Sarcomas

Current Projects
Sidi Chen, PhD

Dr. Chen aims to understand the relationship between small RNAs and cancer.  Small RNAs are important regulators of genetic networks inside the cell; perturbation of these networks can lead to malignant cell growth.  His goal is to develop anti-cancer drugs and therapies by targeting the process of small RNA production.

Project title: "Investigation of Dicer as a novel therapeutic route towards the inhibition of tumorigenesis and neoplastic growth"
Institution: Yale University
Award Program: Dale Frey Scientist
Cancer Type: Lung, Sarcoma
Research Area: Cancer Genetics
Allison Didychuk, PhD

Dr. Didychuk is investigating the mechanism by which the Kaposi’s sarcoma herpesvirus (KSHV) co-opts the cellular host machinery to produce its own gene products in a manner distinct from other viruses and host cells. This research should reveal insights into this unique mode of transcriptional control. KHSV is an oncogenic virus that causes various cancers including, Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease, in immunocompromised individuals.

Project title: Viral mimics of host transcription factors in oncogenic herpesviruses
Institution: University of California, Berkeley
Award Program: Fellow
Sponsor(s) / Mentor(s): Britt Glaunsinger, PhD
Cancer Type: Other Cancer, Sarcoma
Research Area: Virology
Lillian M. Guenther, MD

Ewing sarcoma is an aggressive bone tumor that occurs in children and young adults. Cure rates, particularly when disease has spread, are low with currently available treatments. Dr. Guenther aims to identify critical genes on which Ewing sarcoma cells are dependent for survival, with the goal of discovering weaknesses in these cancer cells that may be exploited to stop cancer growth. CITED2 is of particular interest as a Ewing sarcoma-specific dependency gene based on a genome-wide screen in hundreds of cancer cell lines. In some other cancers, CITED2 is described as important for helping cells repair damage and survive stress, such as when they are exposed to chemotherapy. She has found that CITED2 is present in higher levels in Ewing sarcoma cells than in other types of cancer, and when CITED2's function is turned off in Ewing sarcoma cells, they grow more slowly. She aims to first confirm that CITED2 is critical for Ewing sarcoma survival. She will also investigate what makes CITED2 important in cancer cells, including specific features of Ewing sarcoma cells that contribute to its high levels of activity.  Additionally, she wants to understand CITED2's function in Ewing sarcoma cells, including any role for CITED2 in the repair of damage to DNA after chemotherapy or stress. The goal of this work is to develop new directed cancer therapies for patients with this devastating disease. She hopes that these studies will have an additional impact on the treatment of other cancers where CITED2 has been shown to play a role, including acute myeloid leukemia.

Project title: "Investigation of CITED2 as a novel dependency in Ewing sarcoma"
Institution: Dana-Farber Cancer Institute
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Kimberly Stegmaier, MD
Cancer Type: Pediatric, Sarcoma
Research Area: Cell Biology
Amanda Balboni Iniguez, PhD

Dr. Balboni Iniguez studies Ewing sarcoma, a rare pediatric solid tumor containing a characteristic chromosomal translocation that fuses the EWSR1 gene to the FLI1 gene. The resulting EWS/FLI fusion protein initiates an oncogenic gene expression program, thus promoting tumorigenesis. EWS/FLI represents an attractive tumor-specific therapeutic target; however, it has been difficult to pharmacologically inhibit. Her work will focus on elucidating a novel approach to selectively target EWS/FLI by utilizing a small-molecule inhibitor against the transcriptional regulator proteins CDK12/13. This research will contribute to our understanding of Ewing sarcoma cell biology and has important clinical implications for other cancers driven by similar transcription factor fusion proteins.

Project title: "Targeting the EWS-FLI oncoprotein in Ewing sarcoma with CDK12/13 inhibitors"
Institution: Dana-Farber Cancer Institute
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Kimberly Stegmaier, MD
Cancer Type: Pediatric, Sarcoma
Research Area: Experimental Therapeutics
Chao Lu, PhD

Eukaryotic cells develop sophisticated mechanisms to package and access our genetic information. Recent studies have shown that proteins involved in genome regulation are frequently altered in human cancers. These findings agree with laboratory observations that cancer cells often display abnormal nuclear architecture, and raise the questions of whether, and how, aberrant chromatin organization facilitates tumor development. Collectively, Dr. Lu's previous work has identified the molecular mechanisms by which high-frequency mutations in chromatin regulators reprogram genome-wide chemical modifications of DNA and histones. In addition, his work demonstrated that chromatin mutations are pro-oncogenic through the blockade of cellular differentiation. These studies provide compelling evidence for a causal role of chromatin dysregulation in oncogenesis. He proposes a novel pathway of cancer initiation through accumulation of hyper-proliferative and differentiation-refractory tissue progenitor cells driven by epigenome abnormality. His goal is to apply these mechanistic insights to advance current molecular diagnosis, classification and treatment of human cancers.

Project title: "Chromatin dysregulation as driver of oncogenesis"
Institution: Columbia University
Named Award: Giannandrea Family Scientist
Award Program: Dale Frey Scientist
Cancer Type: Head and Neck Cancer, Sarcoma
Research Area: Chromatin Biology
Monica E. McCallum, PhD

Dr. McCallum studies a compound, called alanosine, which exhibits anti-cancer activity against cells from sarcomas, mesothelioma, and pancreatic cancer. This compound is produced by a soil-dwelling bacterium. She seeks to elucidate how bacteria produce alanosine. Understanding the genes and enzymes that assemble this molecule will guide the discovery of additional novel chemotherapeutic agents that may be produced by bacteria.

Project title: "Understanding alanosine biosynthesis to discover new cancer chemotherapeutics"
Institution: Harvard University
Award Program: Fellow
Sponsor(s) / Mentor(s): Emily P. Balskus, PhD
Cancer Type: Sarcoma
Research Area: Biochemistry
Philip A. Romero, PhD

Dr. Romero is a biomedical engineer whose expertise is in the area of microfluidics. He proposes to develop new technology that can be used to detect circulating tumor cells (CTCs) in the bloodstream. CTCs are cells that have detached from a solid primary tumor and entered into the bloodstream; they can go on to colonize distant sites and form metastases. Detecting CTCs is an enormous challenge, as the cells are present at an ultra-low abundance (1 out of billions of blood cells). His approach is to develop a highly specific system, a “DNA-based logic circuit,” to detect and profile CTCs, which could ultimately be applied for cancer diagnosis, prognosis indication, and measurement of a patient’s response to treatment.

Project title: "Digital circulating tumor cell detection using scalable molecular logic"
Institution: University of Wisconsin, Madison
Award Program: Innovator
Cancer Type: Breast, Colorectal, Lung, Prostate, Sarcoma
Research Area: Biomedical Engineering
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