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McArdle News

2018

Chris Bradfield, professor of oncology and McArdle faculty member, has been named the interim Biotechnology Center director and will begin his new position Aug. 1.

Bradfield has held a number of leadership positions at UW–Madison. He has served as director of the Molecular and Environmental Toxicology Center since 2006, director of the Office of Graduate Support for the UW School of Medicine and Public Health since 2013, and was formerly interim director of the Wisconsin Institute for Discovery.

The UW Biotechnology Center was founded in 1984 by McArdle emeritus faculty member Dr. Richard Burgess, who also served as director for its first 12 years. Congratulations Dr. Bradfield on this new leadership role!

Read more: https://news.wisc.edu/sussman-to-lead-genome-center-of-wisconsin/

The McArdle Laboratory is pleased to announce that Dr. Richard Burgess has received the Wisconsin Medical Alumni Association (WMAA) Basic Sciences Emeritus Faculty Award. This award is given to a basic research scientist who demonstrates long and effective service to the UW School of Medicine and Public Health in teaching, research, and/or noteworthy administration, including program development.

Dr. Burgess is the James D. Watson Professor Emeritus of Oncology and has been a faculty member in the McArdle Laboratory for Cancer Research since 1971. His research has focused on the machinery required for transcription and its regulation. Among his many scientific accomplishments was determining the subunit structure of RNA polymerase, one of the earliest characterized multisubunit protein complexes. Perhaps even more significantly, he also discovered and characterized the first positive transcription factor, the E. coli sigma factor. This pioneering protein biochemical study provided the basis for all subsequent research on transcription factors and their role in normal and abnormal gene regulation.  

Over the course of his tenure at the University of Wisconsin, Dr. Burgess has trained 32 Ph.D. students and published over 250 research papers. He is a major contributor in developing and teaching powerful protein biochemistry methods and in organizing conferences and editing manuscripts and books on protein purification.

In 1984, Prof. Burgess founded the UW Biotechnology Center (UWBC) and served as its director for 12 years. The UWBC sought to help apply basic discoveries in biotechnology at UW-Madison towards meeting the needs of society and the citizens of Wisconsin. This center provided a much-needed focus for the rich biotechnology research community on campus, as well as essential shared equipment and service programs to make cutting edge research tools available to the campus community. These services were also available to the new biotechnology business community, which the UWBC actively encouraged and promoted. In the first 30 years of the UWBC, the number of biotechnology companies in the Madison area grew from 3 to over 200. Dr. Burgess was a pioneer of promoting multidisciplinary research programs, and in championing public education in biology and biotechnology. 

“Dr. Burgess is an internationally recognized, accomplished, and distinguished scientist,” said Gary Tarpley, chief operating officer of the Promega Corporation. “The University of Wisconsin and the Madison-based biotechnology community have benefitted significantly from his many contributions. There are few scientists as distinguished as Dick who have contributed so much to science and the reputation of scientific excellence at UW-Madison.”

Dr. Burgess’s award expands on the legacy of exemplary service by McArdle Laboratory faculty members. Other McArdle faculty who have been honored with the WMAA Basic Sciences Emeritus Faculty Award in the past include Van Potter, James Miller, Henry Pitot, Roswell Boutwell, Gerald Mueller, and William Dove.

 

 

 

A five-year, $3 million grant from the National Cancer Institute will support UW Carbone Cancer Center physician-researcher and McArdle Laboratory for Cancer Research faculty member Dr. Dusty Deming and colleagues in their pursuit of more effective treatments for colorectal-cancer patients.

With the funding, researchers at the McArdle Laboratory for Cancer Research and UW Carbone will grow colon cancer cells from patient-derived tissue to help predict how an individual patient’s cancer will respond to various treatments. By growing tissues from individual patients in three-dimensional, or organotypic, cultures, the researchers will be able to better simulate a given patient’s cancer in a laboratory setting.

“The organotypic cultures allow us to take a patient tissue sample from the clinic, test the treatments that are being considered for the patients, and use the lab results to find the best therapy for those patients,” Deming said. “Specifically, we are looking at whether we can predict the response to chemotherapy and radiation for patients with colorectal cancers.”

The study will use optical imaging techniques developed by Dr. Melissa Skala, a co-investigator at the Morgridge Institute for Research, to monitor the evolution of the organotypic cultures over time. Through this technology, the researchers will investigate how the genetics of individual tumors affect their response to treatments.

“Our long-term goal is to be able to tell a patient who comes into a clinic, ‘We have taken your tissue, tested it in the lab, and based on those results we can tell you this is what your treatment strategy should be,’” Deming said.

