The McArdle Laboratory for Cancer Research is pleased to welcome Dr. Aussie Suzuki as its newest faculty member. Dr. Suzuki’s research uses cutting-edge microscopy techniques to study one of the most fundamental aspects of all cancers: cell division.
Dr. Suzuki and his laboratory are interested in the fundamental molecular mechanisms of chromosome segregation. Proper chromosome segregation is a key component of cell division, allowing for one set of genetic material to be passed down to each daughter cell.
“If you want to study cancer, understanding cell division and chromosome segregation is key to learning how a tumor is established,” says Dr. Suzuki. “Studying cell division is fundamental to studying cancer.”
Dr. Suzuki initially studied pharmacy as an undergraduate in Japan, during which time he participated in research on pharmacokinetics and chronopharmacology. There he investigated how optimizing the timing and sequence of administration of drugs could lead to higher clinical efficacy and reduce side effects.
A particular focus of Dr. Suzuki’s undergraduate research was on the cell cycle inhibitors Irinotecan and Carboplatin, drugs used in cancer therapy that arrest cells at a specific stage of their natural cycle of growth, DNA synthesis, and division to prevent the hyperproliferation required for tumor growth. This early work studying cell cycle inhibitors sparked Dr. Suzuki’s continuing interest in the mechanisms underlying how cells divide. This fascination continued to drive his research focus during his Ph.D. studies at the National Institute of Genetics in Japan, and his postdoctoral work in the laboratories of Dr. Ted Salmon and Dr. Kerry Bloom at the University of North Carolina at Chapel Hill.
“During my undergraduate work, I became very interested in the cell cycle because the most common and universally effective drugs for cancer treatment were cell cycle inhibitors,” says Dr. Suzuki. “Later, as I was working on my Ph.D., I became interested in studying mitosis and chromosome segregation at a more fundamental level.”
As cells divide, they must pass on a copy of their genetic material to each of their two daughter cells. During this process, DNA condenses as chromosomes, which align in the center of the cell. Long protein filaments called microtubules attach to kinetochores, protein complexes in the chromosome’s centromere, and pull the chromosomes apart into two chromatid halves. Each daughter cell will receive one set of chromatids, allowing the amount of DNA in each cell to remain stable over many divisions.
Unfortunately, the process does not always proceed correctly. Improper chromosome segregation gives rise to a range of problems for dividing cells including aneuploidy, an unequal number of chromosomes between daughter cells. A form of genome instability, aneuploidy is implicated in many diseases, including developmental defects and nearly all cancers: approximately 90% of all solid tumors and 50% of blood tumors contain aneuploid cells.
Dr. Suzuki and his laboratory will use advanced light and electron microscopy techniques to study how cells segregate their chromosomes and what factors contribute to proper vs. improper segregation. One promising technique, Fluorescent Resonance Energy Transfer (FRET) microscopy, uses fluorophore constructs as biosensors to measure intracellular tensions with high sensitivity at a miniscule scale - on the order of nanometers! This cutting-edge approach will allow Dr. Suzuki’s lab to better characterize forces the cell generates via its kinetochores and microtubules to segregate its chromosomes.
“A major area of interest in cell and molecular biology right now is how mitotic checkpoints are organized, and what trigger satisfies the cell to move past the mitotic checkpoint,” says Dr. Suzuki. “Is the major factor kinetochore-microtubule attachment or tension on the kinetochore? Does microtubule attachment directly provide tension, or are there other important factors? By constructing a very sensitive in vivo tension biosensor, we can now begin to answer these fundamental questions, and this will open doors to addressing many cancer-related questions as well.”
As he finishes setting up his laboratory and hiring his first round of lab technicians and graduate students, Dr. Suzuki is excited by all the possibilities of conducting research at UW-Madison.
“The research community at UW-Madison and the McArdle Laboratory is very supportive and is also a very interactive and collaborative environment, which is the most important reason I wanted to work here,” says Dr. Suzuki. “My research focus is slightly different from many of the other labs at McArdle, but I hope that my strengths in microscopy will not only power my own research, but also help contribute to all of the amazing research being conducted here.”
To learn more about Dr. Suzuki's laboratory and research, please visit his new website: https://aussiesuzuki.oncology.wisc.edu
McArdle Laboratory faculty members Dr. Shigeki Miyamoto and Dr. Richard Burgess, collaborators on the NIH SBIR, and Dr. Scott Berry of Salus Discovery.
