Emory Researcher Studying Pediatric Osteosarcoma Awarded Grant
Jason T. Yustein, MD, PhD, Professor at the Winship Cancer Institute of Emory University and the Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, has been awarded research funds from MIB Agents, a pediatric osteosarcoma nonprofit dedicated to supporting patients, caregivers, doctors, and researchers. Established in 2017, this grant is awarded to a project focused on moving research forward for osteosarcoma patients.
"We presented this grant to Dr. Yustein to support his great work in researching new treatments for osteosarcoma," said Ann Graham, Founder and Executive Director of MIB Agents. "Sadly, it has been over 40 years since a new treatment has come to market, but through programs like OutSmarting Osteosarcoma, we aim to give patients and their families hope for better treatment options."
MIB Agents OutSmarting Osteosarcoma grants are supported by MIB Agents Family Funds, a group comprised of osteosarcoma patients and families who raise funds in honor of an OsteoWarrior, a patient currently battling osteosarcoma or an OsteoAngel, a loved one who has passed. Collaboration among the scientific and patient community is a key hallmark of MIB Agents that makes the OutSmarting Osteosarcoma grant process unique. Not only does the patient community partner to fund this grant every year, but they have an active voice in the grant review process.
Carolyn R. Bertozzi, PhD, Receives 2023 AACR Award for Outstanding Achievement in Chemistry in Cancer Research
Nobel Laureate Carolyn R. Bertozzi, PhD, will be honored with the 2023 AACR Award for Outstanding Achievement in Chemistry in Cancer Research during the 2023 AACR Annual Meeting. She is the Anne T. and Robert M. Bass Professor of Chemistry in the School of Humanities and Sciences and Professor (by courtesy) of Chemical and Systems Biology and of Radiology at Stanford University, an investigator with the Howard Hughes Medical Institute, and the Baker Family Director of Sarafan ChEM-H. Bertozzi is being recognized for advancing basic and translational cancer research through bioorthogonal chemistry and chemical glycobiology.
The AACR Award for Outstanding Achievement in Chemistry in Cancer Research was established by the AACR and its Chemistry in Cancer Research Working Group in 2007 to recognize the importance of chemistry to advancements in cancer research. The award recognizes outstanding, novel, and significant chemistry research that has led to important contributions in basic cancer research; translational cancer research; cancer diagnosis; the prevention of cancer; or the treatment of patients with cancer. Such research may include, but is not limited to, chemical aspects of carcinogenesis; chemical biology; drug discovery and design; imaging agents and radiotherapeutics; metabolomics and mass spectrometry; proteomics; and structural biology.
Bertozzi is credited with inventing the field of bioorthogonal chemistry, which has enabled the development of numerous experimental approaches in biological research, including innovative imaging methods, chemoproteomics, and in vivo drug targeting. Historically, chemical reaction conditions have been difficult to control in living cells.
To overcome this challenge, Bertozzi hypothesized that chemical reactions could be specifically designed to occur in living organisms by carefully selecting reaction partners instead of attempting to manipulate reaction conditions. Her early research was focused on combining metabolic labeling with bioorthogonal chemistry, demonstrating that this approach allowed for targeted interrogations of biological systems. This fundamental advancement sparked a revolution in the manipulation and understanding of biological systems. However, this method often resulted in off-target reactions in cellular environments with ketone and aldehyde groups. In turn, Bertozzi developed a modified technique that avoided such issues. Now known as copper-free click chemistry, this technology is widely used by researchers worldwide for drug discovery and therapeutic development efforts.
Further advancements by Bertozzi to biorthogonal chemistry approaches have enabled large-scale production of highly stable antibody-drug conjugates, a class of therapeutics being utilized for the treatment of cancer. Advancements in this technology have led to the clinical testing of TRPH-222, a CD22-targeting antibody-drug conjugate for relapsed and refractory B-cell lymphoma. Bertozzi's inventions have also led to the establishment of site-specific protein modification technologies, which are now used for the clinical development of antibody-drug conjugates and the preclinical development of antibody-enzyme conjugates for cancer immunotherapy.
