Pathways to Excellence | Fall 2021

Pathways to Excellence URMC DEPARTMENT OF PATHOLOGY AND LABORATORY MEDICINE | WWW. PATHOLOGY. URMC. EDU | FALL 2021 M. Anwar Iqbal, Ph.D., FFACMG left, professor and director of the DNA Microarray Lab and principal investigator of URMC-Bionano clinical study on optical genome mapping, and Bin Zhang, Ph.D., FACMG, associate professor and director of the Cytogenetics Lab, stands with the Saphyr OGM instrument, which URMC is helping to pilot.

urmc pilots optical genome mapping Potential New ‘Gold Standard’ for Chromosomal Diagnostics Every decade or so, a new technology comes along to help clinical labs identify genetic abnormalities. This has an immediate impact on patients awaiting potentially life-changing information in their lab report. Whether the patient is a pregnant mother, a young child, someone with rare cancer or genetic disease, lab results are the first step in reaching an accurate diagnosis and targeted therapy.

To help advance care, the DNA Microarray Laboratory within the Department of Pathology & Laboratory Medicine is participating in a new multi-institutional study aimed at validating an up-and-coming genomic technology, with the goal of getting it one step closer to clinical application.

M. Anwar Iqbal, Ph.D., FFACMG, professor and director of the DNA Microarray Lab at URMC, is the principal investigator of the

study agreement titled “Clinical research evaluation of optical genome mapping (OGM) technology for the identification of constitutional and somatic genomic variants” using the Saphyr® instrument developed by the San Diego-based Bionano Genomics.

ABOUT THE STUDY The Saphyr has not yet been cleared by FDA for use in clinical labs, and is sold for research use only, so a primary goal of this study is to collect supporting data from participating institutions that demonstrates its utility and effectiveness. In return, URMC has a valuable opportunity to get its feet wet with the most cutting-edge technology and provide helpful insight to the developers as they look to bring it to diagnostic labs.

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IN THIS ISSUE Academic Edge................................................................. 2

New Tech Takes Hold......................................................... 4

From the Chair.................................................................. 3

AP Offsite Moves.............................................................. 5

Tracking COVID................................................................. 4

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

OPTICAL GENOME MAPPING

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URMC’s microarray lab is now running hundreds of (previously validation study is also being done to bring it one step closer to clinical tested and de-identified) abnormal patient samples on the Saphyr. The testing. “We are taking the initiative to show that it can be robust and data will then be compared to those yielded by traditional methods: powerful to use for patient care.”

DNA microarray, FISH, and karyotyping.

Iqbal’s lab is one of the clinical research multi-institutional sites for Iqbal explained that each of these methods has its own strengths prenatal, postnatal and leukemia/lymphoma studies across the U.S. and weaknesses for a variety of reasons. In simple terms, there are certain abnormalities that can be detected by one method but may go HOW IT WORKS undetected by another, so it’s common to test the same patient sample Using this innovative technology starts with isolating ultra large with more than one method. Hopefully, future developments in fragments of DNA from patient samples. To visualize the DNA, a genomics may provide a single platform for all types of tests. chemical label which fluoresces green is added to specific sites across The benefit of OGM, experts say, is the length of it. The labeled DNA is that it combines the best of all three into then put through nanochannels on GAINING AN ACADEMIC EDGE one by scanning the entire genome a specially designed chip which runs to flag and report any and all possible each DNA molecule. abnormalities.

The OGM study has given way to new academic A high resolution camera paired Iqbal expects the existing testing collaborations at URMC. with a microscope allows for precise methods to continue to stick In addition to Iqbal, collaborators who plan optical mapping of the DNA around but is enthusiastic about the to participate in clinical validation studies molecules to a reference genome. This possibilities OGM presents, especially include Monique Ho, M.D. (Reproductive process produces a genome “map” for our institution.

