Skip to main content

Tag: Liang

Unraveling The Enigmas of Melanoma

Meenhard Herlyn, D.V.M., D.Sc., is known internationally as one of the fathers of melanoma research. As the founder of The Wistar Institute Melanoma Research Center, he has led the way with breakthrough discoveries about this mysterious and hard-to-treat cancer. A highlight of his work includes building Wistar’s collection of patient-derived xenografts — a groundbreaking tool that allows tumor cells to be implanted into models for melanoma research.

Now, a new generation of melanoma researchers are building on that foundation. This up-and coming-scientific force includes Chengyu Liang, M.D., Ph.D., a rising star in studying how UV exposure damages cells.

“Dr. Herlyn is a great mentor and a great scientist,” Liang said. “He established the platform, the foundation, that has been indispensable not only for Wistar melanoma research, but for the entire melanoma research field.”


“One of the guiding forces in our research has been to mimic human disease, to figure out what makes cells become cancer, and to use this knowledge for new strategies to develop therapies,” Herlyn said.

One of these strategies involves the use of artificial skin. Lab-grown skin had previously been developed for wound healing. Using this existing technology, Herlyn pioneered its application to melanoma research. Herlyn’s team was the first to use artificial skin to grow and study melanocytes — normal pigment cells — which they have used to understand how cancer cells form and how to make treatment more effective.

“We wanted to really know what tumor cells do, and to understand that, we first need to know what normal cells do and where the tumor cells come from,” he explained.

Herlyn joined Wistar in 1976 and spent the early years of his career focused on developing monoclonal antibody treatments, a breakthrough drug that mimics or enhances the immune system’s natural disease fighting activity to attack cancer cells.

One of Herlyn’s frequent collaborators during this time was his wife, Wistar scientist Dr. Dorothee Herlyn, who is now retired. “She was the immunologist of the family,” he said. Together, they helped develop a number of monoclonal antibody molecules, some of which are still used in cancer therapies today.

Herlyn is also behind Wistar’s patient-derived xenograft program which supports a collection of patient cancer tissues. These samples can be implanted into genetically altered mice to more closely mimic conditions in the human body. It’s a powerful tool scientists can use to conduct cancer experiments and test new treatments under conditions that more closely mimic the disease in humans.

“We now have more than 500 tumors from patients,” Herlyn said. “These come directly from the patient and are implanted without ever being cultured, making them much more like real life tumors.”


Dr. Liang didn’t set out to study melanoma. Originally trained as a medical doctor, she became a research scientist with the mission of improving patient outcomes. Her drive to understand cancer and develop better treatments became more personal after her mother passed away following a two-year battle with cancer.

“When someone you love has cancer, you’re trying to find answers. Why did this person have cancer? Why is this treatment not helping?” she said. “Eventually, that drove me to get my Ph.D. in medical science. I wanted to know more.”

Liang initially focused her research on tumor virology, studying how viruses cause cancer. During her research, she encountered a gene called UVRAG that piqued her interest in melanoma.

Previous work had found that this gene seemed to be involved in protecting skin cells from UV radiation, but the mechanism behind it was unclear. Liang’s team showed how the gene repaired DNA damage from UV radiation, and that disrupting the gene could increase a person’s risk of melanoma and other skin cancers. They nicknamed UVRAG the “sunscreen gene.”

The finding sparked many questions about how UV radiation causes genetic mutations that lead to cancer. “The question we asked is, ‘What makes melanoma melanoma?’” she said.

One thing that sets melanoma apart is its extremely high rate of genetic mutations — much higher than other cancers. “It’s in the skin, which is where the body interconnects with the environment and UV radiation, so in a way, that’s not surprising,” she explained.

Liang’s recent research has focused on identifying signs of DNA-repair deficiency as an early sign of damage that can trigger melanoma-driving mutations. “If we can find genetic signs that can predict this process, we might be able to catch the disease much earlier,” she noted.


