Dialogue | 2018 | Volume 1

2018 Volume I

Wilmot Cancer Institute | University of Rochester Medical Center

Le tt e r f rom t h e Di re ct or Hello Friends of Wilmot Cancer Institute,

Jonathan W. Friedberg, M.D., M.M.Sc. Director, Wilmot Cancer Institute

We are excited to mark the 10th anniversary of the opening of our James P. Wilmot Cancer Center building this year. This building brought cancer care and research at the University of Rochester Medical Center under one roof for the first time in its history. And it became a catalyst for hope, growth and progress against cancer.

As you’ll see in the following pages, this building is a testament to the power of bringing people together. With the support of our community, our researchers and clinicians are collaborating to tackle scientific questions and find novel solutions to clinical challenges.

Our clinical trials program has expanded dramatically, directly translating findings from our research laboratories into the clinics. We have been able to extend our reach across the Finger Lakes region and bring precision cancer care closer to home for thousands of individuals and families.

Construction of this building was just the first step in our goal of becoming a Top 50 Cancer Center in the United States, and our pursuit of National Cancer Institute designation, a prestigious recognition of our research and mission to eradicate cancer. As part of this process, we have refined and re-organized our research programs. We have expanded our clinical trials infrastructure, and we are investing even more in education, screening and prevention services throughout our region.

Central to these efforts is investment in our team. Over the last decade, our staff — including doctors, nurses, social workers, scientists and others — has grown significantly.

On Page 5, you can read about one of our newest recruits, Paula M. Vertino, Ph.D., an internationally renowned expert in epigenetics who will serve as Director of Translational Research and the inaugural Wilmot Distinguished Professor, an endowed position funded by the Wilmot family.

Although our building’s birthday makes us reflect upon 10 years of progress, we at Wilmot are poised for the next decade which no doubt will bring important changes in cancer diagnosis and treatment. Thanks to your generosity and continuing support, we pledge to lead our community in progress against cancer.

Jonathan W. Friedberg, M.D., M.M.Sc.

On the Cover

A Decade of Progress in the Wilmot Cancer Center.

Photo by Christian Scully The Wilmot Cancer Institute is a component of Strong Memorial Hospital.

Wilmot Cancer Institute National Advisory Board Members 2018 Dennis Wilmot, Chair Richard “Dick” Bell Elaine Bucci Michael Buckley Rina Chessin Michael Crumb Patrick Cunningham James Hammer Robert Kessler Kathy Landers Michael Linehan Alyssa Lozipone Jett Mehta Carol Mullin Walter Parkes Barbara Pluta-Randall Mary Pluta Ronald Pluta

Donald Rhoda Steve Whitman Paul “PJ” Wilmot Richard Yates Keith Yeates John Zicari Faculty Members Yuhchyau Chen, M.D., Ph.D. Louis “Sandy” Constine, M.D. Aram F. Hezel, M.D. Gary Morrow, Ph.D., M.S. Christian Peyre, M.D. Emeritus Members Judy Linehan Jim Ryan, Jr. Ex-Officio Members Kellie Anderson Jonathan W.Friedberg, M.D., M.M.Sc.

Hucky Land, Ph.D. David C. Linehan, M.D. Kristie Robertson-Coyne Mark Taubman, M.D. Honorary Board Members Dr. George Abraham Elaine Del Monte Richard DiMarzo Michael Donnelly Joan Feinbloom Janet Felosky Paul Hanrahan Gary Haseley Mark Kokanovich Cricket Luellen Frank Luellen Sandra Hawks Lloyd Ronald Maggio Steve McCluski Michael Norris Jeff Pierce Larry Rabinowitz

Gregory Smith Philip Wehrheim Timothy W. Williams Timothy P. Wilmot Colleen Wilmot Thomas Wilmot Bruce Zicari, II

Dialogue Editor / Writer Lydia Fernandez, Senior Public Relations Associate (585) 276-5788 Contributing Writers Emily Boynton Ruth Harper-Rhode Leslie Orr Art Director / Designer Heather Deal Feature Photography Matt Wittmeyer Contributing Photography Ken Huth Paul Warchol

CONTENTS COVER STORY

Standing Tall In the decade since the James P. Wilmot Cancer Center opened, the building has become a cornerstone of clinical and scientific excellence and a catalyst for hope.

2018 Volume I

6 Dreams and Visions Jean Joseph, M.D., M.B.A., shares his thoughts on his new role as Chair of Urology, the future of urologic oncology, and what keeps him up at night.

10 After the Aha! Moment Inspired by immunotherapy, Wilmot researchers work together to improve these promising new treatments.

20 Seeing Possibilities in RNA Wilmot scientists are studying how this versatile molecule may lead to new cancer treatments.

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News Briefs Community Events

PAGE 12 Wilmot Cancer Institute1

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NEWS BRIEFS

Simple Post-Surgery Step Reduces Bladder Cancer Recurrence

Flushing the bladder with a common chemotherapy drug immediately after surgery significantly reduces the chances of bladder cancer returning, according to a major study led by Wilmot Cancer Institute urologist Edward M. Messing, M.D., and an international clinical trials network funded by the National Cancer Institute.

Published in the Journal of the American Medical Association (JAMA), the study notes this may be the first phase III trial in the U.S. in two decades to show a benefit from this treatment strategy.

An accompanying editorial about the trial noted that the study has “practice-changing

implications.”

“The real importance of this study is that we now have a readily available drug that’s fairly inexpensive, welltolerated, and effective,” says Messing, a professor of Urology, Oncology, and Pathology at the University of Rochester Medical Center and Wilmot Cancer Institute. “One of the biggest issues with low-grade bladder cancer is that it frequently returns. I know some patients who have to undergo four surgeries a year, and if we can cut down on these recurrences, we will save a lot of people a lot of pain, money, and time lost to recovery.”

The clinical trials network, known as SWOG, conducted the randomized, double-blind trial involving 406 eligible patients at 23 cancer centers nationwide. Surgeons removed all cancerous tissue from study participants with a procedure known as TURBT,

or transurethral resection of bladder tumor. Then, 201 —or roughly half — of the patients received the chemotherapy drug gemcitabine, mixed with saline, administered via catheter to the bladder area within three hours after surgery. Gemcitabine works by blocking new DNA and killing any dividing cells.

It’s used to treat several other cancers, including advanced bladder cancer, but had not been studied in this setting among low-grade cancer patients. The second group of 205 patients received saline alone.

Researchers followed all patients for four years — the time period when most bladder cancers return. They found a 34 percent reduction in the risk of recurrence for patients receiving the gemcitabine infusion. Sixty-seven patients in the gemcitabine group, or 35 percent, experienced a recurrence, compared with 91

patients in the saline group, or 47 percent.

Further research is needed to compare various chemotherapy agents for their effectiveness.

About 80,000 Americans a year are diagnosed with bladder cancer, and the low-grade nonmuscle invasive form makes up more than half of the new cases annually.

Messing is a former president of the Society of Urologic Oncology and a recipient of the American Urological Association Ramon Guiteras Award, honoring 35 years of accomplishments that have improved care for patients with urologic cancers.

The trial was supported by the National Cancer Institute under Award Numbers CA180888 and CA180819. Eli Lilly and Co. also supported the work.

-Leslie Orr

Wilmot to Open Study of Hyperbaric Oxygen in Bone Marrow Transplant for Myeloma

Hyperbaric oxygen therapy — a wellestablished treatment for decompression sickness and wound healing — is not often used in cancer care. However, researchers at Wilmot Cancer Institute are opening a clinical trial to study whether it can play a role in the recovery of people who have had bone marrow transplants for multiple myeloma.

Omar Aljitawi, M.D., associate professor of Medicine, Hematology/

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Oncology, has received a $1 million grant from the National Cancer Institute to launch the trial in collaboration with his former colleagues at the University of Kansas.

Hyperbaric oxygen requires patients to be in a pressurized chamber and to breathe 100 percent oxygen. Aljitawi and his team will investigate whether hyperbaric oxygen improves the recovery of white blood cells called natural killer, or NK, cells, which are key components of the body’s immune system. If hyperbaric oxygen therapy boosts NK cells, he says, it has the potential to control the myeloma after the transplant.