Genetics), who will participate in the prenatal with all chromosomal structural “URMC has always wanted to be studies prospective arm of the study. Other variations (SVs) compared to the at the forefront of the most state-offaculty include Bruce Smoller, M.D. reference genome. the-art technology, and received the (Dermatopathology), W. Richard Burack, Most of these variations are benign, full support from the department M.D., Ph.D., Andrew Evans, M.D. but the few which are pathologically chair, Dr. Bruce Smoller and Dr. (Hematopathology), and Bin Zhang, Ph.D. significant are the main cause of Richard Burack, vice chair of clinical (Cytogenetics). Zoltan Oltvai, M.D., and genetic abnormalities. What makes operations, to pursue OGM at Audrey Jajosky, M.D., Ph.D. (Molecular OGM unique is its ability to detect URMC,” he said.

Diagnostics), also plan to collaborate with their all classes of SVs with unprecedented Though OGM is not yet validated academic interests. resolution and accuracy, from

by New York State, a parallel in-house hundreds to millions of individual DNA basepairs, which are the building blocks of the genome.

From a staffing perspective, this manual process requires precision, from the DNA extraction and labeling to loading and running samples on the Saphyr instrument.

The technologists have hit the ground running with Saphyr since they started using it in June.

Microarray Lab Supervisor Mary Shaver said that while there has been a slight learning curve to using OGM, it has invigorated her team to know they are making a difference in patient care.

“It is very hands-on,” said Shaver, who said that getting too see whole strands of DNA is remarkable in itself. “I really believe it might be a game changer for cytogenetic Micorarray Lab Supervisor, Mary Shaver, and technician, Kamel Awayda, observe and analyze Saphyr data plotted on a diagnostics.” genome map – a detailed visual report of DNA results that identifies genetic abnormalities on a molecular scale depicted as Circos Plot.

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FROM THE CHAIR

I

Bruce Smoller, M. D.

Vektra Casler, M.D.

t is my honor and pleasure to wish you a happy autumn from here in Rochester.

Since my last message, we have welcomed nearly a dozen new faculty to our ranks. I have already shared most of their names but inadvertently forgot to include Vektra Casler, M.D., who is leading our new Informatics division. We are excited to add informatics to our subspecialties and her unique expertise will serve to strengthen our academic core.

I’m also pleased to share that next academic year we will be joined by two new faculty. Brian Finkelman, M.D. in Breast/Gyn. is currently finishing his fellowship at Johns Hopkins. And we are happy to welcome back a familiar face, Dr. AnnaKaroline Israel, who will join our Head & Neck division. Anna graduated from our residency program this summer and is now finishing her fellowship at Cleveland Clinic.

This issue of the newsletter focuses on ways our department is piloting and, in some cases, creating brand new ways to use technology to raise the standard of care. As chairman, I am often in the position of advocating for us to stay on the cutting edge, which is sometimes easier said than done. Investing in cutting edge instrumentation must adhere to a long-term approach that makes us pause and ask, is this instrument or platform what we need to bring the laboratory into the future?

When the answer is yes, I have full confidence that we will make good on every opportunity to not only be the first, but the best in our region.

In the midst of a rapidly changing field, I am proud to see us on the forefront of such advancement and innovation. It is no exaggeration to say we are and will continue to set the standard of care, thanks to the hard work of our faculty and staff who aren’t afraid to take the first step into the unknown as we continually venture into uncharted waters.

Our central laboratory has marked a full two years since the first and largest phase of our move to Bailey Road. I would also like to congratulate our onsite laboratories at Strong Memorial, who recently marked one year since seamlessly moving to new space at the hospital during the pandemic. As you will read more about here, the third phase of this relocation and consolidation effort will bring many of our non-acute AP service lines to Bailey Road, though plans remain very preliminary at this stage. I look forward to sharing more about this leg of our journey in coming columns.

An already bustling recruitment season for our residency and fellowship programs continues – much of it again virtual this year. We are pleased to see continued growth in our training programs across the board, and I would like to thank Drs. Jennifer Findeis-Hosey, Linda Schiffhauer, Majed Refaai, Helene McMurray and our whole Education team for their dedication to keep the wheels of learning turning.

Best wishes for a safe and happy holiday season!

Full-strand DNA waiting to be run on the Saphyr instrument as part of our latest exploration of optical genome mapping .

