Meet the Team: Bill Cramer

At the Wright Center, we seek to advance science and foster partnerships that accelerate translational research for the betterment of human health. Our team members come to work every day ready to transform laboratory discoveries into treatments for patients, engage communities in clinical research and train a new generation of clinical and translational scholars, all with the shared goal of bridging the gap between scientific theory and practical medicine.

Each month, we will highlight one member of our team who is contributing to our shared mission of advancing science and fostering partnerships that accelerate translational research for the betterment of human health.

For a full list of staff members, please visit cctr.vcu.edu/aboutus/staff.

There are no targeted drugs to treat triple-negative breast cancer. A VCU student aims to fix that.

By Anne Dreyfuss
VCU C. Kenneth and Dianne Wright Center for Clinical and Translational Research

More than 268,000 people will receive a breast cancer diagnosis in 2019. Of them, 20 percent will learn they have triple-negative breast cancer, an aggressive form of the disease that tests negative for the three most common receptors known to fuel breast cancer growth — estrogen, progesterone and a protein called human epidermal growth factor. Since triple-negative breast cancer lacks the receptors that would allow it to be targeted by currently available drugs, physicians are limited in their ability to treat it.

“Given the current standard of care, patients who are diagnosed with triple-negative breast cancer don’t do as well as patients who have other forms of the disease,” said Tia Turner, a Virginia Commonwealth University M.D.-Ph.D. student.

Turner wants to change that narrative. The VCU School of Medicine graduate student recently received a National Cancer Institute grant to fund her research, which is aimed at uncovering novel drug combinations to treat triple-negative breast cancer. Ultimately, Turner hopes to discover effective, safe, targeted treatment regimens for patients with advanced forms of the disease.

“Triple-negative breast cancer is notoriously hard to treat because we don’t have markers that can be targeted by certain types of drugs,” Turner said, adding that the only currently approved medical therapy — chemotherapy — is highly toxic and often ineffective. “We need new and better treatments to help people who have been diagnosed with this devastating disease.”

For the past few years, Turner has worked in the pathology laboratory of Chuck Harrell, Ph.D., member of the Cancer Molecular Genetics research program at VCU Massey Cancer Center and an assistant professor of pathology in the VCU School of Medicine. Turner performs cell culture screenings of drugs — 1,363 to be exact —most of which are already approved by the Food and Drug Administration for treatment of other diseases.

“We look for patterns in certain classes of drugs,” Turner said. “It is a good way to narrow down drugs that are effective that we otherwise might not have thought of testing against cancer.”

The drugs Turner tests are approved for treating conditions ranging from cardiac arrhythmias to depression. “We have also seen that a vitamin D drug has been effective at killing tumor cells,” she said. By developing effective combinations of drugs that are already FDA-approved, she aims for her research to make breakthroughs in the field of triple-negative breast cancer treatment that could quickly be translated to the clinical setting.

Translating research from the laboratory to the clinic is what fuels Turner’s passion for science. The 29-year-old New York native chose to attend VCU because of the medical school curriculum’s emphasis on a bench-to-bedside mentality, which Turner said is essential to effectively conducting translational science. She most enjoys the interactive, discussion-based courses in which clinicians and researchers lead students in conversations about patients’ clinical cases.

“We discuss the patients’ diagnosis and treatment plan from a clinical perspective, as well as from a more basic science perspective,” Turner said, adding that the program is heavily focused on integrating clinical trials with basic science research. 

Turner is pursuing a Ph.D. in clinical and translational sciences with a concentration in cancer and molecular medicine through the C. Kenneth and Dianne Wright Center for Clinical and Translational Research. After defending her dissertation next spring, she will spend two more years finishing her medical degree. Her goal is to work at an academic medical center where she can maintain a clinical practice, teach and do research.

