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Chengfeng Yang

Chengfeng Yang Photo by Zhishan Wang

By Daniel Dunaief

This is part two of a two-part series.

As Erin Brockovich (the real life version and the one played by Julia Roberts in the eponymous movie) discovered, some metals, such as hexavalent chromium can cause cancer in humans.

Chengfeng Yang and Zishan Wang

Environmental exposure to a range of chemicals, such as hexavalent chromium, benzo(a)pyrene, arsenic, and others, individually and in combination, can lead to health problems, including cancer.

In March, Stony Brook University hired Chengfeng Yang and Zhishan Wang, a husband and wife team to join the Cancer Center and the Pathology Departments from Case Western Reserve University.

The duo, who have their own labs and share equipment, resources and sometimes researchers, are seeking to understand the epigenetic effect exposure to chemicals has on the body. Yang focuses primarily on hexavalent chromium, while Wang works on the mechanism of mixed exposures.

Last week, the TBR News Media highlighted the work of Wang. This week, we feature the work of Yang.

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When he was young, Chengfeng Yang was using a knife to make a toy for his younger brother. He slipped, cutting his finger so dramatically that he almost lost it. Doctors saved his finger, impressing him with their heroic talent and inspiring him to follow in their footsteps.

Indeed, Yang, who earned an MD and a PhD from Tongji Medical University, is focused not only on answering questions related to cancer, which claimed the life of his mother and other relatives, but also in searching for ways to develop new treatments.

A Professor in the Department of Pathology at the Renaissance School of Medicine at Stony Brook University and a member of the Stony Brook Cancer Center, Yang has his sights set on combatting cancer.

“Our research always has a significant clinical element,” said Yang. “This is related to our medical background.”

He is interested in studying the mechanism of cancer initiation and progression and would like to develop new strategies for treatment.

Yang and his wife Zhishan Wang recently joined the university from Case Western after a career that included research posts at the University of Pennsylvania, Michigan State University, and the University of Kentucky.

The tandem, who share lab resources and whose research staffs collaborate but also work independently, are focused specifically on the ways exposures to carcinogens in the environment cause epigenetic changes that lead to cancer.

Specifically, Yang is studying how hexavalent chromium, a metal commonly found in the environment in welding, electroplating and even on the double yellow lines in the middle of roads, triggers cancer. It is also commonly used as a pigment to stain animal leather products.

Yang is focused mainly on how long cancer develops after exposure to hexavalent chromium.

People can become exposed to hexavalent chromium, which is also known as chromium 6, through contaminated drinking water, cigarette smoking, car emissions, living near superfund sites and through occupational exposure.

Yang has made important findings in the epigenetic effect of metal exposure. His studies showed that chronic low-level chromium six exposure changed long non-coding RNA expression levels, which contributed to carcinogenesis. Moreover, his studies also showed that chronic low level exposure increased methylation, in which a CH3 group is added to RNA, which also contributed significantly to chromium 6 carcinogenesis.

“It is now clear that metal carcinogens not only modify DNA, but also modify RNA,” Yang explained. Metal carcinogen modification of RNAs is an “exciting and new mechanism” for understanding metal carcinogenesis.

By studying modifications in RNA, researchers may be able to find a biomarker for the disease before cancer develops.

Yang is trying to find some specific epigenetic changes that might occur in response to different pollutants.

Stony Brook attraction

Yang was impressed with the dedication of Stony Brook Pathology Chair Ken Shroyer, whom he described as a “really great physician scientist. His passion in research and leadership in supporting research” helped distinguish Stony Brook, Yang said.

Yang is confident that Stony Brook has the resources he and Wang need to be successful, including core facilities and collaborative opportunities. “This is a very great opportunity for us, with strong support at the university level,” he said.“We plan to be here and stay forever.”

Yang is in the process of setting up his lab, which includes purchasing new equipment and actively recruiting scientists to join his effort.

“We need to reestablish our team,” he said. “Right now, we are trying to finish our current research project.”

He hopes to get new funding for the university in the next two to three years as well. After he establishes his lab at Stony Brook, Yang also plans to seek out collaborative opportunities at Cold Spring Harbor Laboratory, which is “very strong in RNA biology,” he added.

A return home

Returning to the Empire State brings Yang full circle, back to where his research experience in the United States started. About 23 years ago, his first professional position in the United States was at New York University.

Outside of work, Yang likes to hike and jog. He is looking forward to going to some of Long Island’s many beaches.

He and Wang live in an apartment in South Setauket and are hoping to buy a house in the area. The couple discusses science regularly, including during their jogs.

Working in the same area provides a “huge opportunity” for personal and professional growth, he said.

Yang suggested that his wife usually spends more time training new personnel and solving lab members’ technical issues. He spends more time in the lab with general administrative management and support. Wang has “much stronger molecular biology skills than I have,” Yang explained in an email, whereas he has a solid background in toxicology.

Growing up, Yang said he had an aptitude in math and had dreamed of becoming a software engineer. When he applied to college, he received admission to medical school, which changed his original career path.

Once he started running his own experiments as a researcher, he felt he wanted to improve human health.“Once humans develop disease, in many cases, it’s very expensive to treat and [help] people recover,” he said. “Prevention could be a more cost effective way to improve health.”

