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Renaissance School of Medicine

Represented in this illustration is the authors’ finding that DNA hypermethylation disrupts CCCTC-binding factor (CTCF) mediated boundaries which in turn lead to aberrant interactions between an oncogene and an enhancer, driving hyperproliferation and subsequently tumorigenesis from normal OPCs. Photo by William Scavone/Kestrel Studio

Study in Cell led by Stony Brook researcher provides unique analysis in a glioma model

Gliomas are incurable brain tumors. Researchers are trying to unlock the mysteries of how they originate from normal cells, which may lead to better treatments. A new study published in the journal Cell centers on epigenetic rather than genetic changes that drive normal cells to form tumors. The work reveals the precise genes that are regulated epigenetically and lead to cancer.

Genes make us who we are in many ways and are central to defining our health. Cancer is often viewed as a disease caused by changes in our genes, thus our DNA. Epigenetics is the study of how behavior, environment, or metabolic changes can cause alterations to the way genes work. Unlike genetic changes, epigenetic changes do not change one’s DNA, and they can be reversed.

“We used tumor samples and mouse modeling to discover and functionally demonstrate the role of epigenetic alterations in gliomas,” says Gilbert J. Rahme, PhD, first author and Assistant Professor in the Department of Pharmacological Sciences at the Renaissance School of Medicine, and formerly a postdoctoral fellow at the Dana-Farber Cancer Institute in Boston. “By doing this, we discovered genes regulated epigenetically in gliomas, including potent tumor suppressor genes and oncogenes, that drive the tumor growth.”

In the paper, titled “Modeling epigenetic lesions that cause gliomas,” the research team show in the model that epigenetic alterations of tumor suppressor and oncogenes collaborate together to drive the genesis of this brain tumor.

The authors explain that “epigenetic activation of a growth factor receptor, the platelet-derived growth factor receptor A (PDGFRA) occurs by epigenetic disruption of insulator sites, which act as stop signs in the genome to prevent aberrant activation of genes. The activation of PDGFRA works in concert with the epigenetic silencing of the tumor suppressor Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) to transform a specific cell type in the brain, the oligodendrocyte progenitor cell (OPC), driving the formation of brain tumors.”

Rahme says the next step is to test whether therapies that can reverse the epigenetic changes observed in brain tumors can be helpful as a treatment.

127 RSOM graduates begin residencies in summer; one-quarter will stay at SB Medicine, others to practice in NY and all over the country

The Renaissance School of Medicine (RSOM) at Stony Brook University celebrated its 49th Convocation on May 17 by conferring MD degrees to 127 graduates who will begin their first assignments as resident physicians this coming summer. Collectively, they will practice in New York State and 19 other states. Approximately one-quarter of the class will be residents at Stony Brook Medicine locations.

Peter Igarashi, MD, presided over the convocation for the first time as Dean of the RSOM. He also led the graduates in reciting the Hippocratic or Physicians’ Oath for the first time as MDs. John M. Carethers, MD, Vice Chancellor for Health Sciences, University of California, San Diego, delivered the Convocation Address.

“All of you are beginning a career in medicine when the need for physicians has never been greater, and the skills you have learned while at Stony Brook have laid the foundation for your career,” said Hal Paz, MD, MS, Executive Vice President for Health Sciences, Stony Brook University, and Chief Executive Officer, Stony Brook University Medicine, who delivered the welcome remarks.

“Among you, we have future residents in internal and emergency medicine, anesthesiology, neurology, psychiatry, and pediatrics, to name just a few – all committed to providing compassionate, patient-centered care in a wide range of communities. I’m delighted to learn that a majority of you are staying in New York, with many beginning your careers right here at Stony Brook.”

One of the new graduates who will remain at Stony Brook Medicine as a resident in Emergency Medicine is Erin Lavin. Remarkably, she gave birth just a day before the Convocation and was on hand – with baby girl – at the ceremony.

“For most of you, almost your entire medical school education has taken place under the oppressive cloud of the Covid-19 pandemic. This is certainly not what you signed up for when you arrived in 2019,” said Dr. Igarashi. “When the pandemic struck New York, you rapidly pivoted to remote learning and social distancing. When in-person clerkships were again permitted but vaccines were not yet widely available, you bravely came into the hospital to learn how to take care of patients. Your resilience and dedication have brought you here today.”

