Author: The Wistar Institute

For more than 20 years, The Wistar Institute has been training community college students with relevant, much-needed skills to attain in-demand jobs in the biomedical and biotechnology fields. Since 2000, Wistar understood that biomedical lab technicians would always be highly sought after for their own labs and beyond, and thus set out to create a program to cultivate this much-needed talent.

That program became the flagship Biomedical Technician Training Program, now a registered pre-apprenticeship program. The opportunity to extend hands-on training allowed Wistar to develop the Biomedical Research Technician Apprenticeship—the first registered, non-traditional apprenticeship in biomedical research in the nation.

Upon being awarded a PAsmart grant of $649,551 from the Pennsylvania Department of Labor & Industry, Wistar is now on track to expand both programs further across the region and create additional pre-apprenticeships to offer more students the opportunity to prepare for careers with additional employers in the growing life sciences industry.

Read the Governor’s announcement of all PAsmart grant program winners.

In this virtual event held by the Chamber of Commerce, Wistar’s Associate Dean of Biomedical Studies Dr. David Zuzga spoke about workforce development and the value of apprenticeship programs at the Chamber of Commerce virtual event “Finding Emerging Talent in STEM”.

On April 20, 2022, the Chamber of Commerce for Greater Philadelphia hosted a virtual event reviewing how to address challenges in recruiting and training a STEM workforce. Guest speakers included our Associate Dean of Biomedical Studies Dr. David Zuzga who spoke about strengthening the STEM workforce through education and apprenticeship opportunities such as Wistar’s Biotechnician Training (BTT) Program.

Attracting and retaining STEM talent in the workforce, especially in an increasingly informationally complex and interdisciplinary world, has been a challenge faced by employers and educational institutions alike. As Philadelphia grows into a leading life sciences hub, developing and retaining STEM talent is at the forefront of workforce development initiatives.

Zuzga commented on the advantages of an integrated approach to traditional education with workforce training. He highlighted Wistar’s BTT program which collaborates with Community College of Philadelphia to provide a laboratory orientation boot camp where participants work on authentic Wistar research projects and are then matched with summer internships in academic and industry settings.

“There is a transformation in the program’s participants. It’s remarkable to be so connected to an employer-partner and provide that type of value in a nontraditional program.” said Zuzga. He continues, “It’s essential for employers to begin engaging with educational institutions to better inform the type of competencies they are looking for in a successful workforce.” Zuzga explains that as employers collaborate with training providers to address lab skills that are more specific and relevant, they are creating more value for participants as they receive training more transferable to STEM careers.

Newly published research identifies a mutation associated with scarring of the lungs, revealing a useful diagnostic tool and target for gene therapy.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease that can cause death within five years of diagnosis. In an international research collaboration recently published in the Journal of Experimental Medicine, Wistar scientists and colleagues in the Netherlands identified a mutation on telomeres – which protect the ends of chromosomes – that helps explain this disease. This study directly links the telomeric protein POT1 (Protection of Telomeres Protein 1) to IPF.

Emmanuel Skordalakes, Ph.D., Associate Professor in the Gene Expression and Regulation Program at Wistar and senior author of the paper, previously published research in Nature Communications that delved into the structure and function of POT1, the protein that binds the ends of our chromosomes (telomeres) and protects them from DNA damage response (DDR).

In this new study, Skordalakes and his team used patient data obtained by their Dutch counterparts and conducted a series of biophysical and biochemical experiments to understand how telomeres with mutated POT1 are linked to IPF. Proteins usually have particular sites, which allows them to bind to molecules that match that specific pocket. The team observed that in this chronic lung disease, the mutated POT1 affected how the protein binds to the telomere and thus its ability to prevent DDR.

“We found the mutated POT1 does not bind the telomere as efficiently as the wild type one,” said Skordalakes. The less effective binding of POT1 leaves telomeres exposed to DDR. When this occurs, cells undergo a process called senescence that stops them from functioning and dividing.

“We looked at the [cells of] these patients and they are senescent,” Skordalakes shares. Senescent lung cells build up and contribute to many symptoms of IPF like difficulty in breathing.

The POT1 mutation will be added to a medical database to be used in hospitals to help diagnose patients with IPF as well as provide doctors a target for gene therapy. Skordalakes says, “When you know that your work has an impact on patients directly in the clinic – that’s what’s exciting.”

Dr. Luis Montaner, Wistar’s Associate Director for Shared Resources, and Mark Drinker, Wistar’s Associate Director for Administration of the Ellen and Ronald Caplan Cancer Center, chat about core facilities that support the innovations of our Wistar scientists, particularly spotlighting Wistar’s new Humanized Models of Disease Core.

Q: Can you tell our readers why it is so important that Wistar has Shared Resources? We’re a small biomedical research institute, why do we need it?

Mark: Wistar Shared Resources are mission critical. Every institution needs to have core facilities that support and are tailored to the science taking place in their organizations or institutes. Shared Resources allow faculty to incorporate leading-edge technology into their science in order to advance their research programs. Shared Resources may be created as a result of technology developed within an individual laboratory. For example, a laboratory may develop technology and expertise that is critical to advance their own science, and over time many other labs find they have that same need. This could be the impetus of the technology to be scaled into a Shared Resource designed to meet the needs of many researchers.

