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Victor E. Velculescu | |
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Born | August 16, 1970 |
Nationality | American |
Alma mater | Stanford University Johns Hopkins University |
Spouse | Delia Velculescu |
Awards | Paul Marks Prize for Cancer Research (2011) AACR Award for Outstanding Achievement in Cancer Research (2009) Judson Daland Prize (2008) |
Scientific career | |
Fields | Genomics, Cancer biology |
Institutions | Johns Hopkins University |
Victor E. Velculescu (born August 16, 1970) is a Professor of Oncology and Co-Director of Cancer Biology at Johns Hopkins University School of Medicine. [1] [2] He is internationally known for his discoveries in genomics and cancer research.
Velculescu was born in Bucharest, Romania and moved with his family to Westlake Village, California at the age of seven. [3] He began molecular biology research as an undergraduate at Stanford University, graduating with honors and distinction in biological sciences in 1992. Velculescu completed his M.D. degree, a Ph.D. in human genetics and molecular biology, and postdoctoral studies at the Johns Hopkins School of Medicine where he remains on the faculty. [4]
He is married to Delia Velculescu, an economist and the current IMF mission chief in Greece. [5]
Velculescu and members of his research group have pioneered approaches for discovering molecular alterations in human cancer and applying these discoveries to improve the diagnosis and treatment of cancer.
In 1995 Velculescu developed SAGE (serial analysis of gene expression), a gene expression technology for the global and quantitative measurement of gene activity. [6] The SAGE approach provided some of the first insights into gene expression patterns in eukaryotic cells and the identification of gene expression patterns in human cancer. These studies led Velculescu to coin the term transcriptome in a 1997 paper to describe the comprehensive gene expression patterns that could now be analyzed. [7] SAGE contributed to the development of next-generation sequencing methods used for genome-wide expression analyses. [8]
In the early 2000s, Velculescu and members of his laboratory devised new technologies for characterizing the cancer genome. These included digital karyotyping, which allows for quantitative characterization of amplifications and deletions at the DNA level. [9] This approach provided the underlying methodology for next-generation sequencing analyses to detect chromosomal abnormalities in human cancer as well as in prenatal genetic testing. [10] [11]
In parallel, Velculescu was an early developer of methods for high-throughput sequencing of human cancer, which his group used to identify the PIK3CA gene as one of the most highly mutated cancer genes. [12]
Starting in 2005, Velculescu extended these approaches, and together with Bert Vogelstein, Ken Kinzler and other colleagues at Johns Hopkins performed the first sequence analysis of the coding genome in human cancers, including breast, colorectal, brain, and pancreatic cancers. [13] [14] [15] [16] [17] His group also led the effort to sequence the first pediatric tumor genome for medulloblastoma. [18] [19] These studies defined the genomic landscapes of human cancers and identified alterations in a variety of genes and pathways not previously known to be involved in tumorigenesis, including the IDH1 and IDH2 genes in gliomas, [16] and chromatin modifying genes MLL2/3 and ARID1 in medulloblastomas, neuroblastomas and other tumor types. [18] [19] [20]
In 2010, Velculescu and his group developed the PARE (personalized analysis of rearranged ends) technology that can help detect genomic tumor biomarkers circulating in the blood to enable the monitoring and personalized treatment of human cancer. [21] Using this approach, his laboratory performed the first whole-genome analysis detecting chromosomal alterations in the blood of cancer patients. [22]
Velculescu co-founded the cancer genomics company Personal Genome Diagnostics (PGDx) in 2010 to bring individualized cancer genome analyses to patients, physicians, researchers and drug developers. PGDx was the first clinical laboratory to provide whole-exome sequencing for cancer patients in 2011.
