The cohesin complex plays an essential role in chromosome maintenance and transcriptional regulation. Recurrent somatic mutations in the cohesin complex are frequent genetic drivers in cancer, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Here, using genetic dependency screens of stromal antigen 2-mutant (STAG2-mutant)...
Selenium is a micronutrient that is used by the selenocysteine biosynthesis pathway to produce the amino acid selenocysteine, which is required in selenoproteins. Many of the 25 human selenoproteins, such as glutathione peroxidases and thioredoxin reductases, play important roles in maintaining cellular redox homeostasis. In this study we character...
Presented virtually during the "New Faculty Talks" session at the 25th Annual University of Massachusetts Medical School Research Retreat 2020 on October 26, 2020.
Despite the successes achieved with molecular targeted inhibition of the oncogenic driver Bcr-Abl in chronic myeloid leukemia (CML), the majority of patients still require lifelong tyrosine kinase inhibitor (TKI) therapy. This is primarily caused by resisting leukemic stem cells (LSCs), which prevent achievement of treatment-free remission in all p...
FANCJ, a DNA helicase and interacting partner of the tumor suppressor BRCA1, is crucial for the repair of DNA interstrand crosslinks (ICL), a highly toxic lesion that leads to chromosomal instability and perturbs normal transcription. In diploid cells, FANCJ is believed to operate in homologous recombination (HR) repair of DNA double-strand breaks ...
Breast cancer is the second most common malignancy in the world, accounting for over 1.7 million new diagnoses and an estimated 500,000 deaths per year (1). Overexpression of the receptor tyrosine kinase ErbB2, also known as Her2 or Neu, occurs in over 30% of breast cancers and correlates with metastasis, poor prognosis, and decreased survival (1, ...
The rationale behind targeted molecular therapy in cancer, oncogene addiction, is that tumors rely on driver oncogenes to control their proliferation and survival. Therefore, an efficacious targeted therapy should induce a dual, detrimental response to the tumor. While there have been clinical success stories using targeted therapies, even tumors t...
Published in Oncogene
Although rare, glioblastoma is a devastating tumor of the central nervous system characterized by a poor survival and an extremely dark prognosis, making its diagnosis, treatment, and monitoring highly challenging. Numerous studies have highlighted extracellular vesicles (EVs) as key players of tumor growth, invasiveness, and resistance, as they ca...
Resistance to glucocorticoid (GC) therapy results in poor prognosis for acute lymphoblastic leukemia (ALL) patients. Utilizing a whole genome shRNA screen our lab identified several novel mechanisms of GC resistance. My thesis work established that an orphan nuclear receptor, the Estrogen Related Receptor Beta (ESRRB), is critical for induction of ...
Rhabdomyosarcoma (RMS) represents more than 50% of paediatric soft tissue tumours. Conversely, it is extremely rare among adults, where it shows peculiar biological and clinical features that are still poorly investigated. RMS patients should be referred to a Sarcoma Centre, where the contribution of experienced radiologists plays a relevant role i...
