FALL NEWSLETTER Cellular & Molecular CMP Pathology 2019 Faculty Trainers in the News CMP Trainer news, from Fall 2018 to Fall 2019 as published in the UW-Madison School of Medicine and Public Health News The Melanoma Age of Enlightenment – UW Health News and Events August 16, 2018 Nihal Ahmad, PhD Melanoma medical oncologist Mark Albertini, MD, thinks Screening with a high precision blood-based we are in a “true age of enlightenment” when it comes to treating the skin cancer, especially with immunotherapy- assay for Alzheimer disease- Neurology.org based treatments. August 1, 2019 Barbara Bendlin, PhD Albertini’s research group takes the immunotherapy approach to studying melanoma. Immunotherapies have The use of biomarkers for defining the pathobiology of been incredibly successful in some patients, but other Alzheimer disease (AD) has had a transformative effect on patients have shown no response. His group has already the field, facilitating disease detection prior to autopsy, as developed a way to take blood and biopsy samples from well as substantially altering clinical trial design.1 In the last patients with advanced-stage melanoma and to isolate 5–10 years, there has been a substantial shift toward using immune cells that were activated by the patient’s natural amyloid PET in human research, as well as clinically, to rule out immune response to the cancer. AD (a negative scan meaning little or no plaque is present). Now, in work funded by a UW Carbone pilot grant and melanoma philanthropy group Ann’s Hope, Albertini is taking these activated immune cells and using them to look for markers that will help him and other clinicians predict who is going to respond to immunotherapy. One in a Million: Single-Cell Genomics Enables Deeper Understanding of Cancer- UW Health News and Events May 7, 2019 Emery Bresnick, PhD McArdle researchers suggest that skin might Emery Bresnick, PhD, co-leader of the UW Carbone program be more important to metabolic diseases on Genetics and Epigenetic Mechanisms and director of the Blood Research Program at UW-Madison, and senior than we think- McArdle Laboratory for scientist Kirby Johnson, PhD, are among the first who worked with the Biotechnology Center to perform experiments with Cancer Research June 27, 2019 this technology. Caroline Alexander, PhD Bresnick researches a class of proteins called the GATA family Recent discoveries from Caroline Alexander and Ildiko and how mutations in the DNA that code for these proteins Kasza suggest that skin might be a more important player give rise to blood cancers. in metabolism than previously understood. Loss of heat Though the ability to do single cell genomics experiments through skin, predominantly by evaporation, may throw a at UW-Madison has come about only recently, it is already metabolic switch that determines whether mammals lay fueling innovative research. down body fat and become obese. For cancer research, it will be an enabling tool to “discover The researchers determined that higher rates of heat loss the molecular basis of disease and to leverage these insights through skins of mice in cool housing increases the demand to develop strategies to treat disease,” Bresnick says. “Let’s for bodily heat production, also known as thermogenesis. say you’re looking at population of 500 cells and five were Thermogenesis is powered by the body’s fat tissues. triggered. In a population analysis, you’d never see the “These are early days,” said Alexander, adding, “our change. You have to look at the single cells, otherwise, you’ll studies are turning to human subjects, who show dramatic miss the boat.” differences in the amount of fat associated with their skins. We are testing whether this determines our susceptibility to becoming obese, or developing other diseases, including cancer.” CMP NEWSLETTER FALL 2019 | UW-MADISON 1 Faculty Trainers in the News CMP Trainer news, from Fall 2018 to Fall 2019 as published in the UW-Madison School of Medicine and Public Health News Inflamed monkey guts produce Parkinson’s- related proteins- UW News May 9, 2019 Marina Emborg, MD, PhD Researchers probe cell division defects to gain The intestinal linings of monkeys with inflamed bowels show insight into cancer- UW News chemical alterations similar to abnormal protein deposits in July 8, 2019 the brains of Parkinson’s patients, lending support to the idea Mark Burkard, MD, PhD that inflammation may play a key role in the development of the degenerative neurological disorder. From bugs to plants to animals, for all living things to grow they must create more cells. To do so, each existing cell, A study published by University of Wisconsin–Madison whether in an embryo or an adult, receives cues to copy its researchers today in the Journal of Inflammation Research chromosomes — large pieces of DNA that contain each cell’s found phosphorylated alpha-synuclein — a modified version entire genetic code. In a carefully and elegantly controlled of a protein common to nerve