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Tag: Tempera

Wistar Researchers Discover Potential Target for Gastric Cancers Associated with Epstein-Barr Virus

Written by The Wistar Institute on . Posted in Press Releases.

PHILADELPHIA—(August 22, 2023)—Now, scientists at The Wistar Institute have discovered a potential target for gastric cancers associated with Epstein-Barr Virus; study results were published in the journal mBio. In the paper, Wistar’s Tempera lab investigates the epigenetic characteristics of gastric cancer associated with the Epstein-Barr Virus: EBVaGC. In evaluating EBVaGC’s epigenetics — the series of biological signals associated with the genome that determines whether a given gene is expressed — the Tempera lab highlights a target that could advance as a future treatment for this type of cancer.

The work of Italo Tempera, Ph.D., associate professor in the Gene Expression & Regulation Program in the Ellen and Ronald Caplan Cancer Center, at The Wistar Institute, and collaborators demonstrates that an epigenetically active compound called decitabine disrupts the genome of EBVaGC by epigenetically modifying the cancer’s DNA, a finding that offers the potential for a new approach to treating EBVaGC.

“What we have identified is essentially a self-destruct button within this kind of cancer, and our paper shows that we figured out how to press that self-destruct button,” said Tempera. “Normally, a latent virus that reactivates and starts to kill cells is a bad thing. But by switching that viral lytic process back on in these cancer cells by using epigenetic signaling, we’re effectively getting the virus to kill the cancer cells that it’s responsible for in the first place.”

The research — supported by a research program project grant, otherwise known as a P01-series grant, from The National Institute of Health (NIH) — includes scientists from The Wistar Institute, The Coriell Institute for Medical Research and Brigham and Women’s Hospital of Harvard Medical School.

In EBVaGC, the cancer cells’ DNA is hypermethylated: the DNA contains a high percentage of cytosine with a 5-methyl group attached to it (relative to normal, unmethylated cytosine). As a silencer of gene expression, DNA methylation allows EBV to remain latent. This methylation pattern plays a significant role in regulating the EBV latency-lysis cycle within the cancer cells. DNA methylation, as an epigenetic factor, usually functions as a gene-silencing mechanism, particularly in certain regions of the genome; a methylated gene still exists within the genome — methylation does not delete the genetic information — but methylation can prevent the protein the gene encodes from being transcribed.

To disrupt this epigenetic profile, the researchers turned to decitabine, a compound known for its ability to reduce DNA methylation levels (i.e., to hypomethylate the DNA). Tempera and his co-authors treated two cell lines that were derived from EBVaGC tumors with decitabine. The cell lines that received the treatment demonstrated massive reductions in DNA methylation across the genome relative to the control as assessed by a variety of epigenetic assay techniques.

In observing the effects of decitabine treatment on EBVaGC, Tempera’s team found a significant disruption of the cancer’s epigenetic profile. The EBV genome within EBVaGC treated with decitabine resulted in widespread, mostly uniform hypomethylation of the EBVaGC epigenome (with a few regional exceptions). Tempera and his co-authors discovered that the hypomethylating effect of decitabine treatment reactivated the lytic cycle of the latent EBV in the cancer cells. Because lysis is lethal to cells, the epigenetic reactivation of lysis within gastric cancer associated with EBV offers a promising potential treatment for the specific subset of EBVaGC.

“Now we know that we can use the epigenome of Epstein Barr Virus against the gastric cancer that it affects — that’s an exciting potential cancer therapy we have as a result of investigating the interplay between epigenetic patterns and disease lifecycle,” explained Tempera.

Co-authors: Sarah Preston-Alp, Lisa Beatrice Caruso, Chenhe Su, Samantha S. Soldan, Davide Maestri, Andrew Kossenkov, Giorgia Napoletani, Paul M. Lieberman and Italo Tempera of The Wistar Institute; Kelsey Keith and Jozef Madzo of The Coriell Institute for Medical Research; and Benjamin Gewurz of Brigham and Women’s Hospital of Harvard Medical School.

Work supported by: National Institutes of Health (NIH) grants P30 CA010815, R01 AI130209, R01 GM124449, P01 CA269043, R01 DE017336, R01 CA259171, R01 CA09360, R01 AI1535086, R01 AI164709, R01 CA228700, U01 CA275301, R50 CA211199 and T32 CA09171.