Multiple myeloma is a cancer that accumulates in the bone marrow and interferes with blood cell production, and blood stem cell transplants can help to control the disease and improve quality of

life. In Aljitawi’s study, patients will receive autologous transplants, which reinfuse their own blood stem cells after high-dose chemotherapy to kill the cancer. Some patients will be randomly assigned to receive the additional oxygen therapy.

Aljitawi is collaborating with hyperbaric oxygen therapy experts at the University of Rochester Medical Center and Wilmot experts in the Samuel E. Durand Blood and Marrow Transplant Program, one of the largest BMT centers in New York.

-Leslie Orr

Geriatric Oncology Leader Honored with National Award, Wehrheim Professorship Supriya G. Mohile, M.D., M.S., an oncologist at the Wilmot Cancer Institute and trailblazer in the growing field of geriatric oncology, has been named the 2018 winner of the B.J. Kennedy Award by the American Society of Clinical Oncology (ASCO). She delivered the B.J. Kennedy Lecture on June 4 at ASCO’s annual meeting in Chicago.

The Kennedy Award recognizes an ASCO member for outstanding contributions to research, diagnosis, and treatment of cancer in the elderly.

Mohile spoke about the need for a transformational shift in geriatric oncology, by using data to improve communication between doctor and patient. Data from objective assessments of an older patient’s cognition/memory, other health issues like heart disease or diabetes, and nutrition, for example, aid in making decisions about of the risks and benefits of cancer treatment, she said.

“Cancer is a disease of aging and Americans are living longer,” Mohile says. “I’m proud of the progress we’ve made in our research and grateful for the opportunity to seek practical interventions to improve the quality of life of older adults. I’m also honored to be part of a team of national experts that is so committed to this issue.

We will continue to educate thought-leaders in oncology about the need for more tools for treating older patients.”

Mohile led the efforts to create ASCO’s first-ever, evidence-based geriatric oncology guidelines for doctors, recently published in the Journal of Clinical Oncology. She served as first author on the

guidelines, which lay out for practicing physicians how to manage the unique vulnerabilities of patients 65 years and older with cancer, and how to conduct geriatric assessments. The assessments are not yet routinely used in cancer, but they can change the course of a patient’s care.

Mohile has also been named to the Philip and Marilyn Wehrheim Professorship at Wilmot, pending approval by the University’s Board of Trustees. The endowed chair was established nearly a decade ago to support a scientist involved in translational research.

“Supriya is an outstanding member of our Wilmot faculty, and is now appropriately recognized by ASCO as an international leader in the field of geriatric oncology,” says Jonathan W. Friedberg, M.D., M.M.Sc., director of the Wilmot Cancer Institute. “In addition to her research accomplishments, she leads one of the largest geriatric oncology clinical programs in the country, right here in Rochester.

We look forward to her continuing the great work.”

The geriatric oncology clinic that she founded in collaboration with William Dale, M.D., Ph.D., — called Specialized Oncology Care and Research in the Elderly, or SOCARE — now has four physicians dually certified in geriatrics and oncology and works closely with teams of nurses and doctors in psychiatry and palliative care. It is one of only a handful of geriatric oncology programs in the U.S. A professor of Medicine and Surgery at the University of Rochester Medical Center, Mohile joined the faculty in 2007. She is a graduate of the Thomas Jefferson Medical School in Philadelphia.

She completed an internship, residency, and geriatrics and oncology fellowships, and also earned a master’s degree in health outcomes research, at the University of Chicago.

-Leslie Orr

Epstein Receives Important American Cancer Society Award Ronald M. Epstein, M.D., professor of Family Medicine, Psychiatry, Oncology and Medicine, Palliative Care, has received the American Cancer Society’s most prestigious award, the Clinical Research Professorship, to continue his studies of doctor-patient communication. Every year, ACS awards only two of these professorships, which come with up to $80,000 in funding per year over five years, nationwide.

Epstein, who directs the Center for Communication and Disparities Research, has focused on conversations between doctors and patients who have advanced, incurable cancer and the differences in their understanding of prognosis. His prior studies have shown that despite efforts by doctors and patients to improve communication, some patients will still believe that their cancers are curable, and a majority will have unrealistic beliefs about how long they will survive.

“The consequences are large,” Epstein says. “Patients

get treatments they later regret. Families feel upset and abandoned. For doctors, these conversations are difficult too.”

Epstein’s goal is to improve communication between patients and doctors so that they can achieve shared understanding and expectations about prognosis and care so that patients can make informed choices that maximize their quality of life.

Epstein will partner with M. Ehsan Hoque, Ph.D., assistant professor of Computer Science, to incorporate machine learning into data analysis and communication coaching for

doctors and patients. They will explore the use of avatars that can read facial expressions and other emotional cues to help patients and physicians practice for important conversations.

The avatars are intended to augment, rather than substitute for, in-person practice, Epstein says.

“I am passionate about helping patients and families navigate some of the most difficult moments of their lives and helping clinicians be mindful, attentive and present for patients in times of need,” Epstein says.

-Lydia Fernandez Wilmot Cancer Institute

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NEWS BRIEFS

Late Effects of Testicular Cancer Treatment Require Vigilance

Because testicular cancer has a 95 percent cure rate, it is easier for men to move on and forget about it. But new research in the Journal of Clinical Oncology shows that it’s prudent for patients to stay in touch with their medical team as they age and to be aware of treatment toxicities.

“Testicular cancer is the most common cancer in young men, and while usually curable, our study shows it’s important to be aware of side effects of treatment to ensure that survivors live a full and healthy

life,” says the study’s first author, Sarah Kerns, Ph.D., assistant professor of Radiation Oncology at the University of Rochester Medical Center and a Wilmot investigator.

The main worry is not a return of cancer, but side effects from platinum-based chemotherapy, such as cisplatin, which is associated with health problems that can creep up years later. These problems can include heart disease, hearing loss, pain, neuropathy, and erectile dysfunction.

“Some men are in their mid-20s when they undergo treatment, and they may have 50 or more years of life, and you want that to be a highquality life,” says Chunkit Fung, M.D., a study co-author and oncologist at the Wilmot Cancer Institute who treats people

with genitourinary cancers.

“Screening for and treating some of these long-term toxicities, such as hypertension and heart disease, early on is important.”

The research shows that late-onset side effects can occur in clusters, such as erectile dysfunction paired with thyroid disease, or as different types of cardiovascular problems like coronary artery disease, vessel damage, and obesity, Kerns says.

The study involved more than 1,200 testicular cancer survivors who were treated with chemotherapy. Scientists evaluated the cumulative burden of diseases following treatment and found the most common negative health outcomes were obesity, sensory neuropathy, ringing in the ears

and hearing damage. Only about 5 percent of patients had no negative health effects, and 76 percent had a low-tomedium burden of side effects.

Nineteen percent had a high-tosevere disease burden.

The research further suggests that vigorous exercise might be protective for the one in five testicular cancer survivors who suffered from the more severe side effects, Kerns says.

She and Fung are involved in a pilot study at Wilmot testing the feasibility of exercise to reduce the side effects associated with testicular cancer chemotherapy.

The research is a collaborative effort by multiple institutions, and led by Lois Travis, M.D., of the Indiana University Melvin and Bren Simon Cancer Center.

-Leslie Orr

Pancreatic Tumors May Require a One-Two-Three Punch One of the many difficult things about pancreatic cancer is that tumors are resistant to most treatments because of their unique density and cell composition. However, in a Wilmot Cancer Institute study, scientists discovered that a three-drug combination can simultaneously target the cancer cells as well as the other harmful, inflammatory cells within the tumor, to improve survival.

The research builds on previous scientific data from the lab of David C. Linehan, M.D., and may define a more personalized approach to treating pancreatic cancer.

“Our approach is based on evidence that this disease has particular characteristics involving both the tumor and the immune response,” says Linehan, a surgical oncologist, director of clinical operations at Wilmot, and the Seymour I. Schwartz Professor and Chair of Surgery at the University of Rochester Medical Center. “We believe that treatment must address all sides of the problem.”

