Ten DCI Faculty Awarded Distinguished Professorships
Updated
Duke University has awarded Distinguished Professorships to 44 faculty members from seven Duke colleges and schools this year — including 27 from the School of Medicine. Ten of these faculty are members of Duke Cancer Institute. The honorees were formally recognized by President Vincent Price and Interim Provost Jennifer Francis during a ceremony at the Washington Duke Inn on May 4.
Distinguished Professorships recognize faculty scholars who are well-established members of the Duke academic community and who have achieved distinction as creative scholars in their field or in their ability to transcend disciplines. For School of Medicine awardees, this means faculty who "have demonstrated extraordinary scholarship in advancing science and improving human health."
At the ceremony, Price noted the broad influence the awardees have had through their scholarship, by “shaping our understanding of the world, and advancing opportunities, solutions, and inventions to improve the human condition.”
Peter Allen, MD, PhD, David C. Sabiston, Jr. Distinguished Professor of Surgery
Peter Allen, MD, is a professor of surgery. An accomplished surgeon who specializes in treating disorders of the pancreas, liver, bile ducts, stomach, and adrenal glands, he serves as chief of the Division of Surgical Oncology. Allen is known for his multidisciplinary approach to research and patient care, particularly for those with complex issues involving cancer. In addition to his patient care and research accomplishments, he is a superb medical educator and mentor. His reputation as a leader in his field — serving as an author, editorial board member and visiting lecturer — has elevated the Duke surgical oncology program.
Michel Bagnat, PhD, Nanaline Duke Distinguished Professor in the School of Medicine
Michael Bagnat, PhD, is a professor of cell biology. He is a highly productive scientist who creatively combines tools and approaches from the fields of cell biology, developmental biology, physiology, genetics, biophysics, and computational modeling. His research has provided insight into the molecular physiology of fundamental processes in the gut and other organ systems. His studies of intestinal development and physiology have laid the groundwork for identifying modifiers of intestinal inflammation, and potential drivers of human inflammatory bowel disease. He has an exceptional reputation as a mentor and teacher.
Daniel George, MD, Eleanor Easley Distinguished Professor in the School of Medicine
Daniel George, MD, is a professor of medicine and a professor in surgery. Since 2003 he has led the genitourinary section of the Duke Division of Medical Oncology, and he leads Duke’s participation in the Department of Defense Prostate Cancer Clinical Trials Consortium. His research leading and collaborating on clinical trials of tyrosine kinase inhibitors, anti-androgen therapy, chemotherapy, and immunotherapy has led to advances in the treatment of patients with kidney cancer and prostate cancer. He is vice dean of diversity and equity in the Division of Medical Oncology, and he conducts clinical trials aimed at understanding and addressing the disproportionately poor outcome of Black men with prostate cancer.
Gerald Grant, MD, Allan H. Friedman Distinguished Professor of Neurosurgery
Gerald Grant, MD, is a professor and chair of the Department of Neurosurgery and a professor in neurobiology. He is an internationally recognized pediatric neurosurgeon and surgeon-scientist who focuses on two critical areas: the biological function of the blood-brain barrier (BBB) and mechanisms involved in recovery from brain injury. He studies the unique features of the BBB surrounding brain tumors at the molecular and functional level. His research focuses on innovative ways to open the BBB to improve the delivery of novel drugs and immunotherapy to target brain tumors.
Matthias Gromeier, MD, Cless Family Distinguished Professor in Neuro-Oncology
Matthias Gromeier, MD, is a professor of neurosurgery. He has dedicated his career to unraveling RNA virus/host relations and devising methods of exploiting them for cancer immunotherapy and vaccine design. He has applied his discoveries to design an attenuated poliovirus to activate the immune system to target glioblastoma and other cancers. In addition, his lab has conducted mechanistic studies showing how the attenuated poliovirus stimulates presentation of tumor antigens and antigen-presenting cells.