Dr. Shigeki Miyamoto and Dr. Richard Burgess, faculty in the McArdle Laboratory, are a part of a two-year NIH Small Business Innovation Research (SBIR) grant awarded to the Madison biotech start-up Salus Discovery. Scott Berry, at Salus, is the PI of the grant and is a former scientist from the lab of Dave Beebe, Prof. of Biomedical Engineering and the founder of Salus.
This two-year grant, entitled “Seeing the Unseen”, will allow the researchers to continue to improve and validate a novel method of identifying previously undetectable weak binding components of important protein complexes. Some proteins in a protein complex are tightly bound and co-purify through many steps of a protein purification procedure. However, proteins that are weakly bound, with dissociation half times of a minute or less, are likely to dissociate and be lost during purification. Thus, much of the crucial information is lost using existing technologies.
“One of the problems with the conventional methods of protein purification is that many protein-protein interactions can be relatively weak,” says Dr. Miyamoto. “When trying to isolate them, it takes time and they fall apart, so we miss some potentially key interactions, or we may significantly underestimate the quantity of those interactions.”
It is now clear that there are important regulatory components of protein complexes that are involved in writing, reading or erasing protein post-translational modifications. Many of these regulatory components are specific to the complex, but only weakly or transiently bound. Establishing and refining methods for identifying these otherwise invisible components has the potential to revolutionize the fields of biochemistry and cancer biology.
Salus’s new method uses small magnetic beads with bound antibodies specific to one of the proteins in the complex. The beads are mixed with a crude samples of cell extract, serum, or urine so that the antibodies can link the protein complex to the bead. Unlike conventional protein complex purification techniques that involve several iterative, time-consuming precipitation and washing steps, in the Salus system the bead is removed from the crude sample very rapidly using a magnet, with the protein complexes pulled through a single wash solution before being directly denatured for analysis. The entire process takes only a few seconds and is thus able to capture, better than any prior method, both tightly and weakly bound proteins associated with the complex of interest.
“The idea is to minimize protein-protein disassembly while we’re purifying, and the hope is that we can capture more different types of proteins, and also do it more quantitatively,” says Dr. Miyamoto.
Weak binding proteins that regulate cell signaling complexes represent desirable drug discovery targets, since weak protein-protein interactions may be easier to inhibit by potential therapeutic chemicals. Dr. Burgess’s lab, particularly senior scientist Nancy Thompson, is working with scientists at Salus to improve and validate the system by using engineered model proteins to better characterize the specificity and precision of the technology. Dr. Miyamoto’s lab is testing the method to identify new proteins that are involved in the regulation of the NF-κB system, a key player in the cellular inflammatory and cancer cell survival responses.
“My lab is looking at endogenous proteins in mouse, and evaluating the system in an actual physiological context,” says Dr. Miyamoto. “Once we purify and identify weakly-interacting proteins, we can then knockdown the protein in cell lines and observe if the signaling cascade we are interested in is disturbed.”
Small Business Innovation Research (SBIR) grants are sponsored by the NIH and are designed to support research into cutting-edge biomedical technologies. By providing seed money to companies with innovative ideas and products, these grants help bring new technologies that will benefit the public to market.
SBIR grants are structured to encourage collaboration between the worlds of industry and academic research, bridging the gap in order to deliver solutions faster and to maximize the impact of new technologies. Approximately two-thirds of the funding for Salus Discovery’s SBIR will go to the company, with one-third going to the research collaborators at the McArdle Laboratory.
Over the last several decades, Madison has become a hub for biomedical and biotechnology innovation. There are currently over 200 biotech companies operating in Madison, including Promega and Aldevron, compared to just 3 companies 35 years ago. This is thanks in no small part to the exceptional quality of life sciences research at UW-Madison. Programs such as the UW Biotechnology Center have actively fostered this growth, and many UW-Madison graduate students have gone on to form companies of their own.
“Collaboration between the university and local and nation-wide companies is essential to bring new inventions and discoveries to the point where there is a product or a service made available for the benefit of the general public,” says Dr. Burgess.
Right now, Dr. Miyamoto is excited to apply this new technology to his laboratory’s research, and study key interactions that would otherwise be unobservable.
“Our ultimate goal is to add to the knowledge of discovering unknowns, that’s our main motivation. We might be able to see something no one has seen before, and that potential for discovery is very cool.”