More than 80 percent of a pancreatic tumor is comprised of cells that are not malignant cancer cells, and many of these non-cancer cells act as detrimental “helpers” that play a vital role in promoting the cancer. For example, tumor-associated macrophages (TAMs) prevent the immune system from attacking the cancer, and tumorassociated neutrophils (TANs) further block the immune system 4

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when pancreas cancer is present. Patients who have a high number of TAMs and TANs in their biopsy samples have a poorer prognosis.

The objective of Linehan’s study, which was published in the British medical journal Gut, was to target TAM and TAN with a combination of experimental drugs that would reduce their numbers and allow the body’s own immune defenses to act appropriately and fight the cancer, and to boost the effectiveness of standard chemotherapy. The study was conducted in mice, but researchers also performed correlative analyses on human pancreatic tumor samples.

Results showed that targeting TAM and TAN — as well as the cancer cells — improved antitumor immunity and chemotherapy response better than using any single therapy.

The Gut journal also published an accompanying editorial by a German physician and research leader in pancreatic cancer, who said the Wilmot study provides a strong rationale for using combinations of drugs to overcome immune evasion in pancreatic cancer and other solid tumors.

Linehan began this investigation at Washington University in St. Louis, where he was lauded for bringing novel and innovative therapies to patients with hard-to-treat cancers. Since joining the URMC and Wilmot in 2014, he’s continued pancreatic cancer studies in partnership with Washington University and other scientists.

-Leslie Orr

Inaugural Wilmot Distinguished Professor, Director of Translational Research to Join Wilmot Cancer Institute

“I see a lot of great opportunities in Rochester to interact with faculty doing foundational research, to bring it from concept to application for new treatments or diagnostic advances.”

Paula M. Vertino, Ph.D., will join the University of Rochester Medical Center and Wilmot Cancer Institute as the Director of Translational Research and professor of Biomedical Genetics this fall.

Her appointment is pending approval by the University’s Board of Trustees. Vertino will also serve as the Wilmot Distinguished Professor, an endowed position funded by the family of James P. Wilmot, the cancer institute’s namesake. She will be a member of the institute’s executive committee and Hallmarks of Cancer research program, which focuses on the biology of cancer.

“I see a lot of great opportunities in Rochester to interact with faculty doing foundational research, to bring it from concept to application for new treatments or diagnostic advances,” Vertino says. “It’s a very collaborative environment, all on one campus, and a really great base to build from.”

Originally from the Buffalo area, Vertino pursued graduate work at Roswell Park Comprehensive Cancer Center and received her doctorate from the State University of New York at Buffalo. She completed her postdoctoral training in cancer genetics at Johns Hopkins Oncology Center. Since 1996, Vertino has been on the faculty at Emory University, where she has served

as a professor in Radiation Oncology and led the Cancer Genetics and Epigenetics Program at Winship Cancer Institute. She directed graduate studies for the Cancer Biology Graduate program and served as co-director for research for the Hematology and Medical Oncology Fellowship Program.

Vertino also has served as a regular member on the Cancer Etiology study section at the National Institutes of Health, and she is a member of the NCI-A parent committee that oversees the review of National Cancer Institute designated cancer centers nationwide.

As Wilmot’s Director of Translational Research, Vertino will be responsible for facilitating interaction among scientists and clinicians with the goal of accelerating the development of laboratory discoveries into technologies or treatments for use with patients.

“I look forward to bringing people together to work on common themes and promoting more team science,” Vertino says. “That is how we’ll bring concepts from the bench to the bedside and back again.”

Vertino’s research focuses on epigenetics and how aberrant gene expression leads to cancer. Her work also seeks to understand how these changes in gene expression could serve as therapeutic targets. Over her career, Vertino has had more than 70 peerreviewed scientific publications and more than 20 years of continuous, overlapping cancer-relevant funding. Vertino’s lab will be

located at the Wilmot Cancer Center, which was designed to encourage collaboration between scientists and clinicians.

“Paula’s research on cancer epigenetics will greatly expand our areas of research strengths at Wilmot Cancer Institute from molecules to human populations,” says Hucky Land, Ph.D., Wilmot’s co-director and director of research. “She is an exceptionally important player in her field.

We are absolutely delighted that she will be joining our leadership team and are very much looking forward to working and collaborating with her.”

As a member of the cancer center’s executive committee, Vertino will be able to share her experience at Emory, which recently received NCI comprehensive cancer center status, to assist in Wilmot’s pursuit of NCI designation.

“I am so excited to welcome Paula to our faculty and the executive committee of Wilmot,” says Jonathan W. Friedberg, M.D., M.M.Sc., director of Wilmot Cancer Institute. “Her experience at Emory running a large research program recently helped lead that institution to comprehensive cancer center designation by the NCI. She is a most deserving inaugural recipient of the Wilmot Distinguished Professorship given her international reputation in epigenetic research. Her deep knowledge of cancer centers will be invaluable to our aspirations toward NCI designation.”

-Lydia Fernandez

Wilmot Cancer Institute

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Face-to-Face with a Top Urologist and Wilmot Partner

By Leslie Orr

Jean Joseph, M.D., M.B.A., is hard to miss on the campus of the University of Rochester Medical Center.

At 6 feet, 5 inches tall, the renowned surgeon is often seen striding down corridors in scrubs between cases, busy offering a phone consultation or responding to email. With high-quality technique and skill, Joseph has removed thousands of cancers and taught a generation of surgeons — but he also tries to practice the art of medicine. He calls his patients the night before surgery to answer questions and suggest they get a good night’s sleep. The joke is that they often say, “No, YOU get a good night’s sleep!”

Recently Joseph has taken on bigger challenges. On Jan. 1, the innovator and pioneer in robotic surgery became the Winfield W. Scott Professor and Chair of the Department of Urology at URMC. Four of the top 10 cancers — prostate, bladder, kidney, and testicular — are treated by urologists and the demand for services has caused tremendous growth in the department. URMC Urology has always had a relationship with the Wilmot Cancer Institute but Joseph promises to forge an even closer bond.

We sat down to talk about cancer, his vision, and priorities. Following is an edited version of our conversation.

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Congratulations! Tell us about your new role.

As chair of the department, I oversee every aspect of our mission. That is, to be a destination for patient-centered urological care, to be a place of choice for those pursuing higher learning, and to be an outstanding place to conduct research. I want it to be an outstanding place to work for all involved.

Twenty-something years ago, we had five faculty members and now we have 20 faculty and we’re growing. It’s important that we have the clinical expertise to care for patients from the greater Rochester area and beyond. The Med Center has increased its radius, and our department has played a role in that. Our patients come from Pennsylvania, Canada, and the north corridor of New York state. Oncology is one of the strong pulls that bring our patients here, and you have to be competitive to succeed clinically. But ultimately the quality of our product goes back to how you educate and to our research.

As you look into the future, what is your dream in terms of controlling urological cancers?

The dream would be, really, to be able to scan someone or take a swab of their saliva, do a genomic analysis, and be able to find a targeted way to alter the disease before it actually develops — employing genomics toward disease prevention.

We’re seeing some of that in terms of using genomics to drive treatment decisions. Our approach is not one-sizefits-all. We all have a unique makeup, and personalized medicine is where the field is going, whether it’s in prostate, bladder, or kidney cancer.

We’ve seen the most progress in prostate cancer. For a long time, the PSA (prostate-

Jean Joseph, M.D., M.B.A., and Patricia James, B.S., R.N., C.N.O.R., nurse manager of the main operating room at Strong Memorial Hospital, talk in a surgical suite corridor. He often follows up with his team to discuss what units his patients will go to after robotic surgery.

specific antigen test) has served as the biomarker. But it’s very general. Now it’s important to get to the next level, to use the multitude of data points we have regarding biopsies and family and personal history, to determine whether to treat the disease aggressively or to watch and wait. The future will include more of these biological markers and identifiers that help us to understand the best course for each particular individual.