cells — in samples from process, each cell then divides into two. common marmosets kept in a tissue bank at the Wisconsin National Primate Research Center. “We don’t really understand how chromosome mis- segregation happens in cancer,” says Mark Burkard, a When the Emborg research group heard from primate medical oncologist and researcher with the University of center pathologists that marmosets sometimes deal with Wisconsin–Madison Carbone Cancer Center. “One of the inflamed bowel problems like colitis, they decided to test big disappointments, and opportunities, is that we know marmoset tissue samples for changes in alpha-synuclein. The all these other genes that are mutated in cancers, but no researchers found that marmosets whose medical histories one has really found the smoking gun for how chromosome included inflamed colons had more of the phosphorylated segregation goes wrong.” alpha-synuclein in their intestines. Burkard and two of his UW Carbone colleagues — Beth “It shows us the relationship between inflammation and Weaver, associate professor of cell and regenerative Parkinson’s-like alpha-synuclein pathology,” says Emborg. “It biology, and Aussie Suzuki, assistant professor of oncology doesn’t mean if you have inflammatory bowel disorder, you — are leading efforts to better understand chromosome will get Parkinson’s. The development of a neurodegenerative segregation and its contributions to disease. disorder is multifactorial. But this could be a contributing factor.” ‘This can be changed’: Verona family carries on Wisconsin kidney transplant patients with daughter’s fight to end vision diseases- Channel virus will be studied in hopes of finding cure- 3000 News Milwaukee Journal Sentinel February 28, 2019 August 6, 2019 David Gamm, MD, PhD Arjand Djamali, MD VERONA, Wis. - When you talk about Kenzi Valentyn, no last Researchers at University of Wisconsin Health announced name is really needed. Tuesday they will begin recruiting a small number of kidney transplant recipients for a new trial that will use A Badger fan through and through, there’s maybe only one specially designed white blood cells to treat a complication thing more notable than her fandom -- her smile. called severe cytomegalovirus infection. Her parents say she was always full of laughs, even when life The trial, which has received approval from the U.S. Food and gave her a lot of reasons not to, like in dealing her a lifelong Drug Administration, will enroll 20 adult kidney transplant battle with Retinitis Pigmentosa, a disease that slowly stole recipients with the complication, probably starting in her vision. November, said Arjang Djamali, the trial’s lead researcher “It was a helpless feeling a lot of times, watching her go and a UW professor of medicine and surgery. through that sort of slow, terrible progression,” said Tim Djamali, who is also nephrology division chief at UW Health, Valentyn, Kenzi’s dad. “Yet causes like Dr. Gamm gives us one said white blood cells will be extracted from a patient’s way to feel like you’re fighting back.” parent or sibling. Those cells will then be manipulated At the McPherson Eye Research Institute, Dr. David Gamm is to make them effective at attacking and destroying finding the cure. cytomegalovirus infection. “We’re looking at ways in which we can stop that process from happening in children and young adults who have Retinitis Pigmentosa, as well as how to replace the cells that are lost in the course of the disease,” Gamm said. CMP NEWSLETTER FALL 2019 | UW-MADISON 2 Faculty Trainers in the News CMP Trainer news, from Fall 2018 to Fall 2019 as published in the UW-Madison School of Medicine and Public Health News Novel approach promises ready access to Human respiratory viruses continue to spread in wild chimpanzees- UW News hard-to-study proteins- UW News April 15, 2019 January 18, 2019 James Gern, MD Ying Ge, PhD Less than two years after the first report of wild A team led by University of Wisconsin–Madison associate chimpanzees in Uganda dying as a result of a human professor of cell and regenerative biology and chemistry Ying “common cold” virus, a new study has identified two other Ge reports the development of a novel strategy capable of respiratory viruses of human origin in chimpanzee groups extracting and driving hard-to-reach proteins into water in the same forest. solution where they can be effectively studied using mass spectrometry, a powerful analytical technique. The new Parainfluenza virus 3 is a common cause of croup in approach promises a trove of biological insights and, preschool children. In people, metapneumovirus (MPV) is importantly, may help identify therapeutically relevant a common cause of “wheezing illnesses” in infants, explains proteins and provide new disease diagnostic techniques. James Gern, a co-author of the new study and a professor of allergy and immunology in the UW School of Medicine “Approximately one-third of the proteome in living organisms and Public Health.