Susan Halabi, PhD, James B. Duke Distinguished Professor in the School of Medicine
Susan Halabi, PhD, is a professor of biostatistics and bioinformatics and co-chief of the Division of Biostatistics in the Department of Biostatistics & Bioinformatics. She has been at the forefront of designing and analyzing clinical trials in oncology for over 25 years. She is focused on developing innovative variable selection methods for biomarkers and high dimensional data. Among her key contributions are building and validating prognostic models of outcomes for prostate cancer and identifying surrogate endpoints for overall survival. A past-president of the Society for Clinical Trials and the 2022 recipient of the Janet L. Norward Award, Dr. Halabi is a Fellow of the Society for Clinical Trials, the American Statistical Association, and the American Society for Clinical Oncology.
Seok-Yong Lee, PhD, George Barth Geller Distinguished Professor of Molecular Biology
Seok-Yong Lee, PhD, is a professor in biochemistry and cell biology. As a membrane structural biologist, he has developed advanced tools in X-ray crystallography, electron microscopy, cryogenic electron microscopy (cryo-EM), and electrophysiology and has applied these tools to solve challenging questions about membrane and protein structural biology. He has become a world leader in this field and has made major advancements in three different classes of membrane protein: active transporters, ion channels, and enzymes. He has provided a better understanding of the cold and menthol sensor in mammals and a pain sensor for noxious chemicals. His work has also led to structural drug designs that can improve pharmacological properties.
Steven Patierno, PhD, Charles D. Watts Distinguished Professor of Medicine
Steven Patierno, PhD, is a professor of medicine and pharmacology and cancer biology. He is also a professor in family medicine and community health and deputy director of Duke Cancer Institute. Patierno is a renowned cancer researcher with training in molecular oncology and pharmacology and expertise in lung, breast, and prostate cancer. His work to develop innovative interventions for mitigating health disparities in the cancer patient population is well-recognized locally and nationally. His funding track record includes multiple R01 grants as principal investigator and co-principal investigator. Patierno’s numerous awards and honors include the AACR Distinguished Science of Cancer Disparities Research Award and the Duke University Health System Diversity and Inclusion Award.
John Rawls, PhD, James B. Duke Distinguished Professor of Molecular Genetics and Microbiology
John Rawls, PhD, is a professor of molecular genetics and microbiology and cell biology. He also is a professor in medicine. Rawls studies the influence of the gut microbiome on vertebrate host physiology and is a world leader in using the tractable zebrafish model for such studies. He has used both zebrafish and mouse systems to yield insights about host-microbe interactions relevant to development, homeostasis, metabolism, and disease. The work impacts many areas, including gut motility, fat absorption, effects of diet, visceral adipose tissue, obesity, gut immune responses, diabetes, and neural development.
Beth Sullivan, PhD, James B. Duke Distinguished Professor of Molecular Genetics and Microbiology
Beth Sullivan, PhD, is a professor of molecular genetics and microbiology, professor of cell biology, and associate dean of research training. She studies epigenetic and genetic mechanisms of centromeres, specialized chromosomal sites involved in chromosome architecture and movement, kinetochore function, heterochromatin assembly, and sister chromatid cohesion. Dysregulation of chromosomal segregation underlies many human genetic disorders. Among Sullivan’s major accomplishments have been to define the functions and roles of telomeres. She has made important discoveries regarding the functions of centromeres, mechanisms of chromosomal segregation, and has contributed to the final full sequence of the human genome.
