Science is Global: Building Bridges with Dr. Kris Saha

Dr. Kris Saha works with CRISPR technology in his laboratory (Photo from the Department of Biomedical Engineering at UW–Madison)

By Katie Newcomb, GHI Communications Director, and Kendall Buehl, GHI Staffer

BUILDING BRIDGES

Growing up, Dr. Krishanu Saha always knew he wanted to follow in the inspiring footsteps of his parents.

Saha’s father, a civil engineer, and mother immigrated to the United States from their hometown Kolkata, India, so his father could pursue a PhD.

Saha explained, “My father got a scholarship designed for underrepresented students from lower castes, which was really life-changing for him and my whole family.”

Inspiration from his father’s path led him to think a bit more about the bigger picture of global health.

“I visited Kolkata as a young adult and always thought it would be exciting to be able to generate knowledge that has that kind of broad global impact. Even if I was able to do something here in the U.S., I’d like to be able to have that work positively impact folks back in India,” Saha shared.

Along these lines, what continues to inspire Saha is multidisciplinary action and collaboration.

“My dad’s civil engineering focused on building bridges, and I’ve always been excited about building things–as I think most folks in a developing country are, because they’ve seen the architectures and the infrastructure in other countries be built up in impressive ways compared to their home context. There’s an opportunity, I think, to learn from what has been working in the Global North and what challenges are unique to the Global South. That type of comparative lens is something I’ve always had. It’s helped me think a bit more flexibly across disciplines,” Saha emphasizes.

My dad’s civil engineering focused on building bridges, and I’ve always been excited about building things…

Dr. Kris Saha

Letting this mentality guide him, Saha earned his Bachelor of Science in Chemical Engineering from Cornell University in 2001. Then, he went on to earn his Ph.D. in Chemical Engineering from the University of California, Berkeley, in 2007.

“A lot of my Ph.D. work was designing new types of soft gels and other materials that can engage with cells. Towards the end of my Ph.D., I heard a seminar where there was this amazing discovery that explained how you could turn mature cells back to an embryonic state. That was against dogma and developmental biology, and it was thought to be only done in rare circumstances where you do a cloning technique and physically move the genetic material from one cell to another. This technique didn’t use any of that. So, we got interested in how engineers should think about manipulating not only materials outside the cell but also inside the cell with more genetic engineering,” Saha shares.

From there, Saha went on to complete a postdoctoral study with Whitehead Institute at the Massachusetts Institute of Technology (MIT) to work with a biology lab that was investigating this discovery, and he learned a lot there about how to work with stem cells.

While spending five years as a postdoc at MIT, Saha understood, firsthand, why people look to UW–Madison as a leader for stem cell biology, “Whenever anyone had a question like, ‘How would you grow human stem cells?’ Folks would say, ‘Talk to person X,’ and that person had some sort of connection to Madison. Those connections were either trained here at Madison, went somewhere else and started a lab, or are still here. One, for instance, is at the National Stem Cell Bank. That was kind of one reason why Wisconsin was on my radar early on in my training,” said Saha.

Saha moved to Madison in August 2012, to be an assistant professor. “I came to UW thinking I was going to work in the field of epigenetic reprogramming. About three months in, there was another set of announcements. Three papers came out saying CRISPR-Cas9 genome editing was, one, discovered, and two, could work in human cells. At that time, I had an empty lab and one master student, so it was a great time for me to pivot and try this new technology.”

Saha is now an accomplished and celebrated professor of biomedical engineering and pediatrics leading the Saha Lab at the Wisconsin Institute for Discovery. He and his team research gene therapy, cell therapy, gene editing, CRISPR, and stem cell bioengineering.

CRISPR stands for, “clustered regularly interspaced short palindromic repeats,” and is essentially the heart of immune defense systems in bacteria against invading viruses. Think of it as a clever method devised by nature to help cells identify and dismantle newly encountered viruses. Saha’s lab uses CRISPR-Cas9 technology to edit genomes to program human cells for therapeutic purposes. “I’ve always had an interest in being able to engineer materials to see how they interact and engage with tissues and cells of the body,” said Saha.

