Tags Posts tagged with "Cancer"


Ke Jian Liu

By Daniel Dunaief

Ke Jian “Jim” Liu, who arrived at Stony Brook University in late July, plans to help build effective, interdisciplinary research teams.

Ke Jian Liu

Most recently at the University of New Mexico, Liu joins Stony Brook as a Professor in the Renaissance School of Medicine’s Department of Pathology and Associate Director of Basic Science at the Stony Brook Cancer Center.

“In my mind, Stony Brook, research wise, is outstanding,” Liu said in an interview. “The quality of the faculty is excellent.”

Liu will rely on the team building experience he honed while serving as Distinguished Professor in the Department of Pharmaceutical Sciences and Associate Dean for Research in the College of Pharmacy at the University of New Mexico. He also worked for eight years at Dartmouth Medical School, where he focused on developing larger collaborations.

“I really enjoy working with people and building teams,” Liu said.

In a note announcing Liu’s arrival, Kenneth Shroyer, chair in the Department of Pathology, recognized Liu’s multidisciplinary approaches in his research. Shroyer explained that Liu has used techniques ranging from chemical to biochemical to biophysical, and from the molecular and cellular level to animal models, to answer specific biological questions.

Shroyer wrote that Liu would focus on opportunities for grant development within several programs. 

At the Cancer Center, Liu said he plans to continue the effort to help Stony Brook earn National Cancer Institute designation.

To achieve that designation, Stony Brook will need to continue to provide outstanding medical care, demonstrate community engagement and highlight what makes Stony Brook different from everyone else, he said.

“It takes a village to do that,” Liu said.

He praised the efforts of current Cancer Center Director Yusuf Hannun, who recently announced his plans to step down as head of the center, triggering a nationwide search for a replacement.

Liu said an ideal candidate for that position would have clinical experience.

Player coach

With a busy research effort and lofty leadership goals, Liu explained that he’s able to tackle numerous challenges at once.

“I consider myself a player coach,” he said. “I enjoy research. I have my own research grant and am working with my students and post docs.”

Liu typically maintains a lab with five to six people at different levels. His research has two branches, cancer and stroke, that most people likely consider unrelated, but for which he has found connections.

“People always think, ‘Cancer is cancer and stroke is stroke and they are two entirely different diseases,” Liu  said. As a basic researcher, however, he looks at the cells and the molecules involved in both conditions.

“At a molecular level, a molecule doesn’t care where it is,” he said. “When a disease develops, the biological fundamental process is the same. For me, it’s interesting to look at [whether] certain processes that occur in the brain also occur in cancer.”

Liu’s cancer research focuses specifically on the molecular processes that become carcinogenic when metals like arsenic enter people’s bodies. A well-described poison in numerous murder mysteries, arsenic can contaminate drinking water, get incorporated into crops like rice, or can appear in fruit juices.

When metal enters the body, it doesn’t just cause damage everywhere. It has to find a certain molecular target with which to interact.

What Liu and researchers in his lab have discovered is that the target for arsenic is often the same pathways the body uses in zinc. A transition metal, zinc provides an important element as a part of transcription factors that are critical in biological processes.

Arsenic, however, replaces zinc, which is “one of the major mechanisms for carcinogenesis,” Liu said.

Fortunately for residents of Long Island, arsenic isn’t as prevalent as it is in the midwest and the southwest.

“Long Island doesn’t have too much arsenic in drinking water,” Liu said, although people are still exposed to it through fruit juices, rice and other products.

Arsenic also causes vascular disease issues and anemia. People who develop these other conditions in response to arsenic are also at higher risk to develop cancer. The specific types of cancers arsenic causes are lung, skin and bladder cancer.

“Arsenic is the dirty bomb” in the body as it creates multiple problems, Liu said. “Arsenic interacts with those key zinc molecules.” 

Overlap between stroke and cancer

In highlighting the overlaps between the two fields of research, Liu related how the brain has one of the highest concentrations of zinc in the body.

When people have strokes, their brain cells have oxidative stress, which causes a flood of zinc into the brain tissue that also damages cells.

“We are trying to understand how zinc is released and how zinc causes damage to the brain,” Liu said.

Stroke and cancer also have molecular overlaps regarding oxygen. In a stroke, a blood clot causes a blockage of blood flow. Without oxygen, a situation called hypoxia, neurons start to die.

By contrast, a tumor grows in a hypoxic environment, using energy from sugars like glucose, rather than relying on oxygen for its growth.

Liu emphasized the importance of continuing to provide oxygen to brain regions around a clot even before trying to remove the clot or restore blood flow.

A goal for his 100th year

Originally from Beijing, China, Liu and his wife Jiao Ding enjoy traveling. Their daughter Sarah Liu is a resident at Vermont Medical Center and their son Evan Liu is a PhD student at Stanford.

An avid tennis player who plays the sport at least twice a week, Liu is looking forward to attending his first U.S. Open next year.

He and his former tennis partner in New Mexico joked that their goal is to be in the top 20 in the United States when they are 100 years old.

Liu chose the American name “Jim” because it sounds similar to the second syllable of his given name, Ke Jian.

“If people can’t pronounce your name, they shy away,” he said. He believes it’s important to “make yourself adaptable.”

