The Rein in Sarcoma Board of Directors reviewed the progress and impact of the organization during 2019 and approved several key items, and elected new board members and officers during the Annual meeting on January 27, 2020. Treasurer, Tom McCarthy, reported that the organization had significant growth in donor support and has maintained excellent financial health. Rein in Sarcoma is able to expand the impact of its three pronged mission of education, patient and family support, and funding sarcoma cancer research after a very successful year of donor support. More details to come soon with the 2019 Annual Report.
The Board approved $150,000 in new Sarcoma research grants at the University of Minnesota Masonic Cancer Center. The approved 2020 budget also includes funding RIS Sarcoma Scholars at both at the University of Minnesota and Mayo Medical Schools, and a significant increase in education program spending, involving the Hallie Anne Brown Educational initiative (Natural Language Programming), expanded presentations to medical professionals, and a full-time Education Programs and Communications Manager position.
The Board thanked Debra Cossette, Dr. Larry Seymour and Allan Swartz as retiring board members. Our Nominating Committee presented three excellent candidates for board membership who were elected during the meeting.
Elected board officers:
President: Blake Hastings
Vice-President: Eric Lien
Secretary: Mitch Atherton
Treasurer: Tom McCarthy
Newly elected board members:
Linda Andrean retired from the University of Minnesota after 30 years as a department administrator, mostly in the academic Health Center. In 1995, she was hired as the manager of the Cancer Protocol Review Committee as the Center was seeking the NCI Comprehensive Cancer Center designation.
Hearing about Rein in Sarcoma, she stopped by the 2019 Winter Gathering to find out more about the organization. In talking with members, she decided it would be an organization she would be interested in pursuing. The Education Committee was of particular interest and she has been volunteering with the committee and is now a co-chair.
Brendan Dillon is a Vice President of Global Inventory Management for Target Corporation and previously held various leadership positions at Target. Brendan is motivated to leverage his professional experience to help expand Rein in Sarcoma's impact for sarcoma cancer patients, after seeing his neighbor Blake Hastings and family deal with Blake's sarcoma cancer diagnosis and treatment.
Michelle Kolling is returning to serve on Rein in Sarcoma's board. After a career as a commercial real estate broker, she recently completed training to be an end of life doula. Michelle, who lost her husband Brett Dale to sarcoma cancer in 2011, has volunteered not only as a RIS board member, but as past Red Flags Education Committee Co-Chair, and as a member of the original strategic planning committee. Most recently, Michelle has focused her RIS volunteer time on patient and family support.
As rare disease patient advocacy group, community members of Rein in Sarcoma are invited to participate in Rare Disease Day at the University of Minnesota. The Center for Orphan Drug Research (CODR) within the college of Pharmacy is hosting the event.
Rare Disease Day takes place on the last day of February each year. This is an opportunity to raise awareness with the general public, public policy makers, industry representatives, researchers, health professionals, and all who have a genuine interest in rare diseases. Let’s attend together. RSVP for this free event. by February 14.
We will host a Rein in Sarcoma information table – let us know if you can volunteer to advocate for sarcoma education, patient and family support and sarcoma research funding. Please call the RIS office with any questions or to volunteer: 763-205-1467.
9:00-10:30 | Patient Advocacy Group Breakfast & Networking Session
10:30-12:00 | Poster Symposium
12:00-2:30 | Formal Program
Rein in Sarcoma proudly announces a $150,000 research grant approved by the Rein in Sarcoma Board on January 27, 2020. This brings the cummulative research funding by Rein in Sarcoma to $2 million since the organization’s founding in 2001. All proposals were reviewed though a central electronic review system and had three external reviewers for each proposal following NIH scoring procedures. Based on their review and the UMN Faculty recommendations, the RIS Research Task Force brought forward three proposals for RIS Board approval. This grant will fund the following three exciting University of Minnesota Masonic Cancer Center projects:
eBAT as a Modulator of the Myeloid Immune Checkpoint in Cancer
Jaime Modiano, VMD, PhD – Principle Investigator, Jong Kim, VMD, PhD – Co-Investigator | $50,000