“As a physician, you run the risk of losing sight of where the tools and medications you’re using to treat patients came from,” Turner said. “The majority of the tools we use as clinicians emerged from pre-clinical research. My time working in the lab has made me realize how important that part of the translational science spectrum really is.”

Turner was encouraged by her M.D.-Ph.D. classmates and professors to apply for the NCI grant, which is intended to enhance the integrated research and clinical training of promising dual-doctoral degree students who are interested in pursuing careers as clinician-scientists. The National Research Service Award is highly competitive, and the grant application process is notoriously rigorous. Turner said she relied on her friends and mentors for help preparing it.

“A lot of the other M.D.-Ph.D. students were helpful in providing me with advice on the structure of the grant application,” Turner said.

Now with the help of her fellow classmates and professors in conducting the research, Turner said she is encouraged by the research team’s initial results. She hopes her work one day will lead to new treatment options for people who are battling triple-negative breast cancer.

“I hope that our research can eventually help people with advanced or metastatic triple-negative breast cancer who are not responding to current therapies or who develop recurrences of the disease,” Turner said. “We need to offer more treatment options for those patients.”

 

 

VCU researchers participate in a multi-center study to determine the best strategy to improve survival from cardiac arrest

Researchers at Virginia Commonwealth University, along with several other locations throughout the United States, will be performing a research study to determine whiPhoto of a defibrillator on a wallch of two standard strategies of care after a cardiac arrest produces better outcomes.

The study, called the ACCESS Clinical Trial, will include adults who are having a cardiac arrest and have been successfully treated with a defibrillator shock. Cardiac arrest is a medical condition in which the heart stops beating blood to the brain and other organs of the body. It results in death, unless able to be reversed.

Cardiac arrest, commonly known as a heart attack, is often caused by a blockage in one or more of the arteries supplying blood to the heart. Blockages causing heart attacks must be treated urgently with a heart catheterization to prevent significant heart damage. Typically, heart attacks are diagnosed by certain findings on an electrocardiogram, or ECG, performed when the patient arrives in an Emergency Department. After a cardiac arrest, however, heart attacks cannot be reliably identified by the ECG and therefore can go undetected and untreated. Most patients whose heart has been restarted after a cardiac arrest are unconscious and in a coma, so they are unable to provide medical information. Most patients who come out of the coma after several days will then undergo the heart catheterization to look for blockages, but by this time the damage may have already been done to the heart muscle.

The purpose of the ACCESS Clinical Trial is to determine if more of the patients do better if they are taken to receive heart catheterization at the time of admission. Both strategies, early and late heart catheterization, are currently used clinically and both are considered the standard of care, therefore all patients will receive the standard of care treatment.

Since patients are often in a coma after cardiac arrest due to brain injury from when the heart had stopped, they may not be able to give consent. Attempts will be made to contact the patients’ legally authorized representative to obtain consent for the research study. Since the early heart catheterization must be performed within 90 minutes from the time of admission to result in the most benefit, if the legally authorized representative cannot be contacted to provide consent that would allow the procedure to be done within this time frame, the patient will be enrolled into the study under the Department of Health and Human Services regulations allowing an exception to informed consent under emergency research circumstances. 

Interested persons wishing more information, having questions or concerns, or who do not wish to participate in the trial should they experience a cardiac arrest and would like to request an opt-out bracelet, are encouraged to visit https:/z.umn.edu/accesstrial, email access@vcuhealth.org, or call (804) 828 – 6047.

Clinician-scientist finds a balance between career and family

By Anne Dreyfuss
VCU C. Kenneth and Dianne Wright Center for Clinical and Translational Research

As a clinician-scientist, Sinem Esra Sahingur, D.D.S., Ph.D., teaches at the Virginia Commonwealth University School of Dentistry, conducts research in the laboratory she manages in the school’s Department of Periodontics and the Philips Institute for Oral Health Research, and sees patients at VCU dental clinics.

“Balancing is so important,” the 47-year-old dentist said.