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MORE NEW TECH TAKES HOLD ACROSS THE LABORATORY MOLECULAR MEETS GROWING DEMAND THANKS TO NEW TECH Few of our labs have seen as much growing demand for services as Molecular Diagnostics, led by Director, Zoltan Oltvai, M.D., and Assistant Director, Audrey Jajosky, M.D., Ph.D. The lab has seen a spike in requests for hematology malignancy testing and solid tumor sequencing in since 2019 since adding instrumentation that’s expanded our ability to offer more and different genetic and solid tumor testing. These include an Illumina MiSeq instrument for next generation sequencing (NGS) and most recently, the Idylla platform for rapid hotspot mutation identification. This fall, the lab will also go live with the state-of-the-art Genexus molecular platform.

Oltvai and others including Vektra Casler, M.D., and resident Dingani Nkosi, MBBS, Ph.D., are working on a

translational project to develop a written standard of care – essentially, a collection of best practices for maximizing how clinical labs use the Idylla. They hope to document specific algorithms as a helpful resource for other labs, said Oltvai. “We aren’t going to do whole exome sequencing on everybody – that would be overkill – but I think we need to have a diagnostic algorithm that allows us to provide a standardized service for the patient. And if it’s insufficient, then how do we take the next step beyond that?”

In the future, this group hopes to do the same for the Genexus with help from colleagues in Hematopathology and Wilmot oncologists.

MICROBIOLOGY STEPS UP TO HELP STATE TRACK COVID SPREAD In July, it was announced that our central laboratory was one of will perform whole-genome sequencing on at least 10 percent five labs chosen by New York State to perform whole-genome of positive specimens from our laboratory and report our data sequencing of SARS-CoV-2-positive samples to help track the back to NYSDOH. The whole-genome sequencing method spread of the COVID-19 virus. is also known as next generation "It's our job to try and keep up with the viThe need for broad surveillance sequencing of tiled amplicon rus as it mutates and understand the impact PCR. This will assist in identifying of variants of concern became increasingly important with the hotspots of Delta or other of those mutations," emergence of the Delta variant, emerging viral mutations in the - Dwight Hardy, Ph.D., said Clinical Microbiology Direc10-county Finger Lakes Region.

Director of Clinical Microbiology tor, Dwight Hardy, Ph.D. “We have the technology to learn "It's our job to try and keep up with the virus as it mutates more about these mutations through whole genome sequencing and understand the impact of those mutations," said Hardy. in order to identify how the virus is changing so we can inform As part of an agreement with the Department of Health, we strategies to help protect our community,” Hardy said.

INNOVATION AT WORK: BEDSIDE ABO BLOOD TYPING DEVICE Blood banker Majed Refaai, M.D., and his colleagues have long researched the pros and cons of relying heavily on Type O blood transfusions, citing risk of long-term damage due to prolonged, unnecessary exposure to certain anti-A and/or anti-B antibodies. To help solve this problem, Refaai teamed up with engineer Steven Day, Ph.D., of the Rochester Institute of Technology to design a new device that can use a drop of blood to quickly report a patient’s blood type. Their patent is awaiting approval from both the U.S. Patent Office and FDA, but the duo hopes the device can eventually be used in ambulances and EMS personnel in a variety of settings.

How does it work? A pinprick of blood is applied to the

surface of the cell-phone-sized device and runs down onto a microchip that identifies A and/or B antigens on red blood cells in less than 30 seconds.

While universal blood transfusions are still widely accepted for bedside transfusion, Refaai and others have reported that exact-matched blood is safest for patients longer-term.

“If someone is Type A, for instance, is transfusion-dependent (as in cancer patients) and are receiving O repeatedly, that cumulatively causes harm,” said Refaai.

He says having a tool that can quickly identify your blood type in any setting not only removes these safety risks, but could also help hospitals better utilize their blood supply.

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FOCUS ON FACULTY

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patient’s kidney biopsy. This “detective work” is a way she is making a real difference. On the research end, she and nephrology fellows are now working on two collaborative research studies on autoimmune related kidney disease.

“My interest in renal is understanding human experience, human suffering and being able to explain it. With anything in pathology, we are truth seekers and speakers and that’s what I want to do in the renal arena,” she said.

