• Walther Cancer Foundation $11 million investment to expand IU-Purdue bioinformatics collaboration

    Walther Cancer Foundation $11 million investment to expand IU-Purdue bioinformatics collaboration

    The Walther Cancer Foundation will invest $11 million to advance collaborative cancer research at Indiana University and Purdue University by supporting scientists through bioinformatics—an increasingly critical aspect of their work. 

    Bioinformatics involves managing and analyzing the massive amounts of data generated by scientific research—turning data into knowledge that could lead to new cancer treatments.

    “We hope this gift enables scientists at IU and Purdue to dig more deeply and refine their studies so they can point out new pathways to good patient outcomes in cancer,” said Tom Grein, president and CEO of the Walther Cancer Foundation. “Sometimes, you have so much data, it’s hard to comprehend where it’s leading you. I hope the data-driven analysis will uncover nuggets of opportunity that would otherwise never be seen.” 

    Income from the new Walther Cancer Foundation Bioinformatics Fund will continuously support bioinformatics personnel, technology, and other tools shared by the cancer research programs at both universities. In addition, IU and Purdue will make their own investments into the fund. 

    “The Walther Cancer Foundation leadership understands the central importance of data and analytics in developing better treatments and, ultimately, cures for cancer,” said IU School of Medicine Dean Jay L. Hess, MD, PhD, MHSA. “We are tremendously grateful for their support and the confidence they have in our work.”

    Timothy Ratliff, the Robert Wallace Miller Director of the Purdue Center for Cancer Research, said the latest gift from the Walther Foundation is a continuation of a longstanding collaboration, commitment and investment that will build on the center’s success in cancer drug discovery and development—and will help sustain the center’s Computational Genomics and Bioinformatics Core for years to come. "Once again, we are grateful to the Walther Cancer Foundation’s vision and generosity, which is so important to our research and success. This continuing partnership—plus our own investments and fundraising—will secure what we’ve already established, and enable us to grow into the future."

    Kelvin Lee, MD, named this week as the new director of the IU Melvin and Bren Simon Comprehensive Cancer Center, said having strong capabilities in bioinformatics is essential to cancer research.  

    “The genetic, biochemical, cellular and immune pathways that can lead to cancer are extraordinarily complex and intertwined. Recent cutting-edge advances in technology means that researchers now have unprecedented amounts of data on these pathways, but this seriously challenges our ability to analyze these huge mounds of information to make sense of what is actually going on,” Lee said. “We are fortunate that the Walther Cancer Foundation understands that breakthroughs require the expertise and the tools, like artificial intelligence (AI), to help us analyze all this data so we can understand what’s really important.” 
      
    This level of collaboration—and sharing of a key resource like a bioinformatics core—is unusual among a pair of National Cancer Institute-designated cancer centers. But it also reflects the complementary nature of the two institutions.

    Purdue’s Center for Cancer Research is a basic science cancer research center with more than 110 researchers that is a leader in biomedical engineering and cancer drug development.

    The IU Simon Comprehensive Cancer Center is a comprehensive cancer center with nearly 250 cancer researchers who conduct basic lab work and drug development but who are also engaged in clinical care and population health research.

    “Each of them has different capabilities, different levels of expertise, different interests,” Grein said. “But when you get scientists to collaborate, the outcomes are better.”

    Since its founding in 1985, the Walther Cancer Foundation has invested more than $165 million in cancer-focused medical research, and in research and education aimed at supporting cancer patients and their families.

    Walther has previously supported cancer bioinformatics at IU and Purdue on a year-to-year basis. This new gift establishes a fund that will ensure the bioinformatics work continues in perpetuity.

    The Walther Foundation endowment provides the opportunity to develop the expertise and the tools that are needed to face current and future challenges in biology and the cancer field, said Majid Kazemian, an assistant professor in Purdue’s departments of biochemistry and computer science. His research focuses on integrating computational and experimental approaches to study pathogen interaction with host cells and immune system in infectious diseases and cancers caused by pathogens. 

     "The Purdue University Center for Cancer Research has nearly 100 investigators who are actively engaged in understanding molecular mechanisms of various diseases including lung, liver and prostate cancers, many of which have begun to utilize genomics data in their studies,” Kazemian said. "Large genomic public data on many diseases generated over the last decade are a treasure trove of unexplored information. Walther Foundation's funds endowment will enable analysis of big data generated by our center’s members and collaborators as well as an exploration of growing public genomics data to contextualize and translate our findings."  

    Less-costly access to bioinformatics expertise and resources enabled by Walther Foundation will open up new avenues for many of the Purdue center's scientists to broaden the impact and clinical translation of their discoveries, Kazemian said. "It will also encourage our scientists to perform large-scale genomics assays and will foster new collaborations.” 

    IU School of Medicine breast cancer researcher Harikrishna Nakshatri, PhD, said he relies on bioinformaticians to design experiments, analyze data and assist him in publishing research results more quickly. The Walther Foundation gift supports that very expensive process, and the collaboration means researchers have more bioinformaticians available when they are needed. All of it combines, Nakshatri said, to enable scientists to reach conclusions that have real benefits for patients.

    “If you really believe in your hypothesis,” Nakshatri said, “now you have a chance to test it because you are not burdened by the financial aspects.” 

    According to Hess, the new resources will allow IU’s partnership with Purdue to continue to improve the health of Hoosiers. “We have worked closely for decades,” Hess said. “This new collaboration in data sciences will accelerate our ability to benefit cancer patients across the state—and far beyond.”