Sahingur has balanced a career in academia with raising two sons and accommodating her husband’s professional advancements along with her own. She was 40 weeks pregnant when she defended her doctoral dissertation at the State University of New York at Buffalo. Six days later, she delivered her second child. For more than three years prior, Sahingur worked on her thesis and completed a clinical residency program in periodontics in New York while raising her older son as her husband, Emre, worked in Richmond. After graduating, she interviewed for a faculty position at VCU, but with an infant and young child, she and Emre decided it would be better for the family if she took time off from work.

Sinem Esra Sahingur, D.D.S., Ph.D.

“We don’t have any family here, so I needed to stay at home,” she said.

In 2007, before her younger son’s third birthday, VCU contacted Sahingur asking if she was ready to join the dental school faculty. “I said yes,” she said. “They were very understanding. They asked, ‘Do you want to start part time?’ And I said, ‘No, I think we are good now.’”

Sahingur was hired to contribute to the school’s research enterprise, with additional responsibilities as a faculty member and clinician also competing for her time. Like many women who take time off from work to care for their family, she felt pressured to excel when she returned to the workforce.

Now a full-time, tenured professor with more than $5 million in funding to her name, Sahingur’s academic and professional achievements distinguish her as an exceptional faculty member. With the help of institutional, federal and philanthropic funding, she has obtained National Institutes of Health awards, contributed to academic journal publications and presented at conferences around the world.

She hopes to inspire other women to pursue their career goals in the same way. “If you need some time off to take care of your family, do it,” she said. “You can always start where you left off. It may not be as easy as if you had started earlier, but if you are determined and focused, you can catch up.”

Predestined for academia

A native of Istanbul, Sahingur’s earliest childhood memories are of her father, a physician-scientist at Istanbul University, coming home with stories about his students, patients and fellow researchers.

“I grew up surrounded by academicians,” she said. “It was part of my life.”

Sahingur’s father died when she was 11, leaving her with a desire to continue his legacy. “I always knew I would pursue a career in research and medicine,” she said.

At VCU, she has focused on clarifying the links between gum disease and systemic health issues. She is especially interested in preventing and curing periodontitis, a disease that results from interactions between pathogens in the gums and the body’s immune response.

Periodontal diseases are chronic inflammatory conditions that affect the structures around the teeth. They generally are categorized as either gingivitis or periodontitis. Gingivitis, the mildest form, presents as inflammation of the gums without bone or tissue loss. It can be prevented by adequate home care and regular dental exams. Periodontitis is the progression of the inflammation into the deeper tooth-supporting tissue. If left untreated, it results in destruction of bone and soft tissue, eventually leading to tooth loss.

“I look at how inflammation progresses through the body and try to identify therapeutic targets to reduce the inflammation,” Sahingur said. Specifically, her research team is attempting to characterize the key regulators of inflammation with the ultimate goal of discovering better therapeutics to treat periodontitis.

Nearly half of all adults in the United States suffer from periodontal disease and almost 10 percent of that group exhibits severe forms of the disease. Chronic oral inflammation can raise the risk for several life-threatening conditions such as cardiovascular diseases, diabetes, pregnancy complications, arthritis and cancer. Sahingur aims to discover a treatment that could improve the lives of millions.

“As a clinician, I get to experience the benefits of research firsthand, and I would like for my work to have a broad impact on improving overall health,” Sahingur said. “As a clinician-scientist, I am able to focus my research toward projects that will translate to better clinical care.”

Hard work and a little help

In 2013, Sahingur was an inaugural awardee of the VCU C. Kenneth and Dianne Wright Center for Clinical and Translational Research’s endowment fund. The Wright Center and the VCU Office of the Vice President for Health Sciences created the fund to support meritorious pilot and feasibility research.

That same year, Sahingur was awarded a KL2 scholarship through the Wright Center. Two years later, she was awarded a $1.9 million NIH grant for five years to continue her research, making her the first VCU KL2 scholarship recipient to receive a Research Project Grant.