In addition to her click chemistry work, Bertozzi discovered that tumor-associated glycans promote immunosuppression by engaging Siglec receptors on immune cells. She has been heralded for engineering antibody-sialidase conjugates, which represent a new class of therapeutically relevant molecules for the selective cleaving of immunosuppressive glycans from tumor cell surfaces. Since Siglec receptors are found on multiple types of immune cells, this strategy has the unique potential to unleash stronger antitumor immune responses than first-generation immunotherapies. Underscoring the translational impacts of this work, an antibody-sialidase conjugate is currently being evaluated in Phase I clinical trials.
In addition to receiving the 2022 Nobel Prize in Chemistry, Bertozzi has been honored with numerous awards throughout her brilliant career, including the Welch Award in Chemistry, the University of Pittsburgh Dickson Prize in Medicine, the Dr. H.P. Heineken Prize for Biochemistry and Biophysics, the Wolf Prize in Chemistry, the American Association for the Advancement of Science Lifetime Mentor Award, the Wistar Institute Helen Dean King Award, and the STAT News STATUS List in recent years.
Bertozzi is an elected member of the National Academy of Inventors, National Academy of Medicine, National Academy of Sciences, and American Academy of Arts and Sciences. In 2002, she was elected as a Fellow of the American Association for the Advancement of Science.
AACR Names New Editor-in-Chief of Cancer Research Journal
The American Association for Cancer Research (AACR) announced the appointment of Christine A. Iacobuzio-Donahue, MD, PhD, as the Editor-in-Chief of Cancer Research, one of the 10 highly esteemed peer-reviewed journals published by the AACR.
"The AACR is delighted to welcome Dr. Iacobuzio-Donahue as editor-in-chief of Cancer Research," said Margaret Foti, PhD, MD (hc), Chief Executive Officer of the AACR. "Her extensive publishing record, along with her innovative scholarship and scientific expertise spanning many areas of basic and translational research, make her particularly well-suited for this important position. Under her exceptional leadership, Cancer Research will continue to attract high-quality manuscripts that move the field forward."
Iacobuzio-Donahue is currently Director of the David M. Rubenstein Center for Pancreatic Cancer Research and an attending pathologist at Memorial Sloan Kettering Cancer Center, where she is also an affiliate member of the Human Oncology & Pathogenesis Program. Her research interests include understanding the role of somatic DNA mutations in tumorigenesis, metastasis, and treatment resistance, with a strong focus on pancreatic cancer.
Utilizing both primary and metastatic tumor samples in combination with next-generation sequencing, Iacobuzio-Donahue has discovered distinct patterns of metastatic failure in pancreatic cancer and the relationship of these patterns of failure to the genetics of the primary carcinoma. Her novel research also has identified the origin of distant metastases from subclonal populations that preexist within the primary tumor and has provided insights into the timing of distant metastasis formation using computational models.
"I am extremely honored to serve as the next editor-in-chief of Cancer Research, a journal that is central to the history of the AACR and its mission to advance the cancer research literature," Iacobuzio-Donahue stated. "In this position, I foresee the tremendous opportunity to redefine the role of Cancer Research as a hub for the publication of the most impactful science in the field."
An AACR member since 1995, Iacobuzio-Donahue has served as Chair of the AACR Laboratory Research Awards Committee (2022-2023); Co-Chair of the AACR Annual Meeting Program Committee (2020-2021); Chair of the AACR-Bayer Research Grants Scientific Review Committee (2019-2020); and Chair (2016-2017) and member (2012-2014) of the Pancreatic Cancer Action Network-AACR Pathway to Leadership Grants Scientific Review Committee. She is a member of the AACR Women in Cancer Research constituency group and received the AACR Team Science Award in 2013.
Iacobuzio-Donahue received her undergraduate degree from Adelphi University and her graduate degrees from Boston University School of Medicine. She completed her residency and fellowship at Johns Hopkins University School of Medicine, where she was then a member of the faculty until joining Memorial Sloan Kettering Cancer Center in 2014. Iacobuzio-Donahue was elected to the American Society of Clinical Investigators in 2015 and the Pluto Society of the American Association of University Pathologists in 2017.
Research Grant Awarded to Improve Survival Rates in Esophageal Cancer
R. Taylor Ripley, MD, Associate Professor at the Michael E. DeBakey Department of Surgery at Baylor College of Medicine, has been awarded funding from The DeGregorio Family Foundation and the Esophageal Cancer Awareness Association. Ripley, along with Yuan Xu, MD, PhD , an instructor at Baylor College of Medicine, will evaluate whether the generation of patient-derived explants, in which a tumor is directly removed during surgery and grown in the lab for 3 days, will provide a model to test novel therapeutics. The ultimate goal is to rapidly determine the best approach for treating each individual patient with esophageal cancer.
