Drug Discovery and Delivery

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. 

BIO5 Institute Announces Newest BIO5 Postdoctoral Fellows

2024 BIO5 Postdoctoral Fellows
Eight outstanding postdoctoral researchers were awarded the 2024 BIO5 Postdoctoral Fellowship, which aims to propel interdisciplinary researchers to the next stage of their careers.
Caroline Mosley, BIO5 Institute

Now in its sixth year, this competitive fellowship through the University of Arizona BIO5 Institute provides exceptional postdoctoral researchers with monetary awards and professional development opportunities. 

Since 2019, over 40 BIO5 Postdoctoral Fellows have been awarded $5,000 each to advance their scientific projects and gain the skills they need to become independent researchers in their respective fields. The award can be used to learn new skills in workshops, travel to conferences, or visit peer labs to further collaborations. Each fellow works with a BIO5 member as a primary mentor and forms a mentoring committee that assists them with grant applications, career advice, and job talk preparations.  

The 2024 BIO5 Postdoctoral Fellows are: Marjan AghajaniAngela GreenmanAtsushi IshiiDavid JordanZoe LyskiGemma PurserPhilip Yost, and Ran Zhang.

Seeing a need to invest in the success of postdoctoral researchers, BIO5 member Michael D.L. Johnson, associate professor in the Department of Immunobiology at the UArizona College of Medicine – Tucson, established the fellowship with support of BIO5 leadership to support cross-disciplinary projects aligned with the BIO5 mission. 

The Technology and Research Initiative Fund (TRIF) that helped launch BIO5 more than 20 years ago continues to be a catalyst in enabling effective, cross-disciplinary bioscience research, innovation, and impact at the university and in supporting the next generation of scientists through training opportunities like the BIO5 Postdoctoral Fellowship. 

Learn about the 2024 Fellows and their interdisciplinary research 

Marjan Aghajani, PhD 

Proposal Title: The role of the ER stress-inducible ribosome-binding protein 1 (RRBP1) in cardiomyocyte protection during ischemic stress 

BIO5 Member & Principal Investigator: Shirin Doroudgar, Department of Internal Medicine, UArizona College of Medicine – Phoenix  

Heart problems caused by narrowed heart arteries, or ischemic heart disease, can affect the signaling pathways and survival of the cardiac muscle cells responsible for the contraction of the heart. It's critical to understand the molecular mechanisms of these cells and pathways to prevent cell death and the resulting stress placed on the cardiovascular system. 

With a background in medical physiology, immunology, and cell biology, Marjan Aghajani is pursuing a research career focused on studying abnormal changes in body functions caused by cardiovascular disease.  

“I want to understand how cardiac muscle cells, or myocytes, respond to stressful challenges. My vision is that such responses could become the basis of new therapies for heart diseases that stress cardiac myocytes,” said Aghajani.  

Aghajani will use the BIO5 Postdoctoral Fellowship to study the molecular mechanisms involved in ischemic heart disease. Using human induced pluripotent stem cells (hiPSCs), she will focus on the role of ribosome-binding protein 1 (RRBP1) in cardiomyocyte survival under ischemic stress. The funds and mentorship will help her gain expertise in hiPSC culturing and differentiation and present her work at a heart research conference. 

Angela (Angie) Greenman, PhD 

Proposal Title: Quantifying the super-relaxed state of myosin 

BIO5 Member & Principal Investigator: Samantha Harris, Department of Physiology, UArizona College of Medicine – Tucson 

Understanding the molecular mechanisms of muscle contraction can lead to a better outcome of hypertrophic cardiomyopathy (HCM), a prevalent cause of heart failure in adults.  

Using her expertise in molecular biology, physiology, and muscle function, Angie Greenman plans to use her BIO5 Fellowship to further her career goals of becoming an independent scientist studying and teaching how skeletal and cardiac muscle function in health, disease, and under the stress of exercise. 

"I want to study the effects that cardiac and skeletal muscle proteins have on regulating contraction and relaxation in normal physiology and testing these same proteins under the stress of pathology and under the demands of exercise,” said Greenman.  

