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Turning on the ‘off switch’ in cancer cells
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From
The Daily: A team of scientists led by the
Case Comprehensive Cancer Center (
Case CCC) and the
University of Michigan Rogel Cancer Center has identified the binding site where drug compounds could activate a key braking mechanism against the runaway growth of many types of cancer.
Derek Taylor, PhD, associate professor of pharmacology and biochemistry at Case Western Reserve University and member of the Case CCC is co-senior author on the study.
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Close-up view of the binding pocket where the lead SMAP (small-molecule activation of PP2A) interacts with its PP2A phosphatase target. The drug fits like a key in a lock to stabilize interactions between individual PP2A subunits (shown in red, blue, and orange).
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The discovery marks a critical step toward developing a potential new class of anti-cancer drugs that enhance the activity of a prevalent family of tumor suppressor proteins, the authors say.
The findings, which appear in the leading life sciences journal
Cell, are less a story of
what than
how.
Scientists have known for a while that certain molecules were capable of increasing the activity of the tumor suppressor protein PP2A, killing cancer cells and shrinking tumors in cell lines and animal models—but without information about the physical site where the molecules interact with the protein, trying to optimize their properties to turn them into actual drugs would require endless trial and error.
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Myeloid-derived suppressor cell heterogeneity comprises a sex-specific therapeutic target for glioblastoma
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A study led by
Justin D. Lathia, PhD
(
Bayik et al., Cancer Discovery, 2020
) and conducted in collaboration with multiple Case Comprehensive Cancer Center member investigators (
Ahmad M. Khalil, PhD; Tae Hyun Hwang, PhD; Manmeet S. Ahluwalia, MD and Feixiong Cheng, PhD
) identified sex differences in anti-tumor immune response, which served as the basis for a new therapeutic strategy against glioblastoma (GBM). While previous epidemiological research has shown that males are predisposed to GBM, the most common primary malignant brain tumor; the new findings uncover sexual dimorphism in immune-suppressing myeloid cell subset, prevalence and localization as a contributor of disease pathology. These immunological differences further informed the use of drug candidates for personalized immunotherapy accounting for patient sex. These studies are part of a larger Case Comprehensive Cancer initiative on sex differences in GBM co-led by
Drs. Lathia and Jill Barnholtz-Sloan
.
The study, supported by an active NIH R01 awarded to Dr. Lathia, F32 and the Case Comprehensive Center T32 Cancer Biology Training Grant to the first author,
Defne Bayik, PhD
, reported that monocytic myeloid-derived suppressor cells (mMDSCs) accumulated at higher rates in male tumors in preclinical models, an observation confirmed in patients with GBM. The researchers determined that mMDSCs are actively proliferating and tested the chemotherapeutic fludarabine, a treatment strategy turned out to be only effective in males. mMDSCs along with the related granulocytic myeloid-derived suppressor cell subset (gMDSCs) are known to suppress immune response across many cancers, though their distinct function had not been explored in GBM. The team observed that gMDSCs were increased in the systemic circulation of female mice with tumors. Analysis of re-purposable drug candidates in collaboration with
Feixiong Cheng, PhD
, based on the distinct expression profile of gMDSCs and subsequent validation in preclinical models identified IL-1β as an effective immunotherapeutic strategy in females. High gMDSC and IL-1β signatures correlated with poor prognosis of female patients with GBM, supporting the clinical relevance of these observations.
“These findings highlight the importance of considering sex as a biological variable for development of effective immunotherapeutic strategies against GBM as well as other cancers. We look forward to translating findings of this study through clinical trials with the goal of improving patient outcome.” said
Lathia
, Co- Leader of the
Molecular Oncology Program
at the Case Comprehensive Cancer Center, co-director of the Cleveland Clinic Center for Excellence in Brain Tumor Research and Therapeutic Development, and Leader of the Brain Tumor Initiative.
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Keri elected to Endocrine Society Board
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The Case Comprehensive Cancer Center (Case CCC) extends congratulations to
Ruth Keri, PhD, professor of pharmacology and Case CCC Associate Director for Basic Research on her
recent election to the Board of Directors for the Endocrine Society.