Deming and Skala previously collaborated on a similar approach using organotypic cultures to study personalized therapies for pancreatic cancer. For this new study, they will also work with other UW Carbone members, including gastrointestinal oncologist Dr. Nataliya Uboha, colorectal surgeons Dr. Evie Carchman and Dr. Elise Lawson, radiation oncologists Dr. Mike Bassetti and Dr. Randy Kimple, radiologist Dr. David Kim, statistician Dr. Jens Eickhoff, and pathologist Dr. Kristina Matkowskyj. The preliminary data making this grant possible  were funded by the Funk Out Cancer Event, the Cathy Wingert Colorectal Cancer Research Fund, and the Carbone Young Investigator Award.

“Under the current standard of care, we don’t have a great idea of who is going to benefit from certain treatments and who is not,” Deming said. “Having a way of predicting who will respond to a given treatment will be critical in helping eliminate side effects and toxicities for patients who wouldn’t benefit from those therapies.”

Image of Zhang and lab membersDr. Zhang (fifth from the left) with members of her research group

The McArdle Laboratory is excited to announce that Professor Jing Zhang has been named the new Centennial Professor of Oncology. This professorship, which is endowed through the UW School of Medicine and Public Health, recognizes Dr. Zhang’s outstanding research contributions and provides support for her ongoing research efforts. 

Dr. Zhang completed her undergraduate studies at Beijing University, and received her Ph.D. in pharmacology from the Perelman School of Medicine at the University of Pennsylvania in 2001. After completing her postdoctoral research at the Whitehead Institute for Biomedical Research in Cambridge, MA, she joined the McArdle faculty in 2007. 

A major focus of Dr. Zhang’s research centers on the Ras protein family and the roles of these proteins in blood cancers. Ras proteins are signaling GTPases that play key roles in regulating cell growth and differentiation. Mutated forms of the Ras proteins are heavily implicated in driving the genesis and progression of cancers.

Though the significance of Ras proteins in solid tumor cancers is well established, their role in blood cancers has been more elusive. Recently, researchers including Dr. Zhang have begun to realize that Ras mutations contribute to a wider range of blood cancers than initially thought, including forms of childhood leukemia. Many patients acquire Ras mutations post-chemotherapy, making further treatment of these patients a significant challenge.

“My research group started by focusing on a pair of pediatric and adult rare leukemias, and as our knowledge has expanded we are beginning to study other forms of leukemia as well,” says Dr. Zhang. “The problem of how to treat cancers with Ras mutations is becoming more urgent and widespread than we could have anticipated.”

One area of particular interest to Dr. Zhang and her research group is hematopoietic stem cells (HSCs), stem cells in the bone marrow that give rise to many different lines of blood cells. Mutations acquired by HSCs are passed on as the cells renew and differentiate into specific cell lines, leading to what researchers call “clonal expansion”. Via this mechanism, an initial mutation of Ras, or “first hit”, creates a large colony of mutated cells that are highly susceptible to becoming cancerous.

In addition to her research pursuits, Dr. Zhang is also a Co-Leader of the UW Carbone Cancer Center’s Developmental Therapeutics Program, which works to develop new therapies and treatments for patients with cancer. In her leadership role, Dr. Zhang helps to encourage and facilitate collaborations amongst basic research scientists working to discover targets for novel therapies. Additionally, she works to integrate the basic research side of the program with the drug discovery and clinical trial areas to maximize the yield of research conducted within the program.

“The biggest challenge, but also the biggest potential reward of my research is discovering a way to effectively target the oncogenic Ras pathway,” says Dr. Zhang. “We have a lot of opportunities to collaborate in areas that are both new and exciting.”

McArdle Laboratory Director Paul Lambert accepts the donation check from the Freedom High School studentsMcArdle Laboratory Director Paul Lambert accepts the donation check from the Freedom High School students

Students at Freedom High School recently raised and donated $11,000 for cancer research at the McArdle Laboratory. The students have been raising money for McArdle for several years, and this year’s generous donation was by far and away their largest contribution yet.

The charitable endeavors of Freedom High School students are a traditional part of the high school’s Crystal Ball, their annual winter formal dance. In the weeks leading up to the dance, every club and team on campus nominates a member to serve on the Crystal Ball royalty court, and that nominee is then responsible for spearheading the club’s fundraising efforts. After the fundraising period is over, the club nominees that raised the most money are coronated as Crystal Ball Royalty.

Being nominated as their club’s representative is both an honor and a responsibility which the students take seriously. Each club and its representative choose their own fundraising approaches, and consistently rise above and beyond all expectations through their enthusiasm and creativity.