Dr. Spurgeon at the 2017 Race for Research, and her cousin Ollie
Megan Spurgeon, PhD, is a scientist with the McArdle Laboratory for Cancer Research at the University of Wisconsin, studying how the viruses HPV and Merkel Cell polyomavirus are linked to human cancers. Having a career in cancer research, Spurgeon has participated in the UW Carbone Cancer Center ’s signature fundraising event, Race for Research, a few times before, raising “a little bit of money,” she says. When she signed up last year, she did not expect to become the event’s top fundraiser.
“We found out about Ollie in June of 2017,” Spurgeon says of her cousin’s son, Oliver. “He was diagnosed with stage four neuroblastoma, and it had already metastasized to other sites. All of a sudden I had this personal connection to raising money.”
With her cousin’s blessing, Spurgeon shared Ollie’s story and began fundraising, mainly through social media, for neuroblastoma research at UW Carbone. Meanwhile, Ollie began treatments near his home in Missouri, and later in Texas.
“The treatments are so gruesome, they’re almost archaic,” Spurgeon says. “They’re not really made for children.”
All of the nearly $8,000 raised through Spurgeon’s Race for Research personal fundraising campaign last year went to a neuroblastoma research account at UW Carbone, where neuroblastoma researchers can apply for funds to study the cancer. In addition to improving survival outcomes – currently, stage four patients have only around a 50 percent chance of beating the disease – these researchers strive to develop treatments that are less toxic.
“With chemotherapy, we all know the side effects: it doesn’t attack the tumors specifically, it hurts any cell that’s rapidly dividing, so there’s a lot of toxicity,” says Christian Capitini, MD, a pediatric oncologist who treats neuroblastoma patients and researches it in his lab. “Immunotherapy has become one of the most promising areas for that disease. With immunotherapy, it’s targeted to something that’s on the tumor, so the toxicity we see is much more limited.”
Capitini’s lab studies ways to improve upon the current FDA-approved immunotherapy, itself developed by UW Carbone pediatric oncologist Paul Sondel, MD, PhD. With his research group, Capitini has shown in a mouse model that if they isolate a type of immune cell known as a natural killer cell, and activate those cells with a combination tumor-targeting/immune stimulating drug, then they can reduce the tumor burden in mice and increase overall survival.
“That work has led to a clinical trial here, supported in part by Race for Research funds, that’s testing these activated natural killer cells in neuroblastoma patients,” Capitini says.
And, because he was able to begin this promising research with philanthropy funds, Capitini was recently awarded a $1.75M grant from the National Institutes of Health to continue his neuroblastoma research.
“Philanthropy, such as through Race for Research, helps build the infrastructure to get these clinical trials off the ground, and to earn these federal grants,” Capitini says.
For her part, Spurgeon is again running and fundraising this year in honor of Ollie, who sadly passed away this past July. She is also hoping to raise awareness for childhood cancers.
“I had never really heard about neuroblastoma before Ollie was diagnosed, so raising awareness for this type of cancer is important to me,” Spurgeon says. “I don’t think anyone thinks, ‘Oh, I need to raise money for pediatric cancer,’ until it affects you personally. But research is the only thing that’s going to help us prevent there being another Ollie.”
In 2017, over 1400 Race for Research participants raised over $146,000 for cancer research at the UW Carbone Cancer Center. Run or walk in the 2018 race and help make a difference. For more details and to sign up, please visit carbonesrace.org.
To read more about Ollie and Spurgeon’s team, please visit her Race for Research team page.
This article was originally posted at https://www.uwhealth.org/news/racing-to-improve-cancer-patient-outcomes-through-awareness-and-research/52231
Members of Mrs. Birge’s family pose with Bucky during their visit to the McArdle Laboratory
A generous donation from the estate of Mrs. Ruth Birge has helped to provide crucial pilot and bridge funding for cancer research at the McArdle Laboratory for Cancer Research.
Ruth Birge was born outside of Rosendale, WI, and was raised by her grandparents after both of her parents died when she was very young. She attended Ripon College where she met her husband, Robert. Unfortunately, soon after they were married, her husband was killed in action during the Second World War. After graduating from Ripon College, she began teaching grade school in Fond du Lac and then, until her retirement, in Ripon. Mrs. Birge and her aunt built a house together in Ripon and the two lived there until her aunt’s death due to breast cancer. Witnessing her aunt's fight with cancer inspired Mrs. Birge to support basic cancer research at the McArdle Laboratory.