Dr. Keri will serve a three-year term for the society which has more than 18,000 members, including basic, translational and clinical investigators, as well as educators, nurses, and students in 122 countries. The Endocrine Society is the world’s oldest and largest organization that focuses on hormones and hormone action, including the impact of hormones on cancer risk, treatment, and survival.
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Khorana appointed as Medical & Scientific Advisory Board Chair for the National Blood Clot Alliance
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Please join us in extending congratulations to
Alok Khorana, MD, professor of medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University on his
recent appointment to Chair of the Medical and Scientific Advisory Board of the National Blood Clot Alliance (NBAC).
Dr. Khorana is a widely recognized expert in venous thromboembolism (VTE) and cancer and a member of the Case Comprehensive Cancer Center's
Developmental Therapeutics Program.
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CanSUR scholar receives undergraduate Michelson Morley Award
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The Case CCC extends congratulations to undergraduate
Jack Kincaid on receiving first prize in the 2020
Michelson-Morley Research Competition in the Biological Sciences. Jack works in the lab of member
Nate Berger, MD, sponsored by the NCI R25 Training Grant-sponsored
CanSUR Program organized by
Mark Jackson, PhD.
Jack's presentation was NAD in aging and cancer, a topic Berger has been studying since he was a faculty member at Washington University in St. Louis, Jack's hometown, and continued at Case Western Reserve University since his arrival in 1983.
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Team Case CCC "rides" on into Virtual VeloSano 2020!
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Originally scheduled for July 17-19, 2020 in Cleveland, OH, VeloSano 7 is evolving into
Virtual Velosano
to keep our community safe and healthy during the COVID-19 pandemic. While we won't be able to unite in person this summer, we will continue fundraising as the need for cancer research is more important than ever.
Our continuing goal is to bring sustainable funding to cancer research by enlisting the passion and energy of thousands of people who wish to give back... including
YOU! We raised nearly $94,000 in 2019 and every dollar goes directly toward cancer research. In our six years of participation, more than $1,000,000 of VeloSano fundraising totals have come back to the Case CCC to award researchers as
pilot funding for cancer research projects.
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Case CCC COVID-19 Resource Hub
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As the COVID-19 outbreak progresses, the Case Comprehensive Cancer Center (Case CCC) has centralized COVID-19 related news and resources for our cancer center community. Content is updated regularly.
To have a cancer-focused resource added to the page, please email
cancer@case.edu.
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Mon, May 4
Tumor Immunology and Immunotherapy
Jordan Winter, MD
"Intersection of Metabolism and Immunology in Pancreatic Cancer"
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Weds, May 6
Cancer Microbiome Focus Group
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Fri, May 8
Cancer Center Seminar Series
Rafick-Pierre Sékaly, PhD
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Mon, May 11
Shared Resource Directors Meeting
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Tues, May 12
Cancer Center Special Seminar
Xiaoli Sun, PhD
12p Zoom
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Cancer Center Seminar Series
TODAY, May 1, 12p
Today's Cancer Center Seminar features
Satish Viswanath, PhD presenting "Computational Imaging for AI-enabled Interventions in Oncology" at noon.
Dr. Viswanath is an assistant professor of biomedical engineering at the Case School of Engineering, an assistant professor of Radiology at the Case Western Reserve University School of Medicine and a member of the Case CCC's Cancer Imaging Program.
The research in the Viswanath lab focuses on developing novel radiomics and machine learning tools for disease characterization, intervention planning and treatment evaluation. Specific problems addressed via the new quantitative imaging markers they have developed include: (a) predicting response to treatment to identify optimal therapeutic pathways, as well as (b) evaluating therapeutic response to guide follow-up procedures. His lab will further examine how to account for differences between sites, scanners and acquisition parameters on the performance of AI tools and radiomic features; crucial for wider clinical translation. These will be discussed in the context of clinical applications in colorectal, renal and prostate cancers.
