Leukemia is one of the hardest cancers to treat, but scientists have discovered a new, targetable pathway in one of the worst subtypes of the disease.
The study, although only relevant in mice and human cell cultures at this point, is important because researchers found that an existing drug, known as creatine kinases inhibitor, is effective at attacking acute myeloid leukemia (AML) in the laboratory.
University of Rochester Medical Center and Wilmot Cancer Institute scientists Archibald Perkins, M.D., Ph.D., and Yi “Stanley” Zhang, Ph.D., teamed up with researchers at Harvard University and the Massachusetts Institute of Technology to study a particular gene, EVI1. When this gene is active, certain types of leukemia and some solid tumors, such as ovarian cancer and some breast cancers, are virtually untreatable.
Their study recently was published in the high-impact journal Nature Medicine. The group showed that when EVI1 is abundant in leukemia, it changes the metabolism of immature blood cells as they progress toward becoming cancer—but also leaves EVI1-positive cancers vulnerable to treatments that can strike down that pathway.
The Perkins/Zhang laboratory in the Department of Pathology and Laboratory Medicine has been investigating the EVI1 gene for several years, resulting in a solid track record of publications on the topic. Their goal is to discover new treatments that will target the underlying pathways involved in EVI1-positive cancers. The Perkins/Zhang data supported Harvard’s and MIT’s investigation of what drives the EVI1 gene.
Leukemia is a type of blood cancer in which abnormal blood cells crowd out the healthy white blood cells responsible for fighting infection. More than 10 different major subgroups of leukemia exist. Many types of leukemia are resistant to treatment, although some patients with AML and other blood cancers can achieve long-term remission if they qualify for a stem cell transplant. Wilmot’s Blood and Marrow Transplant Program is the only program in the Finger Lakes region to offer that therapy.
The Nature study was recently highlighted by the American Association of Cancer Research. Perkins and Zhang are working on other leukemia studies as well, supported in part by Wilmot seed funds and by the URMC Clinical & Translational Science Institute.
Just about everyone who knew or worked with Dr. Marilyn Menegus (1943-2017) has a story about her.
There was the time she brought a Cheesy Eddie’s carrot cake to work when she got tired of hearing that her staff had never tried it before. A colleague recalled the way she could cut through complex scientific concepts and make them easy for anyone to understand. And her coworkers can remember how she’d warmly greet them with, “Hey kid,” no matter their age.
Dr. Menegus, known to many as, simply, Marilyn, passed away March 20, 2017 from complications resulting from colon cancer. Since then, the response from those who knew her has been felt deeply by many.
To celebrate her life and legacy, the Department of Pathology & Laboratory Medicine will host an informal event at the University of Rochester Medical Center on Friday, May 12.
Marilyn was an extremely accomplished and well respected microbiologist who joined the Department of Microbiology and Immunology in 1976 with a secondary appointment in Pathology & Lab Medicine.
She trained more than 40 clinical microbiology fellows and five infectious disease fellows during her 41 years at URMC, earning her the title of “mother of the post-doc program.” She stayed in contact with many of her past trainees, whom she treated like family. Many went on to work in prestigious laboratories across the U.S. Her impact on their professional lives remains strong.
“She was truly a mentor, always eager to share interesting clinical cases and inserting educational tidbits along the way,” said former fellow, Kristen Smith, Ph.D. “The depth of her knowledge and passion always amazed me.”
Former Pathology resident Vanesa Bijol, M.D., who now works in the Harvard University health system, said the sheer number of lives touched by Marilyn was huge. “In that sense, her professional impact was huge, and very few of us who devote life to academia can achieve that level of success,” Bijol wrote. “But she never thought of it that way. She just simply enjoyed her work, science, and teaching, and was very humble about her achievements.”
Marilyn was born and raised in Passaic, New Jersey with siblings, Dorothy and Herbert. She earned her bachelor’s degree from the College of Saint Elizabeth and later received her Ph.D. in virology from Cornell University in 1971.
In her early career, she established a clinical virology laboratory at St. Luke’s Hospital in New York City and also founded a clinical virology lab at URMC, which was one of the few of its kind in the U.S. during the late 1970s. During the course of her career, she published more than 100 articles and book chapters as an author and co-author.
She was an active member of organizations including the American Academy of Microbiology, and the American Society for Microbiology. In 2013 she received the Diagnostic Virology Award from the Pan American Society for Clinical Virology.
In what became one of her final professional contributions, Marilyn worked closely with the Finger Lakes Donor Recovery Network to establish a nucleic acid testing lab at Strong Memorial Hospital to significantly expedite the organ transplant process for organ recipients. This was launched successfully in February just weeks before her passing.
Rob Kochik, executive director of FLDRN, said he was heartbroken to hear the news of Marilyn’s death.
“She was always such a joy to work with,” he wrote. “She was committed to helping establish the NAT testing facility because she truly understood how vitally important it was to help the donation process.”
Despite her expertise and accomplishments, many remember Marilyn as an extremely approachable and down to earth person; a lover of gardening, food, wine, and a good joke.
Her brother describes her as “fiercely independent” and a rule breaker at heart. This was evidenced by one of her favorite movies, “Ferris Buehler’s Day Off,” and a stack of unpaid red light tickets.