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    About the IU Simon Comprehensive Cancer Center
    The Indiana University Melvin and Bren Simon Comprehensive Cancer Center is home to the cure of testicular cancer, the world’s only healthy breast tissue bank and is just one of 51 NCI-designated Comprehensive Cancer Centers in the nation. The prestigious comprehensive designation recognizes the center’s excellence in basic, clinical, and population research, outstanding educational activities, and effective community outreach program across the state. Its physician-scientists have made protocol-defining discoveries that have changed the way doctors treat numerous forms of cancer. 

    About the Walther Cancer Foundation
    The Indianapolis-based Walther Cancer Foundation is a private grant-making foundation that supports and promotes interdisciplinary and inter-institutional cancer research, both bench and clinical. The clinical research it supports encompasses clinical trials as well as behavioral studies, the latter as part of the foundation’s commitment to Supportive Oncology. The Walther Foundation has two primary goals: to support cancer research with the aim of discovering better treatments, if not cures, and to develop a comprehensive approach for supporting patients with cancer and their families. Since its founding, the foundation has invested over $165 million cancer-focused research.

    About the Purdue Cancer Center
    Since 1978, the Purdue University Center for Cancer Research has been a National Cancer Institute-designated basic-research cancer center. Only seven institutions in the United States have earned this title. Being a basic-research center means it does not treat cancer patients directly. Its work focuses on investigating cancers where they begin—at the cellular level—to investigate the cause of, and cure for, one of the most devastating killers of our time. Doctors and scientists throughout the world use the center’s discoveries to develop methods, medicines and medical devices to save and enhance patient lives. 


  • IU School of Medicine names new cancer center director, announces $15 million supporting gift from Walther Cancer Foundation

    IU School of Medicine names new cancer center director, announces $15 million supporting gift from Walther Cancer Foundation

    INDIANAPOLIS—Indiana University School of Medicine has announced the hiring of a world-recognized medical oncologist and multiple myeloma researcher to lead the Indiana University Melvin and Bren Simon Comprehensive Cancer Center, bolstered by a $15 million fund established by the Walther Cancer Foundation to support him in this role.   

    Kelvin Lee, MD, has been named the new IU Simon Comprehensive Cancer Center director. In addition, Lee will hold the titles of senior associate dean of cancer research at IU School of Medicine and the H.H. Gregg Professor of Oncology. He will also direct the Cancer Institute, an umbrella entity designed to facilitate collaboration among cancer disciplines at IU School of Medicine and Indiana University Health, enhancing clinical research opportunities for patients here in Indiana and beyond. He will have appointments with both the Department of Medicine and the Department of Microbiology and Immunology.  

    Since 2006, Lee has served as the Jacobs Family Chair of Immunology at the Roswell Park Comprehensive Cancer Center in Buffalo, New York. The co-leader of the Cancer Center Tumor Immunology and Immunotherapy Program from 2006 to 2018, Lee led the group through three successful National Cancer Institute Cancer Center Support Grant renewals before stepping down to take on the position of Senior Vice President for the Basic Sciences.

    The IU Simon Comprehensive Cancer Center has long been a leader in the field. It was recognized in 2019 as one of the top cancer research institutions in the nation when it was designated a Comprehensive Cancer Center by the National Cancer Institute. Home to the cure of testicular cancer, the IU Simon Comprehensive Cancer Center is a critical piece to IU School of Medicine’s world-class research enterprise. The central hub for cancer research across Indiana University, the center’s nearly 250 researchers conduct all phases of cancer research, from laboratory studies to clinical trials to population-based studies that address environmental and behavioral factors that contribute to cancer.

    “Dr. Lee is the ideal leader to build on the IU Simon Comprehensive Cancer Center’s tremendous momentum. The center’s researchers are making great strides in improving health in current and future patients alike through their world-class care and groundbreaking research,” said Jay L. Hess, MD, PhD, MHSA, dean of IU School of Medicine and IU’s executive vice president for clinical affairs. “As an institutional leader, Dr. Lee will play a pivotal role in advancing these goals, and I’m excited for him to join our team at IU School of Medicine.” 

    As cancer center director, Lee will also play a key role in setting the future course for two significant centers at IU School of Medicine—the Vera Bradley Foundation Center for Breast Cancer Research and the Brown Center for Immunotherapy. The recruitment of a top-notch physician-scientist like Lee broadens the range of possibilities for the groundbreaking and potentially synergistic research taking place at both centers. 

    “We are very pleased to welcome one of the country’s top cancer physician-researchers to IU Health,” said Dennis M. Murphy, president and chief executive officer, Indiana University Health. “He joins an already respected program and will play a critical role in advancing our efforts, through the IU Simon Comprehensive Cancer Center and our new Cancer Institute, to expand access to cutting-edge cancer care to patients across and beyond Indiana.”

    Lee assumes leadership at a time when the IU Simon Comprehensive Cancer Center will play a large role in a continued push by IU School of Medicine and IU Health leadership to improve alignment across education, research and clinical care. Earlier this year, the establishment of three institutes was announced, covering the key research areas of cardiovascular, neuroscience and cancer. Transcending multiple departments and centers, the goal of these institutes is to fully realize the promise of academic medicine and better address the most pressing challenges facing patients.

    “I am very excited to join IU School of Medicine to continue to build the world-class effort in cancer research, education and care for the people of Indiana, nationally and globally. The renewal of the IU Simon Comprehensive Cancer Center core grant and achievement of comprehensive designation speaks to the outstanding faculty and staff that are leading this charge,” said Lee. “I have also been incredibly impressed by the deep commitment of IU School of Medicine and IU Health in these efforts, and this was a major reason in my decision to join IU.