The breast cancer genes (BRCA1 and BRCA2) are good illustrations. Everyone has heard about it — especially when Angelina Jolie talked about her situation — and those discoveries led to useful interventions. But we don’t have that for prostate cancer, or for bladder or kidney cancer. So, the dream is to have the same biomarkers that other cancers have, and to be able to identify and help people who are at greatest risk before cancer develops or at

a time when they can live full lives without much medical intervention. Until there’s a cure for cancer, the goal is to improve diagnosis, improve treatment — and even better — to prevent it.

Some of that work is being done here at our cancer center. For example, Dr. Carla Beckham is looking at blood and urine samples from patients with bladder cancer and finding biomarkers associated with tumor development and metastasis.

Another very promising area is in surgery.

We’ve been a pioneer in coming up with ways to use actual patient images to simulate surgery before the event happens.

Dr. Ahmed Ghazi in our department has led this effort, which allows for more precise actions the day of surgery. Our simulation lab is unique in the country and it’s also tremendously valuable for our trainees.

Wilmot Cancer Institute

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When it comes to patient care, you have a reputation for building strong relationships with the people you treat. Why is that important?

We all have unique stories, and I tend to remember my patients not by their names or the state of their diseases, but by their life experiences. I’ve had patients from all walks of life, and yet our conversations click. I think it’s important to treat the person, not the disease.

If someone is coming up to Rochester from another part of the state, keep in mind that their doctor had to counsel them to come here. They could’ve chosen Memorial Sloan Kettering or any number of other places. And so, the caring-for process starts the moment you meet them. When I have a patient who’s staying in a hotel the night before surgery, I realize that can be agony. So I call them. It’s reassuring, and I think they feel as if they’re truly under your care, and that increases their confidence.

They also come in the next morning with a positive mindset, in the right mood and with lower levels of stress, and that mindset may impact the healing process.

I get postcards and gifts of thanks. A

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month ago I got a beautiful flask filled with bourbon from a patient that I took care of 10 years ago. Ten years! I called him, and he said he just wanted to express his appreciation. I had another patient who sent me a cherry wood shoe horn that he made himself. It was a work of art. He told me, “You’re a tall drink of water and you need this.”

When patients show you the impact you’ve made on their lives, that you’ve been able to offer a glimmer of hope in hard times...it’s very humbling. It’s an honor. As physicians and scientists, we don’t always think about the impact we have. It’s an awesome responsibility.

You’re a prostate cancer specialist but when you look across all areas of urological oncology, what are the best opportunities to invest in?

We have a lot of expertise in prostate, bladder, and kidney cancer. And while we’re delivering on the clinical side, I think we need to focus on delivering more with respect to research. Our scientists are working very hard. But prostate cancer in particular is a public health issue. Our

approach for such a common disease has been to diagnose it early with the best technologies, and treat it appropriately.

This institution was the first in the region to have MRI technology to differentiate between aggressive and non-aggressive prostate cancers. And that work must continue. The burden is on us to find ways to decipher who needs immediate treatment, which tumors are not medically urgent, and how to tailor the diagnostic approaches. This is extremely important because most prostate cancers grow slowly, but obviously you don’t want to miss the cases that are likely to grow and spread quickly. As I said earlier, ultimately it’s about personalized medicine — to be able to stratify a personal approach to care, to use the biomarkers that have been identified to help with prognosis.

Bladder cancer is another area to invest in. It’s also common, particularly in the elderly. We have a couple of researchers, Dr. Beckham and Yi Fen Lee, who have done a lot of work in identifying biomarkers to help with diagnosis and also as therapeutic targets. It’s very exciting. And there’s much groundbreaking work to be pursued.

I’ve talked about diagnosis and treatment but the third piece is prevention.

It’s another arm that needs to be elevated.

How do you prevent prostate cancer?

Well, that’s a good question and we don’t have a clear answer. That’s why research has to move in that direction. This is what patients ask us all the time: “How can my kids avoid this cancer? My brother?” There are a number of studies that have looked at vitamins as a possible prevention but as quickly as they were shown to be effective they were disproved. So we don’t have an effective means of preventing it.

At the moment, our conversations with patients tend to focus on lowering the consumption of animal fats (meat, milk, butter, cheese), which are associated with a lower incidence of cancer in general. By lessening the consumption of animal fats, a

cared for at the place of their choosing.

We’re developing relationships with urologists in the region and our approach is to formalize that and be a resource for them. We may not have a faculty member in Ithaca, for example, but we want the physicians and men in Ithaca to think of us first if they have a problem.

Switching gears to a more personal question, you attended medical school at the University of Rochester and did your residency here, but then went off to Europe for additional training before coming back to Rochester. Why did you choose to settle here?

Jean Joseph, M.D., M.B.A., practices his surgical techniques using a robot at the University of Rochester Medical Center.

person can also address a number of other health issues. That’s the best evidence we have.

What’s your department’s relationship with Wilmot and how might it change?

We have a great relationship. We’re an integral part of the Wilmot Cancer Institute and that will continue. In fact, I’ve appointed Guan Wu, M.D., Ph.D., a cancer specialist in Urology, to serve as Director of Urological Oncology. We are working on defining the position, but he will serve both the needs of the cancer center as well as our department. I’d also like to diversify our research a bit, but the focus will remain on oncology. We’ve invested for decades in cancer research and our recruits will target our growth in oncology.

Another goal is to partner with Dr. Jonathan Friedberg, Wilmot’s director, to move toward the University’s objective to obtain National Cancer Institute designation and become a comprehensive cancer center.

This is the highest ranking awarded by the NCI, with special recognition of research expertise in laboratory, clinical, and population-based science. We all need to

be marching in that same direction. We all have the same agenda: To understand the metrics of a comprehensive cancer center and to pursue them aggressively.

In the past few years, Wilmot has expanded in many directions.

We now have 86 inpatient beds, making us the size of a small hospital, and we also provide outpatient care at 11 locations in the Rochester region. Can you talk about how your department fits into the University’s and Wilmot’s regional growth?

Urology is not just based at Strong Memorial Hospital anymore. We are a networked department. Our goal is to have partnerships with all of our affiliates. We’re currently recruiting faculty to be based at F.F. Thompson Hospital in Canandaigua, for example. We already have doctors there, but the demand for urologists is high in Ontario County and the east side of Rochester.

We’re active in Geneva as well, and on the west side, in Batavia. Our tentacles very much parallel those of Wilmot’s. We’re also recruiting for the Dansville, Wellsville, and Hornell corridor. The idea is to have patients

I have been privileged to travel to London and France for training, and I think Rochester is unique. The interface, the education of the next generation, and the research that’s being done here — it’s unparalleled. This medical center has always put these things together and found a way to synergize them. At other fine institutions across the country, you often have hospitals that are very independent from the medical school. And things work okay, but Rochester is unique in its ability to integrate all aspects of medicine in one place. The Rochester region is a great place to practice, and the patient-centered model we have — I can’t imagine finding a better place to pursue my career.

One final question — what keeps you up a night?

How much time do you have? (laughs) As I transition into this new job, a lot of things do. A leader is supposed to provide a vision.

But you can’t just decree the vision, you need to get others to take it on and make it their own. So I think about how to make us an even better team that completes itself, that’s fully integrated. It’s an evolving process and it doesn’t happen on arrival.

I am convinced that in all of us, there’s an appeal to reach the high road. As humans we ultimately want to deliver.

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Leveling Up Driven by Eye-Opening Experiences, These Scientists Want to Improve Immunotherapy’s Impact

By Leslie Orr

When Peter A. Prieto, M.D., M.P.H., was a young clinical fellow at the National Cancer Institute, he had one of those “aha!” moments that turned out to define his mission.

He was on a team that was treating a man who had advanced melanoma, which had spread from the leg to his liver and bones. The treatment was an experimental immunotherapy — an approach known as adoptive cell therapy using tumor infiltrating lymphocytes (TILs). The TILs, which are cancer-fighting T-cells, are extracted from the tumor, expanded in a laboratory, and then infused back into the patient.

But something unexpected and dramatic happened during that case, Prieto says: Before doctors could reintroduce the engineered TILs back into the body, the man’s cancer began to melt away.

“We thought it was a bit of a fluke, but we repeated his imaging in three months, and his tumors continued to shrink. Later, they completely disappeared,” Prieto says.