The methods for fundraising ranged from running bake sales to collecting aluminum cans to providing oil changes or car repairs in exchange for a donation. This year, one club even organized a schoolwide rock-paper-scissors tournament with a two dollar buy-in, one dollar of which went to prizes and the other dollar towards cancer research.

Sadly, this year’s giving effort was motivated in part by the passing of Freedom High School’s longtime band director Jon Delany to cancer. A beloved member of the Freedom community, his many years of service to the school and his battle with cancer inspired the students. The Freedom High School students banded together to raise their largest donation yet, hoping to make an impact in the fight against cancer in memory of their band director and all other members of the community affected by cancer.

“What makes all the students’ efforts extra special is that they go above and beyond every year,” says Mary Jo Bolwerk, a student council advisor and teacher at Freedom High School. “The whole community rallies around the students. Everybody is just so generous and so willing to participate in the fight against cancer.”

Over the past several years, the relationship between Freedom High School and the McArdle Laboratory has continually grown stronger. Several years ago, a group of Freedom students visited the McArdle Laboratories to meet with McArdle scientists and to get a first-hand look at the research their outstanding efforts had made possible. This year Dr. Paul Lambert, the director of the McArdle Laboratory, was invited to attend the Crystal Ball Week pep rally to personally accept the check for cancer research at McArdle.

Reflecting on his visit to the Freedom High School, Dr. Lambert said “I was able to appreciate all of the heart and soul that every student put into this fundraising event, its importance to their community, and what it says about these inspiring young women and men. It was a real pleasure to be able to thank them personally for all their wonderful work, and to share with them a little about how we will use their donations to continue our research into finding new ways to prevent cancer and better treat patients with cancer.”

Cellular and molecular biology graduate student Adhithi Rajagopalan, a student in the lab of Jing Zhang, PhD at the McArdle Laboratory for Cancer Research, recently presented at the American Association of Cancer Research’s annual conference in Chicago. Rajagopalan’s presentation was part of a scientific session focused on animal models of cancer. UW Carbone physician-scientist Fotis Asimakopoulos, MD, PhD, a collaborator of the Zhang lab, co-chaired the session.

Rajagopalan presented on a new mouse model of advanced multiple myeloma. Multiple myeloma is a cancer of plasma cells in the bone marrow, and represents 15 percent of all blood cancers. In the initial phases of the disease, patients are typically asymptomatic. By the time symptoms arise – including anemia, bone pain and kidney disease – patients are in the late stages. Advances in therapies have helped extend survival times by driving the disease into remission, though there is no cure for multiple myeloma.

“It’s important to have some model way to study this disease in the advanced stages,” Rajagopalan said. “Because currently, we don’t fully know what disease mechanisms exist in the later stages or how we can better treat patients.”

A mouse model of early-stage disease exists, but not the advanced disease. Rajagopalan and co-lead author Zhi Wen, a scientist in Zhang’s research group, bred mice from the existing myeloma model with mice that harbored a second mutation in the Ras gene. Ras mutations are found in 45 percent of all advanced myelomas, but rarely in early-stage disease, suggesting the mutation plays a role in driving the later stages.

"In these mice, we can recapitulate much of the human disease,” Rajagopalan said. “This model now serves as a platform to test existing and potential therapeutics for many advanced multiple myeloma patients.” 

Adhithi Rajagopalan was one of over 60 UW Carbone Cancer Center researchers who presented their work at the conference, with dozens more attending to learn about current advances in understanding and developing treatments for cancer.

This article was repurposed from an original piece at https://www.med.wisc.edu/news-and-events/2018/april/carbone-scientists-annual-research-conference/

Headshot of Dr. Drinkwater

Professor of Oncology Dr. Norman Drinkwater is currently serving as Interim Vice Chancellor for Research and Graduate Education at UW-Madison, replacing Dr. Marsha Mailick (School of Social Work) who is on temporary leave from her vice chancellor duties. Prior to the appointment, Drinkwater had been serving as Associate Vice Chancellor for Research in the Biological Sciences since 2015.

Previously, Dr. Drinkwater served as the chair of the Department of Oncology and director of the McArdle Laboratory from 1992 until 2008. He is an accomplished Badger alumnus, completing both his undergraduate and graduate studies at Wisconsin-Madison, graduating with a Ph.D. in Oncology in 1980. Following postdoctoral research at Michigan State, he returned to UW-Madison and the McArdle Laboratory as a faculty member.