Publication information: “Decitabine disrupts EBV genomic epiallele DNA methylation patterns around CTCF binding sites to increase chromatin accessibility and lytic transcription in gastric cancer” from mBio.

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The Wistar Institute, the first independent, nonprofit biomedical research institute in the United States, marshals the talents of an international team of outstanding scientists through a culture of biomedical collaboration and innovation. Wistar scientists are focused on solving some of the world’s most challenging and important problems in the field of cancer, infectious disease, and immunology. Wistar has been producing groundbreaking advances in world health for more than a century, consistent with its legacy of leadership in biomedical research and a track record of life-saving contributions in immunology and cell biology. wistar.org.

Dr. Paul Lieberman talks with two scientists in the lab

Wistar-Led Team Awarded More Than $12 Million Grant from the NCI to Investigate Link Between Epstein-Barr Virus and Carcinomas

Written by The Wistar Institute on . Posted in Press Releases.

PHILADELPHIA — (JULY 26, 2023) — It’s been known since the 1960s that Epstein-Barr Virus (EBV) causes a variety of cancers, but research has overwhelmingly focused on its connection to lymphomas. Now, a multidisciplinary team of scientists led by The Wistar Institute has been awarded a more than $12 million National Cancer Institute (NCI) Program Project Grant (P01), a highly competitive five-year grant that includes a cross section of researchers from various disciplines and institutions throughout the country. The multidisciplinary team led by Wistar scientists is exploring the role of Epstein-Barr Virus in epithelial cancers. Epithelial cells form functional structures in organ tissue throughout the human body; they are often the site for solid organ cancers, including the most common cancers, which are known as carcinomas.

The new research will focus on basic questions about how EBV infection of normal epithelial cells transforms them into cancer-cells. Scientists also intend to build on this research to identify better and more selective therapeutic targets.

“We are investigating unexplored aspects of EBV and malignancies, potentially uncovering unique characteristics or pathways that can be targeted for therapeutic intervention,” said Italo Tempera, Ph.D., associate professor of the Gene Expression & Regulation Program of the Ellen and Ronald Caplan Cancer Center at The Wistar Institute. “This fresh perspective could lead to groundbreaking discoveries and innovative treatment strategies for EBV and epithelial malignancies.”

The project brings together scientists from The Wistar Institute and Harvard University, including experts in epigenetics, metabolomics and drug discovery. It’s the first time researchers from this variety of disciplines have combined their efforts to focus entirely on the EBV-epithelial cancer link.

“We’ve put together a new strategy, a new way of attacking the problem,” said Paul Lieberman, Ph.D., Hilary Koprowski, M.D., Endowed Professor and director of the Center for Chemical Biology and Translational Medicine at Wistar. “By working together across different modalities, there’s an opportunity for each of us to learn from the synergy and expertise of the other investigators.”

EBV is one of the most common human viruses, infecting an estimated 95% of people by the time they reach adulthood. Symptoms are usually mild, and most people recover within a few weeks. However, the virus can remain latent in the human body for years or even decades, and it causes some people to develop cancer later in life.

While research has historically focused on lymphomas, EBV-linked epithelial cancers are both more common and more deadly. Epithelial cancers represent 75% of the 200,000 EBV-related cancer cases diagnosed each year, and these cancers also have higher mortality rates and treatment failures.

“This grant put together a team that is now focused on this type of cancer that has been neglected, even though it’s the most common form of EBV cancers,” Lieberman said. The grant will fund three main research projects. The first will look at how EBV establishes a long-term infection within epithelial cells. The second will study how it causes genetic and metabolic changes to trigger cancer growth. Finally, researchers will use these findings to investigate new therapeutic strategies.

The research builds on past work by Lieberman’s lab, which has focused on developing small molecule inhibitors targeting EBV. He said the new project would focus on studying drugs that are already in development, and looking for ways to make them more targeted or use them in combination with other therapies.

Tempera said the group’s integrated approach sets it apart.“Our project will study both metabolic and epigenetic vulnerabilities simultaneously,” he said. “Combining these two aspects can provide a comprehensive understanding of the role of EBV infection in cancer and its underlying mechanisms, leading to unique insights and therapeutic opportunities.”

Co-authors: Ben Gewurz of Harvard; Joseph Salvino, Samantha Soldan, Andrew Kossenkov, Louise Showe, and Qin Liu of Wistar.