Daniel George, MD, Duke Cancer Institute professor and director of DCI’s Genitourinary Cancer program, has been named a Fellow of the American Society of Clinical Oncology (FASCO), ASCO announced last week in a press release introducing the 2021 FASCO class and presenting other special awards. Thomas Leblanc, MD, MA, MHS, FAAHPM, DCI clinical hematologic malignancies specialist and palliative care physician, was also named a Fellow of ASCO (READ).The FASCO distinction recognizes ASCO members for their extraordinary volunteer service, dedication, and commitment to ASCO.George, who co-leads the DCI Center for Prostate and Urologic Cancers and the Patierno/George/Freedman Lab for Cancer Research, is an internationally recognized clinical oncologist, researcher and thought leader in genitourinary malignancies — specializing in kidney cancer and prostate cancer. His areas of research include improved treatment modalities, the development of new drugs, and the identification of biomarkers in GU cancers with an emphasis on the biological drivers of cancer disparities. He’s the author of more than 200 peer-reviewed publications, including several reviews and position papers on GU cancer disparities.George is a tenured professor (since 2015) in the Department of Medicine, Division of Medical Oncology, with a secondary appointment in the Department of Surgery, Division of Urology, at the Duke University School of Medicine. He received both his BS (1988) and his MD (1992) at Duke and did his residency and fellowship at Johns Hopkins Hospital. George joined the DCI faculty in 2003 from Harvard University Medical School's Dana-Farber Cancer Institute, where he was an assistant professor in the Department of Medicine.George has been a member of ASCO since 2003. His roles with ASCO have included serving on the Scientific Committee for the Genitourinary Cancer Symposium for three years; serving twice on the ASCO Scientific Program Committee (two three-year terms); serving one three-year term as leader of the Scientific Program Committee GU (Non-prostate) Cancer Track; and serving two three-year terms on the Conquer Cancer Foundation grants review committee, including one as chair. He has also, as a volunteer, led GU fellows on poster walks and has volunteered at mentorship luncheons.Most recently (since 2019), George has been serving as a member of the ASCO Research Priorities Decision Group.In addition to ASCO, George has served in a leadership or membership capacity in various other cancer-focused national committees and organizations, including serving on the NCI (National Cancer Institute) Renal Task Force (2012) and the NCI Genitourinary Cancers Steering Committee (2014).George is currently the scientific leader for kidney cancer in the Alliance Cooperative Group (since 2011) and serves on Alliance’s GU scientific committee. He’s been a member of the Advisory Board of the Kidney Cancer Association since 2005, a member of the Scientific Oversight Committee of the Prostate Cancer Clinical Consortium since 2007, a member of the Society for Immunotherapy of Cancer Program RCC Cancer Immunotherapy Guideline Committee (SITC RCC CIG) since 2018, and a member of the American Association for Cancer Research (AACR) Cancer Health Disparities Research Scientific Review Committee since 2019.In addition, he currently serves as senior editor for AACR’s journal, Clinical Cancer Research, and as co-editor in chief of Clinical Advances in Hematology and Oncology.
Research led by Duke Cancer Institute’s Jen-Tsan Ashley Chi, MD, PhD could have implications for the successful treatment of certain types of ovarian, breast and kidney cancerThe American Association for Cancer Research (AACR) has named Jen-Tsan Ashley Chi, MD, PhD, as co-winner of the Molecular Cancer Research Michael B. Kastan Award for Research Excellence on behalf of his all-Duke research team for their paper — A TAZ-ANGPTL4-NOX2 Axis Regulates Ferroptotic Cell Death and Chemoresistance in Epithelial Ovarian Cancer. Chi is co-director of the Cancer Biology Research Program at Duke Cancer Institute and directs his own lab within the Duke Center for Genomic and Computational Biology that's focused on the adaptation and response of cancer cells to various stresses in the tumor micro-environment. He's an associate professor in the Department of Molecular Genetics and Microbiology, an associate professor in the Department of Pharmacology & Cancer Biology, an assistant professor in the Department of Medicine, and an assistant professor in the Department of Radiation Oncology.The Michael B. Kastan Award for Research Excellence is formally bestowed on the first or corresponding author of an article in Molecular Cancer Research (the flagship AACR journal for fundamental cancer research discoveries) that's had a significant impact on the fields represented by the journal, but all co-authors are named as recipients of the award in recognition of the importance of team science. The MCR editor-in-chief and two additional editors for the journal select the award recipient (s) — prioritizing those articles that “have the potential to shift paradigms, inspire translational activity, and raise awareness of new scientific areas” and which are “representative of the journal in terms of originality/ novelty, scientific/clinical merit, and/or impact/significance."Chi’s co-authors on the winning