Sarcomas

Current Projects
Allison L. Didychuk, PhD

Kaposi's sarcoma herpesvirus (KSHV) is a human oncogenic virus and the causative agent of cancers including Kaposi’s sarcoma, primary effusion lymphoma, and Multicentric Castleman disease. The related human herpesvirus Epstein-Barr Virus (EBV) is even more prevalent than KSHV, and is linked to cancers including Burkitt’s lymphoma, Hodgkin’s lymphoma, and nasopharyngeal carcinoma. Dr. Didychuk [The Rhee Family Breakthrough Scientist] is investigating the mechanisms by which KSHV co-opts the cellular host machinery to produce its own gene products in a manner distinct from other viruses and host cells. A molecular understanding of how herpesviruses hijack the late gene transcription machinery will reveal new therapeutic weaknesses in the viral lifecycle and allow for structure-guided design of novel anti-viral drug targets.

Project title: “Viral mimics of host transcription factors in oncogenic herpesviruses”
Institution: Yale University
Named Award: The Rhee Family Breakthrough Scientist
Award Program: Dale Frey Scientist
Cancer Type: Blood, Other Cancer, Sarcoma
Research Area: Virology
Katherine E. Gadek, PhD

Dr. Gadek focuses on the Sonic Hedgehog (Shh) signaling pathway, which can be altered in rhabdomyosarcoma (RMS) patients. RMS is the most common soft-tissue sarcoma in children, but survival rates and treatments for high-risk patients have not improved in three decades. Dr. Gadek will examine the timing of tumor development and the role of Shh signaling in tumor location and formation. This may lead to diagnostic markers and tools for identifying high-risk patients with altered Sonic Hedgehog signaling, which could improve treatment options and outcomes.

Project title: "Defining endothelial progenitor cell pliancy in rhabdomyosarcoma" 
Institution: St. Jude Children's Research Hospital
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Mark Hatley, MD, PhD, and Stacey Ogden, PhD
Cancer Type: Head and Neck Cancer, Pediatric, Sarcoma
Research Area: Developmental Biology
Xin Gu, PhD

Regulation of gene transcription is a major mechanism cells use to modify the levels of certain proteins in response to their environment. A specific class of genes called immediate-early genes (IEGs) responds rapidly to external stimuli to adjust downstream gene transcription programs before any new proteins are synthesized. Abnormal expression of IEGs has been implicated in multiple types of cancers, as well as in neurological syndromes like addiction. Despite extensive study, the regulation of IEGs remains poorly understood. Dr. Gu’s work focuses on revealing the molecular mechanisms of IEG expression in cells and establishing model systems to study the physiological and disease-related outcomes caused by misregulation of this process. Dr. Gu received her PhD from MIT and her BSc from Peking University.

Project title: "Characterization of a novel pathway regulating the protein degradation of immediate-early genes"
Institution: Harvard Medical School
Award Program: Fellow
Sponsor(s) / Mentor(s): Michael E. Greenberg, PhD
Cancer Type: Gastric, Prostate, Sarcoma, All Cancers
Research Area: Cell Biology
Julia Su Zhou Li, PhD

Dr. Li focuses on how cells become cancerous when they have an abnormal number of chromosomes or broken parts of a chromosome. The centromere, which joins two arms of a chromosome, is essential for faithful chromosome segregation during cell division and genome stability. When chromosomes fail to be delivered correctly to each new cell, the abnormal chromosomes may form “neocentromeres” which have been discovered in developmental disorders and cancer. Dr. Li is developing tools to examine and manipulate these neocentromeres, which may lead to a better understanding of how cancer cells evolve and potentially novel anti-tumor strategies.

Project title: "Spatial regulation of the inheritance of genomic abnormalities in cancer cells"
Institution: Ludwig Institute for Cancer Research
Award Program: Fellow
Sponsor(s) / Mentor(s): Don W. Cleveland, PhD
Cancer Type: Blood, Sarcoma
Research Area: Chromatin Biology
Esteban A. Orellana Vinueza, PhD

Dr. Orellana Vinueza is investigating whether changes that modify the shape, stability and function of transfer RNAs (tRNAs) play a role in the development of cancer. The tRNA molecules are involved in the process that translates messenger RNA into a protein. Dr. Orellana Vinueza focuses on a tRNA methyltransferase complex that malfunctions in glioblastoma and liposarcoma. He will assess how alterations in the activity of this enzyme affect global patterns of methylation in normal and human cancer cells. Methylation is the process that controls the timing and amount of proteins that are produced in cells. Understanding how this process breaks down may help decipher the mechanisms that drive cancer and guide the development of new treatments.

Project title: "Role of METTL1-WDR4 tRNA methyltransferase complex in cancer"
Institution: Boston Children's Hospital
Award Program: Fellow
Sponsor(s) / Mentor(s): Richard I. Gregory, PhD
Cancer Type: Brain, Sarcoma
Research Area: RNA (RNA processing, miRNA and piRNA mechanisms, enzymatic RNAs, etc.)
Anand G. Patel, MD, PhD

Dr. Patel studies rhabdomyosarcoma (RMS), a fast-growing childhood cancer that can spread from muscles to other parts of the body. Dr. Patel has discovered that each RMS tumor consists of different subpopulations of cells that mimic different stages of early muscle development. He will characterize how chemotherapy or radiation therapy selects for specific subpopulations of resistant cancer cells that survive treatment within both patient tissue and in patient-derived models of cancer. Using this information, Dr. Patel aims to test whether directing therapy against resistant cell subpopulations improves treatment outcomes. Ultimately, the goal of this research is to uncover novel therapeutic targets and drugs for the treatment of pediatric RMS.

Project title: "Targeting the developmental architecture of rhabdomyosarcoma"
Institution: St. Jude Children's Research Hospital
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Michael A. Dyer, PhD
Cancer Type: Pediatric, Sarcoma
Research Area: Chemoresistance
  • You can support our innovative researchers.