Marco Santello  11:42  

That’s excellent, thank you. And best of luck with that. Thank you so much, Mehdi.

Mehdi Nikkhah  11:46  

Thank you. It was a pleasure. Thank you.

Marco Santello  11:48  

And it’s now my pleasure to introduce to you the next faculty. David Brafman also works in synthetic biology and also regenerative medicine, David.

David Brafman  12:00  

Yeah, thanks, Marco. Yeah, so broadly speaking, my lab employs pluripotent stem cells to investigate various aspects of neurodevelopment and neurodegenerative disease with a focus on Alzheimer’s Disease. So Alzheimer’s Disease comes in two flavors. The first flavor is what’s called familial Alzheimer’s Disease, which is due to specific genetic defects that lead to Alzheimer’s Disease onset and age related progression. So about one percent of the total Alzheimer’s Disease cases are what are called familial in nature. And again, in that they have a specific genetic mutation that causes the disease. The majority, 99 percent of Alzheimer’s Disease cases, are caused by what is termed sporadic, a mixture of environmental and genetic risk factors. And so what my lab does is we use a combination of approaches, bioengineering approaches, and biomaterials approaches and gene editing approaches to investigate these risk factors. So why do some of these risk factors increase a person’s risk to developing Alzheimer’s Disease, and so by using a pluripotent stem cell model, we’re able to introduce these risk factors into pluripotent stem cells using gene editing technologies, then take these cells and differentiate them to the cell types that are representative of those found in the brain. And then we’re able to study the molecular mechanisms by which those specific risk factors increase Alzheimer’s Disease related phenotypes. And so by understanding what are called these genotype to phenotype relationships, then you can identify potential druggable targets to treat Alzheimer’s Disease. So that’s sort of a high level summary of what my lab does.

Marco Santello  14:16  

Thank you very much, David. This is very exciting also. So given that we don’t have a medical school, how, can you explain to the audience, how you were able to implement such a clinically, you know, driven, a clinically oriented program. Since you’ve been a successful program at ASU can you tell us a little bit how you managed?

David Brafman  14:38  

Yeah I think ASU provides an environment where basic research that would be done at a medical school can also be done at ASU. And there are plenty of partners in The Valley with clinical backgrounds that should provide input or context to discoveries that are not only made in my lab, but those of others in the department.

Marco Santello  15:02  

Okay, thank you very much. So one obvious question after hearing your description is, “You guys collaborate with each other?” And so what kind of brought you together and specific projects or questions and this is a question for everybody, of course.

David Brafman  15:18  

Yeah, I could speak to that. So you sort of mentioned that these three thrust areas of ASU, right. That is educating students, doing research and servicing the community. And I think ASU does a really good job, and particularly our program does a good job of integrating those things. And so by integrating those things, then we are able to facilitate collaborations relatively easily. And so one example of that is between Mehdi and my lab. So my lab uses pluripotent stem cells to investigate, as I mentioned, neurodegenerative diseases. Mehdi’s lab is interested in cancer and cardiac related diseases. But he expressed an interest in learning how to culture these cells. And so what we’ve done through sort of integrating all these sort of three thrust areas is we developed training programs for teaching folks how to culture pluripotent stem cells, and how to manipulate them. And folks in Mehdi’s lab, have participated in those programs and other labs. And then they’re able to use that knowledge to go and do the research that’s of interest in their lab. And so I think that’s been a very, very fruitful collaboration that has been fostered out of these sort of types of programs that integrate those three thrust areas.

Marco Santello  16:42  

Okay, thank you.

Mehdi Nikkhah  16:43  

And to add on that also, this is what I wanted to mention also. We actively collaborated Dave’s lab and one was on culture of stem cells. And recently we started on the project with Dave’s lab also and on gene editing and creating a cardiac specific disease on our microengineered chip technologies, which has been very fruitful. So these are these are the opportunities, which are provided because of diversity of expertise in biomedical engineering here at ASU, yeah.

Marco Santello  17:11  

That’s fantastic. Thank you, Mehdi, thank you, Dave.

Lanelle Strawder  17:14  

I would like to thank all of our guests for the work that you are doing to advance research here in cancer innovation, through biomedical engineering. So we’re almost out of time here, Marco, is there anything that we haven’t covered that you’d like our audience to know?

Marco Santello  17:30  

Yeah, there’s one thing of course, this podcast was mostly centered around the research program of, you know, David, Xiaojun and Mehdi which, as you heard they’re really groundbreaking. But there’s one thing I should also point out about their contribution to our work and to the unit and institution is the impact they have had and they continue to have on their trainees. They’ve all made a tremendous effort in making sure that our students, both undergraduate and graduate students, basically get cutting edge training, all of the students have received awards and recognition, very competitive recognition for that matter. As far as federal awards, and all kind of accolades, which speaks really highly about how aligned they are, these faculty are in the context of the ASU charter, and our service to the students. As I mentioned in my previous podcast, you know, ultimately the students are our final in inverted quotes, you know, “product” in terms of, you know, the next generation of researchers, educators et cetera. So this national, to point out something that was not properly emphasized in their overview of their research. They’re also incredibly, incredibly good educators.

Lanelle Strawder  18:47  

Thank you. So Xiaojun, Mehdi and David are just three of the faculty members who are conducting world class research and leading our students into the next phases of biomedical engineering. For the three of you, do you mind sharing your contact information, in case any listeners would like to learn more about your work or are interested in collaborating.

Xiaojun Tian  19:12  

So you can find my lab. The website is tianlaboratory.com, and my email is [email protected]. Thank you.

Mehdi Nikkhah  19:26  

Yeah, also, my email is definitely my email is [email protected] and if you just, the simplest way is to just type in Google my name, Mehdi Nikkah and ASU. First link is my lab, which is in ASU bioengineering so definitely students and other collaborators can contact us. 

David Brafman  19:50  

My contact information is [email protected], b r a f m a n. And our lab website is brafmanlab.com

Lanelle Strawder  20:02  

Thank you so much and we’ll be sure to make sure that all of the contact information is included in the show notes. If you want to learn more about biomedical engineering at ASU, you can visit our website at sbhse.engineering.asu.edu. Again, I want to thank all of our guests today. And for our listeners, we hope that you will join us again for the next episode of Convergence, the podcast.

Outro  20:38  

Thank you for listening to Convergence, a podcast brought to you by the Ira A. Fulton Schools of Engineering at ASU.

Transcribed by https://otter.ai