Octavian Bucur, MD, PhD is an Instructor in Departments of Pathology and Medicine, focusing on experimental and computational pathology, image analysis and genomics. Octavian joined professor Andrew H. Beck's laboratory in the Department of Pathology at Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School in 2014.
CURRENT RESEARCH: Octavian's research interests focus on developing and applying novel experimental and computational strategies to improve disease diagnostics and therapeutics for cancer patients:
1. Developing methods for the identification of the 3D morphological hallmarks of carcinogenesis (received 2015 Award from AACR-Millennium Pharm. for: "3D morphological hallmarks of breast carcinogenesis: Diagnosis of non-invasive and invasive breast cancer with Lightsheet microscopy"). Question: Can the 3D morphological features be used to improve (or even replace) the conventional 2D diagnosis for certain pathologies?
2. Developing expansion microscopy as a new useful tool for diagnostic and research pathology (in collaboration with professor Edward Boyden's laboratory at MIT). Question: Can tissue expansion be used as a diagnostic pathology tool, replacing the need for higher resolution microscopes?
3. Studying the genomewide epithelial-stromal crosstalk network in breast cancer. Question: Using a combination of computational and experimental approaches, can we identify the main epithelial-stromal crosstalk clusters and potential gene targets?
4. Applying and developing the Fluorescence In Situ Sequencing (FISSEQ) for gene expression profiling of cells on normal/cancer tissue sections (in collaboration with professor George Church's laboratory at Wyss Institute of Harvard University). Question: Can we apply FISSEQ for studying breast cancer tumorigenesis, resistance to therapy and epithelial-stromal interactions in situ?
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PREVIOUS RESEARCH: Octavian has uncovered novel strategies of targeting the dysregulated apoptosis pathways in several types of malignancies and of sensitizing resistant cancer cells to available treatments.
1. A novel caspase 8 selective small molecule potentiates TRAIL-induced cell death (Bucur O et al, Sci Rep, 2015). Brief description: For the first time, we describe the discovery and characterization of a small molecule that directly binds caspase 8 and enhances its activation when combined with TRAIL, but not alone. Our (in silico screening and experimental validation) approach is a proof-of-concept strategy leading to the discovery of a novel small molecule that not only stimulates TRAIL-induced apoptosis in cancer cells, but may also provide insights into the structure-function relationship of caspase 8 homodimers as cancer targets.
2. PLK1 is a binding partner and a negative regulator of FOXO3 tumor suppressor (Bucur O et al, Discoveries, 2014). Brief description: Our results revealed the critical cell cycle kinase PLK1 proto-oncogene as a binding partner and a negative regulator of FOXO3 tumor suppressor (and of FOXO-induced apoptosis markers), by using a proteomics screening strategy. Protein phosphatase 2A reactivates FOXO3a through a dynamic interplay with 14-3-3 and AKT (Singh A, Ye M, Bucur O et al, Mol Biol Cell, 2010). Brief description: This study found PP2A as the first known phosphatase that can bind and dephosphorylate FOXO3 tumor suppressors. We show that PP2A is entwined in a dynamic interplay with AKT pro-survival kinase and scaffold protein 14-3-3 to directly regulate FOXO3 localization, activation and its pro-apoptotic functions.
3. Combination of bortezomib and mitotic inhibitors down-modulate Bcr-Abl and efficiently eliminates tyrosine-kinase inhibitor sensitive and resistant Bcr-Abl-positive leukemic cells (Bucur O et al, Plos One, 2013). Brief description: Emergence of resistance to Tyrosine-Kinase Inhibitors (TKIs), such as imatinib, dasatinib and nilotinib, in Chronic Myelogenous Leukemia (CML) demands new therapeutic strategies. Our findings indicate that the bortezomib in combination with four different mitotic inhibitors (paclitaxel, docetaxel, vincristine and BI2536), that repress mitosis by different mechanisms are able to shut down Bcr-Abl activity and result in caspase-dependent cell death in TKIs-resistant and -sensitive Bcr-Abl-positive cell lines.
Other Relevant Publications: Sensitization of prostate carcinoma cells to Apo2L/TRAIL by a Bcl-2 family protein inhibitor. (Ray S*, Bucur O*, Almasan A, Apoptosis, 2005; * - equal contribution); Poor antibody validation is a challenge in biomedical research: a case study for detection of c-FLIP (Bucur O. et al, Cell Death Dis, 2013); An updated h-index measures both the primary and total scientific output of a researcher (Bucur O. et al, Discoveries, 2015).
EDUCATION: Octavian was one of the 20-25 students (less than 2.5% of all applicants) obtaining a Honorary Admission for exceptional accomplishments in Biology (Biology Olympiad) to the Carol Davila University of Medicine and Pharmacy from Bucharest, the main Medical School from Romania. Octavian received his MD degree in September 2005. During his Medical School studies his research activity was recognized and funded by a number of awards and fellowships, including the European Union - Leonardo da Vinci Research Fellowship (2004, Magdeburg, Germany), the Romanian Ministry of Education and Research Fellowship (Cleveland Clinic, OH, USA, 2003) and a Research Scholarship from the International Federation of Medical Students Associations (Spain, 2002). Octavian received his PhD (with highest distinction) in Biochemistry/Biology in 2015 from The Romanian Academy, performing his entire PhD training and research work at BIDMC and Harvard Medical School (with Professor Roya Khosravi-Far, as a research fellow). His PhD thesis advisors were: professor Stefana Petrescu (Director of Institute of Biochemistry of the Romanian Academy), professor Roya Khosravi-Far (Harvard University) and professor Alex Almasan (Cleveland Clinic and Cleveland Clinic Lerner College of Medicine at CWRU).
AWARDS: Octavian received several important Awards, including but not limited to: Best Scientific Poster Award (2017, Harvard Medical School Pathology Retreat),The AACR-Millennium Pharmaceuticals Award (2015, Philadelphia, PA, USA - received by less than 10% of the applicants and less than 1% of all the AACR Meeting participants), IUBMB Travel Fellowship (2010 - received by 50 members from all Biochemical Societies around the world), AACR-Aflac Award (2008, San Diego, CA, USA - <10% of applicants), Lady Tata Memorial Trust International Award for Leukemia Research (2007-2009, London, UK - received by 9-13 researchers/year) and European Union - Leonardo da Vinci Research Fellowship (2004, Magdeburg, Germany).
Boston, MA, USA