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
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: "Understanding the mechanism of histone H3 mutation in cancer initiation and maintenance"
Institution: Columbia University
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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