Pathways to Excellence | Winter 2020

Pathways to Excellence URMC DEPARTMENT OF PATHOLOGY AND LABORATORY MEDICINE | WWW.PATHOLOGY.URMC.EDU | WINTER 2020

Paige Elliott, supervisor of Molecular Diagnostics at the Central Laboratory at Bailey Road.

The ‘Next Generation’ of Molecular Testing When it comes to complex genetic and oncology testing, molecular diagnostics labs everywhere find themselves in a bit of a no man’s land when it comes to interpreting “big data” that comes with DNA testing. Next generation sequencing, or NGS, has the capacity to yield a seemingly infinite amount of data that academic labs rarely have the time or resources to interpret. How do you effectively use the information you get from something so complex to drive targeted therapy for patients who need it?

That task is one that Zoltan Oltvai, M.D., the new director of the molecular lab at Bailey Road, has come on board to help navigate. Historically, the lab has performed two main types of DNA testing: Inherited disease (also known as molecular genetics or germline) and molecular oncology. These test for genetic variants or mutations that are indicative of or help to treat certain diseases or cancers.

The Molecular Diagnostics lab currently has two NGS platforms, but it’s still a long way from moving away from manual operations. A number of new instruments are coming to the lab within the next year, primarily to improve turnaround time in the oncology space, as well as being able to offer more comprehensive testing using NGS and other state-of-the-art technologies.

At the top of the lab’s to-do list for the coming year is getting comprehensive NGS testing for cancer mutations up and running.

Until recently, testing was largely manual and tested for one gene mutation at a time. Molecular panels now allow labs to tackle the testing of many genes at once until they eventually include genome and exome sequencing.

“What the field is undergoing now is a major shift in the extent of sequencing and the comprehensive analysis of the obtained data,” said Oltvai. “Almost everything we’re doing now Continued on page 2

IN THIS ISSUE From the Chair.................................................................. 3

Research News.................................................................. 5

Blumberg Hall of Fame........................................................ 4

Student Visit...................................................................... 5

Recognition Luncheon....................................................... 4

Focus on Faculty................................................................ 6

Molecular Testing

Continued from page 1

is more or less manual, and that’s not going to be sustainable.

NGS is already breaking down that barrier, so labs really need to depend on algorithms to analyze data, and I think that’s only going to accelerate in the future. This will drive the need for computational approaches and artificial intelligence.”

Starting Fresh These are just a few of the many new beginnings for the molecular lab, starting with its relocation into a brand new space at the newly open Central Laboratory on Bailey Road.

At the hospital, Molecular had separation of areas to reduce the potential for contamination with amplified DNA. However, as new technologies came and the team grew, new spaces were tacked on any way they could be to accommodate their need for more space. Supervisor, Paige Elliott, said that while moving from Strong Memorial Hospital was a big change, it provided the opportunity for the team to reorient the lab itself.

“We could start fresh and we tried to think through what made the most sense for our workflow,” said Elliott. “We then tried to arrange it carefully that way.”

The space, four rooms in total – starts with a “clean” area for reagents and incrementally moves to a “dirty” space for working with amplified DNA. The Molecular team currently consists of 10 medical technologists, a bioinformatics specialist, a supervisor, and two designated faculty with cross coverage from Microarray and Cytogenetics.

Saide Okutan is a medical technologist who recently joined the staff after earning her master’s degree in genetics and her medical technologist (MT) degree and NYS clinical license. Why did she choose to work in Molecular over other labs?

“I like that we help cancer patients by helping pathologists diagnose diseases by analyzing variants and genes,” said Okutan.

“It’s a lot of hands-on work that’s challenging and exciting, even when you have to troubleshoot and figure out what went wrong when your run failed.”

There are many different roles in the Molecular lab. Some technologists perform single gene assays, others are on NGS panels, and some technologists work to develop new assays.

And of course there is the ever growing need for bioinformatics analysis and programming. To be successful, all of these parts need to come together.

Keeping an Edge The need for innovative approaches is mounting now more than ever as academic labs face competition from outside organizations. For germline testing specifically, where diseases are often present in patients for years before a diagnosis is established, there are large commercial companies (GeneDx, for example)

2 URMC DEPARTMENT OF PATHOLOGY AND LABORATORY MEDICINE

Saide Okutan, one of 10 medical technologists who work in the molecular lab.

that provide testing at a price point that’s not easy for academic labs to match.