Q: Can you explain your work as the Associate Director for Administration of the Ellen and Ronald Caplan Cancer Center Shared Resources?

Mark: I work closely with Dr. Montaner, our Shared Resources director, and our Cancer Center leadership to position our core facilities as research engines that serve as extensions of our faculty laboratories. The goal is to maintain state-of-the-art Shared Resources that advance the research efforts of Wistar faculty and research partners. To accomplish this, our Shared Resources all contain technology, high-tech equipment, and exceptional personnel who have the expertise to work with each individual laboratory at Wistar.

Q: Can you describe some of the goals of the new Humanized Models of Disease Core, as its Scientific Director?

Luis: With the new Core under Dr. Zhe Yuan as Managing Director, we hope to generate a resource of humanized mice that could be of service to infectious disease scientists within the Vaccine and Immunotherapy Center, as well as the Cancer Center faculty. This model allows researchers to study how tumors from persons grow or respond to therapy if implanted in mice as well as how the human immune cells interact with tumors. The core is an investment to generate enough expertise in-house so we can bring a humanized mouse (differentiated with the human immune system) to the laboratory. The core will allow Wistar teams to utilize the humanized mouse as needed to move their experiments forward.

Q: What are humanized models of disease and why are they important?

Luis: A humanized model of disease is utilizing an animal model to study human physiology. The ability to study human immune cells within tissue enviroments for long periods of time (weeks) provides for studies that may better resemble our human body. We can use these models to study the infectious disease process of pathogens that infect human blood cells such as HIV. We can also use it for understanding human tumors.

Q: What was the impetus behind creating the Humanized Models of Disease Core Facility?

Mark: For many years Wistar faculty, including Drs. Herlyn and Montaner, have been developing mouse models to study cancer and infectious disease. Our scientists need to utilize models that closely replicate the human immune system to test their hypotheses. By creating a Shared Resource, we hope to develop a structure that allows Wistar to maintain this promising technology and offer it broadly to our research teams in order to advance their science.

Luis: Innovative science is made possible by the strong support of our donors. This new facility is just one example of the progress Wistar can accomplish with the generosity from our philanthropic community. The ability to propel research forward is facilitated by those who believe Wistar science is an impactful investment for the future. The creation of the new center is supported by a philanthropic commitment to Wistar’s most important priorities, which is to advance our technologies and scientific resources available to our researchers. The discoveries that will be made are the fruits of investing philanthropically in The Wistar Institute.

Q: Can you give me some examples of the scientific information that can be collected from using these models?

Luis: To study novel therapeutic strategies, you can use a tissue culture plate that just has the cells that you want to interact or understand. But once you start reconstituting the way our bodies are, then you must start scaling up into systems too. How well can I reach the blood with this drug that is in circulation to maintain this change? How well can I add a drug that would reach the cells in a physiological state? If it’s an organ system, how well can I get to that organ for my treatment to still work in the microenvironment of the lung, or the liver, or the gut? As we look for what model systems do, we must start scaling into a whole system.

When it comes to generating a platform to pilot test some proof of principle or evidence that this treatment could work in the context of human cell interactions, the humanized mice model becomes one tool that is a lot less costly and a lot less demanding with respect to using limited resources. The use of the humanized mouse model becomes a tool that could potentially give a researcher more confidence that what they’re working on is worth advancing.

Q: Can you describe some of your own HIV research and how it could be impacted by this new facility?

Luis: The humanized mouse model gives you the ability to screen many ideas within a model. Underway in our BEAT-HIV Martin Delaney Collaboratory efforts at Wistar, we are developing and testing novel strategies of viral eradication by 1) activating the immune system to clear HIV-infected cells, and 2) directly targeting HIV by CRISPR CAS9 and other gene editing approaches to rid the viral infection directly from the cells. This model gives us the ability to screen multiple strategies that either target infected cells directly or target the immune system to clear infected cells due to the immunotherapy.

Q: What do you hope that researchers will get out of using this facility?

Luis: As the technology keeps moving forward, the application of humanized mouse models in cancer research are starting to become a higher priority. For example, we can place patient tumors into mice that have compatible immune systems matched with the tumor. It’s also going to be important to test immunotherapies or chemotherapies in the context of cancer eradication as well as for the infectious disease research of the Vaccine and Immunotherapy Center.

We all have a particular signature to our immune systems, and the best model is to generate a mouse that has the same signature of the person that the tumor has been growing in (i.e., creating a personalized research model). Studying therapy approaches where a tumor also matches the immune system of the person in the same mouse allows us to identify personalized cancer therapies. These types of models are now becoming more possible.

Wistar’s Drs. Kristy Shuda McGuire, dean of biomedical studies, and David Zuzga, associate dean of biomedical studies, spent an evening with students at Vaux Big Picture High School in north central Philadelphia to discuss all the STEM job opportunities available and for the taking here in the region.