Choung lives in Brighton with her mother (who followed her from New Jersey) and her hobbies include Zoom tea parties with her friends – which include decadent scones, sandwiches and tea. Like many during the pandemic, she already has plans to travel when she’s able.

“The dream is to go to England someday and get real tea.”

AN OFFICIAL START TO PLANNING AP’S OFFSITE MOVE The third phase of the Bailey Road project, which will relocate many of our anatomic pathology (AP) services offsite to our central lab, officially kicked off in September.

Design is being led by HDR Architects, the same firm that designed the building where the majority of our clinical pathology testing moved in 2019.

HDR is meeting with all AP groups to determine what services will permanently move out of Strong Memorial Hospital. The goal of these meetings is to collect input from faculty, staff and stakeholders to best determine the scope of this next phase of the project.

Once this is established, the work of designing space can begin to pave the way for construction at Bailey Road, expected to begin next summer (2022).

Vice Chair for AP, Christa WhitneyMiller, M.D., said the move offers an opportunity for Surgical Pathology to grow into its already booming service.

“We have experienced record growth in AP volumes across the board due to growing partnerships with our affiliates, which is exciting. Our current space at URMC does not allow us to keep up with this growth, so devising how to best maximize our service lines offsite will allow us to advance care into the future,” she said.

As with prior moves, our AP teams will retain a footprint at Strong that will include some faculty and essential operations for acute patient care needs:

Accessioning, frozen sections and cytology, to name a few. Histology and immunohistochemistry are among the service lines that are earmarked to move to Bailey.

Others, like Point of Care Testing (POCT), Flow Cytometry/HLA, and Education may move to different space within the hospital. Because we are in the early phase of planning, the plan for some labs is still undecided.

The plans will also address new ways to gain efficiencies, and solutions for much needed storage for paraffin blocks that have resulted from growing volume.

The current timeline is for all relocating groups to move in late 2023 with all operations commencing at Bailey Road in January 2024.

What parts of Surg Path will move offsite? Some services like Cytopathology will retain a footprint at Strong.

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

FOCUS ON FACULTY: GRACE CHOUNG, M.D. When asked what pointed her to the 2006, she interned at the medical examiner’s office. field of pathology, Grace Choung, M.D. These “real-world” experiences were eye opening, Choung says. responded with a single profound truth: While spending the summer working alongside the ME isn’t every It explains how human suffering translates young person’s idea of a joy ride, she saw it as an opportunity to into science. learn.

“Pathologists are explaining someone’s “There were a lot of aspects of public health and community experience, and that’s why I like it,” she life that autopsy explores,” she said. “You see drug overdoses, said. suicide and mental health issues that are germane to a lot of our Choung is a renal pathologist who experiences.” She was hooked. joined the faculty in January 2020. Her The next year, Choung entered Medical School at Tulane, where sharp skill and insight are rooted in a she was surrounded by the vibrant culture of New Orleans for the deep desire to help people – the driving force in a winding path of next four years. She returned to the Northeast to do her residency a career. back at Yale New Haven followed by a renal “With anything in pathology, we are Her family moved from South Korea pathology fellowship at Columbia in 2018. to New Jersey when she was young.

But why renal? In her first year of medical truth seekers and speakers."

She majored in sociology – hoping school, she emailed the entire pathology to one day become a social worker – and used the time before faculty at Tulane looking for help with a project, and the renal getting her master’s in biomedical science at Rutgers to explore pathologist was the only person who responded, a fact that still different opportunities in the medical field: She worked full-time makes Choung laugh. at Cornell Weill Medical College’s Department of Psychiatry where Her work combines her interest in the link between health and they studied trauma in Sept. 11 attack survivors, interned for a socioeconomic factors by looking at the mechanisms on a cellular community-based program that made drug and health care services level. It means interacting with nephrologists and internists to available to low-income residents without health insurance and in identify mechanistic reasons for how disease is expressed in a Continued on Page 5 URMC DEPARTMENT OF PATHOLOGY AND LABORATORY MEDICINE 6