paper, which was published in the January 2020 issue of MCR, include: Wen-Hsuan Yang, PhD (first author of the paper, then a PhD student in the Chi Lab; Zhiqing Huang, MD, PhD (assistant professor in Obstetrics and Gynecology and a DCI member); Jianli Wu, BS (lab research analyst 1 in the Chi Lab); Chien-Kuang C. Ding, MD, PhD (with Duke at time of publication; now a pathology resident with the University of California, San Francisco); and Susan K. Murphy, PhD (associate professor in Obstetrics and Gynecology and a DCI member).Given yearly since 2019, the award was established by AACR in 2018 in honor of Michael B. Kastan, MD, PhD, the journal's founding editor-in-chief (in 2002). (Kastan, who has served as executive director of Duke Cancer Institute since 2011, plays no role in the selection process.)AACR created the award in recognition of Kastan’s “vision and dedication to publishing exceptional scientific findings” that facilitated the field’s understanding of factors that influence cancer development and progression at the molecular level.“It has been humbling that the AACR has honored me in this way for my efforts with this journal over the years," said Kastan, an experienced investigator recognized for his discoveries in molecular biology, signal transduction and DNA damage and repair, "but I have to admit that having the award go to a DCI member this year is truly special. Dr. Chi is an exceptional scientist and I am so proud to have him as a colleague.”“I feel very honored to receive this prestigious award named for Dr. Kastan and I appreciate the excellent work of my lab members, especially first author Wen-Hsuan Yang and Susan Murphy,” said Chi.A Novel ApproachOvarian cancer is the deadliest gynecologic cancer. Despite recent advances in targeted and chemotherapy treatments, ovarian cancer cells like other cancer cells eventually develop a resistance to these treatments. Clinical outcomes remain poor, necessitating novel therapeutic approaches.Chi and his team have found, through nutrient drop-out screening/testing of 15 amino acids on a panel of nine clear cell and serous ovarian cancer cells, that most ovarian cancer cells need and are addicted to cystine — an amino acid (protein building block) that’s found in most high-protein foods, including chicken, turkey, yogurt, cheese, eggs, sunflower seeds and legumes.Depriving ovarian cancer cells of cystine, they discovered, leads to ferroptosis — a form of iron-dependent regulated cell death. Cystine deprivation starts this process of necrosis by generating a pore in the cell membrane that allows water to enter the cell, resulting in its death.Conventional chemotherapy, meanwhile, triggers a different form of cell death called apoptosis. Because these two methods use different mechanisms to kill cancer cells, cystine deprivation may be able to kill tumors that have proven resistant to some chemotherapy treatments.“Ovarian cancer cells have a special need for outside nutrients that may allow us to pre-emptively reduce or eradicate the recurrent disease. Just as we require food (sugars or proteins) and oxygen to live, our cells also rely on outside nutrients they must obtain from their environment for their survival,” Chi explained. “Compared to normal cells, cancer cells often have increased and different demands for nutrients from the surrounding environment, including the extracellular amino acid cystine, for survival. The removal of cystine rapidly triggers a special kind of cell death called “ferroptosis” that even resistant cells are still sensitive to. Most amino acids, when you take them out, the cancer cells just stop growing, but they can still live. Cystine they just can’t deal without, and they die very extensively.”In addition, the research team found that the cell density makes a difference as to how sensitive the tumor cells are to cystine deprivation. While tumor cells grown far apart were very sensitive to cystine-deprived death, the same tumors became much less sensitive when grown crowded together. This discovery led them to the conclusion that a cell density sensor, TAZ, actually promotes the ferroptosis of the ovarian cancer cell lines. Since TAZ is an important protein regulating tumor growth and metastasis, their results suggest that ferroptosis may be particularly effective in TAZ-activated tumors.This research — reported out in the team's award-winning MCR paper — was partially funded, noted Chi, by a previous DCI pilot grant award to him and Murphy. The work will be further supported by a U.S. Department of Defense Ovarian Cancer Research Program grant to determine the therapeutic potential of using ferroptosis to fight chemotherapy-resistant ovarian cancer tumors. The team will attempt to remove cystine in mice (from those with ovarian cancer and also from those with renal cancer) using a novel form of recombinant cyst(e)inase — a human-engineered enzyme that acts on TAZ-activated tumors to trigger this ferroptosis.Recombinant cyst(e)inase is currently being developed by a drug company for clinical trials in various other (non-cancer) diseases.