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Cancer Center Seminar Series
May 8, 12p
Next week's cancer center seminar, our final of the 2019-2020 academic year, features
Rafick-Pierre Sékaly, PhD
at noon via Zoom.
Dr. Rafick-Pierre Sekaly is the Richard J. Fasenmyer Professor of Immunopathogenesis, Co-Director of the Center of Systems Immunology (CSI), and Co-director of the Center for AIDS Research (CFAR) Proteomics and Systems Biology Core at Case Western Reserve University.
His focus on HIV disease immune pathogenesis, immune virology, and immunotherapies has generated pioneering findings that highlight the impact of HIV infection on thymic output, T cell memory, mechanisms of CD4 and CD8 T cell dysfunction, and on innate immunity and mechanisms of HIV persistence. He has also pioneered the use of transcriptomics and bioinformatics to identify predictors/correlates of immune responses that lead to protection from viral infections, including HIV, SIV and flaviviruses, protection from disease progression and successful immune interventions including adjuvants, licensed preventative and therapeutic vaccines.
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Clinical Research Retreat
May 20, 5-7 pm
Zoom
The Case Comprehensive Cancer Center invites members, clinicians and research staff to join us for our first virtual Clinical Research Retreat on Wednesday, May 20, 2020 from 5-7 pm. Two keynote speakers will be addressing exciting topics in clinical research. The retreat agenda is below.
5:00 – Welcome Address
Special Topic: Effectively Communicating Informed Consent in Disparate Population
5:15 – "We've gone over a lot of things today - can you tell me in your own words what your options are?" - Writing and Speaking for Understanding
Speaker:
Lydia Furman, MD, Chair, University Hospitals Institutional Review Board
5:50 – Discussion and Questions
Special Topic: Translational Research Cycle, Bedside to Bench to Bedside
6:00 – "From the concepts to the bed-side: steps to follow"
6:35 – Discussion and Questions
6:45 – Closing Remarks
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Virtual Race for The Place 2020
May 29 - June 7, 2020
Facebook and Instagram Live
The Gathering Place is hosting its annual "Race for the Place" 5K and 1-mile run/walk virtually from Friday May 29 to National Cancer Survivors Day, Sunday, June 7. Proceeds from Race for the Place help support their
free programs and services.
For the safety of participants and the community and in light of the ongoing concerns around COVID-19, The Gathering Place has made the decision to hold a virtual Race for the Place.
They have compiled virtual race ideas and will host their Cancer Survivor Ceremony at 9:00 am Sunday, June 7 on
Facebook and
Instagram Live.
Race for the Place is a particularly important event for The Gathering Place. It is their
only annual fundraiser and provides significant financial support to keep their programs and services
free of charge to help individuals and families cope with the impact of cancer in their lives. COVID-19 has not stopped the needs of our participants and they continue to provide free programs every day through GoToMeeting, Zoom, the telephone and Facebook Live.
The Gathering Place is a caring community that supports, educates and empowers individuals and families currently coping with the impact of cancer in their lives through programs and services provided
free of charge.
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Save The Date: Artificial Intelligence in Oncology Symposium 2020
October 19-20, 2020
Tinkham Veale University Center, CWRU
The second annual Artificial Intelligence in Oncology Symposium will bring together experts in AI and machine learning this October at Case Western Reserve University.
Geraldine McGinty, MD, MBA, FACR will present the symposium keynote, "Fostering a Strong Ecosystem for AI in Medical Imaging." Dr. McGinty is an internationally recognized expert in imaging economics, Chair of the American College of Radiology Board of Chancellors and Chief Strategy and Contracting Officer at Weill Cornell Medicine in New York City.
Beyond the science, attendees will be able to network, explore potential new partnerships and visit exhibitors throughout the day.
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Save The Date: Annual Scientific Retreat (Members and Trainees Only)
July 23-24, 2020
The Case Comprehensive Cancer Center invites all
members and trainees to mark their calendars for Thursday, July 23 and Friday, July 24, 2020 for our
annual scientific retreat!