Scientists Drive Innovation at Wistar’s Ellen and Ronald Caplan Cancer Center

Written by The Wistar Institute on . Posted in Featured News.

Wistar continues to be a dynamic environment prepared to tackle biomedical challenges in a collaborative, innovative, and inclusive culture. Read more about our Ellen and Ronald Caplan Cancer Center commitment to scientific career development, a diverse research community, and how previously introduced recruits are settling in and advancing impactful science.

ENHANCING CAREERS AND EXPANDING DIVERSITY

Italo Tempera, Ph.D., newly appointed Associate Director for Cancer Research Career Enhancement, was a postdoctoral fellow at Wistar and returned as an associate professor in the Gene Expression and Regulation Program in 2020. His research focuses on epigenetic mechanisms behind Epstein-Barr Virus (EBV). He was recently named associate director for Cancer Research Career Enhancement.

Tempera considers the time he spent at Wistar to be formative. With its very collaborative introductory environment, Wistar is an “… opportunity for our students not only to learn about our science but to get in contact with scientists.”

Furthermore, he outlines what he would like to accomplish in his new role. “We’re outstanding scientists and we have excellent mentors. The opportunities for our trainees to do an internship with different departments is something we want to push forward, and we want to expand the Cancer Biology Ph.D. program that we have now with Saint Joseph’s University.”

He shares that Wistar gave him the opportunity to grow as a scientist and advance in his research career. “When someone asks what was one of the most important aspects of a scientist’s pre- or post-doctoral training, my goal is for the trainee to think back and reply that being at Wistar has made all the difference.”

Jessie Villanueva, Ph.D., newly appointed Associate Director for Diversity, Equity, and Inclusion, joined Wistar first as a postdoctoral fellow and then was appointed assistant professor in the Molecular and Cellular Oncogenesis Program. Her work aims to identify targets for therapy to treat melanoma.

“Diversity leads to innovation and scientific excellence. New discoveries and scientific breakthroughs often rely on collaborations, and diverse teams are more creative and resourceful,” she shares.

For her new role, Villanueva aims to lead and inspire everyone at Wistar to integrate inclusion, diversity, and equity into all facets of the Institute. “Our goal is to continue fostering an inclusive community where everyone can develop to their full potential while contributing to Wistar’s mission of scientific discoveries.” To accomplish this, she plans to work with leaders and stakeholders across the Institute to identify challenges and areas for
improvement and propose strategies to address them.

“Diversity supports Wistar’s mission,” Villanueva asserts. She elaborates that many of the Institute’s scientific breakthroughs are largely impactful for biomedical sciences and human health, and these discoveries rely on “… outstanding scientists, trainees and staff with diverse backgrounds and skills who support Wistar’s goals wholeheartedly.”

ADVANCING IMPACTFUL SCIENCE

Nan Zhang, Ph.D., Assistant Professor, Immunology, Microenvironment & Metastasis Program, joined Wistar in September 2021 as an assistant professor and currently researches how immune cells play a role in tumor growth in abdominal cancers.

“Studying disease was always one of my passions,” Zhang shares as he describes both a personal and professional draw to cancer research. He began his career studying the immune system — particularly macrophages, a special population of white blood cells that removes unwanted materials in the body like harmful microorganisms or dead cells.

Upon completion of his postdoctoral position, Zhang felt that cancer in the peritoneal space — the area of the body encompassing the abdomen and the organs within it — would be a great direction to pursue for his future career because of its unique complexity and how it’s less understood relative to other focus areas for cancer research. This is what he works on now at Wistar.

Immersed in the Institute’s world class techniques, resources, and renowned scientists, Zhang continues to push forward his research to tackle how to use specialized cells called macrophages to combat tumors as a checkpoint therapy for cancer. He is also investigating immunological questions about the microenvironment of the peritoneal space and how this knowledge can help inform therapeutics and treatment development.

He shares, “Wistar is competitive, and the support in the Institute for junior faculty is great. We have meetings every week and this is an environment I really wanted for my career and research.”

Noam Auslander, Ph.D., Assistant Professor, Molecular & Cellular Oncogenesis Program, joined Wistar in June 2021 as an assistant professor and conducts her research at the intersection of computer science and biological science. She uses machine learning to investigate genetic factors underpinning cancer evolution to improve diagnostics and therapeutics.

