Posted June 1, 2022

In Fiscal Year 2020 (FY20), the Peer Reviewed Cancer Research Program (PRCRP) offered and invested in the Virtual Cancer Center Director Award (VCCDA) and the Career Development Award-Scholar Option to establish the Convergent Science Virtual Cancer Center (CSVCC). The focus of the groundbreaking CSVCC is to catalyze the growth and professional development of early-career independent investigators (Scholars) in convergent science. The CSVCC will provide access to mentors and research partners across diverse backgrounds, thus exploiting the idea of intersecting multiple disciplines and cancers together in a cross-pollinating research network. This novel opportunity offers Scholars a collaborative training environment to become leaders not only in their individual fields, but also in cancer research in general.

Drs. Dan Theodorescu (Cedars-Sinai Cancer Center) and Peter Kuhn (University of Southern California), who serve as the Director and Deputy Director of the CSVCC, respectively, lead the CSVCC. As Director and Deputy Director, they guide the next generation of Scholars in a collegial, highly dynamic, and cutting-edge cancer center. Their aim is to use convergent science to accelerate patient outcomes and catalyze solutions to problems previously thought insoluble in cancer research and care. Using their innovative training program, Adaptive Catalysis of ConvErgent Research Training (ACERT), Drs. Theodorescu and Kuhn hope to catapult training of the selected Scholars in convergent science. Under their directorship, the CSVCC will offer bespoke mentorship, workshops, and networking on a global scale with experts in different disciplines and varieties of cancers with the goal of making major improvements in patient outcomes in the FY20 PRCRP Topic Areas.

Within the CSVCC, Scholars have their own designated Career Guides, in addition to a network of transdisciplinary experts in cancer research through the Convergence Council. The members of the Convergent Council include 18 scientists, clinicians, entrepreneurs, administrators, and several former military officers. An advisory board, comprised of a group of dedicated patient advocates and the career guides, will evaluate the operations and performance of the CSVCC and the effectiveness of the CSVCC Leadership. The CSVCC also includes a Special Advisor on Military Health, who will advise the CSVCC on matters related to exposure risk factors, mission readiness, and on opportunities for improving cancer care for military personnel, their family members, Veterans, and other military beneficiaries. By emphasizing military health and relevance, the CSVCC maximizes the benefit of cancer research to Service Members and their families as well as training the next generation of future leaders in cancer research to the needs of the military.

In FY20, the PRCRP selected eight outstanding Scholars across various PRCRP Topic Areas to participate in the CSVCC. Total FY20 investment of the PRCRP in this initiative (VCCDA plus Scholars) is $12.6 million. The research projects of the eight CSVCC Scholars are summarized below.

FY20 PRCRP Convergent Science Virtual Cancer Center Scholars
Trajectories of Adjustment in Young Adult Cancer Patient-Caregiver Dyads: A Measurement Burst Study to Examine Short- and Long-Term Change and Variability
Scholar: Dalnim Cho, Ph.D., MD Anderson Cancer Center
Career Guides: Susan Peterson, Ph.D., and Kathrin Milbury Ph.D., MD Anderson Cancer Center
PRCRP Topic Area: Pediatric, Adolescent, and Young Adult Cancers CA200949

Dr. Cho is an Assistant Professor in the Department of Health Disparities Research at MD Anderson Cancer Center. As a health psychologist, Dr. Cho’s research is focused on cancer disparities, particularly in the young adult (YA; 25-39 years) population. Dr. Cho will survey YAs who recently completed their cancer treatments along with their romantic partners. The study aims to identify short- and long-term associations between stress, health behaviors, and quality of life in the transition from treatment to survivorship. Ultimately, the goal is to develop a psychosocial/behavioral intervention to enhance both YA survivors’ and their partners’ quality of life. Dr. Cho is being mentored by Susan Peterson, Ph.D., and Kathrin Milbury, Ph.D. of the Department of Behavioral Science at MD Anderson Cancer Center. Both career guides are experts in behavioral and psychological interventions for cancer patients and survivors.