“This is an extremely rare occurrence, a 10 find us on Facebook and Twitter

spontaneous regression, but it tells us about the body’s ability to use the immune system to completely eradicate cancer.”

Prieto believes that something probably occurred during the surgery to remove the man’s metastatic liver tumor that woke the immune system.

“If we could only capture, define, and replicate exactly what happened — that would be a major breakthrough,” he says.

Immunotherapy is rife with unknowns like this. While often frustrating, these unknowns are also among the most interesting aspects of this field. Why does it work the way it does? Why doesn’t it unfold the same way in every patient?

Although in concept it is not new, immunotherapy has stirred a lot of excitement lately as a cancer treatment.

New studies this spring suggested that in lung cancer, for example, a combination of immunotherapy and chemotherapy should be the new standard of care. And scientists have also demonstrated some success in blood cancers such as lymphoma and leukemia. In fact, recently, the

Wilmot Cancer Institute and other centers across the U.S. began offering a type of immunotherapy, called CAR T-cell therapy, to treat blood cancers and continue to study CAR T-cells for other malignancies.

But scientists are still working to figure out why it hasn’t been as effective in solid tumors such as prostate, ovarian, and colon cancer, and why the responses to immunotherapy vary significantly.

Inspired by his previous experience, Prieto has joined with Minsoo Kim, Ph.D., to launch a TIL investigation that they hope will solve some of the many mysteries about immunotherapy.

“Not all cancers are the same and not all immune systems are the same. So we need to find biomarkers, especially for patients who do not respond well,” says Kim, a Dean’s Professor of Microbiology and Immunology at the University of Rochester Medical Center and director of the Tumor Immunotherapy Research Program at Wilmot. “What is it that dampens the response, and how can we change it?”

Kim also has a longtime interest

in the body’s immune response to foreign invaders. He invented an optical, LED-guided system to steer cancerfighting immune cells toward tumors.

In a study published last year by Nature Communications, Kim showed that in mice with melanoma, the light therapy system could assist immunotherapy drugs in activating a response to cancer.

“Both Peter and I have the same concerns about the need to take immunotherapy to the next level,” Kim says.

“Immunotherapy only works in about 40 percent of patients and we need to find ways to apply it to more people. It’s exciting to be developing platforms that can get us to that point.”

A highly personalized approach They will begin with a TIL platform, based on Prieto’s experience at the NCI, where he earned a coveted, three-year fellowship to work with Steven A. Rosenberg, M.D., Ph.D., one of the fathers of immunotherapy and the first doctor to perform gene therapy as a form of cancer treatment in humans.

Rosenberg pioneered the use of TIL therapy in melanoma, and has gone on to lead further development of immunotherapy with new technologies.

TILs are the immune cells that race from the blood and hibernate in tumors, signaling the immune system to try to attack the cancer.

Prieto primarily treats melanoma, sarcoma, and breast cancer patients, and joined Wilmot last year as an assistant professor of Surgery after being recruited from the MD Anderson Cancer Center in Texas, which specializes in TIL therapy. He is planning to bring this highly personalized TIL therapy to Wilmot patients with advanced melanoma.

He and Kim initially will focus on the best ways to grow and expand extracted patient T-cells, a specialized skill that requires strict lab protocols.

Once they begin offering the treatment, Kim will simultaneously study the immune environment around the tumor in the patient samples, and its interaction with cancer cells — and then connect and compare his laboratory observations

with the real-life outcomes and experiences of Prieto’s patients.

Scientists are also investigating the critical role of the neighborhood of cells and tissues around the cancer cells, known as the microenvironment.

Other research at Wilmot and elsewhere has proven the importance of the microenvironment’s role in many cancers.

For example, manipulating it can make it more favorable for identifying cancer cells and can set the stage for successful destruction of tumors, research suggests.

But untangling the actions of the immune cells and other cells around each tumor is a challenge. As cancer spreads, for example, new tumors with characteristics different from the original tumor spawn new immune environments. On average, there’s only a 50-percent similarity between the primary tumor and the metastatic tumor, Prieto says.

In the pursuit of the microenvironment’s role in melanoma and other solid tumors, the duo will work closely with Prieto’s mentor in Rochester, David Linehan, M.D., director of clinical operations at Wilmot, and the Seymour I. Schwartz Professor and Chair of Surgery at URMC who is also a pioneer in pancreatic cancer immunotherapy.

“Ultimately at Wilmot, “ Prieto says, “we would like far more patients to be eligible for and to respond to this fascinating new form of cancer treatment.”

Opposite page: Wilmot researchers Peter Prieto, M.D., M.P.H., left, and Minsoo Kim, Ph.D., are collaborating to study how cancer-fighting immune cells called tumor-infiltrating lymphocytes, or TILs, can be used against solid tumors such as melanoma.

Above: These images were taken at the site of a tumor. The cells highlighted in green are tumortargeting T cells; they surround the tumor and directly kill the tumor cells. The red cells are non-tumor targeting neighbor T-cells from the immune system.

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By Lydia Fernandez

When it opened in 2008, Wilmot Cancer Center was conceived as a state-of-theart facility that would foster growth and excellence in cancer care, research and community service. Since then, the building has exceeded those expectations, solidifying Wilmot Cancer Institute’s reputation as a leading cancer center in upstate New York. It has enabled growth not just on the campus of the University of Rochester Medical Center, but across the Finger Lakes region. Through novel therapies and new technologies, it has also changed the lives of thousands of people who have faced cancer over the last decade.

“This building is a testament to the power of bringing people together,” says Jonathan W. Friedberg, M.D., M.M.Sc., director of Wilmot Cancer Institute. “It was step one toward our goal of becoming one of the nation’s top 50 cancer centers and

our pursuit of National Cancer Institute designation. Now, we are poised for the next decade, which no doubt will bring important advances in cancer diagnosis and treatment.”

The building opened with four floors and 164,000 square feet of space for outpatient care and research labs. Its outpatient clinics on the first floor created an area where the primary disciplines that treat cancer — medical oncology, radiation oncology and surgery — could physically come together, enabling patients to see their team all at once.

“With this building, we solidified our commitment to combined modality treatment,” says Yuhchyau Chen, M.D., Ph.D., Chair and the Richard T. Bell Endowed Professor of Radiation Oncology

at Wilmot. “Patients can see their medical oncologist, radiation oncologist and surgical oncologist at the same time and place.

Cancer patients benefit tremendously from multi-disciplinary tumor board discussions of each case among oncologists, pathologists, radiologists, and other cancer care specialists. This is made possible by the state-of-the-art audiovisual equipment we have for reviewing imaging studies, tumor pathology, and also allowing remote access.”

Bringing the teams together in the same clinic has allowed the clinicians to implement a truly multidisciplinary approach to care at a time when there are more options for combining surgery, radiation, chemotherapy and other treatments than ever before. And with radiation oncology just steps from medical oncology and a quick elevator ride from

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Twice a day, nurses on WCC7, Wilmot’s Adult Hematology Oncology Unit, have a huddle to update each other. The unit was designed without a central nurses’ station so that nurses could be closer to patients.

These brief meetings help the nursing team stay connected and in tune with what’s happening throughout the day.

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Wilmot’s inpatient units, communication and care became much more efficient.

The addition of the inpatient floors, which began in 2010, created a comprehensive cancer hospital that offers a seamless, full continuum of care. The 86 patient rooms are all private and nearly double the size of those on existing units elsewhere at Strong Memorial Hospital.

“Having the inpatient units here has transformed the patient experience,” Friedberg says. “They’re certainly the nicest, most comfortable hospital beds in the city, and our patients are deserving of that.”

The units — surgical oncology on WCC5, the Samuel E. Durand Blood and Marrow Transplant Program on WCC6, and hematology/oncology on WCC7 — were also designed to facilitate nursing care. In contrast to traditional inpatient units that have a central nursing station, Wilmot’s units have nursing work areas throughout, allowing the nurses to be closer to the patients. This change requires the nurses to find new ways to stay in closer communication.