    “I believe that research cures cancer. For this to be successful, we need to get our science into our patients. The Cancer Institute and IU Simon Comprehensive Cancer Center are well-poised to grow this effort exponentially and will light the way to ending cancer’s darkness.”

    As a physician-scientist, Lee’s research interests are both laboratory and clinical based. In the lab, his research efforts are RO1-funded and primarily focus on multiple myeloma, as well as myeloid dendritic cell differentiation in cancer. Lee currently sees patients with multiple myeloma once a week in clinic and is the principal investigator on active clinical trials of immunotherapy in myeloma at Roswell Park. 

    Lee officially assumes his new role in January 2021. He succeeds Patrick J. Loehrer, MD, who served as cancer center director since 2009. Loehrer led the center through two National Cancer Institute competing renewals, which culminated with the center earning the prestigious Comprehensive Cancer Center designation. He will continue to see patients with gastrointestinal and thymic malignancies and carry on his work focused on global oncology and health equities.

    Walther Cancer Foundation announces major gift
    To help support the Cancer Institute, the Walther Cancer Foundation will contribute $15 million to establish a fund for investments in areas of cancer research and laboratory improvements that the director deems most promising.

    The Walther Cancer Foundation IU Simon Comprehensive Cancer Center Director’s Fund is intended to provide the resources and flexibility needed to advance the work of a world-class cancer center, said Tom Grein, President and CEO of the Walther Cancer Foundation.

    “It is not Walther’s position to decide, ‘This is where we want you to invest or that you need to use these funds in this explicit manner,’” Grein said. “It’s really more to give the director, who is recognized as a leader in cancer research, the ability to make those choices.”

    The Walther Cancer Foundation will continue to fulfill previous commitments to IU cancer research through 2025, at which point its gifts to the Director’s Fund are scheduled to begin and continue for three years. 

    “This incredible gift from the Walther Cancer Foundation will be a tremendous asset in the years to come, offering the flexibility to add resources and attract talent to areas where there is a need,” Lee said.

    Grein said the Walther Cancer Foundation was delighted by the cancer center’s comprehensive designation last year. And leaders at IU said it’s clear that the foundation’s support was a key ingredient in that success. 

    “The Walther Cancer Foundation’s generous support has been an essential element in the progress we’ve made in cancer research and in efforts to support the families of cancer patients,” Hess said. “We’re grateful for the confidence Walther has shown in us as we confront cancer in the lab, in the clinic and in our communities.”

    Media contact: Katie Duffey, kaduffey@iu.edu, 765-427-3553 (cellphone)

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    About IU School of Medicine
    IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.

    About the Walther Cancer Foundation
    Since its founding in 1985, the Walther Cancer Foundation has invested more than $165 million in cancer-focused medical research, and in research and education aimed at supporting cancer patients and their families. More than $100 million of that support has benefitted programs at the IU Simon Comprehensive Cancer Center. Those have included investments in the research of early career scientists, the field of bioinformatics and in supporting research and medical education aimed at helping cancer patients.

  • IU cancer center researcher awarded $5.7 million to study chemo-induced hearing loss, toxicities

    IU cancer center researcher awarded $5.7 million to study chemo-induced hearing loss, toxicities

    INDIANAPOLIS—A researcher at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center has been awarded a five-year, $5.7 million National Cancer Institute grant to evaluate long-term health outcomes for cancer patients who receive platinum-based chemotherapies. 

    An internationally recognized expert on cancer survivorship, Lois B. Travis, MD, ScD, leads the ongoing study that could lessen cancer treatment side effects for millions of patients. 

    Nearly 6 million patients globally are diagnosed with a cancer each year in which first-line therapy potentially includes highly toxic, platinum-based chemotherapies. While the treatment may lead to hearing loss, ringing in the ears, numbness in hands and feet and other side effects, it is the only proven cure for the vast majority of testicular cancer patients. 

    When IU’s Lawrence Einhorn, MD, developed a revolutionary therapy for testicular cancer in the 1970s, he flipped the 95 percent mortality rate for the disease to a 95 percent survival rate. His regimen of platinum-based cisplatin and two other drugs continues to be the standard care for testicular cancer. Einhorn is the Livestrong Foundation Professor of Oncology at IU School of Medicine and a physician scientist at the IU Simon Comprehensive Cancer Center.

    Now Travis, Einhorn and a team of researchers from other top cancer centers are following more than 2,000 testicular cancer survivors who are part of the largest clinical cohort of germ cell cancer survivors worldwide. The alliance of researchers leads The Platinum Study, which was established through a previous NCI grant awarded to Travis in 2012. 

    “We have shown with audiometric examination that 80 percent of the patients had hearing loss with one in five classified as severe to profound, levels at which hearing aids are recommended,” Travis, the Lawrence H. Einhorn Professor of Cancer Research at IU School of Medicine, said. Additionally, researchers found that 56 percent of patients had nerve damage called neuropathy and 40 percent had tinnitus or permanent ringing in their ears.

    With this grant, researchers will tap into the existing cohort of patients who are part of the Platinum Study. The median age at diagnosis for testicular patients is 30, and the cohort’s median age now is 37. As patients age, researchers will continue to follow health changes, including if they are more susceptible to age-related hearing loss.

    “We will examine the role of genetic variants in the platinum toxicities to try to identify high-risk subgroups,” Travis said.