METRO photo

By Matthew Kearns, DVM

Dr. Matthew Kearns

Working in a general practice for many years now, I am commonly asked the question of whether or not a growth under the skin is something to worry about or not. The good news is the majority of subcutaneous (under the skin) lumps are benign, or non-cancerous. They are usually lipomas (benign tumors made up of fat cells), or cysts. Some, however, can be cancerous and are better off being removed before they get too big or invade the surrounding tissues making it more difficult or impossible to remove completely. How are we to tell?

It is always good to bring any new growths to your veterinarian’s attention as soon as possible. When I evaluate any new subcutaneous growths I was taught to look for three characteristics:

Is it hard or is it soft? A growth that is hard is not always malignant, and a growth that is soft is not always benign. However, in my book, a growth that is hard is more concerning than a growth that is soft.

Is it freely movable or well attached to underlying tissues? Growths that are soft and freely movable are more likely to be benign than growths that are hard and well attached.

Is it painful, or non-painful? subcutaneous growths that are non-painful to palpation are less likely to be malignant.

I like to have the three criteria in combination to feel confident in telling a pet owner that the growth is something just to be monitored. Therefore soft, freely movable, non-painful is good, and firm, well-attached, and painful is concerning. 

I also like to recommend owners monitor these growths closely for change. The two changes I look for is a rapid change in size, and/or a change in character. If a growth doubles in size in a month or less, or a change in character (soft to hard, freely movable to well attached, non-painful to painful) then please have your pet seen again immediately.

There are different ways to test these growths. My favorite first test is a fine needle aspirate and cytology. This test involves inserting a needle into the growth and aspirating a sample of cells. The sample is then sprayed onto a microscope slide, allowed to dry and sent to the lab for evaluation by a pathologist. 

Cytology is the evaluation of individual cells so it is not as accurate as a biopsy but one can get a lot of information from individual cells. A fine needle aspirate is something that is well tolerated by most patients so sedation or anesthesia is not usually required to perform this procedure. 

There are cases where the fine needle aspirate and cytology are inconclusive and a biopsy is needed. However, I feel a fine needle aspirate and cytology is an excellent first step. I hope this information helps.

 Dr. Kearns practices veterinary medicine from his Port Jefferson office and is pictured with his son Matthew and his dog Jasmine. 

Concerns about students with health problems prompted the temporary closing of Northport Middle School in 2020 and was one of the reasons the state Department of Health conducted a study of cancer cases in the district. File photo by Lina Weingarten

Residents of the Northport-East Northport school district have waited anxiously for the recent report by the New York State Department
of Health.

According to a NYSDOH study, the investigation of cancer incidents in the school district between 1999 and 2018 was initiated by the department “in response to an inquiry from members of the community who shared information about leukemias and other cancers diagnosed among members of the Northport High School graduating class of 2016 since their graduation and among other children and young adults in the Northport area.” The report also mentioned health concerns cited about Northport Middle School students.

In January 2020, the district decided to close the middle school for a few months after the consulting firm hired by the district, P.W. Grosser Consulting, tested the soil on the grounds and found elevated levels of benzene in two separate septic systems on site. Before a cleanup, three science classrooms in the middle school’s G-wing were closed out of an abundance of caution. During the investigation, it was found science rooms had sinks that drain into the leaching pool, where the mercury and silver were found. While odorless fumes could have potentially migrated through the piping into classrooms, the drain systems rely on P traps that prevent that from occurring, according to the district at the time. Air quality results in the G-wing classrooms were later found to be normal.

The DOH’s primary source of data was the New York State Cancer Registry. For the years after 2018, registry data was not official at the time of analyses, according to the DOH report. 

“We identified 4,593 cases of cancer among district residents, compared with 4,454 that would be expected,” the report read. “This 3% excess was statistically significant, meaning it was unlikely to occur by chance.”

An increase in pancreatic cancer, malignant melanoma of the skin, uterine (corpus) cancer and prostate cancer made up the excess. The report went on to say, “There were significantly fewer than expected numbers of cases of stomach cancer and lung cancer. Numbers of cases of leukemia, other blood cancers (Hodgkin and non-Hodgkin lymphomas and multiple myeloma), and 13 other types of cancer examined separately were not significantly different from expected.”

While the community around East Northport Middle School had about the expected cases, the area around Northport Middle School had 7% higher-than-expected levels of cancer.

Regarding the number of 2016 high school graduates who came down with leukemia, the study concluded, “It is possible that the elevated occurrence of leukemia among 2016 graduates could be related to factors not possible to uncover, including environmental exposures.” 

Robert Banzer, district superintendent of schools, sent out a letter June 23 to community members to notify them that the study was completed. In the letter, he said, “The district fully cooperated with the NYSDOH during this process.”

After summarizing the findings in the letter, he said, “We appreciate the hard work of the NYSDOH in this endeavor and look forward to continuing to provide our students and staff with a safe learning environment.”

Lawsuits and disappointment in health study

Attorney Lilia Factor, of Melville-based Napoli Shkolnik PLLC, said her law firm has filed three lawsuits for nine plaintiffs so far against the Northport-East Northport school district. One of them is a proposed class-action lawsuit on behalf of all Northport Middle School students. The others are on behalf of individuals who have become sick. She is aware of at least five other lawsuits in total as other law firms have filed lawsuits against the district in the Suffolk County Supreme Court.