“They have spot huddles in the hallway to touch base and share issues that are going on and to ensure continuity when new staff come on,” says Dwight Hettler, RN, MS, OCN, NE-BC, Wilmot’s associate director of clinical operations. “They make a concerted effort to keep everyone feeling included and clued in.”

Communication has also played a key role in Wilmot’s expanding clinical trials infrastructure. For both medical and radiation oncology, having research coordinators closer to clinical investigators and patients has helped build stronger relationships and allowed Wilmot to open more trials and recruit more participants.

Throughout the cancer center, the need for more space and more staff came very quickly as growth in new patients has averaged between 15 and 20 percent annually since 2008. To meet the need,

Radiation oncologist Haoming “Carl” Qiu, M.D., works with therapist Kaylee Voorhies, dosimetrist Amy Herman and therapist Rachel Badzinski as they plan a patient’s treatment. Their collaboration is essential for ensuring the best outcomes for patients, especially as technology becomes more sensitive and complex.

Wilmot’s teams have grown substantially.

Today, there are about 120 physicians and more than 200 nurses and nurse practitioners who provide care to patients.

“When we moved in, there were empty offices and rooms, but we’re full now,” Friedberg says. “We’ve filled the building and are looking to expand.”

Advances in technology have also boosted the need for staff. The move to the Wilmot Cancer Center came as advances in technology — particularly the shift from film to digital imaging — began to revolutionize the field of radiation oncology.

“Everything is completely different now,” Chen says, citing developments in treatment-planning technology, intensitymodulated radiation therapy, image-guided radiotherapy, organ-motion management radiotherapy, radiosurgery to ablate hardto-reach tumors, and stereotactic body radiation therapy. “These developments mean we can deliver radiation with greater precision and fewer side effects, and our

patients have a very different experience than before.”

Her team of physicians has nearly tripled since 2008, and she expects her staff to continue to grow as linear accelerators and other radiation technology become more complex. Chen says her department is committed to staying at the cutting edge of cancer treatment — following closely the development of proton beam therapy and other advances, such as the role of radiotherapy in enhancing immunotherapy and ablative radiotherapy for refractory cardiac arrhythmia.

Even for Wilmot’s volunteers, the building has meant growth.

“When I started, there were only two of us,” says Pat Zampi, who began volunteering for Wilmot in 2000. She helps distribute coffee, tea and snacks to patients in the infusion center. She remembers how cramped the old infusion center was, and with limited storage for supplies, volunteers could offer only juices and pretzels.

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Advances in technology have allowed Wilmot’s Radiation Oncology teams to deliver treatments with greater precision and fewer side effects. Above, Michael Milano, M.D., Ph.D.; Kenneth Usuki, M.D.; and Alan Katz, M.D., M.P.H., lead the stereotactic body radiation team and work closely with therapists Kate Reynolds, Jenny Curtis and Stephanie Smith. Below, Deepinder Singh, M.D., and Chair of Radiation Oncology Yuhchyau Chen, M.D., Ph.D., lead the head and neck cancers team and work closely with therapists Anna Roddy and Erika Hagenbach.

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Wilmot volunteer Rosemary Velozzi opens a snack in the Infusion Center for Pat Zampi, a long-time volunteer who is also undergoing treatment for lymphoma.

Zampi was one of two volunteers at Wilmot when the building opened in 2008. The program has since grown to include more than 50 volunteers.

Today, they have a small kitchen where they can brew coffee, heat water for tea or soup, and keep a variety of snacks refrigerated.

“Having that kitchen and a separate storage room is phenomenal,” Zampi says.

“We can serve patient needs better.”

To Zampi, that means engaging patients in conversations if they’re willing and helping them learn about resources and services.

“Our space allows more of this,” says Zampi, who is now herself undergoing a round of treatment for lymphoma.

The Wilmot Cancer Center now has more than 50 volunteers, who help with everything from filling the new-patient binders to rounding on the inpatient floors with books, knit hats and other materials.

They also serve on Wilmot’s Patient and Family Advisory Council, or PFAC. During construction, this committee played a key role in selecting the pull-out sofas in the patient rooms and the chairs in the infusion center, and today, they continue to provide insight and advice to Wilmot’s leadership.

The construction of the Wilmot Cancer Center created not just a physical space, but also a shared identity for all of the cancer care and research at the University of Rochester. In 2014, the cancer center announced its reorganization as the Wilmot Cancer Institute to reflect better its structure and burgeoning programs, including its growing network of locations throughout the Finger Lakes region.

Now the largest cancer center in upstate New York, Wilmot serves more than 17,000 patients each year.

Its clinical programs are only half the story, though. With more than 100 scientists, Wilmot’s research programs focus on understanding the biology of cancer, how cancers thrive in the body and strategies for overcoming treatment resistance. They are also leading national research on treatment toxicity and side effects, the late effects of cancer and ways to help patients live better.

Although cancer research is done throughout URMC, Wilmot Cancer Center’s third floor is filled with cancer-specific

investigators, their labs, and a conference space for meeting and collaboration.

Wilmot’s scientists and clinicians are working together to translate their findings from the laboratory into the clinic. For example, radiation oncologists and immunologists are collaborating to study how radiation can enhance the effectiveness of immunotherapies. Surgeons and medical oncologists are working with exercise physiologists to study how physical activity can improve short-term and longterm outcomes for patients. Clinicians and scientists from a range of fields are studying the role of aging in cancer and how to improve care for older adults.

“Our building has more than fulfilled its promise of improved research and care here in Rochester,” Friedberg says. “Our aspirations now have grown to become a top 50 Cancer Center in the United States.

Given the progress in our understanding of cancer, further emphasizing our research mission positions us to make substantial contributions favorably impacting outcomes in these diseases.”

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Looking Back...

The Wilmot Cancer Center in the 1990s.

Preparing for radiation therapy in the original Wilmot Cancer Center.

Wilmot Cancer Center’s infusion center in the 1990s.

Construction of the original Wilmot Cancer Center lobby.

Construction begins in 2006 on the new Wilmot Cancer Center.

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The lobby of Wilmot Cancer Center in the 1980s.

Radiation oncologist Michael Milano, M.D., Ph.D., and radiation therapist Jenny Curtis in a treatment room.

Construction of the laboratories on Wilmot Cancer Center’s third floor.

Medical oncologist Chunkit Fung preparing to see patients in Wilmot Cancer Center’s clinic.

The lobby of Wilmot Cancer Center shortly after it opened in 2008.

Scientist Kyu Kwang Kim in Wilmot’s Targeted Therapeutics Laboratory for Gynecologic Cancers.

Wilmot Cancer Center when it opened in 2008.

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By Emily Boynton

DNA is at the heart of every cell in your body. It holds the parts list and instruction manual for life — every detail required to make the proteins that enable our bodies’ most basic functions.

RNA, or ribonucleic acid, is crucial for putting those instructions into action, and it’s coming into the scientific spotlight for the potential it may hold for new therapies to treat diseases such as cancer.

At Wilmot Cancer Institute, scientists from the University of Rochester’s Center for RNA Biology are working to understand more about the role of RNA in cancer and how it can be used to disrupt or prevent the uncontrolled growth and division of cells.

Made from DNA, RNA plays a variety of roles in a cell, including the creation of proteins and the expression of genes — functions that, when disrupted, can lead to cancer. Messenger RNA (mRNA), for example, carries DNA’s instructions out of the nucleus to structures called ribosomes, where proteins are made. If the mRNA has

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a bad copy of these instructions, then either a faulty protein or no protein is created, resulting in diseases like cancer.

“We’re learning that what matters most in cancer are the specific changes that occur in an individual’s cells, as opposed to where the cancer starts,” says Lynne E. Maquat, Ph.D., director of the University of Rochester Center for RNA Biology. “RNA is intimately involved in the myriad molecular and cellular changes that can lead to cancer, which is why RNA research is a promising avenue for the next generation of cancer treatments.”

Maquat studies an RNA-based quality control process that blocks cells from making faulty proteins. Called nonsensemediated mRNA decay (NMD), this process comes into play when mRNA has a set of instructions with a mistake that will lead to short or incomplete proteins. NMD acts

like a set of factory inspectors that find and destroy this mRNA before the deleterious proteins can be made.