Greenman will use the BIO5 Postdoctoral Fellowship to expand her laboratory skills, particularly in fluorescent microscopy techniques related to muscle function, to study the role of cardiac myosin binding protein-C (cMyBP-C) in muscle contraction and relaxation. Funding will allow her to visit with an expert in the field at the University of Copenhagen, learning novel techniques for characterizing different states of myosin during relaxation that opens doors to new avenues of research in her field.   

Atsushi Ishii, MD, PhD 

Proposal Title: Gaining tools to probe the dynamics of brain stem cell regeneration during aging 

BIO5 Member & Principal Investigator: Lalitha Madhavan, Department of Neurology, UArizona College of Medicine – Tucson 

Understanding the effects of aging and sex hormones on neurogenesis is important for a deeper understanding of various cranial nerves and psychiatric diseases. Some central nerve diseases develop in a variety of age-dependent manners and go into spontaneous remission, while others, such as autism spectrum disorder, develop from birth and progress chronically, and others, such as Parkinson's disease and Alzheimer's disease, develop in old age. Some symptoms develop and progress over time, and symptoms change with age. 

With his long-standing interests in neurological disorders and a background working as a pediatric neurologist, Atsushi Ishii wants to research regenerative approaches for addressing age-related neurological disorders. 

“Working on neurodevelopmental disorders previously in a clinical setting, I became intrigued with the role of age-dependent changes in these contexts, which although important, were less appreciated and studied,” said Ishii. 

Ishii will use the BIO5 Postdoctoral Fellowship to investigate the molecular pathways associated with the aging of neural stem progenitor cells (NSPCs), particularly focusing on the NRF2 transcription factor and its interaction with sex hormones. He plans to visit an expert in the field at Tohuku University in Japan to learn about NRF2 biology and cutting-edge methods, as well as attend a conference around stem cell research to network and present his work.  

David Jordan, PhD 

Proposal Title: Preliminary biomechanical evaluation of the concurrency of carpal tunnel syndrome and trapeziometacarpal osteoarthritis 

BIO5 Member & Principal Investigator: Zong-Ming Li, Department of Orthopedic Surgery, UArizona College of Medicine – Tucson 

Millions of people are afflicted with carpal tunnel syndrome and osteoarthritis, musculoskeletal disorders of the hand and wrist. 

David Jordan's mechanical engineering expertise, along with his background in physiology, bioengineering, medical imaging, and computer modeling, gives him a unique multidisciplinary perspective on the biomechanical study of the hand and wrist. 

“My current research focus involves the imaging, testing and modeling of the trapeziometacarpal joint, which is the most affected hand joint by osteoarthritis. I aim to develop novel therapeutic treatment mechanisms for this disorder,” said Jordan. 

Using the BIO5 Postdoctoral Fellowship funds, Jordan will study the concurrency of carpal tunnel syndrome and osteoarthritis. He wants to identify and recruit patients with concurrent cases of these disorders and construct apparatuses for testing hand function. Jordan also plans to attend conferences focusing on orthopedic research and biomechanics to jumpstart his independent research career. 

Zoe Lyski, PhD 

Proposal Title: Uncovering mechanisms behind suboptimal immunity in immunocompromised individuals 

BIO5 Member & Principal Investigator: Deepta Bhattacharya, Department of Immunology, UArizona College of Medicine – Tucson 

As the ongoing COVID-19 pandemic has shown, people do not develop equally protective immune responses to infection and vaccination, and those with immunocompromising conditions and cancer are especially at risk. 

With expertise in immunology and virology, Zoe Lyski will use the BIO5 Postdoctoral Fellowship to further study how immune responses influence viral evolution.  

“There is an unmet need to uncover key drivers of suboptimal immunity and develop means of improving vaccine immune responses in immunocompromised patients. My project aims to help fill this knowledge gap,” said Lyski. 

Her project supported by the BIO5 Postdoctoral Fellowship will focus on understanding suboptimal immunity in cancer patients, particularly regarding antibody responses to vaccination and subsequent viral evolution. Funds will help develop targeted mRNA vaccine approaches to improve outcomes in immunocompromised patients and allow her to travel and present her research at an immunology conference.  