On July 12, according to Factor, the court consolidated lawsuits for the purposes of exchanging documents and depositions. A most recently filed case from Napoli Shkolnik was not included as a judge has not been assigned yet.

Tara Mackey is one of the plaintiffs in the class-action lawsuit. She said her daughter suffered from migraine headaches while studying at Northport Middle School and developed asthma. When Mackey brought her daughter to the doctor for her headaches, carbon monoxide was found in her blood.

“She had to get blood tests every four to six weeks for the remainder of time that she was in the school, and it just showed a pattern of when they would test her blood after, say, five days a week of school, she would have very high levels of carbon monoxide in her blood and then when they tested it during holidays or summer break, it was perfectly normal,” Mackey said.

Factor said while Mackey’s daughter was fortunate not to get cancer, she and other students are at a higher risk of developing illness later in life due to latency periods, a fact she said the NYSDOH report acknowledges. If the class-action suit is successful, anyone who becomes sick in later years would be covered. In cases such as this, a fund is established where people can be tested or a protocol would be distributed to local doctors to know what to look for if a patient attended Northport Middle School 

“We want there to be a medical monitoring program established for everyone so that they can screen people and watch them, and if they develop any symptoms of a serious illness that’s associated with these contaminants to try to catch it early,” Factor said.

Mackey said the health issues can weigh heavily on families, and many of them faced criticism in Northport when they brought the problems to the district. She and her family moved to South Carolina after they were harassed by community members creating uncomfortable situations.

“We endured a lot of harassment, along with a lot of other parents, from people in the community that didn’t want bad press about any potential environmental issues that could lead to health problems for people in the school and the community, because people feared for their property values,” she said. “It just made a very uncomfortable situation for many of us, and we moved because we couldn’t keep our kids safe.”

She added, coincidentally, two other families, who she didn’t know while living in Northport, moved near her.

Factor said while it is good that the DOH conducted the report, the study didn’t look at other factors such as families who have moved away and may have been diagnosed with an illness.

“They would not be part of those statistics, which were in themselves pretty disturbing,” Factor said.

She added the DOH didn’t talk to or survey community members and medical providers.

“It’s good that they did something, but it really needs to be a lot more comprehensive if they really want to understand cancer incidence in this community.” Factor said.

The attorney and Mackey added there have been other illnesses that have surfaced such as scleroderma and aplastic anemia. Mackey said that she was also disappointed that the study was cut off at the year 2018 as she has heard of more cases of cancer that have been diagnosed recently and therefore not counted.

“I just think all of the families and the parents, children themselves, they at least deserve the facts and the full facts,” the mother said. “Nothing can change at this point. We can’t change what happened to our children, but at least we can take charge and be observant and try to keep them in the best health possible and at least know what to look for.”

Mehdi Damaghi. Photo from Stony Brook Hospital

By Daniel Dunaief

Do the birds on the Galapagos Islands, with their unique coloration, differently shaped beaks and specific nesting places, have anything to do with the cancer cells that alter the course of human lives?

For Mehdi Damaghi, Assistant Professor in the Department of Pathology at the Renaissance School of Medicine at Stony Brook University, the answer is a resounding, “Yes.”

Damaghi uses the same principles of evolutionary biology to understand how cancer, which resides within human genes, works to adapt, as it tries to win the battle to survive.

“What we try to understand is the Darwinian principals of cancer,” said Damaghi. Cancer “adapts and reprograms themselves” to their environment to survive.

Damaghi, who arrived at Stony Brook four months ago from Moffitt Cancer Center, plans to address numerous questions related to cancer. He recently received a $4 million grant from the Physical Science in Oncology program (PSON) through the National Institutes of Health/ National Cancer Institute. Working with cancer biologists, clinicians, and computational scientists, he plans to define and understand cancer’s fitness.

“We are trying to study the core evolution of cancer cells and the normal stroma around them,” said Damaghi. “We are looking at the evolution of the tumor and some of the host cells.”

Cancer biologists are trying to build mathematical and theoretical models to explore the playbook cancer uses when confronted with threats, either in the form of a body’s natural defenses against it or from therapies against which it can, and often does, develop resistance.

Treating cancer could involve using adaptive therapy, which could enable people to control and live with cancer longer, Damaghi suggested.

In studying cancer’s phenotype, or the way the disease is expressed and survives, he hopes to understand factors in the microenvironment. Many cancers, he reasons, become more problematic as people age. Indeed, centuries ago, cancer wasn’t as prevalent as it is today in part because life expectancy was shorter.

Damaghi also has an evolutionary model to explore metastasis, in which cancer spreads from one organ or system to other parts of the body. He is looking at the earliest stages of breast cancer, to see what factors some of these cancers need or take from the environment that enables them not only to develop into breast cancer, but also to spread to other systems.

Through the microenvironment, he is looking for biomarkers that might signal a potential tumor development and metastasis long before a person shows signs of an aggressive form of the disease.

“We look at the tumor as a part of a whole ecosystem that can have different niches and habitats,” he said. “Some can be hypoxic and oxidative, and others can be like a desert on Earth, where not much grows and then cancer evolves.”

Damaghi challenges cells in a culture or organoids, which are miniature, three-dimensional live models of human cells, with different microenvironmental conditions to see how they respond. He exposes them to hormones, immune cells, and hypoxic conditions.