One of the key areas where Mrs. Birge’s donation has made a difference is in providing pilot and bridge funding for McArdle Laboratory researchers. This funding allows investigators to continue conducting exceptional research while between major funding periods, or to initiate research on new ideas that are high risk/high impact. Ultimately, this crucial form of funding allows laboratories to apply for and be awarded large federal grants to support their novel cancer research efforts.
One of the beneficiaries of funding made possible by Mrs. Birge’s donation is McArdle Professor Dr. Shigeki Miyamoto, who studies the NF-κB signaling pathway, a key cellular pathway related to cancer progression. Much of Dr. Miyamoto’s research focuses on how multiple myeloma and other blood cancers evade the effects of anticancer drugs.
Other researchers at McArdle who Mrs. Birge's donation has helped to support include Dr. Yongna Xing, who was recently awarded an R01 grant to study the PP2A holoenzyme, and Dr. Chris Bradfield, who was recently awarded an R35 Outstanding Investigator grant to study the PAS family of sensor proteins.
In June, eleven members of Mrs. Birge's family visited the McArdle Laboratory, coming from as far as Colorado. As part of their visit they toured the laboratory and met a number of faculty, including those whose research Mrs. Birge’s donation has helped to support.
“It was wonderful to meet the family of Mrs. Birge, learn about her personal life story and that of her family members, and learn the reasons underlying her commitment to supporting the cancer research efforts at the McArdle Laboratory for Cancer Research," remarked Director Dr. Paul F. Lambert. "We hope that her family can continue visiting us to learn how Mrs. Birge's generous donation to McArdle continues to live on through the pioneering research endeavors supported by her estate. Our work to tackle cancer cannot happen without the support of individuals like Mrs. Birge. I speak for all of McArdle in saying a big thank you to Mrs. Birge and her loving family.”
On July 12-13, the McArdle Laboratory for Cancer Research in collaboration with the Institute for Molecular Virology (IMV) and Carbone Cancer Center welcomed 31 grandparents and their grandchildren into the lab to learn about fundamental cancer research techniques and concepts as part of the “Researching Cancer Cures” major for Grandparents University®, or GPU.
This experience was one of 25 different “majors” offered as part of GPU, a program that allows Wisconsin Alumni Association members to return to campus with their grandchildren to immerse themselves in the Badger experience and explore any one of a variety of topics over the course of a two-day major. GPU began at Wisconsin-Madison in 2001 and, over 17 years, has grown from 4 majors and 160 participants to 25 majors and >1,400 participants in 2018. Based on this success, similar programs have since been started at several other universities. GPU majors range from journalism to urban gardening to, of course, cancer biology.
“Researching Cancer Cures” provided grandparents and grandchildren with a taste of what it takes to be a cancer researcher. The first day’s session began with an introductory talk by McArdle director Dr. Paul Lambert. The attendees then donned personal protective equipment (PPE) including lab coats, goggles, and gloves, and then broke out into two different hands-on activities led by members of the Lambert lab. The first activity taught attendees the basics of tissue staining and microscopy, and showed them how to determine whether tissues are normal or cancerous. During the second activity, the grandparents and grandchildren received a primer on how to run a polymerase chain reaction (PCR) to determine whether a gene is mutated.
The second day’s session was hosted at Bock Laboratories in the Institute for Molecular Virology (IMV), and was led by McArdle Associate Professor Dr. Nathan Sherer and Biochemistry Professor Dr. Ann Palmenberg. In the IMV, grandparents and grandkids explored how to detect and study viruses and the roles they play in cancers. Activities included hunting for virus sequences, exploring how to target viruses with antiviral drugs and vaccines, and learning how to detect otherwise invisible viruses using viral growth assays and fluorescence microscopy.
Dr. Sherer served as “Dean” of the “Researching Cancer Cures” major, with organizational help from Drs. Megan Spurgeon, Marchel Hill, and Laraine Zimdars. This was the 4th year that McArdle and the IMV have hosted a GPU major.