“I work on cancer and viruses. Both are complex and have high mutation rates. As a computational scientist, it’s very interesting because there are a lot of computational challenges that can be investigated,” Auslander comments.

She joined The Wistar Institute because of its reputation and expertise, particularly in researching both cancer and viruses. She shares her experience during her first year, “It’s a small institute with a lot of opportunities to collaborate. It’s a very good environment and people are very helpful and supportive.”

Simultaneous to establishing and expanding her lab group, Auslander is currently looking into improving clinical prognosis to cancer and other diseases by uncovering unknown infectious agents and therapeutic biomarkers. To accomplish this, her lab applies the power of advanced computational platforms to very intricate and complex biomedical data to make these predictors of treatment responses more biologically interpretable. She says, “My main focus at the moment is to train my growing lab and develop frameworks to identify new viruses and eventually new microbiomes in cancer.”

An Epstein-Barr virus cell

Wistar Scientists Reveal New Hypothesis in How Epstein-Barr Virus Hijacks a Host

Written by The Wistar Institute on . Posted in Featured News.

Newly published research identifies proteins in EBV-infected cells that decreased expression of genes linked to the spread of the virus, a fresh direction for EBV research.

Epstein-Barr virus is a common, long-lasting virus that affects most individuals. While those infected are often asymptomatic, the virus has been linked to various immunocompromising diseases and cancers—popular news recently reported on a strong connection to Multiple sclerosis (MS). Published in PLOS Pathogens, a new collaborative study led by Italo Tempera, Ph.D., revealed how lamins – proteins in the nucleus of a cell – could affect EBV replication in host cells by influencing the virus genome, ultimately changing how virus genes function.

When a virus such as EBV infects cells, it invades the nucleus of host cells to replicate and spread. Previous research by Tempera – Associate Professor of The Wistar Institute Gene Expression & Regulation Program and Associate Director for Cancer Research Career Enhancement at Wistar’s Ellen and Ronald Caplan Cancer Center – showed that changes to the virus genome helps EBV sustain its infection in hosts.

“Viruses don’t reinvent but use existing machinery,” says Tempera. “EBV has evolved to take every mechanism the host uses to regulate its presence in the nucleus, and it has such profound consequences for the genome that are really fascinating.”

To investigate how genes are regulated to lead to this persistent infection, Tempera and colleagues infected and imaged genetically altered B cells, a type of immune cell. They also employed sequencing to study the virus genome. The team found that lamins – specifically lamins A/C – repressed gene expression linked to replication of the virus’s genetic material.

The team also observed that the infection of B cells with EBV produced the same effect as the activation of B cells by T cells in an immune response. This copying of B cell biology by the virus may help explain why EBV is latent (not recognized by the immune system right away) and further clarify how host cells respond to the invasion of EBV into the nucleus.

“It’s a very basic mechanism,” he says, “but one that can give us a lot of good ideas about how the virus can hijack the host. It’s a really new angle.”

Tempera hopes this work will open new directions in which to study viruses and inspire other researchers to explore how viruses interact with hosts. Regarding therapeutic potential, he muses that with more research, scientists might be able to identify targets for EBV infection that could prevent or turn off genetic expression in cancer. “That could be the long haul of how you move this basic science into something more practical.”

Dr. Italo Tempera poses at his desk with one of his antique microscopes

Zooming in on Microscopes at Wistar

Written by The Wistar Institute on . Posted in Featured News.

From historic machinery in one of our own investigator’s personal collection to the modern technology transforming Wistar research today, microscopes have helped Wistar scientists and researchers around the world pursue innovative investigations.

A Curious Collection

On a wooden desk sits 14 historical microscopes assorted in neat rows, gleaming a metallic gold in the office lighting. Manufactured between the 1800s-1900s in England and France, the instruments make up the personal collection of Dr. Italo Tempera, Associate Professor of Wistar’s Gene Expression & Regulation Program and Associate Director for Cancer Research Career Enhancement at Wistar’s Ellen and Ronald Caplan Cancer Center.

Tempera was interested in microscopy from a young age. “I started with biology when I was 13. I had a microscope at home,” he recalls. “I always wanted to collect and then at the beginning of the pandemic, I got the first one.” The microscope he refers to was made in 1830 in London and is the same kind of model that Darwin had. He also points out another model he finds most intriguing. Manufactured in France, the instrument was sold in Philadelphia from a shop on Chestnut Street, according to an inscription on the scope’s wooden box.