“We try to understand what is the adaptation mechanism of cancer to this new microenvironment and how can we push them back to the normal phenotype,” he said.

Like other scientists, Damaghi has demonstrated that many of these cancer cells use sugar. Removing sugar caused some of the cancer to die.

Increasing the survival for patients could involve knowing what kinds of micro-environments cancer uses and in what order. Deprived of sugars, some cancers might turn to amino acids, dairy or other sources of food and energy.

Damaghi thinks researchers and, eventually, doctors, will have to approach cancer as a system, which might have a patient-specific fingerprint that can indicate the resources the disease is using and the progression through its various diseased stages.

Choosing Stony Brook

Damaghi appreciates the depth of talent in cancer sciences at Stony Brook University. He cited the work of Laufer Center Director Ken Dill and Cancer Center Director Yusuf Hannun. He also suggested that the Pathology Department, headed by Ken Shroyer, was “very strong.”

For their part, leaders at Stony Brook were pleased to welcome, and collaborate with, Damaghi. Hannun suggested Stony Brook recruited Damaghi because his research “bridges what we do in breast cancer and informatics.”

Shroyer, meanwhile, has already started collaborating with Damaghi and wrote that his new colleague’s focus on breast cancer “overlaps with my focus on pancreatic cancer.”

To conduct his research, Damaghi plans to look at cells in combination by using digital pathology, which can help reveal tumor ecosystems and niches.

He also appreciated the work of Joel Saltz, the Founding Chair in the Department of Biomedical Informatics. “In the fight against cancer, we all need to unite against this nasty disease,” Damaghi said. “From looking at it at different angles, we can understand it first and then design a plan to defeat it.”

Originally from Tehran, Iran, Damaghi is the oldest of five brothers. He said his parents encouraged them to explore their curiosity.

Damaghi, whose wife Narges and two daughters Elissa and Emilia are still in Tampa and hope to join him before long, has hit the ground running at Stony Brook, where he has hired three postdoctoral researchers, a lab manager, four PhD students, two master’s candidates, and three undergraduates.

Damaghi is inspired to conduct cancer research in part because of losses in his family. Two grandparents died from cancer, his aunt has breast cancer, and his cousin, who had cancer when he was 16, fought through the disease and is a survivor for 20 years.

Damaghi bicycles and plays sports including soccer. He also enjoys cooking and said his guests appreciate his Persian kebobs.

As for his arrival in Stony Brook, he said it was “the best option for me. It’s a great package and has everything I need.”

David McCandlish, center, with postdoctoral researchers Anna Posfai and Juannan Zhou. Photo by Gina Motisi, 2020/ CSHL

By Daniel Dunaief

If cancer were simple, scientists would have solved the riddle and moved on to other challenges.

Often, each type of the disease involves a combination of changes that, taken together, not only lead to the progression of cancer, but also to the potential resistance to specific types of treatment.

Using math, David McCandlish, Assistant Professor at Cold Spring Harbor Laboratory, is studying how the combination of various disruptions to the genome contribute to the development of cancer.

McCandlish recently published a study with colleagues at Cold Spring Harbor Laboratory in the journal Proceedings of the National Academy of Sciences.

David McCandlish. Photo by Gina Motisi, 2020/CSHL

The research didn’t explore any single type of cancer, but, rather applied the method looking for patterns across a range of types of cancers. The notion of understanding the way these genetic alterations affect cancer is a “key motivating idea behind this work,” McCandlish said.

So far, the method has identified several candidates that need further work to confirm.

“Cancer would be a lot easier to treat if it was just one gene,” said Justin Kinney, Associate Professor at CSHL and a collaborator on the work. “It’s the combination that makes it so hard to understand.”

Ultimately, this kind of research could lead researchers and, eventually, health care professionals, to search for genetic biomarkers that indicate the likely effect of the cancer on the body. This disease playbook could help doctors anticipate and head off the next moves with various types of treatments.

“This could potentially lead to a more fundamental understanding of what makes cancer progress and that understanding would very likely open up new possibilities in cancer treatments,” Kinney said.

To be sure, at this point, the approach thus far informs basic research, which, in future years, could lead to clinical improvements.

“We are working on this method, which is very general and applicable to many different types of data,” McCandlish said. “Applications to making decisions about patients are really down the road.”

McCandlish described how he is trying to map out the space that cancer evolves in by understanding the shape of that space and integrating that with other information, such as drug susceptibility or survival time.

“We are trying to ask: how do these variables behave in different regions of this space of possibilities?” he said.

McCandlish is making this approach available to scientists in a range of fields, from those scientists interpreting and understanding the effects of mutations on the development of cancer to those researchers pursuing a more basic appreciation of how such changes affect the development and functioning of proteins.

“This is accessible to a wide array of biologists who are interested in genetics and, specifically in genetic interactions,” said McCandlish.

The main advance in this research is to take a framework called maximum entropy estimation  and improve its flexibility by using math to capture more of the underlying biological principals at work. Maximum entropy estimation is based on the idea of inferring the most uniform distribution of behaviors or outcomes with the least information that’s compatible with specific aspects of experimental observations.

Using this philosophy, scientists can derive familiar probability distributions like the bell curve and the exponential distribution. By relaxing these estimates, scientists can infer more complicated shapes.

