Precision Medicine

Revolutionizing liver tissue engineering and transplants

Science Talks Podcast Episode 52 Featuring Ekta Minocha
Dr. Ekta Minocha shares how her research on stem cells aims to provide hope and innovative solutions to people suffering from liver disease and cancer.

Induced pluri-potent stem cells (iPSC) are widely used in therapeutics for disease modeling, regenerative medicine, and drug discovery. Using patients’ cells, scientists can regenerate their cells into iPSC and recreate new organs for patients who need them. Amy Randall-Barber from the BIO5 Institute was joined on Science Talks by Dr. Ekta Minocha, a 2023 BIO5 postdoctoral fellow working in the Jason Wertheim lab at the University of Arizona College of Medicine – Tucson. Dr. Minocha's work focuses on the development of bioartificial liver tissues. She hopes that one day they can replace a failing liver in the human body and expedite the waiting time associated with organ transplants.


This interview has been edited for length and clarity.

ARB: Let’s start with a couple of ice-breaker questions as usual. Do you have a hidden talent? If so, what is it?

Yes, I like doing embroidery and glass painting. I remember, when I was in school during my summer vacations, I used to do embroidery on cushion covers and pillow covers. I also gave my grandma a handkerchief which I embroidered as a gift. And gifted a few glass paintings to my friends and relatives.

 

ARB: So, now I know that you like embroidery! What other kind of designs do you like to make?

I like making flowers and embellishing items like cushion covers or pillow covers with mirrors and colorful threads. I enjoy adding different types of stitches to make them beautiful. 
 

ARB: Who is your favorite Disney character and why?

Mickey Mouse is my favorite Disney character. I like him for his cute smile, innocence, and kindness.

 

ARB: Would you rather travel to the past or the future?

I would like to travel to the future because I am a curious person. I want to know what is going to happen in the future.

 

ARB: So, what brought you to the University of Arizona and BIO5 Institute from India, where you attended Sanjay Gandhi Post Graduate Institute of Medicine?

Since my school days, I have always had a passion for science, particularly biology. The concept of how a single cell can develop into a whole individual has always fascinated me. So, I decided to pursue my passion for science by getting a doctorate degree in the field of stem cells and tissue regeneration.  

As I was nearing the completion of my thesis, I learned about Dr. Jason Wertheim's research at the University of Arizona, which aligned perfectly with my interests and expertise in stem cells and regenerative medicine. I applied for a postdoctoral position in his lab, went through the interview process, and was fortunate enough to be selected.  

I have found the environment here to be incredibly supportive, with people open to collaborations and exciting research happening at the University of Arizona and BIO5 Institute.

 

ARB: Ah, that is good to hear about stories of such exciting research happening. Can you tell us about your overall research goals? Or the overall research goals of Dr. Wertheim’s lab?

The overarching research objective is to create transplantable liver tissues capable of repairing or replacing failing organs, thereby reducing transplantation waiting times. To achieve this goal, I am focused on generating liver organoids, miniature organs in a dish that mimic the functions of a normal liver. Particularly, I am utilizing these organoids to model a liver disease known as non-alcoholic steatohepatitis (NASH) and to investigate the underlying mechanisms of this condition.

 

ARB: Does Dr. Wertheim's lab only work on liver?

In addition to liver research, Dr. Wertheim's lab also works on kidney studies and is involved in bioprinting and the development of bioartificial scaffolds.

 

ARB: Can you tell us about your specific project in the lab and how you became a part of that project?

Yes, my main project is developing liver organoids. So, I am using these organoids to model liver disease called nonalcoholic steatohepatitis. And I am also using them to understand the underlying mechanisms of how this disease is caused.  

So, the long-term goal is to see whether we can transplant them into patients. Right now, I am waiting to see whether these liver organoids have the potential to be transplanted into animals to assess their functionality and engraftment abilities.

 

ARB: Can you tell us what challenges you've had during some of your experiments over your time in science?