Link:
Public and Technical Abstracts: Trajectories of Adjustment in Young Adult Cancer Patient-Caregiver Dyads: A Measurement Burst Study to Examine Short- and Long-Term Change and Variability

Therapeutically Targeting Superclusters at Genes Driving Childhood Sarcoma
Scholar: Berkley Gryder, Ph.D., Case Western Reserve University
Career Guide: Pete Scacheri, Ph.D., Case Western University
PRCRP Topic Area: Pediatric, Adolescent, and Young Adult Cancers CA201094

Dr. Gryder is an Assistant Professor in the Department of Genetics and Genome Sciences at Case Western Reserve University. As a chemist, molecular biologist, and computer scientist, Dr. Gryder’s research is focused on the epigenomics of childhood sarcomas. Rhabdomyosarcoma is driven by super-enhancers, which are large clusters of transcription factors that accumulate at oncogenes. Dr. Gryder discovered that in some cancers, there are DNA mutations that cause the formation of “super-clusters,” or abnormal accumulations of transcription factors at cancer-causing genes. This project will first aim to characterize these “super-clusters” using 3D-epigenetic approaches. Secondly, Dr. Gryder will focus on degrading or inhibiting two super-cluster proteins, BRD4 and p300, using newly developed therapeutics. Dr. Gryder will be mentored by Dr. Pete Scacheri, a world-renowned leader in cancer genomics and epigenetics. Additionally, Dr. Gryder will collaborate with Jun Qi at Dana-Farber Cancer Institute to synthesize the BRD4 and p300 inhibitors, and investigators at St. Jude Children’s Research Institute to study the efficacy of the inhibitors in animal studies.

Link:
Public and Technical Abstracts: Therapeutically Targeting Superclusters at Genes Driving Childhood Sarcoma

Determining the Molecular Basis and Therapeutic Potential of Hyperactive Stem Cell Programs in Colorectal Cancer
Scholar: Nilay Sethi, M.D., Ph.D., Dana-Farber Cancer Institute
Career Guides: Adam Bass, M.D. and Ramesh Shivdasani, M.D., Ph.D., Dana-Farber Cancer Institute
PRCRP Topic Area: Colorectal Cancer CA201084

Dr. Nilay Sethi is an Assistant Professor of Medicine at Harvard Medical School and a physician at Dana-Farber Cancer Institute/Brigham and Women’s Hospital. As a medical oncologist, Dr. Sethi’s research interests are to combine clinical observations and patient-derived data with rigorous basic science investigation to yield opportunities for impactful translational advances in gastrointestinal cancers. With the support of the FY20 Career Development Award – Scholar Option, Dr. Nilay Sethi plans to uncover the critical regulators of aberrantly active stem cell programs and convert this understanding into effective treatment for colorectal cancer (CRC). Previously, Dr. Sethi defined a new subtype of CRC that has a high number of mutations in the stem cell transcription factor SOX9. For this project, Dr. Sethi plans to investigate the SOX9 stem cell program to identify new therapeutic agents and generate a mouse model to further characterize SOX9 alterations in the development of genome stable CRC. Dr. Sethi will be guided by Dr. Adam Bass, a recognized leader in functional genomics of gastrointestinal cancers, and co-Career Guide Dr. Ramesh Shivdasani, a pioneering leader in epigenomics and intestinal biology.