“We learn through our eyes. Microscopy is important because microscopes can reveal a lot of things we may not see through our experiments.” Tempera comments. “When you have a very powerful microscope image, you can really show and deliver your messages.” he continues.

The valuable knowledge that microscopes have given the scientific field – including how our cells work and are organized – emerged from these tools. In fact, Tempera and his colleagues recently used one from his collection (circa. 1890s – early 1900s London) to look at cancer tissue. “It was pretty good actually.” Tempera reveals in happy surprise.

The Horner Microscope

Tempera’s collection are not the only historical microscopes housed at The Wistar Institute. Nestled behind a glass display in the first floor Atrium is a microscope from 1830 made for Philadelphia anatomist William E. Horner. Made by Austrian optical instrument maker Simon Plossl, this microscope is still functional today. In 2017, Wistar’s Imaging Facility Managing Director James Hayden used the Horner microscope to image tumor cells and reconstructed skin from Wistar labs. He imaged the same samples with a modern Nikon microscope in Wistar’s Imaging Facility and compared the results.

“One of the things that surprised me was just how good it was. The fact that you could still separate cells and you could still see nuclei means that people 150 years ago could see the same stuff we can see now.” Hayden shares. “Even though technology has marched ahead, the basics haven’t changed much.”

What has changed with advances in microscopy is how images are used in scientific research. “The images are not just documentary anymore. They can be quantified. They become the data.” Hayden emphasizes.

Modern Microscopy at Wistar

Now many types of advanced microscopes exist, enhanced by the innovative technology of today’s world. From confocal microscopy to electron microscopy, the ability to magnify and quantify what would normally go unseen has expanded. Wistar research is helped tremendously by such powerful microscope technology at the Imaging Facility. For example, the Facility has imaged drug treatments on melanoma cells, stitched tissue images together, and recorded live cell behavior over mere milliseconds.

As a Shared Resource, Wistar’s Imaging Facility impacts diverse realms of research both internal and external to the Institute. “We have biological questions that need to be answered, so we take our existing technology, and we work with our industry partners to come up with new ways of imaging something to bypass the problem.” Hayden describes.

Whether it is virology or anatomy, biochemistry or chemical engineering, microscopy can be applied. Hayden says that it is the “investment in a facility that can keep up with the technology and more importantly, the hiring of people that can continually train others to support research” that makes microscopy at The Wistar Institute special.

Microscopes at Wistar
Dr. Italo Tempera in the lab with two lab members

Wistar Scientists Identify Therapeutic Target for Epstein-Barr Virus

Written by The Wistar Institute on . Posted in Press Releases.

PHILADELPHIA — (Jan. 17, 2022) — A new study by researchers at The Wistar Institute, an international biomedical research leader in cancer, immunology, infectious disease, and vaccine development, has identified a new potential pathway for developing therapeutics that target Epstein-Barr virus (EBV). They discovered that the way the EBV genome folds, and thereby expresses itself and causes disease, is more complex than researchers originally thought, and they identified molecules that could be targeted to disrupt this folding.

“We identified two cellular proteins that are important to folding the EBV genome.” said Italo Tempera, Ph.D., associate professor in the Gene Expression & Regulation Program at The Wistar Institute and corresponding author on the paper. “There are existing drugs that target one of these proteins. And our data suggests that if we use that drug on EBV infected cells, we have a way in which we can actually interfere with the folding. That means we can interfere in the way in which the EBV viral genome is functioning.”

EBV, which affects more than 90% of individuals worldwide, is a dynamic virus, meaning that it can change its gene expression. If certain viral genes are expressed, the virus infects B-cells and causes them to overmultiply, which is especially problematic in individuals with suppressed immune systems, such as transplant patients.

Tempera and his colleagues wanted to understand the mechanics behind how the virus manipulates its genetic expression. To do this, they used a modified DNA sequencing technique to examine how the genome folds under different conditions.

“The virus was clever to use the same machinery that regulates the conformation of the human genome to also regulate its own gene expression,” said Tempera. Specifically, the researchers found that EBV uses two proteins, CTCF and PARP1, that also play a role in the expression of the human genome.