Dr. Shuda McGuire spoke to Wistar’s education programs—available to high school students and upwards to postdoctoral fellows. She discussed how collaboration with academia and industry have made Wistar’s Biomedical Technician Training Program and Biomedical Research Technician Apprenticeship effective and successful vehicles to give students the needed skillset to enter coveted biomedical and biotechnical jobs. Then she imparted a little history on where and how Wistar fits into the dynamic regional life science hub we know today—from its beginnings as the first biomedical research institute in the nation, to how it has become a connector and engine for education in the burgeoning Philly biotechnology space.

Dr. Zuzga laid the groundwork on all the amazing science taking place in Philadelphia—from CAR T cell-trained assassins that became the first FDA-approved cell therapy to cure cancer in people who had no other options, to a new gene therapy company that created the first medicine to cure blindness. Dr. Zuzga drove home the point that the industry is booming in Philadelphia and students should set out and stake their claim in it. He emphasized that 10-years ago there were one or two cell and gene therapy companies and now there are more than 40 and the number is growing.

Basir Fulmore, a graduate of Cheyney University who is working in science, wrapped up the event and spoke to the students about his career trajectory. He talked about where he came from, the life lessons he learned in the process of attaining his science education and the true affinity he holds for science. He is a math and science teacher now but shared many stories of working in a Cheyney lab carrying out aquaponics—using fish to grow plants hydroponically. He compelled the students to enter science as more diversity is needed.

The Lower North Philadelphia CDC is a key partner, providing event coordination and sponsorship, as well as being an organization connector. Their friends at Give and Go Athletics brought a great group of students, who took part in the event and should be commended for taking two hours on a 70° day—after school—to learn more about science! It all seemed well worth it when they got to conduct their own scientific experiments and precipitated DNA from a solution. Eyes widened and smiled through masks. In those few moments you could see in each face that the magic of science homed in and made its first introduction.

Dr. Diana Bautista has dedicated her professional life to the science of literal human connection: our sense of touch.

A Howard Hughes Medical Investigator and professor of cell and developmental biology at University of California, Berkeley, Bautista runs a lab that conducts basic scientific research on touch, particularly itch, pain, and inflammatory diseases.

“Among the five senses, we really know the least about our sense of touch,” Bautista said. “This is surprising given how important touch is in our everyday lives.”

She points to pain as an example of why we need touch to stay healthy and safe. Acute pain, the feeling you get when you touch a hot frying pan, acts as a warning—it triggers a reflex to pull your hand back and prevent tissue damage. Likewise, inflammatory pain from a sunburn will prompt protective behaviors, like covering up before you go back outside, and learning behaviors, like proactively wearing sunscreen.

Chronic pain, however, serves no purpose. It’s like a siren that keeps ringing long after the fire has been put out. It’s a serious problem, afflicting more than 10 million Americans every year. “Which is why we’re working to understand the mechanisms underpinning touch and pain,” said Bautista. She and her colleagues are trying to determine why some people’s pain goes away when they recover from injury or disease, while other people suffer from chronic pain for the rest of their lives.

Bautista’s lab focuses primarily on the first step of feeling physical touch, which is called transduction. In this step, sensory neurons convert a physical stimulus, like the pressure of a handshake or the prick of a pin, into the electrical signals the nervous system uses to communicate. By identifying how these signals are triggered, Bautista hopes to identify new therapeutic targets for mediating pain.

“Our challenge is to discover new genes that underlie the persistence of chronic pain so we can develop new therapies that target pain at its source.” she said.

One gene her lab is researching is TRPM8, which is responsible for sensing cold and menthol. To verify this gene’s function, the scientists set up a mouse experiment. They created a small two-room chamber with an open doorway between the rooms. One room had a comfortably heated floor plate, and the other room had a very cold floorplate. When a regular mouse was put in the chamber, it avoided the cold side. However, when a mouse lacking the TRPM8 gene was placed inside, it traveled between the two chambers indiscriminately, demonstrating no sensitivity to the cold.

The discovery of this gene’s role in cold perception could help lead to treatment for patients suffering from cold allodynia (oversensitivity to cold), chemotherapy-induced neuropathy, and even certain types of migraines.

Another gene Bautista’s lab is studying is S1PR3. Rather than cold, this gene regulates sensitivity to mechanical pain. To test this, the researchers poked mice’s paws with a pin. Normal mice responded to this sensation 100% of the time, whereas mice lacking S1PR3 responded only 40% of the time. This finding is important because the gene is also expressed in human skin, as well as in a variety of other species.

Finally, Bautista’s lab is studying chronic itch, a condition that will affect one in ten people at some point in their lifetime. Like pain, acute itch is protective; it helps to ward off burrowing insects that might carry disease. However, chronic itch can be debilitating.

Historically, chronic itch has been associated with diseases of the integumentary (skin) and immune systems. However, Bautista’s lab has found that the nervous system interacts with the immune system in ways that can trigger inflammation from the skin all the way to the spinal cord. These interactions, which occur early in the sensation of itch, play a significant role in later chronic states of itch and can even go so far as to affect the onset of asthma.

“We’re really excited about this research,” said Bautista. “Very basic science can lead to the discovery of novel therapeutics.”