    The team of investigators wants to understand better which patients are at higher risk for these adverse outcomes and the daily effects of the toxicities. 

    Collaborators of the Platinum Study gathered in Indianapolis in 2015.
    Collaborators of the Platinum Study gathered in Indianapolis in 2015.

    “The goal is to follow this cohort for many decades to characterize the longitudinal trajectory of toxicities related to platinum-based chemotherapy,” she said. “For the first time, we will evaluate the impact and severity of the hearing loss and tinnitus on the patients’ physical, emotional and social functioning.”

    Patients will complete questionnaires to track the different facets of their lives that are affected by hearing loss, or pain and numbness associated with neuropathy, as well as other toxicities. Researchers will also investigate the social and emotional consequences of the constant ringing in the ears, such as difficulty sleeping or concentrating.
    Additionally, researchers will continue to analyze previously collected patient blood samples to track platinum levels, which can remain in the body for decades after chemotherapy is completed.

    “Platinum is not completely excreted and is believed to be held in several body reservoirs. As tissue is remodeled with age, platinum regains access to the circulation,” Travis explained. “We will continue to measure the residual serum platinum levels.”

    While cisplatin is used for many cancers, Travis notes that the testicular cancer patient cohort offers researchers a unique opportunity to study the toxicities.

    “If we want to improve our understanding of long-term cisplatin-related toxicities, this is an ideal population,” she said. “When doing genetic studies, we know that all patients received about the same cumulative dose of cisplatin. We can then consider: who developed hearing loss and who didn’t, and what genetic and other factors are associated with this outcome?”

    Ultimately, Travis hopes this research can determine which patients are most likely to experience adverse effects from cisplatin and then provide guidelines that could decrease damaging side effects, such as duration of treatments or improved symptom management.

    “This is a critical part of my life’s mission: to decrease the cost of the cure for cancer survivors,” Travis said.

    Collaborators include researchers from Memorial Sloan Kettering Cancer Center (Darren Feldman, MD), Dana-Farber Cancer Institute (Neil Martin, MD), University of Pennsylvania (David Vaughn, MD), University of South Florida (Robert Frisina, PhD), Vanderbilt University (Nancy Cox, PhD), University of Chicago (Eileen Dolan, PhD), Princess Margaret Hospital (Robert Hamilton, MD), the Royal Marsden Hospital (Robert Huddart, PhD), University of Rochester (Chunkit Fung, MD), Loyola University (Heather Wheeler, PhD), Harvard School of Public Health (Howard Sesso, ScD), and the British Columbia Cancer Agency (Christian Kollmannsberger, MD).

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    IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.

  • IU School of Medicine findings set new standard for use of blood-based biomarkers in clinical trials for prediction of cancer recurrence

    IU School of Medicine findings set new standard for use of blood-based biomarkers in clinical trials for prediction of cancer recurrence

    INDIANAPOLIS– Indiana University School of Medicine researchers Milan Radovich, PhD, and Bryan Schneider, MD, have discovered that the presence of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) in the plasma of women’s blood who have undergone chemotherapy prior to surgery for the treatment of stage 1, 2 or 3 triple negative breast cancer are critical indicators for the prediction of disease recurrence and disease-free survival. Their findings, published today in the prestigious international peer-reviewed journal, JAMA Oncology allow for a stratification of patients in clinical trials around the world, that didn’t exist prior to their discovery.  The pair also spoke about their findings as part of a JAMA Oncology podcast

    “These findings from the Vera Bradley Foundation Center for Breast Cancer Research, located at IU School of Medicine, enable a scientific basis for predicting relapse and disease-free survival, which are both important questions for women who live in constant fear of their disease returning,” said Jay L. Hess, MD, PhD, MHSA and dean of IU School of Medicine. “The discoveries reflect our long history as  leaders in genomics, bioinformatics and medical innovation.”

    Specifically, Radovich and Schneider, who are also researchers at the IU Melvin and Bren Simon Comprehensive Cancer Center, along with colleagues from the Hoosier Cancer Research Network, analyzed plasma samples taken from the blood of 196 women, as part of a preplanned secondary analysis of women who were participants in clinical study BRE12-158. This is the largest known data set of patients to date. 

    They discovered that the detection of ctDNA was significantly associated with poorer outcomes on three important measures for patients: distant disease-free survival, disease-free survival and overall survival. When the presence of ctDNA was combined with the presence of CTCs, the outcomes were even worse.

    • At two years post-surgery and chemotherapy, distant disease-free survival for women with the presence of ctDNA in their blood was 56 percent, when compared with 81 percent for women without ctDNA
    • Patients with the presence of both ctDNA and CTCs at two years had a 52 percent likelihood of distant disease-free survival versus 89 percent who were negative for both markers.

    Approximately one-third of patients will achieve remission from their triple negative breast cancer, following surgery and chemotherapy. However, two-thirds will have residual disease, putting them at high risk of relapse. These findings will be the focus of the PERSEVERE study, which will stratify women with triple negative breast cancer based on being ctDNA positive and assign them a targeted therapy matched to the patient’s genomic sequencing. The study is powered to help discover a personalized therapy for patients at high risk for relapse and for whom no treatments currently exist. More information about the PERSEVERE study will be provided in the coming months.

    “A diagnosis of triple negative breast cancer is very scary to the patient. The discovery and utilization of circulating tumor DNA and circulating tumor cells to better predict recurrence, by Drs. Schneider and Radovich, has provided a huge step forward toward more certainty for treatment decision making,” said Mary Lou Smith, co-founder of the Research Advocacy Network. “This significant scientific advancement will help personalize treatments for those still battling residual disease.”