Yes, working with induced pluripotent stem cells, or iPSCs, is quite challenging, as everyone knows. We come to the lab every day to change the media. Plus, iPSCs are like spoiled children! They behave differently, sometimes, you do everything in an analogous way, following the same pattern. But the next day, you come to the lab and see that all the cells have died. There is no apparent reason for this, but iPSCs behave that way. So, the major challenge is culturing iPSCs and working with them. Since our starting material is iPSCs, we must depend on them. They must grow better so we can make the organoids to progress our research.

 

ARB: So where do you get these IPSCs from?

We acquired some iPSCs from a stem cell bank in California. Additionally, we reprogram some of them from patients with NASH (nonalcoholic steatohepatitis). For this, we collect peripheral blood mononuclear cells (PBMCs) from NASH patients or patients undergoing liver transplantation. The reprogramming of PBMCs into iPSCs is conducted at Northwestern University, where we collaborated with Dr. Richard Green.  

Once we obtain the stem cells, we perform experimental work here at the University of Arizona.

 

ARB: You were a 2023 BIO5 postdoctoral fellow. Can you share how you first discovered this opportunity and discuss how the fellowship supported your project?

I learned about the BIO5 postdoctoral fellowship opportunity through my mentor, Dr. Wertheim. He encouraged me to apply for the grant.

The specific aim of the fellowship was to investigate the interrelationship between innate and environmental factors in non-alcoholic steatohepatitis (NASH). To achieve this, I used IPSC-derived hepatocytes and cultured them under various stiffness conditions to explore how the environment influences their behavior. This research focused on understanding the connection between innate biological factors and environmental drivers in the development of NASH. We observed that changes in stiffness altered the lipid species and influenced the gene expression levels of genes responsible for lipid production.

 

ARB: Can you tell us how close we are to being able to use the tissues that you have developed for organ transplants in place of traditional organ transplants?

Currently, we are still in the preclinical trial phase, so there is still a long way to go before we can proceed to clinical trials for transplantation. Induced pluripotent stem cells offer numerous benefits but also come with limitations. One significant challenge is their inherent heterogeneity and the variability observed from batch to batch. For example, in liver organoids, we expect the major cell population to be hepatocytes, but sometimes we observe an abundance of non-parenchymal cell types instead. Overcoming this batch-to-batch variation is crucial before considering transplantation into patients.

 

ARB: Thank you for doing this important work. Eventually, you will nail this and be able to heal many people hopefully. So, do you have a mentor that has impacted your life?  

Yes, certainly, I have been incredibly fortunate to have had outstanding mentors throughout my life. My parents have been my biggest mentors, providing unwavering support, encouragement, and motivation every step of the way. I owe a great deal of gratitude to them for their constant guidance.  

Additionally, during my educational journey, I have been privileged to have mentors like Dr. Soniya Nityanand, Dr. C.P Chaturvedi, Mr. Vinod Pandey, and Leena Chatterjee, who have played pivotal roles in shaping my path. Here at the University of Arizona, Dr. Jason Wertheim has been a remarkable mentor. His guidance, motivation, and inspiration have been instrumental in my growth and development. Working under his mentorship has truly helped me refine my skills and abilities.

 

ARB: Yeah, I can only imagine what it must be like to be in your shoes, pursuing a PhD and then working for Dr. Wertheim. His work is renowned, and he is known to be a brilliant and wonderful man! Do you think you will stay at the University of Arizona, or you will go elsewhere?

I'm a J1 scholar, so I am subject to a two-year home residency rule after completing my current program. Therefore, I will be heading to India for the next two years. During this time, I will be seeking job positions in India while also applying for grants here. My long-term plan is to pursue faculty positions in India.

 

ARB: Do you already know who you would like to work with in India?

I will see, there are positions, I will apply for them, but they are extremely limited.

 

ARB: Well, I'm sure they will be glad to have you and everything you have learned while you were here. Can you elaborate on why you do what you do? What got you into it?  

Liver cancer is a significant cause of mortality, and currently, transplantation is the primary therapeutic option available to patients. However, this approach has limitations, particularly the need for a matched donor.  

Therefore, my focus is on developing transplantable liver tissues using the patient's own cells to avoid rejection. If successful, this could revolutionize treatment by providing alternative therapeutic options and significantly reducing transplant waiting times.  