Dr. Sherer notes, “”Researching Cancer Cures” has been a really great outreach and education event for McArdle, the IMV, and Carbone. We receive great feedback from the grandparents and grandkids alike. They enjoy learning about cancer and viruses, love the activities and using the cutting-edge facilities at WIMR and Bock, and think it’s an amazing treat to get to interact directly with the incredible students, post-docs, and staff donating their brains and talents to make this a special event. It’s also really fun and rewarding for us - a chance to give back in the spirit of the Wisconsin Idea, and a valuable opportunity to convey the crucial role basic cancer research plays in developing tomorrow’s needed cures.”
Above: a panel from the JKX comic strip "EBV and the Replication Dance" (left), an image of Stanford mathematics professor Maryam Mirzakhani from the JKX Women's History Month feature "Women in STEM" (top right), and the JKX founders Jaye Gardiner, Ph.D., Khoa Tran, Ph.D., and Kelly Montgomery (bottom right, from left to right). Featured image on home page: a clip from the JKX comic strip "Did You Know: About HIV and Cancer?". All images used with permission courtesy of JKX Comics.
"A picture is worth a thousand words."
The scientists behind JKX Comics have taken that mantra to heart in their endeavor to help engage and educate young people about science.
JKX Comics was founded in 2015 by Jaye Gardiner, Kelly Montgomery, and Khoa Tran, three then-graduate students at the University of Wisconsin-Madison. Inspired by the wide array of cutting-edge research and the diversity of exciting scientific topics they encountered, they saw the potential to present STEM education in a more captivating way to young students.
“We felt that the way science is presented can be unengaging sometimes, so we wanted to use stories and humor to make science more exciting for kids in schools, and comic books seemed like a great way to do that,” said Jaye Gardiner, who completed her Ph.D. research in Dr. Nate Sherer’s lab as part of the Cancer Biology Graduate Training Program and is now a first-year postdoctoral researcher at Fox Chase Cancer Center studying pancreatic cancer. “No one from JKX had any formal training in visual arts or media. We mostly just figured it out as we went along.”
JKX highly values the accessibility of their content, choosing to make all of their individual comics available online for free at www.jkxcomics.com. The organization is almost entirely self-funded, and most of their promotion is done via social media. Collaborative by nature, JKX is always open to new members looking to make an impact in science communications. One new collaborator, Bayleigh Benner, is a third-year microbiology graduate student affiliated with the McArdle Laboratory, also training in the Sherer lab.
Some of the scientific topics JKX have helped illuminate for young people so far include the relationship between HIV and cancer, the role of gut bacteria in fighting infection, and the life cycle of Epstein-Barr virus. One of their next projects will be a CSI-style comic series, going through the different organs of the body and inviting readers to piece together the clues to diagnose what is wrong. JKX has also featured comics for Black History Month and Women’s History Month, spotlighting some of the overlooked people behind amazing scientific advancements.
“One of the things we try to focus on is representation,” said Gardiner. “A lot of young black girls who I’ve met through the Trip Initiative high school research program I am a part of have really gravitated towards me, and it blew my mind how excited they are just because I exist as a black female scientist. It’s so important for all young people to realize that science can be for everyone.”
Looking forward, JKX Comics is also seeking to expand public engagement with science via outreach events. JKX and collaborators were recently awarded a first-place prize of $2000 at the UW-Madison Arts Business Competition, with a project aimed at helping to teach scientists how to create stories to communicate their research to the public via comic strips and other visual media.
“Most people don’t know very many scientists or their work. In fact, a recent study showed that only 19% of Americans could name a single living scientist,” Gardiner said. “By facilitating outreach for the general public, we can help change that by connecting people to the scientists at the University of Wisconsin making amazing discoveries.”
“Our students face constantly changing career paths, and I’ve been incredibly impressed with how quickly Jaye, Bayleigh, and the JKX team made this project a huge success both in terms of their outreach mission and also in terms of their professionalism, dedication, and the high quality of the product," says Associate Professor Nathan Sherer. “We’ve already used some their comics for outreach events including Grandparents University, and plan to ramp up distributing them to visiting groups, prospective students, and undergraduate scholars doing research in McArdle or taking our cancer virology and cancer biology coursework. JKX Comics is truly a spectacular idea and emphasizes the breadth and innovative contributions of our remarkable trainees.”
JKX comics is currently looking for collaborators as part of their “Gaining Steam!” project. Apply to join their team at https://www.jkxcomics.com/gainingsteamapplication.
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!
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.”
Dr. 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.”