Dr. Drinkwater cites UW’s unique culture as a research institution as a key reason he has been drawn back to the university at various steps of his education and career. He highlights the focus on training graduate students and the collaborative environment of the university as two primary factors contributing to the success of research at Wisconsin. 

“When you start to work on a new problem or move in a direction that you don’t know much about, you can almost be guaranteed that one of the world’s experts on the subject is on this campus. And all it takes is a phone call,” says Dr. Drinkwater. “What makes Wisconsin different is that everybody here is invested in each other’s success.”

In 2014, the leadership of the Graduate School at the University of Wisconsin-Madison was reorganized to maximize the potential for research being conducted on campus. Traditionally, the dean of the graduate school had also served as the vice chancellor for research. The creation of a separate office of the vice chancellor for research and graduate education provided the opportunity for dedicated personnel to focus their full efforts on fulfilling the university’s research mission.

“We now have a significant number of people who spend their full time thinking about the research enterprise on campus,” says Dr. Drinkwater. “This includes what sort of investments we need to make to grow and be successful, what areas of research are ripe for new investment, new directions the campus can take, and what areas of campus research need to be invested in so they can be rebuilt.”

Drinkwater joined the new office as an Interim Associate Vice Chancellor at the request of Vice Chancellor Mailick in 2014. Wanting to give back to the university, he valued the opportunity to bring lessons learned from his 16 years of leadership in at McArdle Laboratory to his new role. Following an open search, he was formally selected for the position in 2015. 

“I took the Associate Vice Chancellor position to try and make a contribution to the success of the campus,” says Dr. Drinkwater. “Within the McArdle Laboratory, there has always been a strong sense among the faculty that we are all in this together, and that we should all work to grow and improve our institution. That stuck with me after I finished serving as chair.”

“Dr. Drinkwater has been an important and valuable resource and mentor to me throughout my career; he always has thoughtful advice and experience relative to successfully navigating both local and national research issues,” says Dr. Howard Bailey, director of the UW Carbone Cancer Center.

Says UW School of Medicine and Public Health dean Dr. Robert Golden, “I am delighted that Norm will be serving as Interim Vice Chancellor for Research and Graduate Education. He brings the perspectives of an experienced scientist, successful department chair, and university leader to this vitally important role.”

By Simon Blaine-Sauer

We are pleased to announce that McArdle Laboratory alumnus Dr. Lynne Maquat has been awarded the 2018 Wiley Prize in Biomedical Sciences. This prestigious honor is awarded annually to one or more premiere scientists by the Wiley Foundation to “recognize and foster ongoing excellence in scientific achievement and discovery.” Dr. Maquat was awarded the prize for her work elucidating the mechanism of RNA nonsense-mediated decay, which is a key process by which cells eliminate defective transcripts which could give rise to toxic proteins. 

Dr. Maquat conducted her postdoctoral research in the McArdle Laboratory, where she trained with Dr. Jeff Ross (now Professor Emeritus of Oncology). Dr. Maquat is the J. Lowell Orbison Endowed Chair and Professor in the Department of Biochemistry and Biophysics at the University of Rochester School of Medicine and Dentistry.

Read more about Dr. Maquat’s award and research here.

Dr. Dusty Deming

McArdle Laboratory and Department of Medicine scientist Dusty Deming knew he wanted to be a physician ever since he was in grade school. Since then, his desire to positively impact the lives of patients as both a clinician and a researcher has been reinforced many times over.

During his first semester of medical school at the University of Wisconsin School of Medicine and Public Health, Deming began working in the lab of Kyle Holen, a gastrointestinal oncologist at the UW Carbone Cancer Center. Having worked in a basic science laboratory as an undergraduate at Marquette, he was already passionate about research, and was excited to continue his laboratory work as a medical student. 

Deming’s time under Dr. Holen also allowed him to interact with patients in the clinic who were coping with cancer. Working directly with patients and witnessing first-hand the benefits research could have on their lives solidified Deming’s interest in oncology and cemented his desire to make research a prominent focus of his practice. 

“From that experience alone, I knew that for the rest of my career I wanted to be both a clinician seeing patients directly and also a researcher trying to develop the next, newest, greatest treatment options patients with cancer,” Deming says. 

Today, Deming is an assistant professor of medicine at the UW Carbone Cancer Center, specializing in gastrointestinal cancers. His primary appointment is in the Department of Medicine, but he holds a zero percent appointment in the McArdle Laboratory (Department of Oncology). This joint appointment allows him to participate fully in research and training as a McArdle faculty member with his salary support coming from his work as a physician.