This more subtle approach enhances the predictive value, which captures the distributions of data better, McCandlish explained. “We’re trying to capture and model cancer progression in a new and more expressive way that we hope will be able to tell us more about the underlying biology.”

The idea for this paper started when McCandlish, Kinney and  Jason Sheltzer, a former fellow at Cold Spring Harbor Laboratory and a current Assistant Professor of Surgery at Yale School of Medicine, discussed the possibilities after McCandlish attended a talk by Wei-Chia Chen, a post doctoral researcher in Kinney’s lab.

Chen will continue to pursue questions related to this effort when he starts a faculty position in the physics department at National Chung Cheng University in Taiwan this spring.

Chen will use artificial intelligence to handle higher dimensional data sets, which will allow him “to implement effective approximations” of the effect of specific combinations of genetic alterations, Kinney said.

Kinney believes teamwork made this new approach, which the high-impact, high-profile journal PNAS published, possible.

“This problem was an absolutely collaborative work that none of us individually could have done,” Kinney said. He described the work as having a “new exploratory impact” that provides a way of looking at the combination of genomic changes that “we haven’t had before.”

Working at Cold Spring Harbor Laboratory, which McCandlish has done since 2017, enables collaborations across different disciplines.

“We have this quantitative biology group, we also have people working on neuroscience, cancer, and plant biology,” McCandlish added.

McCandlish is also currently also working with Professor Zachary Lippman and his graduate student Lyndsey Aguirre to understand how multiple mutations interact to influence how the fruit on tomato plants develop.

“The idea is that there are these huge spaces of genetic possibilities where you can combine different mutations in different ways,” McCandlish explained. “We want to find those key places in that space where there’s a tipping point or a fork in the road. We want to be able to identify those places to follow up or to ask what’s special about this set of mutations that makes it such a critical decision point.”

A native of Highland Park, New Jersey, McCandlish was interested in math and science during his formative years. 

As for the work, McCandlish appreciates how it developed from the way these collative researchers interacted.

“This would never have happened if we weren’t going to each other’s talks,” he said.

The Comsewogue boys soccer program hosted its inaugural “Kicks for Cancer” fundraiser at home against Deer Park Oct 12. Bill Landon photo

The Comsewogue boys’ soccer program, both varsity and JV, put on the inaugural “Kicks for Cancer” game — a fundraising event to honor of two former players whose mothers are battling breast cancer. 

The Oct. 12 event was the brainchild of seniors Dan Dein, Matthew Sparhuber, Josh Carroll and Ryan Carnaxide, according to Comsewogue boy’s booster club member Kathy Dein.

“These boys have known both moms all through growing up and decided to hold a Kicks for Cancer fundraiser to benefit the ‘Triple Negative Breast Cancer Foundation’ in their honor,” said Dein, who added that both the JV & Varsity have raised over $1,100 for the cause and still going. 

The team all wore pink jerseys adorned the field with posters to promote the event. 

“I’m tremendously proud that our boys realize that it’s more than just a game it’s bringing the community together and this is their way to give back,” Dein said.

With the game under way the Warriors evened the score late in the game when Ryan Harding to tie the game at 1-1. Despite two overtime periods both teams drew the tie keeping the Warriors atop the league IV leaderboard at 10-1-1.

— All photos by Bill Landon

Dave Tuveson. Photo by Gina Motisi/CSHL

By Daniel Dunaief

While one bad apple might spoil the bunch, the same might be true of one bad cancer gene.

Cold Spring Harbor Laboratory’s Cancer Director Dave Tuveson and Derek Cheng, who earned his PhD from Stony Brook University while conducting research in Tuveson’s lab, recently explored how some mutant forms of genes in pancreatic cancer can involve other proteins that also promote cancer.

A gene well-researched in Tuveson’s lab, mutated KRAS promotes cell division. Mutant versions of this gene continue to produce copies of themselves, contributing to cancer.

Derek Cheng

Turning off or blocking this gene, however, doesn’t solve the problem, at least not in the laboratory models that track a cancer cell’s response.

In laboratory models of pancreatic cancer, a disease for which the prognosis is often challenging, other proteins play a role, creating what researchers call an “adaptive resistance” to chemotherapy.

In a paper published in the journal Proceedings of the National Academy of Sciences, Cheng, who is the first author and is currently in his final year of medical school at the Stony Brook Renaissance School of Medicine, and Tuveson showed that a protein called RSK1 interacts at the membrane with mutated KRAS. When KRAS is inhibited, the RSK1 protein, which normally keeps RAS proteins dormant, becomes more active.

“If you antagonize KRAS, you would get a rebound” as the cancer cells develop a resistance to the original drug, Tuveson said. “We found a feedback loop.”

The research “focused on identifying protein complexes with oncogenic KRAS that would potentially be relevant in pancreatic cancer,” Cheng explained in an email. “My work suggests that an RSK1/NF1 complex exists in the vicinity of oncogenic KRAS.”

While Cheng was able to show that the role of membrane-localized RSK1 provided negative regulation of wild-type RAS, it “remains to be studied what the role of the RSK1 at the membrane [is] in the context of oncogenic KRAS.”

KRAS is a molecular switch that turns on and off with the help of other proteins. With certain mutations, the switch doesn’t turn off, continuing to signal for copying and dividing, which are hallmarks of cancer cells. With specific activating mutations, the switch can lose its ability to turn off and constitutively signal for proliferation, metabolic reprogramming, and other behaviors characteristic of cancer cells, Cheng explained.

