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: “Understanding the mechanism of genome packaging 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
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 [National Mah Jongg League Fellow] 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
Named Award: National Mah Jongg League Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Michael E. Greenberg, PhD
Cancer Type: Gastric, Prostate, Sarcoma, All Cancers
Research Area: Cell Biology
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: St. Jude Children's Research Hospital
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Mark E. Hatley, MD, PhD
Cancer Type: Pediatric, Sarcoma
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
Benjamin A. Nacev, MD, PhD

Sarcomas are a family of tumors for which there are few targeted treatments and outcomes are poor once the cancer has metastasized. Many sarcomas harbor recurrent mutations in proteins, known as epigenetic regulators, that control which genes are expressed and when. Among the regulators most frequently impacted is ATRX, which condenses regions of DNA into tightly packaged chromatin that cannot be accessed for transcription, effectively “silencing” these genes. The effect of ATRX loss in sarcomas is poorly understood, however, and treatments that leverage ATRX deficiency are lacking. Using patient-derived sarcoma cell lines and tumor samples, Dr. Nacev aims to understand epigenetic dysregulation in ATRX-deficient sarcomas, to determine how this affects antitumor immunity, and to identify new therapeutic vulnerabilities.

Project title: "Understanding and targeting chromatin reorganization in ATRX deficient sarcomas"
Institution: University of Pittsburgh
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Jeremy N. Rich, MD
Cancer Type: Sarcoma
Research Area: Chromatin Biology
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.