Zhishan Wang. Photo from Chengfeng Yang

By Daniel Dunaief

This is part one of a two-part series.

As Erin Brockovich (the real life version and the one played by Julia Roberts in the eponymous movie) discovered, some metals, such as hexavalent chromium can cause cancer in humans.

Chengfeng Yang and Zhishan Wang

Environmental exposure to a range of chemicals, such as hexavalent chromium, benzo(a)pyrene, arsenic, and others, individually and in combination, can lead to health problems, including cancer.

Recently, Stony Brook University hired Chengfeng Yang and Zhishan Wang, a husband and wife team to join the Cancer Center and the Pathology Departments from Case Western Reserve University in Ohio.

The duo, who have their own labs and share equipment, resources and sometimes researchers, are seeking to understand the epigenetic effect exposure to chemicals has on the body. Yang focuses primarily on hexavalent chromium, while Wang works on the mechanism of mixed exposures. 

In part one, TBR News Media highlights the work of Wang. Next week, we will feature the efforts of Yang.

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In certain areas and specific job sites, people can be exposed to environmental pollutants.

Sometimes, the introduction of a metal or element can cause cancer after long term exposure. The effect of another carcinogen can be synergistic in triggering disease, triggering a stronger progression of cancer than an individual exposure alone.

Zhishan Wang, who joined Stony Brook in March and is a Professor of Research in the Department of Pathology, is trying to understand what changes this mixed exposure creates at a molecular level.

“If we find out some gene or pathway change, we can try to intervene,” said Wang, who is a member of the Stony Brook Cancer Center and earned MD and PhD degrees from her native China.

Among the many possible environmental triggers, Wang chose to study arsenic, which is common in rock soil and water and is present in some places in drinking water.

“People living in high exposure areas to arsenic and [who] are also cigarette smokers have a significantly higher risk of lung cancer,” she said.

Arsenic can cause three different kinds of cancer: skin, bladder and lung cancer. For skin cancer, Wang explained that direct contact can lead to the kind of irritation that promotes the disease. 

As the heavy metal works its way through the body, parts of it get excreted through the urine system, which means that bladder cells come into contact with it as well.

For a long time, scientists knew arsenic exposure through drinking water caused lung cancer. The underlying mechanism for the development of that cancer was not well understood. 

Wang’s lab studies the mechanism by which arsenic and benzo(a)pyrene (or BAP) co-exposure increases lung cancer risk. Exposure to arsenic alone causes cancer, but it takes a long time in animal models. Arsenic and BPA co-exposure significantly increases lung cancer risk.

Wang’s study showed that co-exposure increases lung tumor burden and malignancy. She plans to continue to study the mechanism of how arsenic and BAP co exposure increases lung cancer risk.

“That’s our big goal: to try to find some useful method to prevent this tumor from happening,” she said.

Wang believes the cancer cells caused by the mixed exposure increases the number of cancer stem cell-like cells, which could mediate therapeutic resistance.

Wang explained that generating the mouse model took considerable time and effort. She tried to find the exposures during particular windows of time that lead to cancer.

“By using this model, we can do a lot of data analysis” including single cell analysis and can determine which cluster or pathway will change.

Choosing SBU

Wang suggested she and her husband chose Stony Brook for several reasons. The couple would like to help the University earn a National Cancer Institute (NCI) designation, which would give scientists the ability to compete for ambitious, well-funded, multidisciplinary efforts.

Both Wang and Yang “lead NCI-funded research programs that will enhance the [Cancer Center’s] eligibility for NCI designation,” explained Kenneth Shroyer, chair of the Pathology Department at Stony Brook.

Shroyer, who described both researchers as “highly competitive candidates with the potential to enhance the status of any cancer center,” is looking forward to working with his newest recruits.

Wang is eager to use the tissue bank at Stony Brook, which Shroyer explained has also attracted other cancer research scientists recruited to the Renaissance School of Medicine at Stony Brook.

The new scientists also hope to tap into the expertise at nearby Cold Spring Harbor Laboratory, which has become one of the leading centers in creating organoids. 

In the early years of her training during her MD and PhD years in China, Wang developed her technical skills. Through her career, she has worked on several genes that play important roles in carcinogenesis. Down regulation of the gene known as SOCS3, for suppressor of cytokine signaling 3, plays an important role in arsenic and BAP co-exposure caused lung tumorigenesis.

Early in their careers, Wang worked in her husband’s lab for seven years until she received her own research funding.

Outside of work, Wang enjoys playing badminton and ping pong. She also cooks every day. She and her husband bring her home cooked meals to work.

When she was in high school, Wang had ambitions to become a writer. Her teachers regularly read her work out loud to the class.

Her father, who was a lawyer, had encouraged her to join the legal profession. She had heard that people called others “smart” when they joined the fields of Science, Technology, Engineering and Mathematics. “I want people to call me smart,” she said, so she changed her career and went to medical school at Tongji Medical University where she earned top scores. 

Her father had a stroke, surviving afterwards for seven years. When she was in medical school, Wang hoped to learn ways to help him. Wishing she could have done more, she pursued clinical research in the lab. She passed the tests to become a practicing physician in the United States, but she was more inspired to work as a scientist.

As for her work at Stony Brook University, Wang appreciates the beauty of Long Island. She hopes this is their “last move,” as they continue their careers.