PARP1 is already a target of the drug, olaparib (sold under the brand name Lynparza), which is used to treat patients with ovarian cancer. This new study suggests that the drug may have a use for treating EBV positive lymphomas, as well.

“Usually PARP1 is targeted in the context of DNA damage,” said Tempera. “Our paper shows that there is another role of PARP1 in the chromatin folding, so this suggests that maybe we can expand the way in which we can use this drug not only to interfere with DNA damage, but we also might interfere with DNA folding and gene expression, which is something that we are testing now in the lab.”

Co-authors: Sarah M. Morgan, Lisa Beatrice Caruso, Andrew Kossenkov, Sarah Boyle, Paul M. Lieberman, and Italo Tempera from The Wistar Institute; Hideki Tanizawa from University of Oregon; Michael Hulse from Fels Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine at Temple University; Jozef Madzo and Kelsey Keith from The Coriell Institute for Medical Research; Yinfei Tan from Fox Chase Cancer Center.

Work supported by: National Health Institutes (NIH) grant R01 AI130209.

Publication information: The Three-Dimensional Structure of Epstein-Barr Virus Genome Varies by Latency Type and Is Regulated by PARP1 Enzymatic Activity, Nature Communications, 2022. Online publication.

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The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. wistar.org.

Viruses and Cancer

Written by The Wistar Institute on . Posted in Featured News.

Viruses impact human health in many ways and can be the underlying agents that cause cancer.

The pandemic has reminded us how pervasive viruses are in human life. We know they can cause infection, making us very sick, but did you know that about 15 percent of all human cancers worldwide may be attributed to viruses?

Drs. Paul Lieberman, professor, and Italo Tempera, associate professor, both in the Gene Expression & Regulation Program of The Wistar Institute Cancer Center, investigate the link between the Epstein-Barr Virus (EBV) and malignant transformation to find ways to treat EBV-related cancers.

EBV is a very common virus. You know it as mononucleosis, and it is spread through saliva, but also through sexual contact, blood transfusions and organ transplants. It mostly infects B cells, a type of white blood cells that produces antibodies. The majority of the world population is infected and carries the virus in a silent state for life. However, in people with compromised immune systems, EBV increases the risk of B-cell lymphomas including Burkitt’s lymphoma and Hodgkin’s lymphoma.

Since it can also infect other types of cells, this virus is not only associated with blood tumors, but also with ten percent of all gastric cancers and most cancers of the nasopharynx, the region behind the nose and above the back of the throat.

How are viruses implicated in cancer?

They are particles made up of DNA or RNA surrounded by a protein coat. With such frugality comes the lack of the necessary machinery to replicate their genome or build proteins, so viruses hijack a host cell and use its machinery to make copies of themselves. In the case of oncogenic or cancer-causing viruses, this process can meddle with the cell’s genes and derail the mechanisms that keep cell proliferation in check, leading to uncontrolled growth.

Oncogenic viruses establish chronic but latent infections that don’t cause obvious symptoms in healthy individuals, because their immune system keeps infection at bay. In immunocompromised people, however, viruses are more likely to cause malignancies.

One approach to control EBV infection is by interfering with the complex and dynamic patterns of how viral genes are switched on or off — a process known as gene expression. The Tempera lab has explored the role of gene expression in the regulation of EBV latency, unveiling some viral and host cell factors that play key roles in regulating these patterns.

An EBV protein called latent membrane protein 1 (LMP1) is essential for the virus’s ability to make B cells cancerous.

The Tempera lab studies just how this protein affects the host cells. They discovered that LMP1 affects the function of an enzyme called poly(ADP-ribose) polymerase 1 (PARP1) and that inhibiting this protein suppresses malignant transformation, uncovering an important role of PARP1 in EBV-induced oncogenesis.

In a recent paper1, Tempera and colleagues demonstrated that LMP1 causes a switch in how infected cells produce the building blocks of fat that support tumorigenesis and cancer progression. Researchers also showed that targeting these metabolic changes could be an effective therapeutic strategy to treat EBV-associated cancer and that PARP1 inhibitors offset the metabolic changes caused by LMP1 that drive tumorigenesis.

“We have uncovered a potential new use for PARP inhibitors, which are currently used to treat recurrent ovarian cancers in women who have defects in their DNA repair system,” said Dr. Tempera. “Repurposing existing drugs saves time and money in the process of creating new therapies.”