Link:
Public and Technical Abstracts: Determining the Molecular Basis and Therapeutic Potential of Hyperactive Stem Cell Programs in Colorectal Cancer

Developing Novel Immunotherapy to Suppress Cancer Metastasis and Recurrence in Bone
Scholar: Hae Lin Jang, Ph.D., Brigham and Women’s Hospital, Harvard Medical School
Career Guide: Shiladitya Sengupta, Ph.D., Brigham and Women’s Hospital, Harvard Medical School
PRCRP Topic Area: Metastatic Cancer CA201065

Dr. Hae Lin Jang is an Assistant Professor in the Department of Medicine at Brigham and Women’s Hospital with experience in cancer immunology and materials science. With funding from the FY20 Career Development Award – Scholar Option, Dr. Jang will study cancer metastasis to the bone. Although 70% of malignant cancers metastasize to the bone, there are currently no effective treatments for bone metastases. Furthermore, Dr. Jang and Dr. Shiladitya Sengupta (Dr. Jang’s Career Guide) recently published their observations that cancer cells can “hijack” mitochondria (cellular “energy factories”) from immune cells, thereby depleting the immune cells’ metabolic functions and ability to fight the cancer cells. The objectives of Dr. Jang’s FY20 Career Development Award - Scholar Option are to: (1) create a bone-on-a-chip model where she can study the role of mitochondrial hijacking in facilitating cancer metastasis to the bone and (2) develop an immunomodulatory drug-delivering bone-like material that will inhibit mitochondrial hijacking from the immune cells while also stabilizing the bone at the metastatic site.

With the assistance of the training and networking resources provided through the VCC and with mentorship from Dr. Shiladitya Sengupta, Dr. Jang hopes to become a leader in treating bone metastasis and establish a strong research team to develop innovative engineered immunotherapies to defeat cancer.

Link:
Public and Technical Abstracts: Developing Novel Immunotherapy to Suppress Cancer Metastasis and Recurrence in Bone

Multicyclic Peptide-Based Protein-Protein Interaction Modulators for Inhibiting Oncogenic MYC Activities
Scholar: Min Xue, Ph.D., University of California – Riverside
Career Guide: Yinsheng Wang, Ph.D., University of California – Riverside
PRCRP Topic Area: Brain Cancer CA201050

Myc is a critical developmental protein that plays a role in regulating cell growth, differentiation, metabolism, and cell death. It is frequently dysregulated in many types of cancers, such as CRC, stomach cancer, and brain cancer. Myc inhibition is a promising therapy that may help treat more than 75% of human cancer cases. However, an effective Myc inhibitor remains elusive, which represents a major gap in current cancer treatment. With a FY20 Career Development Award – Scholar Option, Dr. Min Xue plans to identify lead compounds that can inhibit Myc and halt cell proliferation in a glioblastoma model. Dr. Xue, has developed multicyclic peptides as a novel drug modality to inhibit challenging drug targets. Using this tool, Dr. Xue aims to develop an effective Myc inhibitor and examine the therapeutic implications of Myc inhibition in glioblastoma cells. With the mentorship of Distinguished Professor Yinsheng Wang at University of California – Riverside, a renowned chemical biologist, Dr. Xue hopes to develop cancer drugs that tackle previously undruggable oncogenic proteins and become a leader in brain cancer therapy

Link:
Public and Technical Abstracts: Multicyclic Peptide-Based Protein-Protein Interaction Modulators for Inhibiting Oncogenic MYC Activities

Mechanism and Therapeutic Potential of PTEN-Regulated MDSCs in Glioblastoma
Scholar: Peiwen Chen, Ph.D., Northwestern University
Career Guide: Maciej (Matt) Lesniak, M.D., MHCM, Northwestern University Feinberg School of Medicine
PRCRP Topic Area: Brain Cancer CA200965

Glioblastoma (GBM) is the most common and lethal form of brain tumor in adults, with a median survival averaging 14-16 months following the initial diagnosis. Cancer cells can modulate the behavior and function of immune cells in the tumor microenvironment (TME), and blockade of the tumor-TME communication is a powerful means for GBM treatment. Currently, targeted therapies have failed in clinic and no effective therapeutic drugs are available against signaling pathways known to be altered in GBM. With the support of the FY20 Career Development Award – Scholar Option, Dr. Peiwen Chen, an assistant Professor at Northwestern University Feinberg School of Medicine, will examine the nature of immune cells in the TME of GBM and their role in regulation of antitumor immune responses. Dr. Chen also aims to study the role of signal peptides in triggering recruitment of specific immune cells and the potential of targeting TME immune cells as a promising therapeutic intervention. Dr. Chen will be guided by Dr. Matt Lesniak, a Professor at Northwestern University Feinberg School of Medicine, and expert in brain and spinal cord tumors.