A cell with an oncogenic KRAS has the tendency to be more fit than a normal cell without one. Such cells will likely grow at a faster rate under stressful conditions, which, over time, can enable them to outcompete normal cells, Cheng continued.

When KRAS is in an oncogenic state, another protein, called RSK1 is hanging around the membrane. RSK1 has several functions and can participate in numerous cellular signaling pathways.

KRAS cytoplasm

While RSK1 is involved in protein translation by phosphorylating S6 kinase, it also has other functions at the plasma membrane, where it shuts down wild type RAS proteins.

Other researchers have suggested a negative feedback for RSK1 and NF1.

“Our contribution demonstrated some relevance of this interaction in pancreatic cancer cells,” Cheng explained in an email.

Cheng said RSK is known to have various effects, depending on the context. In the paper, the scientists showed that RSK has a “negative feedback properties, such as that, upon the removal of mutant KRAS, it has this negative regulatory role.”

Graduate student Sun Kim and post doctoral researchers Hsiu-Chi Ting and Jonathan Kastan are currently exploring whether RSK has a pro-oncogenic function on the membrane in the tumor cell.

So far, these studies suggest that while a direct inhibitor against oncogenic KRAS would likely be the greatest target for an effective therapy, cancer cells may still be able to use signals from other RAS isoforms.

“A combination of targeting KRAS and modulating regulators of RAS such as RSK1/NF1 and SOS1 may enhance therapeutic efficacy,” Cheng suggested.

Cheng is grateful for the opportunity to learn from numerous Tuveson lab members on ways cancer cells differ from healthy cells.

The discovery of the potential roles of RSK1 in cancer provides some possible explanation for the potential resistance mechanisms of mutant KRAS inhibitors.

While he was encouraged that a prestigious journal published the research, Tuveson said he hopes this type of observation “will lead to something that will be useful for a pancreatic cancer patient and not just” provide compelling ideas.

Cheng attended medical school for two years before joining Tuveon’s lab for the next six years.

Cheng defended his thesis in 2020 during the pandemic on a zoom call.

“I was one of the first people to defend with this format for both CSHL and SBU,” Cheng explained. “I was able to invite many friends and family that probably would not have been able to make the trip.”

Cheng’s family has battled cancer, which contributed to his research interests.

When he was an undergraduate, he had an uncle develop glioblastoma, while another uncle and his grandfather developed colon cancer.

“I knew I wasn’t going to be able to do much about their medical condition, but I wanted to work on something that people cared about,” Cheng explained.

Outside of the lab, Cheng enjoys working on his car and his motorcycles. He feels a sense of autonomy working on his own projects.

He’s most proud of a motorcycle for which he rebuilt the front end with parts from another model to outfit a larger brake system.

A native of St. Louis, Cheng is a fan of the hockey team, the Blues. He owns a game-worn jersey from almost every member of the 2019 cinderella team that won the Stanley cup, with some of those jerseys coming from Stanley Cup final games.

Cheng plans to apply to residency in internal medicine this year because he wants to continue applying what he learned in his scientific and medical training.

The clinical work reminds him to treat patients and not just the tumors, while scientific research trained him to loo at evidence and literature carefully to find clinical gaps, he explained.

Otto Heinrich Warburg

By Leah S. Dunaief

Leah Dunaief

There are two good stories in “Ravenous: Otto Warburg, the Nazis, and the search for the Cancer-Diet Connection.” The newly released book, by Sam Apple, is about the Nazi’s hunt for the cause of cancer and the remarkable support Hitler gave, before and during World War II, to Otto Warburg, a premier scientist, homosexual and Jew.

Hitler’s mother, possibly the only person he loved, died a painful death from breast cancer. Hitler, reportedly a vegetarian and a hypochondriac, periodically thought he was dying of cancer. Otto Warburg, who won the Nobel Prize in 1931 and had been nominated repeatedly for the prize during his career, did in-depth biochemical research on the metabolism of tumors, especially cancer cells. Despite Warburg’s several obvious drawbacks and outspoken criticism of Nazi values — he refused to have Nazi flags in his lab or offer the Nazi salute — Hitler protected him and allowed him to do his work.

Otto Heinrich Warburg, born in 1883 into a prominent family of bankers and scientists, first distinguished himself in the elite cavalry regiment, the Uhlans, during WWI. He won the Iron Cross for bravery and was still fighting at the front in 1918 when Albert Einstein, a close friend of his physicist father, wrote him a letter urging him to come home. Einstein told him that science needed him. That, combined with his breakthrough research before the war on sea urchins, and his aristocratic family, did much to solidify his lifetime arrogance.

He did return home, continued his distinguished work, and was named director of a Kaiser Wilhelm Institute in Berlin founded by the Rockefeller Foundation, designed by him in the Rococo style, in 1931. He proceeded with his investigations into the causes of cancer, which had been relatively rare until the 19th century but was exploding in numbers in the early 20th century. The German people, along with people in the United States and elsewhere, were terrified of the disease.