Herlyn not only laid the groundwork for Liang and fellow cancer researchers. He also serves as a leader and mentor who is generous with his knowledge and support, Liang said. “He’s like a big dictionary of melanoma,” she described. “When you have a question, he can always share something instructive.”

This philosophy of collaboration, Herlyn shared, has been a driving force in his work. “One of the major strengths at Wistar has been our flexibility and our ability to look for collaborators,” he pointed out. “My approach has always been to look for the best people I could work with.”

This has included a longtime collaboration with oncologists, pathologists, and other clinical colleagues at the University of Pennsylvania as well as other institutions. “I’ve always believed strongly in a good connection between the laboratory and the clinician,” he said.

Herlyn also helped found the Society for Melanoma Research, the first ever medical conference dedicated to bringing together researchers, clinicians, and patients to share knowledge about melanoma. Liang emphasized that with such a complex and unique disease, it’s critical for scientists to work together to find new diagnostic tools and treatments.

“There’s still a lot of mystery,” she stated. “Despite all the tremendous progress we have made in the melanoma field, I think we are still at the tip of the iceberg.”

Discussing the Mysteries of Melanoma

A Q&A with Drs. Chengyu Liang and Meenhard Herlyn on skin cancer research at The Wistar Institute, including a few questions from melanoma survivors.

Melanoma is the most aggressive form of skin cancer. Work at The Wistar Institute’s Melanoma Research Center aims to understand the biology behind the disease to help develop new therapies and improve existing treatments. In this Q&A, we spoke with Dr. Chengyu Liang, a professor in the Molecular & Cellular Oncogenesis Program at Wistar’s Ellen and Ronald Caplan Cancer Center who joined Wistar in 2020 and Dr. Meenhard Herlyn, director of The Wistar Institute Melanoma Research Center and Professor in the Molecular & Cellular Oncogenesis Program. The research they conduct aims to have impacts on melanoma patients and survivors. Thus, this National Melanoma and Skin Cancer Awareness Month, we included questions from melanoma survivors and staunch Wistar supporters Eleanor Armstrong and Pat Dean who organize an annual fundraiser walk for the Institute’s melanoma research program.

Dr. Liang, what attracted you to studying melanoma?

Dr. Chengyu Liang: My passion and curiosity! A few years ago, we identified a so-called “sunscreen” gene that helps cells to repair after they have been damaged by UV rays; and we know that UV-induced DNA damage is a major risk factor for melanoma – the most aggressive type of skin cancer. This inspired us to find out more about how this genetic sunscreen system plays in human beings and what it means to melanocytes (the origin of melanoma) and melanoma when the system is running out of order.

What are you working on now specifically regarding melanoma and what is this work’s potential impact on cancer treatments?

CL: The question that we are always intrigued by is: What makes melanoma melanoma? Compared to most other types of human cancers, one striking feature of melanoma is that its genome is flooded with mutations associated with UV-induced damage. Now, the burning questions are: What drives such genetic change? What are the molecular mechanisms underlying the UV-footprint in melanoma? Understanding these mechanisms not only enable early-risk prediction but also help oncologists and researchers to develop cancer treatments with responses that have long-term durability.

Second, melanoma originates from an easily spread and multipotent cell population, which can help explain the inborn aggressiveness and treatment resistance of the skin cancer. In addition to targeting specific pro-cancer mechanisms to kill cancer cells that are often, if not always, encountered by tumor resistance, is it possible to force cancer cells to resume the process of normal growth control or differentiation? To this end, we are trying to understand the molecular mechanisms that control melanoma differentiation. This work holds promise to identify new vulnerabilities in melanoma that can be targeted to revert the negative effects of mutations and strengthen anti-tumor immune responses to melanoma.

How important is a person’s immune system in preventing skin cancer and is there anything that can be done to strengthen a person’s immune system against melanoma?