Molecular oncology faces similar competition in the industry, Oltvai explains; “I would say it’s a threat to academic medical labs,” he said. “It’s also a challenge that, at least the high end molecular companies are providing high quality work that’s difficult to compete with. It’s something that we have to keep in mind when evaluating the molecular diagnostics economy as a whole.”

These realities help shape the goals and vision for UR Medicine Labs to not only compete, but be a leader in the everevolving field. For example, similar advances have already been seen in other areas of pathology with the gradual adoption of digital imaging approaches. While this was slow in the uptake at first, software applications that in select applications can match a pathologist’s diagnostic accuracy have started to gain momentum.

Oltvai says the same could be done in the molecular sphere, when coupled with morphology.

“It’s not an easy bridge to build between the computational people and the clinical people,” Oltvai said. “But we are starting to see university programs that understand the need for a workforce that can meaningfully contribute to translational research and clinical service using these algorithms.”

One idea is to create diagnostic teams that bring in computational data experts to work alongside clinicians and pathologists. It’s a new approach, but more needed than ever as the demands of “big data” create new opportunities, he added.

“Molecular as we do it right now is limited, but I think in the next five years, we are on the cusp of this becoming a reality.”

FROM THE CHAIR

Bruce Smoller, M.D.

Erin Marner, M.D.

Happy New Year! And now the site shifts … literally. Bailey Road is temporarily in consolidation mode as we figure out how to handle the logistics of a two-site department. In the meanwhile, the Strong Memorial Hospital relocation project has begun in earnest. The Blood Bank and the residual Hematology/Chemistry automated laboratories (and a small piece of Microbiology) are moving into new space in the 2100 wing of the building.

The deconstruction phase of the new space has begun and plans for the new construction are “finalized.” The chief supervisors and medical directors have worked diligently to ensure the best possible new laboratories and I am excited for the change to “get it right.” The hope is that they will be able to move into the new spaces by the early summer or late spring.

Since the last newsletter, Dr. Tony Yeung has joined the faculty in Hematopathology and Dr. Zoltan Oltvai has arrived as the new Director of Molecular Pathology. They both hit the ground running and already feel like full members of the team. Over the next month, Dr. Erin Marner will be joining the team as the new Medical Director of the Clinical Trials Unit as Dan Ryan continues to transition into a full retirement. We are busily recruiting new faculty members to replace retiring ones (Drs. Rothberg, Corsetti, Kirkley) and those moving to part-time (Drs. Kwong and Goldman). We are also recruiting for new faculty members in head and neck pathology, genitourinary pathology, and pulmonary pathology as the department continues to grow at a rapid pace.

We have also engaged a search firm to help us to recruit a new Vice Chair for Experimental Pathology, as a joint recruitment with the Wilmot Cancer Institute.

We also recently completed a busy year for residency interviewing, meeting almost 70 graduating seniors in hopes of filling seven spots through this year’s match. One novel development was an off-site interviewing session in Chicago, at which we met five terrific applicants. We continue to seek novel solutions to improve the quality of our program, which is currently filled with terrific trainees. We expect to hear in January about the approval of our new Pediatric Pathology and Dermatopathology fellowship training programs. We received approval for the Forensic Pathology fellowship and hope to fill that position for July 2020.

We had a successful CAP inspection at Strong Memorial Hospital in December. Thank you to everyone involved for all your hard work! And last but not least, a quick congratulations to Dr. Neil Blumberg who was named to the National Blood Foundation Hall of Fame.

URMC Alumni Reception at USCAP 2020

Monday, March 2 from 5:30-7:30 p.m.

Olympic I Room The Ritz-Carlton, Los Angeles 900 W. Olympic Boulevard Los Angeles, CA 90015

3 URMC DEPARTMENT OF PATHOLOGY AND LABORATORY MEDICINE

BLUMBERG INDUCTED INTO THE NATIONAL BLOOD FOUNDATION HALL OF FAME Neil Blumberg, M.D., professor of Pathology and Laboratory Medicine and director of Blood Bank/ Transfusion Medicine at the University of Rochester Medical Center, was inducted into the National Blood Foundation Hall of Fame on Oct. 19, 2019.