NMD plays a part in one-third of all inherited diseases, such as cystic fibrosis and muscular dystrophy, and one-third of all acquired diseases, including a number of cancers. These cancers often occur when cells produce defective tumor suppressor proteins that enable the growth and spread of cancer cells. Tumors can also influence how NMD works, leading to the proliferation of cancer cells.

Maquat, the J. Lowell Orbison Distinguished Service Alumni Professor of Biochemistry and Biophysics, and her team

Wilmot scientist Yi-Tao Yu, Ph.D., here with graduate student Meemanage Dezoysa, is researching ways to modify mRNA so that it can override mistakes in genetic instructions.

are looking for ways to stop tumors from interfering with NMD with the goal of finding new ways to treat cancer.

Yi-Tao Yu, Ph.D., dean’s professor of Biochemistry and Biophysics, also studies mRNA and its role in cancer. His lab is researching various ways to modify mRNA so that it can override mistakes in genetic instructions.

The genetic instructions carried by mRNA have start and stop signals that guide the production of different proteins.

Many cancers come from mutations that

introduce early stop signals — known as premature stop codons — into the genetic instructions. These signals order a cell to stop reading the genetic instructions in mRNA partway through the process, resulting in an incomplete and potentially deleterious protein.

Yu’s team is artificially manipulating mRNA in ways that turn these “stop” signals into “go” signals. The goal is to insert a molecule into cells that alters the mRNA, enabling cells to read the genetic instructions of a mutated mRNA from start to finish, as though the premature stop signal was never there in the first place.

These so-called “read-through”

therapeutics are a long way from the clinic, but could help a broad swath of cancer patients. For example, the p53 gene is involved in making an important tumor suppressor protein, which keeps cells from growing and dividing unchecked. If an early stop signal is present, cells fail to produce a functional p53 protein, and this allows cancer cells to grow and divide uncontrollably. Techniques like Yu’s could eventually lead to treatments that would ensure p53 is made and cancer cells are kept under control.

“When I first started studying mRNA in graduate school many years ago, no one knew we could modify it,” says Yu. “The

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progress that’s being made in this area is very exciting because it’s helping us address mutations in genes like p53, which play a part in many tough-to-treat cancers, including bladder, lung, brain, and ovarian cancers.”

Another area of cancer-related investigation in the Center for RNA Biology involves microRNAs, very small RNA molecules that regulate the expression of tens of thousands of genes.

Maquat and her team have identified a protein called Tudor-SN that controls

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many microRNAs and is important as cells prepare to divide. Scientists found that when Tudor-SN is removed from human cells, the levels of hundreds of microRNAs go up, putting the brakes on genes that encourage cell growth. This slows down the process of cell division known as the cell cycle, which goes awry in cancer.

Maquat and Reyad A. Elbarbary, Ph.D., a former post-doctoral fellow in her lab, have filed a patent application for methods that target Tudor-SN for the treatment and prevention of cancer. They continue to study how Tudor-SN works in concert with other molecules and proteins so that scientists

can identify the most appropriate drugs to target it.

Center for RNA Biology scientist Mitchell O’Connell, Ph.D., an assistant professor of Biochemistry and Biophysics, is using the gene-editing technology known as CRISPR to learn more about how RNAs can modulate the way genes are expressed and lead to cancer.

CRISPR was originally designed to help researchers edit parts of the genome by removing, adding or altering sections of our DNA. O’Connell has adapted the

technology to edit RNA, which has several benefits. Once you make a change in DNA, it’s permanent. RNA, on the other hand, gets turned over all the time; it’s produced and then degraded, so any changes are short term. This makes editing RNA a safer option, allowing scientists like O’Connell to test various strategies without making lasting alterations that could end up causing more harm than good.

“More and more we are seeing how RNA is involved in disease, and also how we can begin to manipulate RNA in so many ways,” O’Connell says.

Using CRISPR, he’s exploring how alterations in RNA metabolism influence genes that control cancer cell growth.

Fusion genes, which are formed from two previously separate genes, are a potential target. They play a role in several cancers, including blood cancers, sarcomas, and prostate and ovarian cancers. These genes often contribute to tumor formation because they produce much higher levels of abnormal proteins than regular genes.

The research is in the early stages, but O’Connell’s lab wants to determine if manipulating RNA can inhibit the activity of fusion genes, reducing their ability to drive

Above: Lynne Maquat, Ph.D., director of the University of Rochester Center for RNA Biology, with Tatsuaki Kurosaki, Ph.D., studies an RNA-based quality-control process that blocks cells from making faulty proteins that could lead to cancer.

Opposite page: Wilmot scientist Mitchell O’Connell, Ph.D., with graduate student Feng Jiang, is using the gene-editing technology CRISPR to learn more about how changes in RNA metabolism influence genes that control cancer cell growth.

tumor cell growth.

RNA’s flexibility and ability to do so many different things in cells gives researchers like Maquat, Yu and O’Connell an opening to correct diseases that don’t succumb to conventional drugs.

RNA-based drugs are in development for a variety of diseases, and in the last five years the U.S. Food and Drug Administration has approved RNA-based therapies for conditions including spinal muscular atrophy and Duchenne muscular dystrophy. More than 100 clinical studies are underway for RNA-related treatments for cancer, and Wilmot’s team is excited about what the future will bring.

“The work that’s happening in the field of RNA biology highlights the importance of basic research and its relevance to human disease and therapies,” says Maquat. “As new information continues to emerge, I’m confident it will lead to clinical and technological advances that will take precision and personalized cancer care to a whole new level.”

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CALENDAR OF COMMUNIT Y EVENTS July 14 Second Annual Brockport Elks Club Dice Run In its second year, this event takes place at the Brockport Elks Club and raises funds in support of research conducted by radiation oncologist Hong Zhang, M.D. To learn more, visit the organization’s Facebook page at facebook.com/ Elks2110 or call (585) 637-5110.

July 23 PCAWNY Golf Tournament in Memory of Michael F. Contestabile Held in memory of Michael F. Contestabile, who died from pancreatic cancer, this event takes place from 8 a.m. to 6 p.m. at the Deerfield Golf and Country Club in Brockport. Proceeds benefit both the Michael F. Contestabile Scholarship Fund and pancreatic cancer research at Wilmot Cancer Institute. To learn more, visit pcawny.org.

July 30 Edelman Gardner Ladies Golf Tournament Proceeds from this golf tournament benefit the Edelman Gardner Cancer Research Fund. The event starts at 8 a.m. and takes place at Timber Ridge Golf Club in Brockport. To learn more, visit edelmancrf.com.

Aug. 5 Eleventh Annual Coop Cup This annual golf tournament takes place at the Batavia Country Club and raises funds for brain cancer research. To learn more, visit coopcup. com.

Aug. 13 Fourth Annual Palmer/Head-Strong Golf Tournament This golf tournament takes place at Greystone Golf Course in Walworth and benefits both pancreatic cancer and lung cancer research. To learn more, call (585) 764-9431 or email keith@ startwithcatalyst.com.

Aug. 18 Fourth Annual SEA Blue Ribbon Walk for Prostate Cancer This family-friendly event takes place at Genesee Valley Park starting at 8:30 a.m. Proceeds benefit prostate cancer research. Learn more by visiting the group’s Facebook page at facebook.com/ ustoorochester or by calling (585) 478-0897.

Oct. 11 Fourth Annual Adding Candles for the Cure This fundraiser supports brain cancer research at Wilmot. Taking place at Oak Hill Country Club from 6 to 9:30 p.m., it features hors d’oeuvres, raffles and more. Details are available at www. addingcandles.com.

Sept. 9 Wilmot Warrior Walk The Warrior Walk is a Wilmot premier community event. It takes place at the Highland Park Bowl in Rochester and features a certified 5K, 10K and 1-mile walk, plus tons of fun at the post-race celebration. Proceeds support cancer research and the Judy DiMarzo Cancer Survivorship Program at Wilmot Cancer Institute. Learn more or register at WarriorWalk.URMC.edu.