CL: It can’t be more important! Our immune system is like the ‘shepherd’; its duty is to keep ‘sheep’ protected. Melanoma is like the ‘wolf’. A powered immune system is an experienced shepherd that could easily and quickly identify and target the wolf in the flock and clear it up. As a matter of fact, what immunotherapy does is release the built-in brake system of our immune system and revive and direct its killing energy to cancer cells.

The immune system is an ecosystem – a complex network of cells, tissues, and organs that orchestrate to maintain homeostasis to protect human bodies against internal and/or external assaults. If a well-balanced immune system is considered healthy to life, a well-balanced life would also be considered beneficial to the immune system. Many tips have been suggested such as healthy diet, exercise, mental and physical support, etc. Notably, fasting and calorie restriction (CR), have been shown experimentally and in clinical trials, to be able to slow and even stop the progression of cancer, kill cancer cells, boost the immune system, and significantly improve the effectiveness of chemotherapy and radiation therapy. With our growing understanding of this sophisticated system, we might be able to come up with more effective strategy to boost it or manipulate it to outsmart cancer.

You’ve previously done research on UV radiation causing mutations that contribute to melanoma. What are some daytime hours that have the highest risk of damaging UV radiation and sun exposure?

CL: This depends. The lighter the skin, the more sensitive to sunburn and/or skin damage by UV rays. Human skin pigmentation is an evolutionary adaptation to UV radiation. Fair skinned people may easily burn within 20 minutes of exposure to direct sunlight, thus wearing a broad-spectrum sunscreen is always encouraged. Certainly, you also want to have a strong genetic sunscreen system as noted before.

What future directions will you take your work?

CL: Our ultimate goal is to make melanoma a curable disease. The current challenge is that we still have more than 50% of melanoma patients who are not responsive to any treatment. We need to solve this puzzle. We also need to figure out what’s the right therapy to be used for the right patient at the right time. Why does therapy work in some patients, but not others? We believe that prevention is the most effective treatment of melanoma. Thus, identifying a new biomarker for early detection is equally important and urgent. All these challenges depend on a deeper understanding of the biology of melanoma as a cancer, and the biology of melanoma interaction with the human body as a system.

Dr. Herlyn, why is building the cancer research talent at Wistar important (eg. Dr. Chengyu Liang joining the Cancer Center)?

Dr. Meenhard Herlyn: Every research field needs a critical mass of researchers, both junior and senior. Any institution needs ‘new blood’, meaning investigators who may have experience, knowledge, and connections in the critical field. Dr. Liang brings important expertise not only to Wistar but the entire larger field here and beyond. Her work on DNA damage and repair fills an important gap for us.

What would you like to see for the future of melanoma research at Wistar?

MH: Melanoma has been a major focus for research at Wistar. We have developed a strong outreach program in which we collaborate not only with our colleagues at Penn but also with numerous national and international research laboratories. Melanoma research at Wistar should remain multi-disciplinary. Our strong biology is the foundation and platform for collaborations that ensure continuing progress. Melanoma investigators should incorporate cutting edge technologies and strategies. We have developed strong ties to our clinical colleagues, and we expect that in the future these ties will strengthen as our research more and more directly benefits patients. Thus, we not only translate research from bedside-to-bench but also from bench-to-bedside.

Why are supporters such as those fundraising and donating to the Institute important?

MH: There are many areas of research that are essential to run a successful program but that cannot be funded through National Institute of Health or industry grants. For example, there are meetings with other scientists to exchange ideas and develop new collaborative strategies, seed funding for new projects that are still in the exploratory phase, collaborations with clinicians for specimens and preparing reagents for diagnostic studies, developing high risk/high gain projects and ideas, and obtaining new research tools. Supporters like our donors and fundraisers are integral to our work at Wistar, without whom we could not have as great an impact as we do.