“We believe that triggering ferroptosis in cancer cells may overcome resistance to chemotherapy in ovarian and other TAZ-activated cancers as novel treatments,” said Chi, who’s spent the past 10 or 11 years investigating and publishing on the nutrient addictions of cancer cells in breast, ovarian and kidney cancers. “We have also found cystine addiction in triple-negative breast cancer cells and in renal (kidney) cancer cells that have lost the VHL tumor suppressor genes.”Chi added that treatment with cyst(e)inase could be further enhanced by adding immunotherapy or radiation to the treatment mix."Dr. Chi is an exceptionally creative scientist," said Steven Patierno, PhD, an internationally recognized expert in cancer control, cancer causation and molecular carcinogenesis who serves as deputy director of DCI. "He and his team are at the forefront of a rapidly evolving and critical aspect of translational cancer biology, at the intersection between tumor cell addiction to specific micronutrients and activation of novel pathways of cell death that may further sensitize tumor cells to targeted therapies. The pathways that this team are teasing out are themselves highly druggable and may be targets for future precision oncology approaches. Dr. Chi is highly deserving of this extraordinary award."Chi’s research team shares the 2021 Michael B. Kastan Award for Research Excellence with a research team led by David Maag, PhD, senior scientific director of AbbVie, Inc. in North Chicago, Illinois, for their paper — PARP1 Trapping by PARP Inhibitors Drives Cytotoxicity in Both Cancer Cells and Healthy Bone Marrow — published in the February 2019 issue of Molecular Cancer Research.The awardees and their winning papers are being highlighted this week at the 2021 (virtual) AACR Annual Meeting — April 10 to 15. (Week two will be held from May 17 to 21). The award is accompanied by a $500 cash prize and a certificate to each of the team leaders.Previous winners of the Michael B. Kastan Award for Research Excellence include Mohamed E. Salem with Levine Cancer Institute (2020) and Kenjiro Sawada with Osaka University Graduate School of Medicine, Suita, in Japan (2019).
Daniel George, MD, Duke Cancer Institute professor and director of DCI’s Genitourinary Cancer program, has been named a Fellow of the American Society of Clinical Oncology (FASCO), ASCO announced last week in a press release introducing the 2021 FASCO class and presenting other special awards. Thomas Leblanc, MD, MA, MHS, FAAHPM, DCI clinical hematologic malignancies specialist and palliative care physician, was also named a Fellow of ASCO (READ).The FASCO distinction recognizes ASCO members for their extraordinary volunteer service, dedication, and commitment to ASCO.George, who co-leads the DCI Center for Prostate and Urologic Cancers and the Patierno/George/Freedman Lab for Cancer Research, is an internationally recognized clinical oncologist, researcher and thought leader in genitourinary malignancies — specializing in kidney cancer and prostate cancer. His areas of research include improved treatment modalities, the development of new drugs, and the identification of biomarkers in GU cancers with an emphasis on the biological drivers of cancer disparities. He’s the author of more than 200 peer-reviewed publications, including several reviews and position papers on GU cancer disparities.George is a tenured professor (since 2015) in the Department of Medicine, Division of Medical Oncology, with a secondary appointment in the Department of Surgery, Division of Urology, at the Duke University School of Medicine. He received both his BS (1988) and his MD (1992) at Duke and did his residency and fellowship at Johns Hopkins Hospital. George joined the DCI faculty in 2003 from Harvard University Medical School's Dana-Farber Cancer Institute, where he was an assistant professor in the Department of Medicine.George has been a member of ASCO since 2003. His roles with ASCO have included serving on the Scientific Committee for the Genitourinary Cancer Symposium for three years; serving twice on the ASCO Scientific Program Committee (two three-year terms); serving one three-year term as leader of the Scientific Program Committee GU (Non-prostate) Cancer Track; and serving two three-year terms on the Conquer Cancer Foundation grants review committee, including one as chair. He has also, as a volunteer, led GU fellows on poster walks and has volunteered at mentorship luncheons.Most recently (since 2019), George has been serving as a member of the ASCO Research Priorities Decision Group.In addition to ASCO, George has served in a leadership or membership capacity in various other cancer-focused national committees and organizations, including serving on the NCI (National Cancer Institute) Renal Task Force (2012) and the NCI Genitourinary Cancers Steering Committee (2014).George is currently the scientific leader for kidney cancer in the Alliance Cooperative Group (since 2011) and serves on Alliance’s GU scientific committee. He’s been a member of the Advisory Board of the Kidney Cancer Association since 2005, a member of the Scientific Oversight Committee of the Prostate Cancer Clinical Consortium since 2007, a member of the Society for Immunotherapy of Cancer Program RCC Cancer Immunotherapy Guideline Committee (SITC RCC CIG) since 2018, and a member of the American Association for Cancer Research (AACR) Cancer Health Disparities Research Scientific Review Committee since 2019.In addition, he currently serves as senior editor for AACR’s journal, Clinical Cancer Research, and as co-editor in chief of Clinical Advances in Hematology and Oncology.
