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Bentley Discovers Bacterial Phenomenon in Bone Implant Infections

5/31/2017

Karen de Mesy Bentley (formerly Jensen), M.S., director of the Electron Microscopy Shared Resource Laboratory and faculty associate in the Department of Pathology and Laboratory Medicine, has discovered something new about the behavior of Staphylococcus aureus bacteria and why it may resist antibiotic treatment and recur in patients who have had a hip or joint implant.

Karen BentleyBentley is the lead author in an NIH funded study published in the Journal of Bone and Mineral Research (May 2017) where she utilized transmission electron microscopy (TEM) to examine the bones of mice with implant associated S. aureus chronic osteomyelitis.

While examining sections of bone under TEM high magnification, Bentley discovered that some bacteria were able to change shape and squeeze into submicron spaces which are called canaliculi. Her study describes round bacteria becoming rod-shaped to accommodate the submicron diameter space of canaliculi. The bacteria are then protected from treatment with traditional antibiotics delivered via blood vessels. 

“When I saw this, I was shocked,” said Bentley. “Staph has never been described as being able to deform. It’s always been described as round, one micron in diameter to grow in clusters like grapes on a vine.”

Soon after documenting this bizarre shape shifting behavior in a mouse model, Bentley initiated studies on human S. aureus infected bone specimens and in December of 2016, discovered the same bacterial phenomenon occurs in human bone.

The initial findings explain, among other things, why a staph infection in humans may return despite weeks or months of antibiotic treatments and bone debridement when replacing an infected implant. It also explains why infections can recur, sometime years – even decades – later, after going undetected in the patient. 

Bentley will soon be a co-investigator in a P50 NIH-funded grant working with the principal investigator, Edward Schwarz, Ph.D., the director of the Center for Musculoskeletal Research and his team to continue studies on human S. aureus chronic osteomyelitis specimens.

“If we can identify a gene that allows S. aureus to shift into rod shaped bacteria, then maybe we can develop a drug to prevent invasion of osteocyte canaliculi and also recurrence,” she said.

Cancer Biology, thanks to Green Lizards

5/26/2017

What can green lizards and “dark matter” teach us about cancer?green lizard

First a bit about genomic dark matter: It refers to DNA sequences that make up a large part of the human genome but do not encode proteins, some of which are known as IncRNAs. They play a role in tissue development, tumor formation, and cancer progression—but many key questions remain about dark matter and IncRNAs.

University of Rochester Medical Center scientist Bin Zhang, Ph.D., and a team of researchers discovered how IncRNAs function and evolve in the genomes of green lizards. Their work is published in Cell Reports, in collaboration with scientists at Cold Spring Harbor Laboratory, Long Island, N.Y., where Zhang worked before joining URMC in 2015.

One particular IncRNA—MALAT1 (Metastasis-Associated Lung Adenocarcinoma Transcript 1)—was first associated with lung cancers that were likely to spread and later found to be over-abundant in many other tumor types. The MALAT1 gene contains a unique tail structure that stabilizes the RNA molecule. Zhang’s team pioneered a series of computer models and algorithms allowing them to turn the tail structure into a searchable module. They discovered a class of 130 different vertebrate IncRNAs with similar structures to MALAT1, and then further conducted evolutionary studies into the activity of the IncRNAs in green lizards. The National Cancer Institute and National Institute of General Medical Sciences funded the study.

An assistant professor in Pathology and Laboratory Medicine and Pediatrics, Zhang also specializes in clinical cytogenetics and molecular genetics. He conducts detailed genetic tests and evaluates blood, bone marrow, lymph nodes, and other tissues for cancer.

Pathology Graduate Student Awarded in Three-Minute Thesis Event

5/15/2017

Sarah CathelineCongratulations to Sarah Catheline for winning the People’s Choice Award at the University of Rochester’s Three Minute Thesis public competition held on May 11 at URMC.

Sarah is a fourth-year graduate student in the Pathways of Human Disease Ph.D. program and works in the lab of Dr. Jennifer Jonason. Her presentation, “Inhibiting Inflammaging to Treat Osteoarthritis (OA),” was one of eight to be accepted into the final round.

This year marks the second annual Three Minute Thesis public competition at the University of Rochester, which encourages participants to share their research in simple language that's both persuasive and easy for the average person to understand. 

The event is open to current Ph.D. and professional doctorate (research) candidates in or beyond their third year of study. It’s also open to postdoctoral researchers. Winners receive travel awards ranging from $250-750.

The event is sponsored by the School of Medicine and Dentistry Center for Professional Development, the School of Arts, Science and Engineering Graduate Studies Office, the Graduate Student Society, and Graduate Student Association.

Three Minute Thesis Awards: 

  • Judge’s Winner: Thuy-vy Nguyen (Runner Up: Scott Friedland)
  • People's Choice Award: Sarah Catheline 

Presentations: 

  • Stephanie Carpenter: Solving the Mystery of Iron Chemistry
  • Scott Friedland: Pancreatic Cancer and the Tale of the Broken Librarian
  • Sarah Catheline: Inhibiting Inflammaging to Treat Osteoarthritis (OA)​
  • Claire McCarthy: Investigating the Toxicological Effects of Dung Biomass Smoke Exposure
  • Taylor Moon: The New Epidemic
  • Thuy-vy Nguyen: Solitude
  • Manisha Taya: Understanding Lymphangioleiomyomatosis (LAM): The “Other” Steroid-Dependent Cancer From Bed-Side to Bench and Back Again
  • Janelle Veazey: Role of Protein Kinase D in Epithelial Cells During Respiratory Infection

 

 

Gene Study Points Researchers toward New Pathway for Leukemia

5/8/2017

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.leukemia cells

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.

'Memories of Marilyn' Event to Honor the Late Dr. Menegus

4/26/2017

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. 

Marilyn MenegusDr. 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.”

EVENT INFO: 

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

 

 

 

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