Deming describes three main focuses for his lab’s research: precision medicine, sensitivity testing, and immunotherapy. In precision medicine, a patient’s genome is analyzed, allowing a treatment plan to be designed which will be most effective for that patient. Sensitivity testing involves growing patients’ cancer cells in vitro to predict how well the patient’s tumor might respond to various treatments. Immunotherapy, a rapidly accelerating area of cancer research, focuses on harnessing the power of the body’s natural defense system to fight cancers.

Consistent across Deming’s clinical practice and research focuses is his commitment to a more individualized approach to medicine.

“A major reason why more personalized medicine is becoming a major focus is that we know a heck of a lot more about the biology of cancers today,” Deming says. “When you understand the biology of a particular cancer, you realize that not all cancers are created equally and that there are certain things in different cancers that we as physicians can take advantage of in different situations.” 

As both a physician and researcher, Deming emphasizes that the goal of all of his lab’s research is ultimately to benefit patients. His lab is translational and collaborative by nature, with a mix of medical and graduate students, residents and postdocs.

“The relationship between basic and clinical research is absolutely critical,” Deming says. “You can’t do good clinical research without solid translational research, and you can’t do solid translational research without great foundational research.” 

The collaborative and transdisciplinary nature of research at the University of Wisconsin is one of the primary reasons Deming has remained here throughout the different stages of his education and career. One of his many current projects involves working with Dr. Melissa Skala, an investigator for the Morgridge Institute for Research and UW Carbone Cancer Center, to apply fluorescence imaging technology towards improving cancer treatments. Together, they are working on using optical fluorescence imaging to track the viability of cancer cells in response to different treatments and the sensitivity of cancer cells to various drugs.

Beyond his clinical interactions, Dr. Deming has an even more personal connection to colorectal cancer. In an ironic twist of fate, he was diagnosed with colon cancer himself several years ago. Although his own diagnosis did not alter his lab’s focus, it did underscore the urgency of his research for helping to improve the lives of cancer patients.

Looking ahead, Deming is optimistic about the future of cancer research, and sees tremendous promise in a wide array of research areas.

“My lab will tell you that I’m excited about everything, almost to an annoying level. With the ability to interact with great collaborators at McArdle and across the UW, and by working together in a team science format, we are going to make big strides and we are going to make them fast.”

By Simon Blaine-Sauer (blainesauer@wisc.edu)

Image on home page: Dr. Deming, second from right, with members of his laboratory group.

Night of HopeMcArdle Laboratory Director Dr. Paul Lambert (left) and UW School of Medicine and Public Health Dean Dr. Robert Golden (right) speak at the Night of Hope event.

On January 19th, McArdle students, staff, and faculty gathered together with teachers, staff, and supporters from Verona Area High School at Gray’s Tied House for the 13th Annual “Night of Hope” fundraiser. Festivities included a silent auction and raffles, with live performances by MUD Music and The Fauxtons. The annual fundraiser, which has grown steadily since its inception in 2005, raises money to benefit basic cancer research at the McArdle Laboratory (Department of Oncology). Additionally, Gray’s generously donates a portion of all food and drink sales made during the event.

The “Night of Hope” was inspired by the life of Verona Area High School teacher Anne Boehm. Ms. Boehm was a beloved member of the Verona community and a mother of three who passed away from breast cancer in 2006. The first “Night of Hope” was held to raise money towards supporting Ms. Boehm’s medical expenses and to allow her and her family to take a vacation.

In subsequent years, as more members of the Verona Area High School community were affected by cancer, the teachers of Verona decided to continue holding the event, and to donate the money to fund new cancer research. 

“The teachers of Verona wanted to raise money for a cancer institution where they could assure that 100% of the money was going to research, and they wanted to keep the money local,” said Nancy Cahill, who helps coordinate the event.

Over the years, the relationship between the McArdle Lab and the Verona Area High School staff has grown strong. McArdle faculty and staff have hosted several tours of their facilities for members of the Verona Area High School community, allowing them to meet with researchers and see the work that their generosity makes possible. Every year, McArdle faculty and staff look forward to participating in the festivities at Gray’s Tied House.

To date, the “Night of Hope” event has raised over $35,000 for research at McArdle and shows no signs of slowing down. This year’s event boasted one of the strongest showings yet by both Verona and McArdle staff, raising over $5,000.

The McArdle Laboratory wishes to thank the Verona Area High School staff, the amazing bands who performed, all who donated gift baskets and raffle items, and Gray’s Tied House for hosting. Your generosity and efforts make the cancer research breakthroughs at McArdle possible!

Coming up: On July 14, Nancy Cahill will host her annual Be The Cure event, to benefit the UW Carbone Cancer Center. More information on that event can be found here.  

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