Research led by Duke Cancer Institute’s Jen-Tsan Ashley Chi, MD, PhD could have implications for the successful treatment of certain types of ovarian, breast and kidney cancerThe American Association for Cancer Research (AACR) has named Jen-Tsan Ashley Chi, MD, PhD, as co-winner of the Molecular Cancer Research Michael B. Kastan Award for Research Excellence on behalf of his all-Duke research team for their paper — A TAZ-ANGPTL4-NOX2 Axis Regulates Ferroptotic Cell Death and Chemoresistance in Epithelial Ovarian Cancer. Chi is co-director of the Cancer Biology Research Program at Duke Cancer Institute and directs his own lab within the Duke Center for Genomic and Computational Biology that's focused on the adaptation and response of cancer cells to various stresses in the tumor micro-environment. He's an associate professor in the Department of Molecular Genetics and Microbiology, an associate professor in the Department of Pharmacology & Cancer Biology, an assistant professor in the Department of Medicine, and an assistant professor in the Department of Radiation Oncology.The Michael B. Kastan Award for Research Excellence is formally bestowed on the first or corresponding author of an article in Molecular Cancer Research (the flagship AACR journal for fundamental cancer research discoveries) that's had a significant impact on the fields represented by the journal, but all co-authors are named as recipients of the award in recognition of the importance of team science. The MCR editor-in-chief and two additional editors for the journal select the award recipient (s) — prioritizing those articles that “have the potential to shift paradigms, inspire translational activity, and raise awareness of new scientific areas” and which are “representative of the journal in terms of originality/ novelty, scientific/clinical merit, and/or impact/significance."Chi’s co-authors on the winning paper, which was published in the January 2020 issue of MCR, include: Wen-Hsuan Yang, PhD (first author of the paper, then a PhD student in the Chi Lab; Zhiqing Huang, MD, PhD (assistant professor in Obstetrics and Gynecology and a DCI member); Jianli Wu, BS (lab research analyst 1 in the Chi Lab); Chien-Kuang C. Ding, MD, PhD (with Duke at time of publication; now a pathology resident with the University of California, San Francisco); and Susan K. Murphy, PhD (associate professor in Obstetrics and Gynecology and a DCI member).Given yearly since 2019, the award was established by AACR in 2018 in honor of Michael B. Kastan, MD, PhD, the journal's founding editor-in-chief (in 2002). (Kastan, who has served as executive director of Duke Cancer Institute since 2011, plays no role in the selection process.)AACR created the award in recognition of Kastan’s “vision and dedication to publishing exceptional scientific findings” that facilitated the field’s understanding of factors that influence cancer development and progression at the molecular level.“It has been humbling that the AACR has honored me in this way for my efforts with this journal over the years," said Kastan, an experienced investigator recognized for his discoveries in molecular biology, signal transduction and DNA damage and repair, "but I have to admit that having the award go to a DCI member this year is truly special. Dr. Chi is an exceptional scientist and I am so proud to have him as a colleague.”“I feel very honored to receive this prestigious award named for Dr. Kastan and I appreciate the excellent work of my lab members, especially first author Wen-Hsuan Yang and Susan Murphy,” said Chi.A Novel ApproachOvarian cancer is the deadliest gynecologic cancer. Despite recent advances in targeted and chemotherapy treatments, ovarian cancer cells like other cancer cells eventually develop a resistance to these treatments. Clinical outcomes remain poor, necessitating novel therapeutic approaches.Chi and his team have found, through nutrient drop-out screening/testing of 15 amino acids on a panel of nine clear cell and serous ovarian cancer cells, that most ovarian cancer cells need and are addicted to cystine — an amino acid (protein building block) that’s found in most high-protein foods, including chicken, turkey, yogurt, cheese, eggs, sunflower seeds and legumes.Depriving ovarian cancer cells of cystine, they discovered, leads to ferroptosis — a form of iron-dependent regulated cell death. Cystine deprivation starts this process of necrosis by generating a pore in the cell membrane that allows water to enter the cell, resulting in its death.Conventional chemotherapy, meanwhile, triggers a different form of cell death called apoptosis. Because these two methods use different mechanisms to kill cancer cells, cystine deprivation may be able to kill tumors that have proven resistant to some chemotherapy treatments.