The graduates join more than 5,800 Stony Brook alumni who earned their MD degrees from the RSOM. This latest group of newly minted physicians joins the healthcare workforce in a post-pandemic era that requires a continuing need for more physicians because of such trends as aging populations, the prevalence of chronic diseases, and new long-term illnesses emerging from the pandemic. The transformation of healthcare such as the growth of telemedicine and more specialty care services will also broaden these new physicians’ opportunities.

Primary Care services such as Medicine and Pediatrics will remain as needed and growing practices in our society. According to an Association of American Medical Colleges (AAMC) 2021 report, our country faces primary care shortages ranging from 21,000 to 55,000 practitioners over the next decade. A significant portion (21 percent) of the graduates will enter primary care fields starting with their upcoming residencies.

Some of the new graduates moved into the field of medicine more quickly than the traditional four years. The RSOM’s 3-year MD program continues to add students. This year, 11 students graduated from that track, the highest number in the school’s history.

 

Dr. Peter Igarashi is the incoming dean of the Renaissance School of Medicine. Photo from University of Minnesota

Stony Brook University’s Renaissance School of Medicine has named Dr. Peter Igarashi, a nephrologist and physician scientist, as its new dean, effective Sept. 12.

Igarashi comes to Stony Brook from the University of Minnesota Medical School, where he is the Nesbitt Chair, professor and head of the Department of Medicine.

At the University of Minnesota, the new dean oversaw 600 full-time and affiliate faculty, 100 adjunct faculty, and over 240 residents and fellows, all while increasing National Institutes of Health funding by 60%.

At UMN, he also helped to cut gender pay disparities, appointed women to leadership positions, developed new multidisciplinary programs, and created an Office of Faculty Affairs and Diversity.

“Dr. Igarashi is a superb, academically accomplished physician leader with a highly successful track record of clinical program growth and research advancement,” Dr. Hal Paz, executive vice president of Health Sciences at SBU and chief executive officer of Stony Brook University Medicine, said in a statement. 

Igarashi has received over $25 million in funding from the NIH during a career in which he has studied polycystic kidney disease, transcriptional regulation, epigenetics and kidney development.

Polycystic kidney disease, or PKD, is an inherited disorder that involves the development of clusters of cysts, primarily in the kidney. Symptoms of the disease can include high blood pressure, loss of kidney function, chronic pain and the growth of cysts in the liver, among others.

His lab developed unique lines of transgenic mice that he has used to study kidney-specific transgene expression and gene targeting.

In addition to writing nine chapters in textbooks, Dr. Igarashi has also authored more than 100 peer-reviewed journal articles.

Before his seven-year stint at the University of Minnesota, Dr. Igarashi had been Chief of the Division of Nephrology and founding director of the O’Brien Kidney Research Core Center at the University of Texas Southwestern Medical Center in Dallas.

At the University of Texas, Dr. Igarashi created services to provide regular kidney dialysis to undocumented and other often marginalized patients. He also led an effort to use artificial intelligence to identify and optimize co-management of patients with hypertension, diabetes, and chronic kidney disease in primary care practices.

A recipient of the NIH Merit Award, Dr. Igarashi also won the 2015 Lillian Jean Kaplan International Prize in polycystic kidney disease. The award honored his contribution to the goal of developing treatments and a cure for polycystic kidney disease.

Dr. Igarashi earned his medical degree from the UCLA School of Medicine and completed an internal medicine residency at the University of California Davis Medical Center. He did a nephrology fellowship at Yale University and also taught at the Yale University School of Medicine.

Dr. Igarashi is board-certified by the American Board of Internal Medicine. He is a member of the American Heart Association Kidney Council, the American Physiological Society, the American Society for Clinical Investigation, the American Society of Nephrology and the Association of American Physicians.

Dr. William Wertheim had been the interim dean of the Renaissance School of Medicine since February 2021, following Dr. Kenneth Kaushansky’s retirement after serving as dean and senior vice president of health sciences for 11 years.

Dr. Wertheim will return to his role as vice dean for graduate medical education. He will also have a leadership role at the Stony Brook Medicine Community Medical Group, which is an arm of Stony Brook Medicine and includes over 35 community practices with over 50 locations across Long Island.

Director of the Heart Rhythm Center at Stony Brook Heart Institute Dr. Eric Rashba is holding the new Watchman FLX device, which provides protection from strokes for people with atrial fibrillation. Photo from Stony Brook Medicine

The butterflies that color backyards are welcome companions for spring and summer. The ones that flutter towards the upper part of people’s chests can be discomforting and disconcerting.