An avid gardener, she once served as president of the Genesee Region Orchid Society and had more than 200 orchids in her house, in addition to a lush garden at her Rochester home where she lived with two cats, Bella and Luigi, and frequently hosted parties for friends.
Whether you knew her for 20 years or 20 minutes, Marilyn made a warm and lasting impression on the people she encountered at or outside of work. Debra Jesien, chief supervisor of Clinical Microbiology at URMC, worked closely with Marilyn for many years.
“She could bond with people very quickly,” said Jesien. “She was the type of person you could talk to once and you felt like you knew her.”
What: Memories of Marilyn, an informal memorial to celebrate the life of Dr. Marilyn Menegus. Guests are encouraged to bring their stories and photos to share.
When: Friday, May 12 from 12:00-2:00 p.m.
Where: LeChase Assembly Hall (G-9576) University of Rochester Medical Center. Drinks and light refreshments will be provided.
RSVP: Please follow this link to enter your RSVP online or contact Bethany Bushen for more information.
Read the obituary of Dr. Menegus in the Democrat and Chronicle
Jorge Yao, M.D. is a former URMC Pathology fellow-turned-faculty member. He first came in 2003 as a genitourinary pathology fellow and was offered a faculty position in 2004.
He worked closely with the Urology Department on research and clinical projects, helping to set up the institutional biospecimen repository. After a productive decade, he left in 2013 as an associate professor with an MBA from Simon Business School. He now works for Pathline Emerge in Ramsey, New Jersey.
Education & Training
Dr. Yao received his MD from University of the East - Ramon Magsaysay Memorial Medical Center and completed an internship in general medicine at St. Luke’s Medical Center in the Philippines. He did residency in pathology at Brooklyn Hospital Medical Center and Philippine General Hospital and completed internships in surgical pathology and cytopathology at New York University.
Where are you from originally?
I was born and raised in the Philippines and came to the U.S. to finish my training.
Wife, Grace Candelario
What first sparked your interest in pathology?
My uncle is a pathologist and visiting him at work sparked the interest, but I like anatomic pathology mainly because it is like being a consulting detective.
How would you describe your job to someone who’s never heard of it before?
I push around bits of people under the microscope then write a report about it.
How do you like to spend your free time? Do you have any hobbies/interests?
I have become a kaizen nerd lately, so most of my free time is spent reading and trying to find small improvements I can implement in my life. I used to have hobbies but they are getting together to file a class action suit for neglect.
What’s one piece of advice you have for up-and-coming pathology trainees looking to start their careers?
The best piece of advice I can give to new pathologists is that no matter how specialized the field becomes, there will always be a need for anatomic pathologists with a good grasp of basic pathology and an excellent foundation of general surgical pathology.
Results from the 2015 CTSI Incubator project suggest there is a connection between gut microbes in obesity and impaired musculoskeletal health. Members of the Incubator project team presented results at the Orthopaedic Research Society (ORS) Annual Meeting this week that suggest manipulating the gut microbiome in obese animals can slow osteoarthritis and speed healing after fracture.
Obesity and type 2 diabetes have been known to delay fracture healing and accelerate erosion of joint cartilage in osteoarthritis. The 2015 Incubator project, led by Michael Zuscik, Ph.D., associate professor of Orthopaedics; Robert Mooney, Ph.D., professor of Pathology; and Cheryl Ackert-Bicknell, Ph.D., associate professor of Orthopaedics, aimed to understand how and why this occurred.
The group found that all of these negative effects of obesity were linked to changes in the gut microbiome. Feeding mice a high fat diet to mimic obesity and type 2 diabetes altered the types of bacteria in their colon, favoring pro-inflammatory bugs. This coincided with greater systemic inflammation, which may have contributed to accelerated osteoarthritis and delayed fracture healing.
Not only did the team find a link between the obese gut microbiome and impaired musculoskeletal health, but they think they can reverse it. In preliminary studies, obese mice were fed a fiber supplement that they cannot digest, but that certain helpful gut microbes love. Despite continuing to feed the mice a high fat diet, the non-digestible fiber shifted their microbiome back toward the non-inflammatory bacterial profile seen in lean mice.
That microbiome shift in the obese mice also reduced systemic inflammation, slowed osteoarthritis progression, and restored fracture healing. Essentially, the non-digestible fiber completely reversed the negative effects of obesity on the musculoskeletal system, making the obese mice indistinguishable from their lean counterparts in terms of musculoskeletal health.
Members of the Incubator project team presented these and other related results this week at the ORS Annual Meeting in San Diego, CA. Christopher Farnsworth and Eric Schott, both graduate students in Pathology, gave podium talks and Ashlee MacDonald, Orthopaedics resident, presented a talk as part of a special Late-Breaking session.
Schott also earned a young investigator travel award to present his research about the effect of the obese microbiome on osteoarthritis at next month’s Osteoarthritis Research Society International Meeting, where he will be featured in a special session and an award ceremony.
After a very successful interview season, the Pathology residency program at URMC is pleased to announce that it has filled all 6 open spots for the coming academic year.
Meet the PGY-1 residents for 2017-18:
Kansas City University of Medicine and Biosciences
Anna Karoline Israel
Friedrich-Schiller-Universität Jena Medizinische Fakultät
St. George's University School of Medicine
University of Ibadan College of Medicine
Zhongshan School of Medicine, Sun Yat-Sen University
University of Pittsburgh School of Medicine
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