    “Since uncovering these findings in women diagnosed with triple negative breast cancer, we have learned that others are applying this stratification of patients based on ctDNA and CTCs to other cancers, including breast and colon,” said Radovich.

    “This is an important step forward in the treatment of women with triple negative breast cancer, who have not had much scientific evidence to point to—until now—for treatment of their disease,” said Schneider. “We are going to use these findings and continue on until we find a treatment that works for each individual woman. This effort not only involves finding the best way to kill cancer, but to minimize side effects.”

    As a further testament to the significance of these findings, Radovich presented the initial findings as part of an oral, plenary session on December 13, 2019, at the San Antonio Breast Cancer Symposium, the most influential gathering of breast cancer researchers and physicians in the world.

    Access the full media kit.

    Study BRE12-158 was funded by the Vera Bradley Foundation for Breast Cancer and the Walther Cancer Foundation. It is part of the Indiana University Precision Health Initiative Grand Challenge. The study was managed by the Hoosier Cancer Research Network and enrolled at 22 clinical sites across the United States.

    Media contact: Christine Drury, cldrury@iu.edu, 317-385-9227

    # # #

    IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.

  • IU cancer researcher earns $1.6 million NCI grant for multiple myeloma bone disease therapies

    IU cancer researcher earns $1.6 million NCI grant for multiple myeloma bone disease therapies

    INDIANAPOLIS – An Indiana University Melvin and Bren Simon Comprehensive Cancer Center researcher has been awarded a five-year, $1.6 million grant from the National Cancer Institute to study ways to build bone and decrease tumor growth in multiple myeloma bone disease.

    Multiple myeloma is a blood cancer that begins in plasma cells within the bone marrow. As the multiple myeloma cells build up, they form tumors and can damage and weaken bones.

    G. David Roodman, MD, PhD, distinguished professor at IU School of Medicine, is leading the research to investigate a molecule developed with collaborators at the University of Pittsburgh that could repair bone, decrease tumors and improve outcomes for multiple myeloma patients on specific targeted therapies.

    “We've been very interested in understanding the mechanisms underlying the horrific bone disease associated with multiple myeloma, which occurs in up to about 85 percent of patients and causes devastating pathologic fractures, bone pain and impacts survival,” Roodman said.

    Previously, Roodman and colleagues had shown the importance of the marrow microenvironment on the growth of the tumor cells in the bone destructive process. They, with collaborators at the University of Pittsburgh, developed a small molecule called XRK3F2 to target that bone disease. Animal models and preclinical tissue models have shown that the molecule could have an important role also in stopping drug resistance in myeloma cells.

    “This grant allows us to look at using a small molecule to show how we can overcome resistance to some of the most potent drugs that are in use for myeloma,” Roodman said. “Many patients develop drug resistance over time, and it becomes very difficult to treat them.”

    Among newer treatments developed for multiple myeloma are targeted therapies called proteasome inhibitors, including the drugs Bortezomib and Carfilzomib. In models developed by Roodman’s research team, the XRK3F2 molecule enhanced the effects of these drugs in preclinical models of multiple myeloma.

    The molecule also caused new bone formation in animal models, which could lead to treatments for healing bone lesions. Currently, there are no safe therapies to build bone mass that are approved for multiple myeloma bone disease.

    Roodman and his team will further explore the XRK3F2 molecule to understand the mechanism responsible for its effects on multiple myeloma cells and its potential for new therapies for the disease.

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    IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.

  • Cancer center researchers identify checkpoint target for colorectal cancer immunotherapy

    Cancer center researchers identify checkpoint target for colorectal cancer immunotherapy

    Researchers at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center have identified a target for colorectal cancer immunotherapy.

    Immunotherapy uses the body’s immune system to target and destroy cancer cells. Considered the future of cancer treatment, immunotherapy is less toxic than chemotherapy. Colorectal cancer is the third most common cancer among men and women, yet chemotherapy remains the standard of care as limited numbers of patients respond to current immunotherapy treatment options.

    The findings published May 7 in JCI Insight could provide additional treatments for a larger number of colorectal cancer patients via a new immunotherapy pathway. Researchers identified ST2 as a novel checkpoint molecule that could help T cells become more effective.

    The research is a collaboration between IU School of Medicine cancer researchers Xiongbin Lu, PhD, Vera Bradley Foundation Professor of Breast Cancer Innovation and of Medical and Molecular Genetics, and Sophie Paczesny, MD, PhD, Nora Letzter Professor of Pediatrics and of Microbiology and Immunology.

    Immune checkpoints are an essential part of the immune system with the role of preventing immune cells from destroying healthy cells. T cells are immune system cells that attack foreign invaders such as infections and can help fight cancer. But cancer is tricky, and often the tumor microenvironment creates ways to prevent T cells from attacking cancer cells by misusing several factors including the activation of checkpoint molecules.

    Within the tumor microenvironment, the body’s immune system knows something is wrong and sends a stress signal such as the alarmin IL-33, which brings in immune cells called macrophages that express ST2 (the receptor for IL-33) to help. What is at first a “good” response is quickly overwhelmed and the macrophages become the enemy in fighting colon cancer.

    The authors investigated using patient tumor genetic data and found that T-cell functionality, one of the key factors in fighting the cancer using the adaptive immune responses, is reduced in patients displaying high ST2 levels. Using tumor tissue samples from IU Simon Comprehensive Cancer Center tissue bank, researchers found abundant expression of ST2 in macrophages in tumor tissue samples from early to late-stage colorectal cancer.