This is the driving force behind my work—to offer hope and innovative solutions to patients suffering from liver cancer.

 

ARB: Well, thank you so much for being here with us today and telling us about your work. Do you want to share anything about your work or time here at the university?

It has been an incredible experience collaborating with some amazing researchers. Dr. John Purdy has been instrumental in our lipidomics work, while Dr. Nathan Cherrington, a mentor during my postdoc, has been invaluable for our studies on drug metabolism.  

Additionally, we are exploring the impact of flow on organoids through microfluidics research, with assistance from Dr. Yitshak Zohar from the aeronautical and mechanical engineering department.  

The collaborative atmosphere here is truly remarkable. People are helpful and open to collaboration, which makes it more enjoyable. Science thrives on collaboration, doesn't it? I would also like to add that Dr. Wertheim always encourages collaboration. He is consistently open to collaborations and promotes me to take on leadership roles during collaborative meetings, encouraging me to explain my work and contribute actively.

 

ARB: That's wonderful. Well, thank you again for being here. We really appreciate your time and you for sharing your information about your project and your story.

Pioneering technologies in nanoscience and medicine

Science Talks Podcast Episode 51 Featuring Frederic Zenhausern
Dr. Frederic Zenhausern shares his long and fascinating scientific journey, from rapid DNA testing to organoid-based drug discovery, that spans the ever-evolving landscape of scientific innovation.

See how an interdisciplinary scientific approach shaped the future of molecular diagnostics and personalized healthcare on a global scale. Amy Randall-Barber from the BIO5 Institute was joined on Science Talks by Dr. Frederic Zenhausern, director of the Center for Applied NanoBioscience and Medicine (ANBM) at the University of Arizona College of Medicine - Phoenix, among many other appointments in the college including in Basic Medical Science, Radiation Oncology, Biomedical Engineering, and Clinical Translational Science. Prior to coming to the university, Dr. Zenhausern co-founded and directed the Flexible Display Center at ASU MacroTechnology Works. He received his bachelor’s degree in biochemistry from the University of Geneva, an MBA in finance from Rutgers University, and his doctorate in applied physics from the Department of Condensed Physics Matters at the University of Geneva in Switzerland. Dr. Zenhausern is an inventor, mastering interdisciplinary work in science, technology and healthcare, to drive clinical translation.  

  


This interview has been edited for length and clarity.

 

ARB: Let’s start with a couple of ice-breaker questions to lighten up the mood. What was your dream job as a kid? 

When I was a kid, I loved animals and I wanted to be a vet. 

 

ARB: What would you like to be known or remembered for? 

What I think is interesting is in my training and professional career, I call myself a true interdisciplinary scientist.  

I think I demonstrated how interdisciplinary science brings ideas across many different areas of scientific and engineering technologies. I developed some basic optical sciences while I was at IBM, a product platform at Motorola labs. Even now at the University of Arizona, we have developed a technology that goes through the FDA and brings practical solutions in life sciences, bio defense and healthcare. We have a very broad portfolio of technological impact. 
 

 

ARB: You started off in Switzerland, and you ended up in Arizona. Can you tell us how you ended up here?  

That’s a long story. When I was in Switzerland, I did my PhD thesis in partnership between the University of Geneva and University of Lausanne, but also IBM Research in Zurich. And after my PhD, I was looking for a postdoctoral position. I got a beautiful location at UC Santa Barbara with a nice beach and my wife was happy! We were ready to move to California, but IBM twisted my arm and said you should come and work for us at the IBM Research Lab, located in Bronx. And it was a difficult sell, but ultimately a great experience for us. 

In the years that the MIT-IBM Watson AI Lab would develop different technology platforms, including DNA sequencing, I was the first to bring a real virus for IBM to look at using high resolution microscopy techniques. We made a lot of different discoveries which then led me to develop all kinds of technologies.  

In a move to Princeton, New Jersey, I was a part of a Swiss chemical company developing new technology mimicking the human nose and looking at electronic nose technology. I also joined a photonic center at Princeton University as an industry member, which led me to start a new startup company in Princeton that was a subsidiary of a French startup, commercializing electronic nose technology. At the time, we were also discussing with David Wald at Tufts University the technology that started Illumina, that we all now know in the field of DNA sequencing.  