Dr. Tempera joined Wistar as an associate professor in 2020, but that was not his first time working at the Institute. He had trained as a postdoctoral fellow in the Lieberman lab, which helped him launch his career in cutting-edge research on the epigenetic mechanisms underlying EBV infection. Returning to Wistar with his lines of research as an established investigator, he strengthened our program on virology and cancer.

“The outstanding scientific environment and technological support that benefited me during my training are a strong asset to further expand my research program.”

The lab of his mentor Dr. Lieberman is a reference point for EBV research as they have made seminal discoveries in the field and described several mechanisms that control replication and gene expression in latent EBV infection. One focus of their research is the Epstein-Barr nuclear antigen 1 (EBNA1) protein that is essential for efficient viral DNA replication. The team has been pursuing the development of small molecule inhibitors of EBNA1 as potential treatment against EBV-associated malignancies.

One of the lab’s latest studies2 led to an important basic discovery in the field, expanding the understanding of EBNA1’s function and providing new possibilities for inhibiting EBNA1 activity as an anticancer strategy.

The link between virus infection and human cancer is a complicated matter to unravel and has been studied for more than 100 years. The research underway in the Tempera and Lieberman labs is crucial to understanding the role viruses play in malignant transformation and hopefully finding future treatments to halt this process.

1 Epstein-Barr Virus-Encoded Latent Membrane Protein 1 and B-Cell Growth Transformation Induce Lipogenesis through Fatty Acid Synthase, J Virol, 2021
2 Cell-cycle-dependent EBNA1-DNA crosslinking promotes replication termination at oriP and viral episome maintenance, Cell, 2021

Dr. Italo Tempera

The Wistar Institute Appoints Italo Tempera, Ph.D., as Associate Director for Cancer Research Career Enhancement of Its Cancer Center

Written by The Wistar Institute on . Posted in Press Releases.

PHILADELPHIA — (Aug. 31, 2021) — The Wistar Institute announces the appointment of Italo Tempera, Ph.D., as Associate Director for Cancer Research Career Enhancement at the Institute’s Cancer Center. In this role, Tempera, who is also an associate professor in the Gene Expression & Regulation Program, will lead the educational mission of the Institute and its Cancer Center to train scientists and create workforce development programs in the life sciences.

Tempera will be working closely with Cancer Center faculty and the Dean of Biomedical Studies to coordinate the diverse Cancer Center educational initiatives, expanding and strengthening partnerships for high-school, undergraduate, graduate and postdoctoral training programs in cancer biology.

Graduate and postdoctoral training programs leverage Wistar’s close collaborations with neighboring and international world-renowned academic institutions, including the University of Pennsylvania, Drexel University, University of the Sciences, University of Bologna, Italy, and Leiden University, Netherlands, for experiential training in Wistar laboratories.

Wistar’s Biomedical Technician Training (BTT) Program and Biomedical Research Technician (BRT) Apprenticeship, built on meaningful collaborations with the Community College of Philadelphia, Cheyney University and a growing list of partnering educational institutions and biotechnology companies, are uniquely tailored to support talent development, customized skills and workforce training to best prepare students for job opportunities in the life sciences ecosystem.

“We are grateful to Italo for taking on this role that comes with important responsibilities for the cultivation of scientific talent and the training of future generations of cancer researchers,” said Dario Altieri, M.D., president and CEO of The Wistar Institute, director of the Cancer Center and the Robert & Penny Fox Distinguished Professor.

Tempera’s research is focused on the Epstein Barr virus (EBV) and how it regulates expression of its genes in the host cell during infection. Since EBV infection has a causative role in the development of some types of cancer in people with a compromised immune system, the Tempera lab aims at disrupting the natural capacity of EBV to modulate gene expression as a new approach for treating EBV-associated cancers.

“This is a time of substantial growth across Wistar’s education programs and I am thrilled by the opportunity to play a part in this process,” said Tempera. “Looking back to my own early career steps, education and training are probably the most exciting periods for a scientist, because they come with the realization of the vast potential for their career growth and for their ability to make impactful discoveries.”

Tempera graduated with a B.Sc. in molecular biology and a Ph.D. in biochemistry from the Sapienza University of Rome, Italy. Before joining Wistar in 2020, he was an associate professor at the Lewis Katz School of Medicine of Temple University.

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The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. wistar.org.