We hope to once again host TED talks from prominent Cleveland researchers and advocates late Thursday afternoon at Tinkham Veale University Center accompanied by poster presentations from students, postdocs, and fellows, and continue the retreat on Friday at Corporate College East. As in past years, Friday's agenda features an update from Director Stan Gerson and highlights research from across each of our scientific programs.
We are also looking forward to a keynote presentation from
Timothy Rebbeck, PhD, the Vincent L. Gregory, Jr. Professor of Cancer Prevention at the Harvard T.H. Chan School of Public Health and the Dana-Farber Cancer Institute. Dr. Rebbeck is founding director of the Zhu Family Center for Global Cancer Prevention at the Harvard TH Chan School of Public Health and leads the Cancer Outreach and Engagement activities for the Dana-Farber Harvard Cancer Center.
Mindful that we must do everything we can to keep our cancer center community safe and healthy, we are also planning an alternate abridged virtual agenda should we not be able to gather in-person in July. Please save the dates at this time, and we will provide additional details of the retreat's format and agenda in the weeks to come.
Please contact Mary Wright (
maw143@case.edu) should you have any questions about the retreat.
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Additional Upcoming Events
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Translational Cancer Research for Basic Scientists Workshop
November 8-13, 2020
Hilton Boston Back Bay, Boston, MA
The American Association for Cancer Research invites applications to attend the Translational Cancer Research for Basic Scientists Workshop.
This week-long workshop will provide basic scientists with a better understanding of translational research and strategies for adapting their research for maximum clinical impact. Committed to building and training a diverse cancer research workforce, the AACR encourages applications from those who are underrepresented in the field.
Deadline to apply is May 7, 2020.
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AACR Virtual Annual Meeting: Part II
June 22-24, 2020
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The AACR Virtual Annual Meeting II, June 22-24, will feature the originally planned Opening Plenary Session that explores the range of impactful cancer research and clinical translation; award lectures from individuals who have made extraordinary contributions to the cancer field; a special talk from National Cancer Institute Director Ned Sharpless, MD; and thousands of proffered papers in minisymposia and on an e-poster platform.
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Internal LOI deadline: Sunday, June 21, 2020
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The Case Comprehensive Cancer Center has been invited to submit applications from junior faculty for the Gabrielle's Angel Foundation 2020 Medical Research Awards. Gabrielle’s Angel Foundation funds cutting-edge research in the fields of leukemia, lymphoma, and related cancers of the blood.
The awards provide $75,000 of support per year over three years, not to exceed $225,000. Applications in conventional and integrative research are being accepted.
Interested candidates are asked to submit an LOI (including PI contact information and an abstract/project summary) and biosketch to
casecccpilots@case.edu
by Sunday, June 21, 2020. Contact casecccpilots@case.edu with questions.
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Available award: $40,000
EXTENDED Full Application Deadline: May 4, 2020
Proposals accepted on a rolling basis subject to fund availability
Available award: $50,000
Deadline: May 8, 2020
Available award: $50,000
Deadline: May 8, 2020
Available award: $75,000
Deadline: May 18, 2020
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The Daily - April 23, 2020
A medical device based on technology developed by three faculty members from Case Western Reserve University and University Hospitals Cleveland Medical Center (UH) has won a prestigious 2020 Edison Best New Product Award.
Amitabh Chak, MD, MS,
Sanford Markowitz, MD, PhD, and
Joseph Willis, PhD are all members of the
Case Comprehensive Cancer Center.
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Radiology Business - April 27, 2020
“Our role may be for helping healthcare professionals deal with the triage situation in a more informed way because these are gut-wrenching decisions about who is going to get the most help against an aggressive disease,” said
Anant Madabhushi, PhD, a professor of biomedical engineering and head of the Center for Computational Imaging and Personalized Diagnostics at Case Western Reserve University.
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Weekly NIH Funding Opportunities and Notices
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Notices
Funding Opportunities
Standard dates apply. The first standard due date for this FOA is October 05, 2020.
Standard dates apply. The first standard due date for this FOA is October 05, 2020.
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Use the button below to submit all your news, events, announcements and communications requests to the Case CCC Marketing and Communications team!
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