Oct. 20 Scare Brain Cancer Away 5K This race takes place at East Rochester High School starting at 9 a.m. Proceeds benefit Wilmot’s Patient Needs Fund for brain cancer patients. Learn more by emailing Paul Richards at paul@pcr-timing.com or calling (585) 381-7978.

Sept. 15 Sixteenth Annual Steve Coleman Memorial Golf Tournament Held in memory of Steve Coleman, this golf tournament at Holley Creek Country Club raises funds for the Wilmot Cancer Institute general research fund. To learn more, email Laura Coleman at lsdbcole@frontiernet.net.

Oct. 7 Go Pink! Towpath Community Foundation Breast Cancer Bike Event and 5K This fundraiser features a 5K run as well as 10-mile, 25-mile and 50-mile bike rides. It takes place at Mendon Ponds Park from 9 a.m. to noon, and proceeds support breast cancer research.

Learn more by emailing sales@towpathbike.com.

Oct. 20 Shear Emotion Cupcakes for Cancer Proceeds from this bake sale at Shear Emotion Salon, 1026 Hilton Parma Road in Hilton, benefit cancer research. The sale takes place from 9 a.m. to 4 p.m. For questions or more information, contact the salon at (585) 392-0466.

Nov. 17 Ninth Annual Step It Up! Cure Pancreatic Cancer Indoor 5K & Family Fun Day The Pancreatic Cancer Association of Western New York hosts this annual event to raise funds for pancreatic cancer research. The event takes place from noon to 4 p.m. at the RIT’s Gordon Field House. To learn more, visit pcawny.org.

Oct. 9 Highlands at Pittsford Fashion Show Proceeds from this fashionable event benefit geriatric oncology research and Wilmot’s Comprehensive Breast Care at Pluta. To learn more, email Ann_Julien@URMC.Rochester.edu.

SAVE THE DATE Survivors Night at the Ballpark Friday, Aug. 10, 2018 Celebrate life beyond cancer during Wilmot Cancer Institute’s Survivors Night at Frontier Field in Rochester. All cancer patients, survivors and caregivers are invited to attend at a reduced rate.

The game starts at 7:05 p.m.

Watch for details, including ticket information, at wilmot.urmc.edu/events.

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Discovery Ball Focuses on Cancer Control & Survivorship Research The 19th annual Wilmot Cancer Institute Discovery Ball raised more than $461,000 to support the Cancer Control & Survivorship Research Program. The program — one of the longest-running of its kind in the country —focuses on addressing treatment toxicity and side effects, the late effects of cancer, and ways to help patients live better.

The event honored Gary Morrow, Ph.D., professor of Surgery and Deans Professor of Oncology, who founded Wilmot’s Cancer Control program, with the Inspiration Award. Trained in psychology, Morrow was a pioneer in addressing chemotherapy-associated nausea and vomiting, and his work has helped millions of patients nationwide over the years.

“Over a 40-year career, Gary has made seminal contributions in the field of cancer control, most notably anti-emetic therapy, allowing patients to better tolerate chemotherapy and radiation,” says Jonathan W. Friedberg, M.D., M.M.Sc., director of Wilmot Cancer Institute. “His lasting legacy will be scores of trainees, including many faculty here at Wilmot, who are following in his footsteps to make life better for patients with and after cancer.”

As the director of Wilmot’s program, Morrow oversees a team that operates a national research hub for NCORP, which stands for the National Cancer Institute Community Oncology Research Program. In this role, Wilmot researchers design and manage clinical studies that are implemented nationwide. Survivorship research has become a national priority as millions of people live actively with cancer or achieve years of remission.

Wilmot board members Patrick Cunningham, with wife JoEll, and Mark Cronin, with wife Melissa, co-chaired the Discovery Ball this year.

“It was an honor to serve as co-chairs, along with our wives, for this year’s Discovery Ball and to be able to raise funds and awareness for the great work at the Wilmot Cancer Institute,” Cronin says.

“It was a very enjoyable and inspiring evening and the people who attended seemed to have a wonderful time,” Cunningham says. “We were thrilled with how everything went.”

MOMENT Mr. & Mrs. Richard & Marianne Bell Mr. & Mrs. Jay & Sandra Gelb & Wolk Family Mr. & Mrs. Thomas & Colleen Wilmot CONNECTION Mr. & Mrs. Gerard & Caryl Wenzke Mr. & Mrs. Daniel & Meredith Wilmot COLLABORATION Accountable Health Partners Mr. & Mrs. Martin & Jill Birmingham Bristol Meyers Squibb Dr. Yuhchyau Chen & URMC Radiation Oncology Faculty Cobblestone Capital Advisors, LLC Commodity Resource Corp Mr. & Mrs. Andrew & Loretta Conroy Constellation Brands Mr. and Mrs. Patrick & JoEll Cunningham del Lago Resort & Casino DGA Builders, LLC Dr. Jonathan Friedberg & Dr. Laura Calvi Friends of Patrick & JoEll Cunningham Hahn Automotive Hammer Packaging Harris Beach, PLLC Harter Secrest & Emery Highland Hospital

Mr. & Mrs. Willy & Holly Hillberg Interlakes Oncology Hematology, P.C. James P. Wilmot Foundation Dr. Hucky Land & Ms. Colleen Buzzard LeChase Construction and Affiliated Companies Dr. Jane Liesveld & Dr. Deepak Sahasrabudhe Mr. & Mrs. Paul & Judy Linehan Dr. Gary Morrow, Dr. Karen Mustian, & Dr. Luke Peppone Nixon Peabody, LLP O'Connell Electric Company The Pike Company, Inc. Pluta Cancer Center Foundation Rochester Museum & Science Center Mr. & Mrs. Peter & Susan Schottland Mr. & Mrs. Chris & Kerry Sherman Strong Memorial Hospital Leadership URMC Cancer Control and Survivorship URMC Department of Gastroenterology & Hepatology URMC Department of Orthopaedics & Rehabilitation URMC Department of Surgery URMC Division of Hematology Oncology URMC Division of HPB-GI Surgery URMC Division of Neurosurgery URMC Division of Thoracic and Foregut Surgery URMC Geriatric Oncology Research Group URMC Pathology & Laboratory Medicine Ward, Greenberg, Heller & Reidy, LLP Wegmans Food Markets Inc.

Mr. & Mrs. Dennis & Katie Wilmot Mr. & Mrs. James & Shannon Wilmot Dr. Patrick Wilmot Mr. Alan Winchester & Dr. Larissa Temple Wisteria Flowers & Gifts OPPORTUNITY Mr. & Mrs. Ronald & Katherine Bielinis Brown & Brown of New York, Inc. Mr. & Mrs. Joseph & Elaine Bucci Canandaigua National Bank & Trust Gallina Development Corporation Mr. & Mrs. Wes & Alyssa Jones Mr. & Mrs. Mark Kokanovich & Jean Maess Mr. & Mrs. Brian & Julie Martin Ms. Michele Mosca Ms. Marie Rampello Mr. & Mrs. Thomas & Betty Richards Mrs. Kristie Robertson-Coyne & Mr. Christopher Coyne Roswell Park Cancer Institute Sonitrol Security Systems Mr. & Mrs. Steven & Christine Whitman UNDERWRITING SPONSORS Mr. & Mrs. Peter and Kathy Landers Manning & Napier Advisors Mr. & Mrs. Richard and Caroline Yates

Wilmot Cancer Institute would like to extend a sincere thank you to our special sponsors of the 2018 Discovery Ball.

Your generosity has demonstrated your strong support for advancing Cancer Control and Survivorship research as well as your commitment to our community.

Wilmot Cancer Institute

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Wilmot Cancer Institute 601 Elmwood Avenue, Box 704 Rochester, NY 14642

Wilmot Warrior Walk Sunday, Sept. 9, 2018 Highland Park Bowl Back for its sixth year, the Wilmot Warrior Walk aims to celebrate all cancer survivors and caregivers, as well as remember those we’ve lost to cancer, while raising funds for cancer research and the Judy DiMarzo Cancer Survivorship Program at Wilmot Cancer Institute. Join us!

WarriorWalk.URMC.edu

/wilmotcancerinstitute

@wilmotcancer

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