In an effort to spread the word about the most common form of heart arrhythmia amid American Heart Month, the Stony Brook Heart Institute recently held a public discussion of Atrial fibrillation, or A-fib.

Caused by a host of factors, including diabetes, chronic high blood pressure, and advanced age, among others, A-fib can increase the risk of significant long-term health problems, including strokes.

In atrial fibrillation, the heart struggles with mechanical squeezing in the top chamber, or the atrium. Blood doesn’t leave the top part of the heart completely and it can pool and cause clots that break off and cause strokes.

Dr. Eric Rashba, who led the call and is the director of the Heart Rhythm Center at Stony Brook Heart Institute, said in an interview that A-fib is becoming increasingly prevalent.

A-fib “continues to go up rapidly as the population ages,” Rashba said. It occurs in about 10% of the population over 65. “As the population ages, we’ll see more of it.”

The Centers for Disease Control and Prevention estimates that 12.1 million people in the United States will have A-fib over the next decade.

As with many health-related issues, doctors advised residents to try to catch any signs of A-fib early, which improves the likely success of remedies like drugs and surgery.

“We prefer to intervene as early as possible in the course of A-fib,” Dr. Ibraham Almasry, cardiac electrophysiologist at the Stony Brook Heart Institute, said during a call with three other doctors. “The triggers tend to be more discreet and localized and we can target them more effectively.”

Different patients have different levels of awareness of A-fib as it’s occurring.

“Every single patient is different,” said Dr. Roger Ran, cardiac electrophysiologist at the Stony Brook Heart Institute. Some people feel an extra beat and could be “incredibly symptomatic,” while others have fatigue, shortness of breath, chest discomfort, and dizziness.

Still other patients “don’t know they are in it and could be in A-fib all the time.”

Doctors on the call described several monitoring options to test for A-fib.

Dr. Abhijeet Singh, who is also a cardiac electrophysiologist at the Stony Brook Heart Institute, described how the technology to evaluate arrhythmias has improved over the last 20 years.

“People used to wear big devices around their necks,” Singh said on the call, which included about 150 people. “Now, the technology has advanced” and patients can wear comfortable patches for up to 14 days, which record every single heartbeat and allow people to signal when they have symptoms.

Patients can also use an extended holter monitor, which allows doctors to track their heartbeat for up to 30 days, while some patients receive implantable recorders, which doctors insert under the skin during a five-minute procedure. The battery life for those is 4.5 years.

Additionally, some phones have apps that record heartbeats that patients can send by email, Singh said. “We have come a long way in a few years.”

Dr. Roger Fan, a cardiac electrophysiologist at the Stony Brook Heart Institute, added that all these technologies mean that “we are virtually guaranteed to get to the bottom” of any symptoms.

Drugs vs. surgery

Doctors offer patients with confirmed cases of A-fib two primary treatment options: drugs or surgery.

The surgical procedure is called an ablation and involves entering the body through veins in the groin and freezing or burning small areas that are interfering with the heart’s normal rhythm. The procedure breaks up the electrical signals in irregular heartbeats.

Performed under general anesthetic, the procedure generally takes two to three hours. Patients can return home the same day as the operation, Rashba said.

As with any surgery, an ablation has some risks, such as stroke or heart attack, which Rashba said are “very rare” and occur in fewer than one percent of the cases. Additionally, patients may have groin complications, although that, too, has declined as doctors have used ultrasound to visualize the blood vessels.

In extremely rare occasions, some patients also have damage to the esophagus behind the heart, said Rashba, who is also a professor of medicine.

For patients experiencing symptoms like A-fib, doctors recommended a trip to the emergency room, at least the first time.

“If it’s not going away, one, you can reassure yourself, two, you can get treatment, and three, you can get a diagnosis quickly,” said Almasry.

The Stony Brook doctors said choosing the best treatment option depends on the patient.

“Everybody has different manifestations of their A-fib,” said Fan.

Among other questions, doctors consider how dangerous the A-fib is for the patients, how severe the symptoms are, and how much they affect the quality of life.

Doctors urged residents to make the kind of healthy lifestyle choices that keep other systems functioning effectively. Almasry cited a direct correlation between obesity and A-fib.

Reducing body weight by 10%, while keeping the weight off, can reduce the likelihood of A-fib recurrence, he said.