SCIENCE IS GLOBAL

When asked about his work with global health, Saha shares, “Overall, one of the motivations for me to think about global health is, any improvements and advances we make in manufacturing and in making these types of new cell products and gene therapies here in the U.S., that those same advances could be replicated or manufactured in a better way – potentially even outside the U.S.”

Challenges of accessing gene and cell therapy products in the U.S. include cost and a limited number of vendors who can safely make and administer.

“Thinking through what’s possible, and who else is thinking about this outside of the U.S., GHI (Global Health Institute) has really catalyzed those relationships and it’s one of the reasons why we’re working in India – because that community has generated many innovations in this field over the last five years.”

GHI CONNECTIONS IN COLOMBIA AND INDIA

Through GHI’s mission to connect UW researchers and students with opportunities in academia, industry, and government at its One Health Centers (OHC), GHI Director Jorge Osorio recognized the link among Saha’s work and research being done locally with GHI’s OHC-Colombia and India partners.

“I think relationships and connections with alumni is really what catalyzed this. I had a discussion about what is being done in India initially because Jorge said, ‘We have an alumnus that’s interested in working with GHI to have a presence in India. Does your work intersect at all?’ And I said, ‘Yeah, I could see all sorts of connections,’” Saha shared.

I think relationships and connections with alumni is what catalyzed this.
I had a discussion about what is being done in India initially, because Jorge said,
‘We have an alumnus that’s interested in working with GHI to have a presence in India.
Does your work intersect at all?‘

Dr. Kris Saha

From there, GHI connected Saha to Dr. Krishna Ella, UW–Madison alumnus (Ph.D. CALS), GHI board member, and co-founder & executive chairman of Bharat Biotech International Limited, a biotechnology company whose mission is to deliver affordable, safe, and high-quality vaccines and bio-therapeutics. Subsequent discussions, including Saha visiting with Bharat’s leadership in India, sparked a whole new set of ideas, conversations, and synergies between the teams at Bharat and Saha’s lab.

Strategic discussion continued between GHI and Saha’s lab, leading to GHI’s financial investment in the Lab to expand research into Colombia.

“The financial support has also been instrumental. I have two senior scientists that spend approximately a quarter of their time thinking about how to establish connections in Colombia and India with the latest research that’s being done here,” said Saha. “There are opportunities supported by the Government of Colombia and the Government of India, that are looking to support biotech, or improve public health and access, to advanced therapies. These are all opportunities that we’ve learned about through GHI, and sparked our thinking on how we could generate a potent cell therapy with those types of inputs, infrastructure materials, and people as well,” Saha continued.

These are all opportunities that we’ve learned about through GHI, and sparked our thinking…

Dr. Kris Saha

“It’s very enriching in a research and development way for not only me, but also my trainees. Because they get to see they’re not constrained by equipment availability and find themselves asking if there is a way to get the same end product with different workflow or processes. To me, it’s enriching to think more creatively about manufacturing processing and needs when presented with this context of patients coming into a very different healthcare system with different conformities at some level, and then at other levels it is molecularly the same target.”

These opportunities to collaborate and examine capabilities in new ways help expand cell therapy research. Currently, cell therapy in the U.S. works with one patient’s blood sample going back to the same patient. This tends to be more expensive because of the one-to-one model. But the allogeneic approach, taking one person’s material and manufacturing hundreds or thousands of doses, or pooling together material from multiple people to create one large batch to reach more people, is being explored in academia, government, and industry in the U.S., Canada, UK, India, Colombia, China and many more.

“My sense is countries like Colombia and India, which are developing low-middle income countries, have more of a focus on public health than precision medicine or personalized health; they are trying to understand these types of advanced therapies that are really expensive through those frames. There’s a different set of considerations about access than here in the U.S., and that could justify a different set of investments through academia, industry, or government that brings new types of resources to that question.” 