Wistar’s Women and Science Program Talks Melanoma Research

After a day of virtual scientific talks that concluded Wistar’s 4th annual Noreen O’Neill Melanoma Research Symposium, a lay-friendly examination of melanoma with a group of interdisciplinary scientists continued into the evening during the Women & Science event Advances in Melanoma and Skin Cancer Research.

Distinguished epidemiologist Dr. Marianne Berwick, from the University of New Mexico, and Wistar Drs. Chengyu Liang, Jessie Villanueva, and Noam Auslander met for a roundtable discussion on melanoma research, prevention, diagnosis, and treatment advances. Dr. Maureen Murphy moderated a lively exchange that touched on the history of melanoma up to the latest solutions to treat and prevent this dangerous skin cancer.

Dr. Berwick kicked off the conversation by addressing why melanoma seems much more prevalent than in the past.

“We wear less clothing, we test for skin cancer with more biopsies, and people spend more time indoors,” says Berwick. “Melanoma incidence increased because we are not covered by our clothes like we were during Victorian times. Also, we have more sensitive detection tools and folks that spend a lot of time indoors then get intermittent but intense sun exposure, increasing the risk of sunburns and developing melanoma.”

Berwick went on to remind the audience of the ABCDs of melanoma and how important it is to know our bodies as any changes in Asymmetry, Border, Color, and Diameter (no wider than a pencil eraser) can be a sign of melanoma.

Cancer researcher Dr. Chengyu Liang spoke of melanoma treatment and why it’s so stubborn to treat.

“For some patients with melanoma, we have different treatments to stimulate their immune system. We can use immunotherapy—finding the wolf (or cancer) in sheep’s clothing, or we can use targeted therapy—finding a way to stop or put on the brakes of an out-of-control car,” says Liang. “Wistar is a front runner in melanoma-targeted therapies and Wistar’s cell bank is vital in the research and treatments that have been accomplished thanks to Dr. Meenhard Herlyn’s lab.”

Dr. Liang joined Wistar less than a year ago and is recognized for her study of melanoma development and progression, with a particular focus on autophagy, or “self-eating”— a process in which cells digest and recycle waste.

“We now can have many patients survive and have their disease controlled through targeted or immunotherapy or a hybrid combo therapy,” said Liang. “But we want 100% survival, and we want to know the right therapy for the right patient at the right time.”

Dr. Jessie Villanueva is a research leader in how tumor cells become resistant. She discussed the challenges of therapy resistance in melanoma—when tumors become indifferent to drugs and escape therapy.

“Some tumors rewire and bypass the effect of the drugs,” says Villanueva. “Sometimes treatment works great for a period, but then tumors become resistant. The genetic make-up of the cancer cells is highly variable within tumors, and even from one another, so drugs can work on some cells but not others. Cancer cells that ‘escape’ treatment can remain asleep and then can be triggered to reawaken, which leads to tumor relapse.”

Dr. Villanueva is developing ways to target NRAS mutations in melanoma.

“The tumors that I work on harbor mutations in NRAS and account for 25-30% of all melanomas,” says Villanueva. “These tumors are highly aggressive and can spread to other organs. NRAS acts as a molecular switch controlling (molecular) signals that instruct the cell to grow or proliferate. A mutation in NRAS breaks the molecular switch, causing cells to proliferate indefinitely and accumulate additional mutations.”

Villanueva continued, “At Wistar, we have the tools and sophisticated models to mimic what happens in a patient’s tumor and we have faculty with diverse skills and backgrounds—from cancer biology, proteomics, and structural biology—to develop novel drugs to combat drug resistant melanoma.”

Dr. Noam Auslander is a computer scientist and uses artificial intelligence to interpret biomedical research data and extract and identify new information. She joined Wistar in June and focuses on the question of who responds to which cancer treatments.

“I do computational work and analyze data sets to generate research questions,” says Auslander. “I build predictors for treatment responses to predict who will respond and who will be resistant. Using these predictors and evaluating large scale data sets for the next drug targets, I hope to find new solutions to drug resistance.”