    “In all of the patient samples, we were able to identify ST2 expressing macrophages, which would potentially mean that targeting these ST2 macrophages would be relevant to the patients,” Kevin Van der Jeught, PhD, said. Van der Jeught is a post-doctoral researcher in Lu’s lab and first author of this study.

    In preclinical mouse models, researchers found that by targeting the ST2-expressing macrophages, they were able to slow tumor growth. By depleting these inhibitory cells, the T cells became more active in fighting cancer.

     

    Collaboration connects cancer research interests

    Research collaborator and scientist at the Herman B Wells Center for Pediatric Research, Paczesny’s previous research led to the discovery of ST2 and is the subject of her National Cancer Institute “Cancer Moonshot” grant focusing on immunotherapy for pediatric acute myeloid leukemia (AML). While leukemia and colorectal cancer are very different diseases, researchers have found commonality and collaboration in the ST2 protein.

    “This research is bringing together the pathway in two different diseases,” Paczesny said.

    Lu’s research focuses on cancer cell biology in diseases such as triple negative breast cancer and colorectal cancer.

    “We have to develop new tools and new approaches for solid tumors, and this is the kind of collaboration we need for advancing future treatments,” Lu said. Researchers from two other institutions, the University of Maryland’s Marlene and Stewart Greenebaum Comprehensive Cancer Center and the VIB-UGent Center for Inflammation Research in Belgium, have contributed to this publication.

    Researchers also are exploring combination therapy with existing immunotherapy, such as PD-1 checkpoint inhibitors, which work to boost T cells directly, while attacking ST2 on macrophage cells increased T cells by stopping the inhibitors.

    “Potentially through a combination of two checkpoints at work on different immune cells, we could enhance the current response rates,” Van der Jeught said.

    The researchers plan to explore these findings further and pursue the development of ST2 for cancer immunotherapy.

    Additional authors with Van der Jeught, Paczesny and Lu are IU School of Medicine researchers Yifan Sun; Yuanzhang Fang, PhD; Zhuolong Zhou, PhD; Hua Jiang, PhD; Tao Yu, PhD; Jinfeng Yang, PhD; Malgorzata M Kamocka, PhD; Ka Man So; Yujing Li, PhD; Haniyeh Eyvani; George E Sandusky, DVM, PhD; and Michael Frieden; Xinna Zhang, PhD, and Chi Zhang, PhD, IU Simon Comprehensive Cancer Center; Harald Braun, PhD, and Rudi Beyaert, PhD, Ghent University, Ghent, Belgium; and Xiaoming He, PhD, Greenebaum Comprehensive Cancer Center, University of Maryland.

    This research was supported by IU School of Medicine Strategic Research Initiative fund; NIH R01CA203737 (Lu); and NIH U01CA232491 (Paczesny). A supplemental grant application has been submitted to NCI for funding further studies in hereditary non-polyposis colorectal cancer also called Lynch syndrome.

  • Researchers develop publication with collaborator quarantined in China during COVID-19 outbreak

    Researchers develop publication with collaborator quarantined in China during COVID-19 outbreak

    Putting together research for publication can be a challenging and time-consuming process, heightened even further because of the current COVID-19 situation, during which non-essential labs at Indiana University School of Medicine have been hibernated and many researchers are now working separately and remotely, instead of collaborating within the same space. Despite those obstacles, Jie Zhang, PhD, Jun Cheng PhD, and Kun Huang, PhD, had their research published in Nature Communications on April 14, which is an even more significant feat considering one of their leading authors has been quarantined in Wuhan, China for the last two months of their work.

    The study that brought about this opportunity for publication was led by Zhang, who is an assistant professor of medical and molecular genetics. It focuses on the application of machine learning and image analysis to help researchers distinguish a rare subtype of kidney cancer (translocational renal cell carcinoma, or tRCC) from other subtypes by examining the features of cells and tissues on a microscopic level. Zhang said the structural similarities have caused a high rate of misdiagnosis. Within this publication, the researchers studied 74 tRCC samples, which constitutes the largest tRCC collection in the world.

    “The phenotype of this tRCC looks very much like clear cell renal cell carcinoma, or ccRCC, the most common type of renal cell carcinoma, so it’s kind of difficult for pathologists to distinguish between the two,” said Zhang. “To improve that, we tried to use the machine-learning technique, feeding in the digitized pathological image data to the analysis pipeline to train the computer to extract the features related to tRCC. This will help pathologists confirm the case, instead of just relying on their eyes.”

    Jun Cheng, PhDThe first author of this paper, Jun Cheng, PhD, started working with Zhang and Huang back in 2016, while he was a visiting PhD student from China. Cheng visited for the first time when Zhang and Huang were researchers at Ohio State University, before they joined IU School of Medicine, and has also visited them since they transitioned to their current roles. Cheng is currently an assistant professor at Shenzhen University and had traveled to his hometown of Wuhan for winter vacation.

    “I was planning to stay at home for 10 days,” said Cheng. “Three days later, the whole city of Wuhan was in lockdown (due to concerns of COVID-19) and the lockdown lasted for over two months.”

    The city of Wuhan became the epicenter of the pandemic, with more than 50,000 confirmed cases of COVID-19 among the population of 11 million people. As he was working to revise their publication, Cheng could not return to his lab at Shenzhen University, since teachers and students who left for vacation weren’t allowed to go back due to the pandemic. He only had a laptop at his home, but needed a high-performance computer to conduct data analyses.