Gemma Purser, PhD 

Proposal Title: Investigating the role of urban forest soils in mitigating atmospheric volatile organic compound driven air pollution in cities 

BIO5 Member & Principal Investigator: Laura Meredith, School of Natural Resources and the Environment, College of Agriculture, Life & Environmental Sciences 

Volatile organic compounds (VOCs) contribute to air pollution, which has implications for human health particularly in urban areas. The presence of VOCs in the atmosphere has a variety of sources, but of rising concern are those originating from personal care items, cleaning products, and industrial solvents.

Specializing in atmospheric and analytical chemistry, Gemma Purser wants to further her understanding of microbial analysis and urban ecosystems to better study VOCs.  

“This fellowship offers a unique opportunity to explore critical questions at the intersection of urban ecology, atmospheric chemistry, and microbiology. I am excited about the potential impact of this research on understanding the role of urban forest soils in buffering the newly emerging sources of atmospheric volatile organic compounds in cities,” said Purser.  

Using funds from the BIO5 Postdoctoral Fellowship, Purser will start a collaborative independent research project with Urban Biogeochemistry program at Boston University and Aerodyne Research, Inc. (ARI) to study the interplay between urban green spaces and volatile organic compounds in improving air quality. She will use the funds to conduct soil experiments using advanced mass spectrometer instrumentation at ARI and work with Boston University to further develop her microbial analysis techniques. 

Philip Yost, PhD 

Proposal Title: Biomimetic 5-module chimeric antigen receptor therapy 

BIO5 Member & Principal Investigator: Michael Kuhns, Department of Immunology, UArizona College of Medicine – Tucson

When our immune system works correctly, it deploys T cells to detect and eliminate viruses, bacteria, and other organisms that cause disease. However, sometimes these cells go rogue, attacking healthy cells and causing autoimmune diseases such as Type 1 diabetes. 

With an extensive background in cellular and developmental biology, Philip Yost wants to have a meaningful impact on human health research using a novel approach – biomimetic engineering – to genetically engineer cells that can lead to new immunotherapy treatments. 

“Since joining the Kuhns lab in fall 2022, I have successfully established a workflow for a second-generation chimeric antigen receptor as a platform to expand from just the treatment of Type 1 diabetes and extend as an application for treatments against other diseases,” said Yost. 

Yost will use the BIO5 Postdoctoral Fellowship to design and develop a second-generation biomimetic chimeric antigen receptor (CAR) for T-cells in immunotherapy, capable of redirecting T-cells effectively. He will use the funds to enhance his immunology training through advanced courses and attending conferences.  

Ran Zhang, PhD 

Proposal Title: A fluorescence-based high throughput screening assay to target the Nsp14 ExoN of SARS-CoV-2 

BIO5 Member & Principal Investigator: Hongmin Li, Department of Pharmacology & Toxicology, R. Ken Coit College of Pharmacy 

Emerging and evolving coronaviruses present challenges to researchers as they must continually advance their understanding of antiviral therapies.  

With her expertise in veterinary medicine, microbiology, and virology, Ran Zhang aims to provide valuable insights into potential antiviral drug development for coronaviruses. 

“Given the current global emphasis on antiviral research, particularly considering recent pandemics, there's a heightened demand for professionals with specialized knowledge in antiviral drug development. I want to contribute to groundbreaking discoveries that can have a profound effect on public health,” said Zhang. 

With the BIO5 Postdoctoral Fellowship, Zhang will research the role of non-structural protein 14 (nsp14) in coronaviruses' replication, particularly SARS-CoV-2, and develop a high-throughput screening assay to identify inhibitors of nsp14 activity. The funds and mentorship allow Zhang to design, implement, and test experiments that will help her understand viral replication mechanisms and add to the development of antiviral therapies. 

Dr. Bonnie LaFleur Named to NIH Data Safety Committee

Bonnie LaFleur
UArizona Health Sciences

 

Dr. Bonnie LaFleur, a research professor in the University of Arizona R. Ken Coit College of Pharmacy, has been appointed to a five-year term on the Data Safety Monitoring Committee for the National Institutes of Health Common Fund’s Nutrition for Precision Health, powered by the All of Us Research Program.

Todd Vanderah, PhD, Named UArizona Alumni of the Year

Todd Vanderah
College of Medicine

Todd Vanderah, PhD, professor and department head of the University of Arizona College of Medicine – Tucson’s Department of Pharmacology, was named an Alumni of the Year for 2023 by the University of Arizona Alumni Foundation.