Sinem Esra Sahingur flanked by VCU School of Dentistry postgraduate students.
Sinem Esra Sahingur, middle, flanked by VCU School of Dentistry postgraduate students. (Photo courtesy of Sinem Esra Sahingur)

“The KL2 scholarship and endowment fund were tremendously helpful because they gave me the time and money I needed to be involved more with research,” she said. “In addition, being part of the Wright Center enabled me to build lasting relationships with colleagues from different disciplines.”

Paying it forward

Sahingur intends for her research in oral health to improve the lives of patients beyond the dental clinic.

“Research shows that poor oral health does not only lead to tooth loss, but also has a negative impact on different parts of the body and ultimately quality of life,” she said. “As we move to a new era of precision medicine which aims to personalize treatments, it will be important to integrate oral health as part of overall health to generate more effective preventive and treatment options and better serve our patients.”

While developing her research program, Sahingur pursued interdisciplinary collaborations with colleagues whose research related to the systemic health effects of oral health. The collaborations led to peer-reviewed publications that reported on topics ranging from the effects of newly emerged smoking products to the effects of periodontitis on conditions such as cirrhosis, oral cancer and preterm birth.

“Future research success and translation to the clinics will only be possible through interdisciplinary projects,” Sahingur said. “My goal is to build on the studies we have already started and look for more opportunities to bridge the gap between dental and medical professions.”

Sahingur is on track to achieve her goal. In June, she received a second NIH grant of nearly $2 million to further her research.

“Dr. Sahingur is a vital member of the School of Dentistry’s research enterprise,” said the school’s dean, David C. Sarrett, D.M.D. “During her time at VCU, she has developed a national and international reputation as a dental researcher and clinician-scientist. We are proud to have her as a member of our faculty.”

Sarrett recognized Sahingur’s achievements in September with the Dean’s Faculty Excellence Award for Research. The award came on the heels of a string of laurels last year, including the VCU Office of Research and Innovation’s Outstanding Faculty Mentor Award in April and the university’s Women in Science, Medicine and Dentistry Professional Achievement Award in May.

Sahingur with David Sarrett, dean of the School of Dentistry.
Sahingur with David Sarrett, dean of the School of Dentistry. (Photo courtesy of University Relations)

While her focus has remained on research, Sahingur has devoted much of her time to supporting the next generation of clinicians and scientists by teaching, directing courses and serving as a mentor for faculty and students. For the past three years, she also has been involved in developing the school’s recently launched Ph.D. program in oral health research.

“Although Dr. Sahingur has an abundance of responsibilities as a researcher, professor and periodontist, she never forgets about her mentees,” said Nitika Gupta, a senior biology student who worked in Sahingur’s lab and nominated her for the Outstanding Faculty Mentor Award last year.

Gupta plans to attend the University of Pennsylvania School Of Dental Medicine in the fall to pursue a doctorate in dental medicine.

“Dr. Sahingur invested her time in enhancing my education,” Gupta said. “My passion for molecular and cellular biology and biochemistry grew exponentially while working in her lab. I hope to inspire others the way she inspired me.”

A delicate balance

Not long after Sahingur started at VCU, Emre was offered a job in Washington and the family was again separated. For nearly a decade, she lived in Richmond with her two sons while Emre lived in Washington. “He was there during the weekdays and I was here taking care of the children while I worked,” she said. Two years ago, her older son started college and Sahingurmoved with her younger son, who is now 14, to Washington. She commutes two hours each way to work in Richmond.

“As women, we make sacrifices to balance our commitments to our families with our professional aspirations,” she said.

So far, the sacrifices have paid off, Sahingur said.

“I am dedicated to my family and my work,” she said. “Life is full of surprises and often steers us in unexpected directions. The most important thing is not to give up on our ambitions and direct our positive energy to continue chasing the things that fulfill us.”