    “Fortunately, one student in my lab didn't go home and stayed in school during winter vacation,” said Cheng. “She helped boot the computer in my lab and then I did all the experiments on it remotely.”

    Cheng also needed to repeat some of the analysis for the revision, which required a transfer of previously downloaded public data to China from Huang’s lab in Indiana, and it took a week to complete the data transfer.

    “It was quite stressful to revise the publication during the quarantine, but finally we made it,” said Cheng.

    Huang described this publication as a true team science effort, involving both internal and international collaborations, both of which he said are essential. Liang Cheng, MD, Virgil Moon Professor of Pathology from IU School of Medicine and one of the corresponding authors in this paper, was able to collect additional tRCC and ccRCC samples within two weeks from a collaborator in Michigan for the additional analysis, which itself was an amazing accomplishment.

    “In many cases, we collaborate internationally because there is a huge innovation base that can help with our research,” said Huang, who is also the Director of Data Sciences and Informatics for the IU Precision Health Initiative. “Even in difficult times, as long as we have enough resources and means of communication, we can still carry out collaborative research.”

    While cancer has traditionally been characterized by the location of the disease, this research focuses on renal cancer based on the genetic markers instead. This study was supported in part by the IU Precision Health Initiative.

    The city of Wuhan was reopened last week.

  • IU cancer researcher identifies new areas in human genomes linked to skin cancer risk

    IU cancer researcher identifies new areas in human genomes linked to skin cancer risk

    INDIANAPOLIS — An Indiana University cancer researcher has identified eight new genomic regions that increase a person’s risk for skin cancer.

    Jiali Han, Ph.D., and colleagues discovered eight new loci—locations on a person’s genome—that are susceptible to the development of squamous cell skin cancer. Han is the Rachel Cecile Efroymson Professor in Cancer Research at IU School of Medicine, professor and chair of the Department of Epidemiology at the IU Richard M. Fairbanks School of Public Health at IUPUI, and a researcher at the Indiana University Melvin and Bren Simon Cancer Center.

    Researchers previously identified 14 loci with increased risk for squamous cell skin cancer. This study confirmed those findings while adding eight new genomic locations, bringing the total identified risk loci to 22. Their research is published this month online in Nature Communications.

    “This is the largest genetic-associated study for squamous cell carcinoma of the skin,” Han, an epidemiologist, said. “Our multidisciplinary research sheds light on new biology and the etiology of squamous cell carcinoma, confirming some important genes and also identifying genes involved in this particular cancer development.”

    Han and colleagues analyzed six international cohorts totaling approximately 20,000 squamous cell skin cancer cases and 680,000 controls, or people who haven’t had squamous cell skin cancer. More than one-third of the genomic data came from genetic testing company 23andMe research participants. Additional datasets came from the Nurse’s Health Study, Health Professionals Follow-up Study, the Icelandic Cancer Registry and the Ohio State University Division of Human Genetics sample bank.

    Research findings confirmed that pigmentation genes can also be a person’s skin cancer susceptibility gene, but they also identified additional molecular pathways.

    “We can certainly say there is some genetic overlap between squamous cell carcinoma, basal cell carcinoma and melanoma—the three major types of skin cancer—but we also found some genes are specific for squamous cell carcinoma,” Han said.

    Squamous cell and basal cell are also known as non-melanoma skin cancers. Both usually respond to treatment and rarely spread to other parts of the body, according to the National Cancer Institute. Melanoma is more aggressive, however, and can spread to other parts of the body if it’s not diagnosed early.

    Physical genomic traits such as fair skin, freckles, blue eyes and brown hair were associated with the risk loci. Researchers have long known that fair skin and sun exposure are risk factors for squamous cell skin cancer.

    “Avoiding sun exposure is always the primary prevention strategy, regardless of your skin pigmentation,” Han said.

    Han and collaborators are continuing to build the population sample to identify more risk loci. Even with the 22 genomic regions identified, the study found those explain only 8.5 percent of the heritable risk for squamous cell skin cancer.

    Kativa Sarin, M.D., Stanford University School of Medicine, is the co-lead author. Additional authors of the study are Yuan Lin and Wenting Wu, Fairbanks School of Public Health; Roxana Daneshjou, Adam Rubin, Paul Khavari and Alice Whitemore, Stanford University; Andrey Ziyatdinov and Peter Kraft, Harvard T.H. Chan School of Public Health; Gudmar Thorleifsson and Simon N. Stacey, deCODE genetics/Amgen Inc., Reykjavik, Iceland; Luba M. Pardo, Tamar Nijsten, Andre Uitterlinden, Erasmus University Medical Center, Rotterdam, The Netherlands; Amanda E. Toland, Ohio State University Comprehensive Cancer Center; Jon H. Olafsson, Bardur Sigurgeirsson and Kristin Thorisdottir, Landspitali-University Hospital and University of Iceland, Reykjavik, Iceland; Eric Jorgensen, Kaiser Permanente Northern California; Kari Stefansson, University of Iceland; and Maryam M. Asgari, Massachusetts General Hospital.

    The study was supported in part by grants from the National Human Genome Research Institute of the National Institutes of Health (grant number R44HG006981), the National Cancer Institute (R01 CA49449, P01 CA87969, UM1 CA186107, UM1 CA167552, R03 CA219779, K23 CA211793) and Indianapolis-based Walther Cancer Foundation.