Also, I was recruited as one of the advisory board members in the Motorola Company. They were establishing a new biosystem in Arizona to start DNA microarray technology, and I got recruited to come to Arizona. 

 

ARB: You were inducted into the National Academy of inventors as a fellow in 2013, for the invention of a rapid DNA processor. Since you mentioned working with the inventor of Illumina, can you explain how we use the DNA processor today and how it has evolved since then? 

The goal for us has always been to try to do molecular diagnostics. When we started the technology using microfluidic devices to automate and simplify the workflow processes for preparing a specimen, we realized that any application in medicine would be a long project for us since we needed to go to the FDA for regulatory compliance.  

We also looked at other applications, where there were some elements of regulations but not as stringent. At that time, there was a big backlog of DNA fingerprinting. It was taking years until a sample could be processed. So, the Department of Justice decided to promote a new technology to solve the backlog. We came up with that technology focused around reducing work through laboratory processes and put it into a small machine.   

And that’s what we did initially with our contract with the FBI. The FBI introduced us to other countries and police forces, including the UK Forensic Science Services, or FSS. They were the leading inventors of the technology with a group at a university in the UK. They had the vision of bringing technology closer to the crime scene. Initially, we developed a technology that would go into a police van. But that scenario changed and ultimately, that technology was deployed at a police station instead. That allowed the screening of potential offenders and finding a sample much easier.  

It was a complex regulatory validation. We were a part of a larger European program called MIDAS consortium, where we validated the technology between the police forces in the UK, Germany, Austria and the Netherlands, which proved successful. In 2017, the DNA Act was modified to include rapid DNA Act to court proceedings. This marked the commercial development and widespread adoption of our technology within the Justice Department. 

 

ARB: Wow, I’m just blown away. You are currently the director of the Center for Applied Nano Bioscience here at the University of Arizona. Can you briefly tell us about the research there? 

We have a large portfolio of activities. The center consists of a group of 15 members, including mechanical engineers, physicists, MDs, PhDs, and molecular biologists. Our goal is to identify medical needs in healthcare delivery by applying engineering principles to find solutions. Collaboration is at the heart of our approach, as we work with various agencies and industry partners including NASA, NIH, and DOD.   

Typically, our projects are early-stage discovery projects.  For example, we are exploring novel drug delivery systems, using plant-derived lipids, an intrinsic agent with anti-inflammatory and antioxidant properties. Loading these lipids with different drugs or utilizing these plants for gene delivery, represents a promising avenue for drug development. 

Furthermore, we have developed an invitro system that could potentially replace animal models for testing drugs. On this platform, we combine organic chips with organoids for 3D cell culture. Under a partnership with Mitsubishi Gas Chemical company in Japan, we are scaling up the production of this technology for commercialization as it holds potential for drug testing and personalized treatment.  

We are exploring personalized medicine using organoid-based techniques to analyze genomic signatures of tumors and adapting therapies. For example, if at a hospital consultation you extract tumor cells and treat that tumor in a model, you can look at different combination of therapies that might be more appropriate for that person. By integrating these technologies, we are trying to improve patient outcomes. 

 

ARB: How long does it take for something like this to come into use? 

So, it depends. For example, when we talk about rapid DNA testing, it took about 15 years from development to implementation. On the other hand, the COVID test we developed, approved by the FDA and available on Amazon, was developed in less than a year. Now, these kinds of platform technologies for organoids will take a few years, about five years, until they can be deployed in the marketplace, because they will still be in the research platform phase. 

 

 

ARB: Thank you. Just curious because this is such amazing technology, and it is needed. 

It is a good point. Sometimes we think about getting a grant for five years, but most of the time, it's not enough time to mature technology.  

So, what are the mechanisms in academia that allow us to keep going and be part of its development, until a new company can take it? There are a few mechanisms that the government is offering. And that is why I think getting to the university's vision and sustainability of developing those kinds of technology is crucial. 