For more than 30 years, Blumberg and a team of collaborators have been investigating how to make blood transfusions safer for the millions of hospitalized patients who receive them every day. He’s been an ardent local, regional, and national advocate for fewer transfusions, despite push-back from many in the medical field.

Some of his earliest work, which established Blumberg as a leader, showed poorer outcomes for cancer patients who received donor blood. These study results changed clinical practice at URMC and increased the survival odds for young leukemia patients. Later, Blumberg showed that filtering the foreign white blood cells from donor blood when transfusions are necessary resulted in fewer cardiopulmonary complications for patients.

And in 2014, Blumberg and co-authors published a groundbreaking JAMA analysis showing that doing fewer blood transfusions reduces infection rates by nearly 20 percent. The study was the first to show conclusively — by analyzing 18 randomized clinical trials involving 8,700 patients — that reducing the number of transfusions not only saved lives but can decrease health care costs significantly.

“My advice to young physicians, medical technologists, scientists and nurses who want to do research is to find problems you think are important and are passionate about,” Blumberg said, in a recent article in the American Association of Blood Banks newsletter that honored his Hall of Fame recognition.

“Don’t allow failure or disapproval of your results by others discourage you too much,” he said. “Consider feedback, but if you find results contrary to the conventional wisdom, read about Semmelweis, whose instructing physicians to wash their hands prior to delivering babies was met with Neil Blumberg, M.D. contempt. Read about Bernard Fisher, the surgeon whose work demonstrating that the Halstead radical mastectomy was ineffective and only created suffering was met with a mixture of disbelief and anger. It is always first and foremost the work and its benefit to patients that should be your focus.”

None of his research would have been possible, he said, without help from numerous close associates, including his spouse, Joanna M. Heal, MBBS, retired physician at the American Red Cross and UR Medicine’s Hematology/ Oncology unit; the technical staff and attending physicians in the Transfusion Medicine service at Strong Memorial Hospital; the nursing staff at Wilmot Cancer Institute and Strong Memorial; and several faculty from Pediatric Surgery, Pulmonary and Critical Care Medicine, and from Wilmot.

The AABB featured Blumberg as a keynote speaker at its annual meeting in San Antonio, Texas, where the Hall of Fame induction took place.

—Leslie Orr

More than 70 staff were recognized at the department’s annual Years of Service Recognition Luncheon at Helenwood Hall son November 15.

4

RESEARCH NEWS Welcome to the first of a new column where you can read about new publications, funding, clinical and basic science projects by our faculty, trainees, and graduate students. We look forward to showcasing this important aspect of our work at the Medical Center. Got a research item to share? Email: Bethany_Bushen@ urmc.rochester.edu.

You may have known it by a different name, but our department has a longstanding doctoral degree program, the Cell Biology of Disease program in Pathology, that trains the next generation of scientists while enabling those trainees to advance our research mission alongside of their faculty mentors. We currently have 40 students enrolled, with five slated to defend their doctoral work in the next few months. Our trainees continue their scientific careers through post-doctoral fellowships or employment in industry, government and higher education. I’d like to take this opportunity to highlight a few of their many notable achievements. Five of our students have secured external funding for their Ph.D. work, including NIH F31 fellowships held by John Bachman, Katherine Best, Felicia Gilels, Courtney Kellogg, and Jessica Ackerman. Moreover, Jonathan Bartko is the recipient of a fellowship from the American Heart Association.

Senior Ph.D. candidate Brianna Shares was awarded the 2019 American Society for Bone and Mineral Research Young Investigator Travel Grant. She also received an Orthopaedic Research Society Travel Grant for the Herbert Fleisch Workshop in Belgium, a meeting designed to bring together excellent international investigators and young and mid-career scientists working in bone and cartilage research for vigorous data discussion and networking. Following her Ph.D. thesis defense in December, Brianna will join the staff of the Upstate Cell Therapy cGMP Facility.