Before the event ended, the scientists shared challenges or helpful advice they considered key to their success and reminded the attendees to check and protect their skin.

A Gene That Shields Our Skin From the Damages of UV Rays

Dr. Chengyu Liang, who joined the Wistar faculty in July 2020, leads an exciting research program that investigates fundamental cellular processes in the context of infectious disease  and cancer, with particular focus on melanoma. 

Her lab studies how a specific gene can protect our skin from the damage caused by ultraviolet (UV) radiation by examining the many functions of the UV radiation resistance associated gene (UVRAG).

Exposure to UV radiation from the sun is a major risk factor for the development of melanoma, as it leads to the accumulation of mutations in our cells. The Liang lab discovered that the UVRAG gene is responsible for promoting repair of the DNA damage caused by UV in skin cells.

Dr. Liang originally identified this gene as a promoter of autophagy — a natural mechanism cells use to digest, remove and recycle unwanted components. Her team then demonstrated UVRAG’s involvement in DNA damage repair and showed that melanoma patients with lower levels of UVRAG tend to have higher amounts of UV-associated mutations in their DNA. 

The team also discovered that UVRAG controls production of the melanin pigment in the skin, which provides a first-line protection against UV radiation and the risk of skin cancer.

The key role played by UVRAG in protecting our skin from UV-induced damage points to this gene as a tumor suppressor in melanoma and a new, promising prognostic and predictive biomarker. 

Further explore the work of the Liang lab in this article by Scientia.

The Wistar Institute Appoints Chengyu Liang, M.D., Ph.D., as Professor in Its Cancer Center

PHILADELPHIA — (July 6, 2020) — The Wistar Institute, an international biomedical research leader in cancer, immunology and infectious diseases, announces the appointment of Chengyu Liang, M.D., Ph.D., as professor in the Molecular & Cellular Oncogenesis Program of The Wistar Institute Cancer Center.

The Liang laboratory is focused on understanding the mechanisms that regulate fundamental cellular processes such as autophagy, cell death, DNA damage repair, and membrane trafficking in the context of cancer and infectious disease.

Autophagy, which means “self-eating”, is a natural mechanism used by cells to digest, remove and recycle unwanted components. This process also represents a barrier against malignant transformation. The Liang lab studies autophagy in leukemia, colorectal cancer, melanoma, and viral persistency, optimally bridging cancer and infectious disease, the two main research areas at Wistar.

Among their accomplishments, Liang and her team have identified a novel autophagy pathway controlled by a tumor suppressor gene called UV-radiation Resistance-Associated Gene (UVRAG) that also plays a direct role in DNA repair and chromosomal stability.

“We are absolutely thrilled to be able to welcome a world-renowned research leader like Chengyu at Wistar,” said Dario Altieri, M.D., president and CEO, director of The Wistar Institute Cancer Center and the Robert and Penny Fox Distinguished Professor. “Her contributions have tremendously advanced our understanding of autophagy and other molecular pathways of cellular quality control, with enormous disease relevance for melanoma development and progression. Chengyu’s work is an ideal complement to the long-standing commitment of the Institute to melanoma research and uniquely poised to make far-reaching discoveries that will ultimately benefit our patients.”

“Joining Wistar is an invaluable opportunity,” said Liang. “I think it will be the perfect home for my lab: a not-too-big and high-caliber community, with strong research programs and core facilities, offering exceptional scientific diversity and connections.”

Prior to joining Wistar, Liang was a tenured associate professor at the Keck School of Medicine of the University of Southern California, which she joined in 2009 as an assistant professor.

She obtained her M.D. degree from Qingdao University School of Medicine, in China, and her Ph.D. degree in molecular genetics from State University of New York (SUNY) at Stony Brook, New York. She received her postdoctoral training at Harvard Medical School, in Boston.


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.