 

ARB: Absolutely. Can you share what inspired you to pursue this interdisciplinary work? Was it something you always wanted to do, or did you find your way here unexpectedly? 

That's a good question. My journey began with a background in biochemistry during college. When I reached my senior year, I embarked on a research project. Coincidentally, IBM Research in Zurich had just seen two of their scientists awarded the Nobel Prize in Physics for the discovery of the scanning tunneling microscope. This device could profile surfaces and see atoms, which fascinated me. I saw the potential for its application in molecular studies.   

So, I reached out to those scientists at IBM for a summer internship. They said, ‘we don’t do biology, we do physics.”  However, I secured the internship and, although we didn’t know what to do, we started to look at molecules using the technology. I was so excited by the experience that I decided to pursue a PhD in physics. That's how I found my passion for interdisciplinary work and everything else fell into place. 

 

 

ARB: You have focused on various scientific arenas throughout your career. However, you also pursued an MBA in finance. How do you believe that has influenced your professional journey? 

Yes, indeed. Let me provide some context first. It was back in the year 2000 when I was residing in the bustling New York area amidst a booming economy. There was this prevailing notion that Wall Street held the promise of substantial wealth creation, attracting scientific talent like mathematicians and physicists from esteemed institutions such as Princeton into venture capitalist circles.  

I was influenced by this trend. However, I also recognized that one day I wanted to have a startup company, and adding financial and managerial skills would be helpful. That’s why I enrolled in a finance-focused MBA program. Finance, with its heavy emphasis on mathematics, seemed conducive to the scientific mindset.  

The program not only equipped me with financial acumen but also enhanced softer skills crucial for effective people management and interaction. In retrospect, it proved to be an asset, and I found myself applying those principles right from the outset of my career. 

 

 

ARB: What are you currently looking forward to in your academic or personal life?  

On a personal level, I feel incredibly privileged to have two outstanding adult children who are now embarking on exciting ventures in medicine and engineering. It is a great source of immense joy for me, especially as our family continues to grow, welcoming our first grandchild.  

Professionally and academically, my focus remains on serving the community and addressing some of the grand challenges in our society. I am deeply committed to continuing this work and exploring innovative solutions.  With the rapidly changing economy, we find ourselves at the intersection of cleantech, biotech, and space tech. This convergence presents exciting opportunities as we explore and venture into new frontiers. It’s a very exciting time for us. Oh, and on a different note I love mountain biking and would like to start a new club here in Phoenix for biking enthusiasts. 

 

 

ARB: That would be so cool. We thank you again for being here with us today and sharing about your journey, your inventions, and everything that you are doing now. 

Flinn Foundation funds Arizona research teams to drive discoveries into clinical settings

Picture of Pathogens
Flinn Foundation

Ten research teams from three Arizona institutions have been awarded $100,000 each from the Flinn Foundation Seed Grants to Promote Translational Research Program to help turn their findings into viable treatments and diagnostics.

Goodrum accepted into executive leadership fellowship

Dr. Felicia Goodrum
UArizona Health Sciences

Felicia Goodrum, PhD, interim associate department head and professor of immunobiology in the University of Arizona College of Medicine – Tucson has been accepted into the Hedwig van Ameringen Executive Leadership in Academic Medicine program hosted by Drexel University. She is also a professor in the BIO5 Institute, a member of the UArizona Cancer Center and a member of the AEGIS Consortium.

Women to Watch in Medicine and Science – Shirin Doroudgar, PhD

Shirin Doroudgar, PhD
UAZ Med Phoenix

Shirin Doroudgar, PhD, works as an assistant professor in the University of Arizona College of Medicine – Phoenix’s Department of Internal Medicine and is an active member of the Translational Cardiovascular Research Center, where she leads a research group in cardiac molecular biology, focused on understanding changes in protein homeostasis and cellular stress responses that contribute to heart disease.

College Of Medicine – Tucson Researchers Tackle Immune Rejection Of Biomedical Implants

College of Medicine -- Tucson
UArizona Health Sciences

Biomedical implants, such as breast implants and pacemakers, improve patient health and quality of life but may be rejected as foreign bodies. Suppressing production of an immune protein could reduce this risk.