In addition to her fellowship, Katherine Best was recently awarded the Randy Rosier Award for Excellence in Science at the Center for Musculoskeletal Research

Symposium in September and will defend her thesis in the spring semester. Instead of resting on her laurels, Katie will use her final months at URMC to undertake an internship in the Center for Health and Technology / Clinical Trials Coordination Center to learn more about the clinical and translational side of research.

Also slated to defend his thesis in December, Madison Doolittle has accepted a post-doctoral position at the Mayo Clinic and will move from Rochester (NY) to Rochester (MN) this winter – brrr! Madison will join the lab of Dr. Sundeep Khosla to study the pathology of osteoporosis and other age-related disorders by focusing on the mechanisms of cellular senescence.

Not to be outdone, our more junior students are accruing their own accolades. Fourth year Ph.D. candidate Andrea Amitrano, studying immunotherapy under the mentorship of Dr. Minsoo Kim, received an Excellence in Science Award at the 5th Annual Immune Imaging Symposium. First year M.D., Ph.D. trainee H. Mark Kenney also received such an award, in addition to the Student Achievement Award from the Rheumatology Research Foundation of the American College of Rheumatology (ACR), both of which will fund his travel to the ACR national meeting.

Congratulations to all, and keep up the good work!

—Helene McMurray, Ph.D.

Fifth grade students from the Academy of Health Sciences Charter School came to visit the new Central Lab at Bailey Road to learn about pathology and laboratory careers.

5

Department of Pathology and Laboratory Medicine University of Rochester Medical Center 601 Elmwood Avenue, Box 626 Rochester, NY 14642

FOCUS ON FACULTY: LI LIU, M.D., PH.D. Li Liu, M.D., Ph.D. always knew she would be a doctor. Her mother was a gynecologist, her aunt, uncle, and cousin were also physicians.

“At a very young age I grew up listening to medical terms that adults were discussing things I didn’t understand, but it made me want to be a doctor when I grew up,” said Liu, associate director of clinical chemistry at URMC. Her path to clinical pathology began with medical school. After earning medical degree in China, she finished internal medicine residency and worked for several years as an internist. She and her husband, Rongchao, who was studying to become a chemistry professor, then decided to move to the U.S. and continue their education at Northwestern University in Chicago. Liu spent the next five years immersed in basic research, and completed her Ph.D. in molecular and cellular biology.

In 2008, Liu began what would be a decade-long stay at the University of Pittsburgh Medical Center (UPMC) – starting as a research associate, followed by a postdoctoral fellowship in clinical chemistry, and finishing with four years of clinical pathology residency.

Going from medicine to basic research gave her the chance to step back and evaluate the things she enjoyed most, professionally.

Liu says she has always enjoyed interpreting “big data,” and problem solving. But she also wanted to get back into medicine, and clinical pathology gave her the chance to do so.

Her postdoc fellowship advisor encouraged her to combine these skills with her desire to get back into medicine. Liu

completed her residency in clinical pathology in 2018 and applied to an opening at URMC. She was hired almost immediately into her current role, and recently celebrated her one-year anniversary.

Liu knew her medical knowledge would serve her well, as someone who’s used to thinking like a clinician.

“As an internist, I would review lots of lab results every day,” said Liu. “I know how clinicians look at the numbers, and the things that they care about. That’s why I knew clinical pathology would be the best fit for me.”

Between balancing the daily clinical workload, Liu still remains very active in research. She recently published a paper on removing interference of therapeutic monoclonal antibody with serum protein electrophoresis. She is also working to expand upon her poster presented at this year’s ASCP on how to efficiently monitor multiple myeloma patients by laboratory tests into a publication. Her other research effort involves collaboration with Nephrology and Oncology, looking at the role of a new biomarker in the prediction of cisplatin-induced acute kidney injury.

In the future, she is very interested in exploring the mechanism of decreased kidney function affecting serum cardiac troponin levels.

“If we understand whether and what fragments of cardiac troponin build up in serum during renal insufficiency, it’ll help develop new troponin assays that are not affected by decreased renal clearance.”

Liu lives in Brighton. She and her husband have two daughters; Evie, 18, and Ruby, 12. In her free time, she enjoys tackling large jigsaw puzzles (ones with 1,000+ pieces only), word puzzles, and furnishing their family’s new home.

URMC DEPARTMENT OF PATHOLOGY AND LABORATORY MEDICINE 6