Warburg’s hypothesis was that cancer growth was caused by tumor cells generating energy (to reproduce) mainly by the anaerobic (no oxygen) fermentation of glucose. Healthy cells, by contrast, generate energy mainly from oxidative breakdown with the salt pyruvate in the mitochondria (part of the cell responsible for producing the cell’s energy.)  If you don’t understand those last sentences, it doesn’t matter. The point is that Warburg believed the primary cause of cancer was the replacement of the respiration of oxygen in normal body cells with the fermentation of sugar. Therefore the culprit: SUGAR. 

Today the understanding of the cause of cancer is mutations in oncogenes and tumor suppressor genes that lead to a malignant transformation. The metabolic changes in cells that Warburg observed were not causative, today’s scientists believe, but the result of those mutations.

Warburg’s work offered support for the role of metabolism in the mitochondria in aiding tumor suppression. He oversimplified the complex interactions between the mitochondria and the cell nucleus, between metabolism and mutations.

After the war, Warburg did come to the United States, but his self-important personality, his tyrannical behavior in the lab, his imperiousness with his peers and finally his inability to admit error, all helped to push his research out of sight. He ultimately returned to Switzerland.

In the 1960s, scientific attention turned to the newly defined DNA and cancer-causing genes. Only with the new century has there been a metabolism revival and attention to the role of insulin and the link with obesity.

The book offers us interesting history, both about the Nazis and scientific research into the causes of cancer. Reading it will certainly make us think about what we eat.

METRO photo
Mouthwatering barbeque options can decrease health risks

By Daniel Dunaief

Dr. David Dunaief

What better way than the unofficial launch of summer holidays – and summer barbeques – to kick-start you on the path to preventing chronic diseases? In the past, I have written about the dangers of processed meats in terms of causing chronic diseases, such as cancer, diabetes, heart disease and stroke. These are foods commonly found at barbeques and picnic meals. Therefore, I think it is only fair to talk about healthier alternatives and the evidence-based medicine that supports their benefits. The Mediterranean-style diet is a key to success. It is composed of thousands of beneficial nutrients that interact with each other in synergistic ways. 

The Mediterranean-style diet, as I have mentioned previous articles, includes green leafy vegetables, fruit, nuts and seeds, beans and legumes, whole grains and small amounts of fish and olive oil. We all want to be healthier, but these are the summer holidays – doesn’t healthy mean tasteless? Not at all!

At a memorable family barbeque, we had a bevy of choices that were absolutely succulent. These included a three-bean salad, mandarin orange salad with mixed greens and a light raspberry vinaigrette, ratatouille with eggplant and zucchini, salmon fillets baked with mustard and slivered almonds, roasted corn on the cob, roasted vegetable shish kebobs, and large bowl of melons and berries. I am drooling at the memory of this buffet. Let’s look at the scientific evidence that explains why these foods help us.

Cancer prevention

Fruits and vegetables may help prevent pancreatic cancer. This is very important, since by the time there are symptoms, the cancer has spread to other organs and the patient usually has less than 2.7 years to live (1). Five-year survival is only five percent (2). In a case control (epidemiological observational) study, cooked vegetables showed a 43 percent reduction and non-citrus fruits showed an even more impressive 59 percent reduction in risk of pancreatic cancer (3). Interestingly, cooked vegetables, not just raw ones, had a substantial effect.

Garlic plays an important role in reducing the risk of colon cancer. In the IOWA Women’s Health Study, a large prospective (forward-looking) trial involving 41,837 women, there was a 32 percent reduction in risk of colon cancer for the highest intake of garlic compared to the lowest. Vegetable consumption also showed a statistically significant reduction in the disease, as well (4). Many of my patients find that fresh garlic provides a wonderful flavor when cooking vegetables.

Diabetes – treatment and prevention

Fish plays an important role in reducing the risk of diabetes. In a large prospective study that followed Japanese men for five years, those in the highest quartile of intake of fish and seafood had a substantial decrease in risk of type 2 diabetes (5). Smaller fish, such as mackerel and sardines, had a slightly greater effect than large fish and seafood in potentially preventing the disease. Therefore, there is nothing wrong with some grilled fish on the “barbie” to help protect you from developing diabetes. 

Nuts are beneficial in the treatment of diabetes. In a randomized clinical trial (the gold standard of studies), mixed nuts led to a substantial reduction of hemoglobin A1C, a very important biomarker for sugar levels for the previous three months (6). As an added benefit, there was also a significant reduction in LDL, bad cholesterol, which reduced the risk of cardiovascular disease.

The nuts used in the study were raw almonds, pistachios, pecans, peanuts, cashews, hazelnuts, walnuts and macadamias. How easy is it to grab a small handful of unsalted raw nuts, about 2 ounces, on a daily basis to help treat diabetes?

Stroke prevention

Olive oil appears to have a substantial effect in preventing strokes. The Three City study showed that olive oil may have a protective effect against stroke. There was a 41 percent reduction in stroke events in those who used olive oil (7). Study participants, who were followed for a mean of 5.2 years, did not have a history of stroke at the start of the trial.

Though these are promising results, I caution you to use no more than one tablespoon of olive oil per day, since there are 120 calories in a tablespoon. 

It is not difficult to substitute the valuable Mediterranean-style diet for processed meats, or at least add them to the selection. This plant-based diet offers a tremendous number of protective elements in the prevention of many chronic diseases. So this Independence Day and beyond, plan to have on hand some mouth-watering healthy choices.