Link:
Public and Technical Abstracts: Mechanism and Therapeutic Potential of PTEN-Regulated MDSCs in Glioblastoma

Mutagenic Deaminase Activity in Cancer
Scholar: Abby Green, M.D., Washington University in St. Louis
Career Guide: Daniel Link, M.D., Washington University in St. Louis
PRCRP Topic Area: Blood Cancer CA200867

Dr. Abby Green is an Assistant Professor in the Department of Pediatrics and the Center for Genome Integrity at Washington University in St. Louis. Dr. Green is a pediatric oncologist and her research is focused on investigating the etiology of somatic mutations that contribute to blood cancers in both children and adults.APOBEC3 proteins are found in healthy cells which, when functioning normally, are responsible for limiting virus infection by causing mutations in viral DNA. However, when APOBEC3 proteins act abnormally, they are capable of mutating DNA in human cells. The overall goal of Dr. Green’s FY20 Career Development Award – Scholar Option award is to identify the contribution of APOBEC3 mutagenesis to the development and progression of blood cancers. Using both in vitro and in vivo models, Dr. Green aims to identify other cellular factors that enable abnormal activity of APOBEC3A and investigate whether the mutations caused by APOBEC3A promote the development and progression of blood cancers. By evaluating APOBEC3 proteins as a cause of DNA mutations in blood cancers, Dr. Green’s research is poised to generate foundational groundwork toward developing pharmaceutical options for targeting APOBEC3 activity in order to prevent aggressive blood cancers. Dr. Green will be mentored by Dr. Daniel Link, a professor at Washington University in St. Louis, and an expert on DNA mutation in blood cancers.

Link:
Public and Technical Abstracts: Mutagenic Deaminase Activity in Cancer

Defining Leukemia Stem Cells in Acute Lymphoblastic Leukemia
Scholar: Grant Rowe M.D. Ph.D., Boston Children’s Hospital
Career Guide: Leonard Zon, M.D., Harvard Medical School, Boston Children’s Hospital
PRCRP Topic Area: Blood Cancer CA201001

Dr. Grant Rowe is an Assistant Professor of Pediatrics at Harvard Medical School and attending physician at Boston Children’s Hospital. As a pediatric hematologist-oncologist, Dr. Rowe’s research interests are focused on normal and diseased blood stem cells, with the aim of translating his research findings into new therapies. With the support of a FY20 Career Development Award – Scholar Option, Dr. Rowe aims to study the role of oxidative metabolism on leukemia stem cells that control acute lymphoblastic leukemia (ALL) growth and disease progression. Dr. Rowe also plans to investigate if oxidative metabolism can be effectively targeted as means of blunting ALL progression. Upon completion of this study, Dr. Rowe hopes to advance a new therapeutic intervention that would have the potential to help ALL patients. Dr. Rowe will be guided by Dr. Leonard Zon, a Professor of Pediatric Medicine at Harvard Medical School and Howard Hughes Medical Institute Investigator, and leader in the field of hematopoietic development and disease.

Link:
Public and Technical Abstracts: Defining Leukemia Stem Cells in Acute Lymphoblastic Leukemia

In summary, Scholars in the CSVCC will have the opportunity to grow and broaden their cancer research understanding through a diverse community from many disciplines and a variety of cancers. Together, the CSVCC Leadership and the Scholars are forging the future of cancer research and care through convergent science and collaboration.

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Last updated Wednesday, June 1, 2022