eBAT (EGF bispecific angiotoxin) is a drug with excellent safety profile that has shown efficacy against sarcomas in vitro, in small laboratory animal models, and in dogs with spontaneous vascular sarcomas. Our goal is to determine eBAT’s mechanisms of action to rationally expand its use to treat human sarcomas where it will provide comparable benefits and address a critical unmet need. The hypothesis is that eBAT eliminates immunosuppressive myeloid cells in the tumor environment, promoting enhanced anti-tumor immunity. We will test the hypothesis through one aim, to determine the effect of immunosuppressive myeloid cell depletion or persistence in the therapeutic efficacy of eBAT against sarcomas. The experimental model will consist of syngeneic mouse fibrosarcoma, where we have deleted the urokinase receptor (uPAR) using genome editing, uPAR-knockout mice, and a novel methodology to generate bone marrow chimeras in newborn mice which will promote full donor chimerism of myeloid cells, lymphoid cells and tissue macrophages. eBAT, and its mouse specific homolog, meBAT, will be tested in this model to examine their ability to induce tumor responses and immune infiltration in animals with wild type and uPAR-deficient tumors implanted in wild type mice and in chimeric mice with uPAR-knockout myeloid cells and macrophages. We predict that eBAT will have modest effects to reduce tumor growth in this model, due the low affinity binding to mouse UPAR. On the other hand, we expect meBAT will reduce growth of uPAR+ tumors in all recipients, but will only reduce growth of uPAR-KO tumors in mice with uPAR+ bone marrow. We anticipate tumor reduction will be associated with fewer myeloid-derived suppressor cells and macrophages in the tumors, as well as increased numbers of infiltrating T cells and NK cells. This experiment will allow us to define appropriate conditions for subsequent experiments to study the immune response in greater depth and to test the effect of eBAT in combination with drugs that block the PD-1/PD-L1 T-cell exhaustion checkpoint.
Using Propranolol to Generate an Anti-Tumor Microenvironment
Erin Dickerson, PhD – Principle Investigator, Kaylee Schwertfeger, PhD – C0-Investigator | $50,000
Macrophages can be programmed within the tumor microenvironment toward anti-tumor or pro-tumor responses. Tumor cells can promote the pro-tumor functions of macrophages by scavenging cholesterol from the membranes of macrophages. In contrast, cholesterol accumulation in macrophages promotes an anti-tumor phenotype. We recently found that propranolol, a drug commonly used to treat heart disease, disrupts the ability of tumor cells to scavenge extracellular substrates such as cholesterol. Based these findings and our preliminary data, we propose that propranolol inhibits tumor cells from scavenging cholesterol from tumor associated macrophages, programming macrophages toward an anti-tumor phenotype and harnessing their ability to promote adaptive, anti-tumor immune responses. Studies are proposed to determine if propranolol prevents sarcoma cells from scavenging cholesterol from macrophages, and whether propranolol promotes a shift toward an anti-tumor microenvironment. Using a combination of in vitroand in vivoapproaches, these studies will provide novel information regarding the ability of propranolol to remodel the tumor microenvironment, resulting in decreased immune suppression and enhanced anti-tumor responses. Successful completion of the proposed work investigating the positive impact of propranolol on reprogramming of the tumor microenvironment will accelerate our progress in the identification of synergistic drug combinations and the inclusion of tumor immunotherapies.
Computationally Deciphering the Paths of Genomic Catastrophe in Osteosarcoma
Ruping Sun, PhD – Principle Investigator, Lauren Mills, PhD – Co-Investigator | $50,000
Osteosarcoma is characterized by massive genomic catastrophes. Timing and relative ordering between the genomic catastrophic constraints should allow both earlier diagnosis and better prediction of tumor progression. However, such evolutionary trajectories remain elusive due to the lack of advanced computational methods that robustly deduce the paths of somatic changes from next-generation sequencing (NGS) data. Drawing on the full spectrum of somatic alterations detectable from NGS data, we seek to fill a lacuna in knowledge on cancer evolution through innovating reconstructive computational algorithms to decipher the time ordering of genomic catastrophe in osteosarcoma. Our algorithms will enable the inference of the relative ordering of loss of heterozygosity, whole genome doublings, structural changes and other localized catastrophes in osteosarcoma using public NGS data. Backtracking the chaos to discover the initiating genomic event may reveal novel drivers of this devastating disease and strategies to therapeutically intervene. The mode of evolutionary trajectories of catastrophes is a key genomic feature allowing better patient stratification in terms of tumor evolvability. The computational framework established here, whereas inspired by the complexity of the OS genome, will have an immeasurable impact on tracking the dynamics of other sarcoma subtypes showing genome instability, particularly given the urgent need to account for copy number alterations in studies of tumor evolution.
Recent and Upcoming Events
Everyone is invited to our 2020 Party in the Park Kickoff celebration at Forgotten Star Brewing Co. in Fridley! All day, 10% of sales will be donated to RIS, so come for food and beverages before or after the kickoff. This is the 20th Anniversary, be a part of planning the best Party in […]