(1) Nature. 2010;467:1114-1117. (2) Epidemiol Prev Anno 2007;31(Suppl 1). (3) Cancer Causes Control. 2010;21:493-500. (4) Am J Epidemiol. 1994 Jan 1;139(1):1-15. (5) Am J Clin Nutr. 2011 Sep;94(3):884-891. (6) Diabetes Care. 2011 Aug;34(8):1706-11. (7) Neurology. 2011 Aug 2;77(5):418-25.

Dr. David Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com. 

Dr. Paolo Boffetta

By Daniel Dunaief

Dr. Paolo Boffetta, who joined Stony Brook University as Associate Director for Population Sciences in the Cancer Center in the midst of the pandemic last April, asks the kinds of questions doctors, scientists and non-scientists also raise when they look at illnesses among groups of people.

An epidemiologist who worked for 20 years at the World Health Organization and at Mt. Sinai Hospital in New York City for 10 years, Boffetta joined Stony Brook because he saw an opportunity to replicate the kind of success he and others had at Mt. Sinai, where he helped the institution earn a National Cancer Institute designation. Cancer centers can apply for NCI designation when they have a well-established portfolio of research.

Dr. Paolo Boffetta

“The idea to try to get the Cancer Center” at Stony Brook “to the NCI level was very appealing,” Boffetta said. Stony Brook was looking to build out its population sciences work.

In addition to the big picture goal of helping Cancer Center Director Yusuf Hannun and other researchers earn that designation, Boffetta has partnered with several scientists at Stony Brook and elsewhere to address questions related to various illnesses.

Boffetta has applied for $12 million in funds over six years from the National Cancer Institute for a new water project.

The research will recruit people who are over 50 years old across several towns, primarily in Suffolk County to explore the link between the potential exposure these residents had to different chemicals in drinking water and types of cancers.

“The main idea is that people may be exposed to carcinogens through drinking water according to where they have been living,” Boffetta said.

The scientists will follow these residents over time to determine the health impact of their town of residency. “If this is funded, this will be a major project that will involve many institutions,” he added.

The chemicals they will study include nitrates, chlorinated solvents, 1,4-dioxane, and perfluoroalkyl substances.

While he awaits word on potential funding for the water effort, Boffetta and others are looking at another project to explore the link between various environmental factors and bladder cancer. This is not limited to drinking water contamination. The group plans to analyze tumor samples to see whether they can detect fingerprint mutations.

World Trade Center Studies

Boffetta also plans to continue and expand on work he’s done at Mt. Sinai with responders of the World Trade Center attacks, a group that has received considerable attention from numerous scientists at Stony Brook.

He has been “doing a number of quite detailed analyses on cancer, including survival of workers and responders to developing cancer,” he said. The WTC survivors are enrolled in a medical monitoring treatment program, sponsored by the Centers for Disease Control, which means they “should be getting good cancer care.”

Boffetta has been comparing their survival to the population at large in New York, analyzing how the risk of cancer evolved over the almost 20 years since the attacks.

Boffetta has started to look at one particular new project, in which he studies the prevalence of clonal hematopoiesis of indeterminate potential (or CHIP), which is an asymptomatic condition that increases the likelihood of leukemia and cardiovascular disease. He is studying 350 healthy World Trade Center responders and a group of historical controls from the literature.

He plans to use the results of his study to develop strategies to prevent these diseases in WTC responders.

In some of his WTC studies, Boffetta is working with Ben Luft, Director of the Stony Brook WTC Wellness Program at the Renaissance School of Medicine at SBU, who has been involved in providing extensive research and clinical support for WTC responders.

Boffetta is an “internationally renowned cancer epidemiologist” who contributed his “vast experience on the impact of environmental and occupational exposures [that were] seminal in our understanding of how the disaster of 9/11 would eventually lead to increased numbers of cancer cases among responders,” Luft wrote in an email.

Boffetta’s contribution and understanding will “transcend the events of 9/11 and its impact on the responder community to a general understanding of the increased incidence of cancer on Long Island,” said Luft.

While Boffetta has several academic affiliations with institutions including Harvard University, where he teaches a class for a week each year, and Vanderbilt University, his primary focus involves the work he conducts at Stony Brook and at the University of Bologna.

Boffetta plans to keep his research team considerably smaller than the 80 to 100 people who worked with him at the World Health Organization. Indeed, he said he mainly focuses on working with collaborators. He plans to hire his first post doctoral researchers soon.

As for teaching, Boffetta has been working with the program directors of the Masters of Public Health to develop a tract in epidemiology. He plans to start teaching next year.

Boffetta, who spoke with Times Beacon Record News Media through WhatsApp from Italy, said he often works double shifts to remain in contact with his colleagues in the United States and Europe. When he’s in the United States, meetings can start at 6 in the morning to connect with his European counterparts in the middle of their day. When he’s in Italy, his last meetings sometimes end at 11 p.m. or midnight.

Boffetta, however, said he has “a normal life,” which, prior to the pandemic, included trips to the opera and museums. He also enjoys skiing and hiking.

Married to Antonella Greco, who used to teach Italian, Boffetta lives in New York City. He has three daughters, who live in Brooklyn, Italy and Uruguay. He has been vaccinated against COVID-19 and is looking forward to the opportunity to interact with his colleagues in person once restrictions caused by the pandemic ease.