Resistance to apoptosis is a well-established hallmark of cancer, yet Ripley noted a critical gap in knowledge of biological processes that enable resistance to cancer therapy in esophageal adenocarcinoma. He and his team have reported that esophageal tumors resisted cancer cell death through an anti-apoptotic protein that is part of the mitochondria-small structures in a cell that make most of the energy. The protein is called Myeloid Leukemia Cell-1v (McI-1). When they targeted McI-1 with drugs called BH3 mimetics, apoptosis increased five-fold when combined with chemotherapy.
Their central hypothesis is that treatment resistance is mediated by the mitochondria and BH3 profiling acts as live-cell measurement to predict which mitochondrial proteins to target. In this phase of the research, they will establish a patient-derived explant model to test whether targeting Mcl-1 in esophageal adenocarcinoma provides a therapeutic window by affecting the tumor to a greater extent than normal tissue.
Beth Karlan, MD, Named Inaugural Holder of Nancy Marks Endowed Chair
Beth Karlan, MD, Professor of Obstetrics and Gynecology and Vice Chair of Women's Health Research at UCLA has become the inaugural holder of the Nancy Marks Endowed Chair in Women's Health Research.
"Beth Karlan is the ideal physician-researcher to lead new investigations and mentor others for this vital work," Nancy Marks said. "Beth continues to treat and prevent cancer in families that may have otherwise been ravaged by genetic cancers. Her compassion and creativity make her uniquely suited for this work."
Nancy Marks has long been an advocate for preventive medicine, especially while serving on the boards of NewYork-Presbyterian Hospital and its integrative health center. She is a trustee of the Lynne Cohen Foundation, which provides support and care for women with ovarian cancer and breast cancer, and a member of the board of the Melanoma Research Alliance, among other nonprofits.
The need for increased emphasis on women's health is clear. As recently as the second half of the 20th century, women were largely overlooked in medical research. Scientists generally considered women to be smaller versions of men and failed to take into account gender differences in biology and disease-even the study of biology in animals utilized all-male cohorts. As late as the 1970s, few women worked in medical research and the study of gender-based conditions was a low priority.
The early 1990s saw major steps forward with the passage of the National Institutes of Health Revitalization Act of 1993, which set requirements for including women and minorities as subjects in clinical research, and the NIH's formalization of a rule in 1994 that the government would not fund clinical studies that did not include these groups. But since then, researchers have had to make up a lot of ground to reach parity in terms of the inclusion of women in medical research and drug development.
Karlan is recognized as one of the nation's foremost authorities on ovarian cancer. She earned her medical degree at Harvard Medical School before completing her residency at Yale New Haven Hospital. She then completed a fellowship in gynecologic oncology at UCLA before joining the faculty; shortly thereafter, she also joined Cedars-Sinai Medical Center, where she served as Director of Gynecologic Oncology. Karlan has earned international accolades for her efforts to improve the detection, treatment and prevention of ovarian cancer and other gynecologic malignancies.
"Dr. Karlan is a pioneer in the use of cancer genetics to inform treatment decisions, improve survival and quality of life, and empower families with elevated genetic risk factors to take informed action," said Steven Dubinett, MD, interim Dean of the Geffen School of Medicine. "She led the creation of a tumor biorepository for gynecologic cancers, which continues to prove critical to advancing our understanding of hereditary cancers."
The endowment will enable Karlan to allocate funds to support promising research studies and the investigators leading them, mentor OB-GYN fellows, and continue her own cancer research. In her current investigations, she is working on making cascade genetic testing for families with elevated cancer risk the standard of care, as well as other avenues to prevent and treat cancer.
"I cannot thank Nancy and Howard enough for their generosity and vision," Karlan said. "Nancy has long been a champion of the work we do, providing cutting-edge and compassionate care to women with cancer while striving to find new ways to treat and prevent the disease. I am humbled to hold the chair that carries her name as I seek to foster new talent and expand the reach of research that will improve the well-being of more and more women-and men-everywhere."
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