Saha goes on to say, “Science is global. We publish, and it gets read and translated in all sorts of ways that I don’t often anticipate. I do think there are opportunities to have an impact beyond the immediate community here with the type of knowledge and research that we’re generating.” Saha also says, “It’s very hard to make anything, especially something this complex, with inputs that are not coming from outside the state and outside the U.S.”

Science is global.
We publish, and it gets read and translated in all sorts of ways that I don’t often anticipate.

Dr. Kris Saha

“Both locally and abroad, my sense is there are unknown questions we’re asking, and there’s a mutual interest in being able to solve them for advancing healthcare. The role of a public university is to try to answer those questions for public benefit and, yes, to help make a company that can produce it in a sustainable and safe way – to get that impact and employ people in the process. When I say science is global, I think technology is global too. The biotech sector typically has products that are not only in the U.S., and are certainly marketed across the world. That’s a reality of doing this work.” 

Saha discussed additional work he and his team are working on with the Wisconsin Institutes for Medical Research at the University of Wisconsin School of Medicine and Public Health to integrate more of the CRISPR technology.

“We’re designing a new type of cell therapy facility with data we’re collecting here in Madison. But we could also get double, triple, or maybe ten times more data if we do parallel experiments out with our partners through GHI. That could help us design our facility ten times faster or more, and certainly informs how we are investing in particular types of technologies, infrastructure, and workflows in a global competitive environment. There are real questions about large investments that may not be very sustainable if there’s new technologies around the corner and a service can do it. The genomics community knows this very well because there’s a new sequencing platform that’s being innovated by U.S. companies, in many ways, almost every six months. To be able to keep up, and have a sustainable way to be at the forefront of that field, requires some different key choices. If we can have some insight by experience in additional labs and contexts, and hear about them through our relationships in a timely way, it should help us make the most of our investments here.” 

ADVANCING IN INDIA

Later this month, a UW delegation (including Saha and members of GHI) will be traveling to India to participate in the Wisconsin Alumni Association’s Badger Utsav II and strengthen current relationships and create new connections.

The timing is fortuitous, as Saha, GHI, and delegation members will attend a ribbon cutting ceremony at Bharat Biotech to celebrate their gene and cell therapies facility where advanced medicinal therapeutic products will be manufactured. In the past, the facility was mostly used as one of Bharat Biotech’s spaces manufacturing life-saving vaccines. Now this facility will focus on research and development of gene and cell therapy products – a first for Bharat Biotech. But this is just the beginning according to Saha.

“We’ve spent the most time (with Bharat Biotech) discussing how we could design next generation cell therapies, and how some of the designs of those would be informed by machine learning and AI through some work here at UW. We’ve also discussed how the different indications and health burdens in India would inform the design of those types of cell therapies, and how different bioprocessing manufacturing supply chains affect rolling a product like that out. We’ve sent some designs of how to genetically engineer some of those cells with a senior scientist in my lab, Dr. Srikumar Sengupta, who’s been helping us make that connection.” 

WHAT’S NEXT FOR THIS MADISON/INDIA CONNECTION

According to Saha, gene and cell therapy innovations in Madison come with continued collaborations with Bharat.

“All of the local impact we have in Wisconsin with our technology is fantastic. But I think it also has a potential global impact. Being able to show, in a facility like the one at Bharat, with very different sets of constraints, resources, people, and opportunities, is where we want to focus our innovation. I don’t think it’s an either/or type of choice that we just generate some of these technologies that have impacts here, but we want to work with the alumni community, the folks coming to the Utsav, and the private sector where they see application opportunities for the work we’re doing.” 

All of the local impact we have in Wisconsin with our technology is fantastic.
But I think it also has a potential global impact.

Dr. Kris Saha

“I think this could be the beginning of something really big. I would love for a set of products to be manufactured that have applicability and impact in India, and I’d love to see that happen here as well. It bodes a vision of impact beyond the lab in the discovery building, and that’s certainly what we’re striving for.”

LEARN MORE AT 20TH GLOBAL HEALTH SYMPOSIUM: APRIL 8

You can find more information about Dr. Saha and his work at his Saha Lab website.