  • IU Simon Cancer Center researchers receive $3 million in NIH grants to investigate cell functions within bone marrow

    IU Simon Cancer Center researchers receive $3 million in NIH grants to investigate cell functions within bone marrow

    INDIANAPOLIS — More than $3 million from the National Institutes of Health will allow Indiana University Melvin and Bren Simon Cancer Center researchers to improve understanding of the complex system of how hematopoietic stem cells (HSC) survive and sustain their function in the bone marrow.

    Edward F. Srour, Ph.D., the Robert J. and Annie S. Rohn Professor of Leukemia Research, and Melissa A. Kacena, Ph.D., professor of orthopaedic surgery, are building on a decade of research collaboration on how bone cells help HSC function. Both Srour and Kacena are Indiana University School of Medicine faculty.

    HSC, which produce red and white blood cells, reside in the bone marrow in the core of bones. The complex system of multiple cell types that are responsible for maintaining those stem cells is called the hematopoietic niche.

    “Years ago, we discovered that a molecule named CD166 is important for the maintenance of stem cells because it is also expressed on immature osteoblasts, the bone-forming cells that are an important component of the hematopoietic niche,” Srour said. Both young osteoblasts and stem cells interact together through CD166 to maintain stem cell function.

    Researchers know that the CD166 molecule is critical because stem cells lose activity without it, but for which cells is it most important and which don’t need it?


    Video extra: Why a single molecule called CD166 could unlock new cancer therapies


    With a $1.7 million grant from the National Institutes of Health, Srour and colleagues will delete CD166 from different cell types found in the hematopoietic niche to figure out where the molecule is essential and where it is not.

    “Molecules and their receptors are basically like a key and a lock; you have a key on one cell and a lock on another cell,” Srour said. “With CD166, it is both the key and the lock—it binds to itself. We have to find who carries the most important lock and what does the turning of the key in that lock do to activate the cell.”

    Separating look-alike cells

    IU Simon Cancer Center researchers are also investigating another cell type formed in the hematopoietic niche called osteomacs, which are a specialized bone-resident macrophage. Macrophages are vital to the immune system with the job of engulfing and destroying foreign pathogens and sometimes cancer cells.

    While macrophages reside in every tissue in the body, their jobs differ a little depending on location. Working inside the bones are specialized macrophages called osteomacs.

    “We found that osteomacs play an important role in sustaining the stem cell function within the niche of the bone marrow,” Srour said. “The major struggle we have with these cells is they look like and function like bone marrow macrophages, so there is no easy way for us to separate one from the other.”

    With a five-year, $1.5 million grant, Srour and colleagues aim to identify a molecule that allows them to separate osteomacs from macrophages.

    In the search to find a distinguishing marker, researchers found that osteomacs—unlike other macrophages—express CD166. The molecule is vital to osteomacs, too; osteomacs that don’t have it lose their function. Now Srour wants to know why and form a better understanding of osteomacs’ role within the complex bone marrow environment.

    Srour and IU researchers also have found that CD166 also is expressed on a rare population of myeloma cells that can initiate and make myeloma more aggressive. Multiple myeloma is a blood cancer of plasma cells within the bone marrow. Understanding the role of different cells in sustaining myeloma and identifying how to block CD166 in important cells of the cancer may provide pathways to stopping or slowing some cancers.

    “We believe these are the cancer-initiating or so-called cancer stem cells,” Srour said.

    Beyond myeloma, CD166 is present in many metastatic cancers, including breast cancer and pancreatic cancer. “The overexpression of that molecule is associated with the ability of cancer cells to metastasize (to spread),” Srour said.

     

  • IU School of Medicine hosting “Us vs. HPV” webinars for HPV Prevention Week

    IU School of Medicine hosting “Us vs. HPV” webinars for HPV Prevention Week

    The Indiana University School of Medicine National Center of Excellence in Women’s Health is getting ready for a week of raising awareness about human papilloma virus (HPV).

    “We have to protect our community,” said Theresa Rohr-Kirchgraber, MD, FACP, FAMWA, executive director of the National Center of Excellence. “We have to protect our children, and we need to make our Hoosiers healthier, happier and lead productive lives.”

    Each year, more than 12,000 women are diagnosed with cervical cancer, which is caused by HPV. About 90 percent of those cases could be prevented with the Gardasil HPV vaccine, which was partially developed by IU School of Medicine researchers in the 1990s. HPV can also lead to some head and neck cancers, anal cancer and anal warts in both men and women.

    HPV Prevention Week is a global initiative against HPV and the cancers HPV causes. A week of webinars, called “Us vs. HPV,” are scheduled every day from January 27-31. The webinars are hosted by the American Medical Women’s Association (AMWA), Global Initiative Against HPV and Cervical Cancer (GIAHC) and IU School of Medicine National Center of Excellence. Topics include community initiatives and challenges, medical societies’ efforts against HPV, gathering momentum for the global elimination of cervical cancer, HPV-associated head and neck cancers and how HPV affects us all.

    Rohr-Kirchgraber is one of the moderators for this year’s event, which is free and open to anyone to watch and listen online.

    “We want you all to listen and learn, and we invite you to send in questions and share your thoughts and ideas,” Rohr-Kirchgraber said. “We will also have testimony from patients who have been through some of these cancers so that they can share with you directly the impact of having to deal with these types of cancers and diseases.”

    Other speakers include international physicians and scientists actively researching ways to prevent and treat HPV and HPV-related cancers. To learn more about the agenda and to register for the webinars, visit the event registration webpage.