“Ovarian cancer cells have a special need for outside nutrients that may allow us to pre-emptively reduce or eradicate the recurrent disease. Just as we require food (sugars or proteins) and oxygen to live, our cells also rely on outside nutrients they must obtain from their environment for their survival,” Chi explained. “Compared to normal cells, cancer cells often have increased and different demands for nutrients from the surrounding environment, including the extracellular amino acid cystine, for survival. The removal of cystine rapidly triggers a special kind of cell death called “ferroptosis” that even resistant cells are still sensitive to. Most amino acids, when you take them out, the cancer cells just stop growing, but they can still live. Cystine they just can’t deal without, and they die very extensively.”In addition, the research team found that the cell density makes a difference as to how sensitive the tumor cells are to cystine deprivation. While tumor cells grown far apart were very sensitive to cystine-deprived death, the same tumors became much less sensitive when grown crowded together. This discovery led them to the conclusion that a cell density sensor, TAZ, actually promotes the ferroptosis of the ovarian cancer cell lines. Since TAZ is an important protein regulating tumor growth and metastasis, their results suggest that ferroptosis may be particularly effective in TAZ-activated tumors.This research — reported out in the team's award-winning MCR paper — was partially funded, noted Chi, by a previous DCI pilot grant award to him and Murphy. The work will be further supported by a U.S. Department of Defense Ovarian Cancer Research Program grant to determine the therapeutic potential of using ferroptosis to fight chemotherapy-resistant ovarian cancer tumors. The team will attempt to remove cystine in mice (from those with ovarian cancer and also from those with renal cancer) using a novel form of recombinant cyst(e)inase — a human-engineered enzyme that acts on TAZ-activated tumors to trigger this ferroptosis.Recombinant cyst(e)inase is currently being developed by a drug company for clinical trials in various other (non-cancer) diseases.“We believe that triggering ferroptosis in cancer cells may overcome resistance to chemotherapy in ovarian and other TAZ-activated cancers as novel treatments,” said Chi, who’s spent the past 10 or 11 years investigating and publishing on the nutrient addictions of cancer cells in breast, ovarian and kidney cancers. “We have also found cystine addiction in triple-negative breast cancer cells and in renal (kidney) cancer cells that have lost the VHL tumor suppressor genes.”Chi added that treatment with cyst(e)inase could be further enhanced by adding immunotherapy or radiation to the treatment mix."Dr. Chi is an exceptionally creative scientist," said Steven Patierno, PhD, an internationally recognized expert in cancer control, cancer causation and molecular carcinogenesis who serves as deputy director of DCI. "He and his team are at the forefront of a rapidly evolving and critical aspect of translational cancer biology, at the intersection between tumor cell addiction to specific micronutrients and activation of novel pathways of cell death that may further sensitize tumor cells to targeted therapies. The pathways that this team are teasing out are themselves highly druggable and may be targets for future precision oncology approaches. Dr. Chi is highly deserving of this extraordinary award."Chi’s research team shares the 2021 Michael B. Kastan Award for Research Excellence with a research team led by David Maag, PhD, senior scientific director of AbbVie, Inc. in North Chicago, Illinois, for their paper — PARP1 Trapping by PARP Inhibitors Drives Cytotoxicity in Both Cancer Cells and Healthy Bone Marrow — published in the February 2019 issue of Molecular Cancer Research.The awardees and their winning papers are being highlighted this week at the 2021 (virtual) AACR Annual Meeting — April 10 to 15. (Week two will be held from May 17 to 21). The award is accompanied by a $500 cash prize and a certificate to each of the team leaders.Previous winners of the Michael B. Kastan Award for Research Excellence include Mohamed E. Salem with Levine Cancer Institute (2020) and Kenjiro Sawada with Osaka University Graduate School of Medicine, Suita, in Japan (2019).