Bert Vogelstein is director of the Ludwig Center, Clayton Professor of Oncology and Pathology and a Howard Hughes Medical Institute investigator at The Johns Hopkins Medical School and Sidney Kimmel Comprehensive Cancer Center. A pioneer in the field of cancer genomics, his studies on colorectal cancers revealed that they result from the sequential accumulation of mutations in oncogenes and tumor suppressor genes. These studies now form the paradigm for modern cancer research and provided the basis for the notion of the somatic evolution of cancer.
The phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha, also called p110α protein, is a class I PI 3-kinase catalytic subunit. The human p110α protein is encoded by the PIK3CA gene.
Oncogenomics is a sub-field of genomics that characterizes cancer-associated genes. It focuses on genomic, epigenomic and transcript alterations in cancer.
AT-rich interactive domain-containing protein 1B is a protein that in humans is encoded by the ARID1B gene. ARID1B is a component of the human SWI/SNF chromatin remodeling complex.
Colorectal mutant cancer protein is a protein that in humans is encoded by the MCC gene.
AT-rich interactive domain-containing protein 2 (ARID2) is a protein that in humans is encoded by the ARID2 gene.
Ectoderm-neural cortex protein 1 is a protein that in humans is encoded by the ENC1 gene.
Carboxypeptidase A1 is an enzyme that in humans is encoded by the CPA1 gene.
Endosialin is a protein that in humans is encoded by the CD248 gene.
Plexin domain-containing protein 1 is a protein that in humans is encoded by the PLXDC1 gene.
Cancer genome sequencing is the whole genome sequencing of a single, homogeneous or heterogeneous group of cancer cells. It is a biochemical laboratory method for the characterization and identification of the DNA or RNA sequences of cancer cell(s).
Isogenic human disease models are a family of cells that are selected or engineered to accurately model the genetics of a specific patient population, in vitro. They are provided with a genetically matched 'normal cell' to provide an isogenic system to research disease biology and novel therapeutic agents. They can be used to model any disease with a genetic foundation. Cancer is one such disease for which isogenic human disease models have been widely used.
Recombinant adeno-associated virus (rAAV) based genome engineering is a genome editing platform centered on the use of recombinant AAV vectors that enables insertion, deletion or substitution of DNA sequences into the genomes of live mammalian cells. The technique builds on Mario Capecchi and Oliver Smithies' Nobel Prize–winning discovery that homologous recombination (HR), a natural hi-fidelity DNA repair mechanism, can be harnessed to perform precise genome alterations in mice. rAAV mediated genome-editing improves the efficiency of this technique to permit genome engineering in any pre-established and differentiated human cell line, which, in contrast to mouse ES cells, have low rates of HR.
Genome instability refers to a high frequency of mutations within the genome of a cellular lineage. These mutations can include changes in nucleic acid sequences, chromosomal rearrangements or aneuploidy. Genome instability does occur in bacteria. In multicellular organisms genome instability is central to carcinogenesis, and in humans it is also a factor in some neurodegenerative diseases such as amyotrophic lateral sclerosis or the neuromuscular disease myotonic dystrophy.
Retinal guanylyl cyclase 2 also known as guanylate cyclase F (GUCY2F) is a protein that in humans is encoded by the GUCY2F gene.
Tumour heterogeneity describes the observation that different tumour cells can show distinct morphological and phenotypic profiles, including cellular morphology, gene expression, metabolism, motility, proliferation, and metastatic potential. This phenomenon occurs both between tumours and within tumours. A minimal level of intra-tumour heterogeneity is a simple consequence of the imperfection of DNA replication: whenever a cell divides, a few mutations are acquired—leading to a diverse population of cancer cells. The heterogeneity of cancer cells introduces significant challenges in designing effective treatment strategies. However, research into understanding and characterizing heterogeneity can allow for a better understanding of the causes and progression of disease. In turn, this has the potential to guide the creation of more refined treatment strategies that incorporate knowledge of heterogeneity to yield higher efficacy.
Saurabh Saha is an American biotech entrepreneur.
Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA in the bloodstream that is not associated with cells. ctDNA should not be confused with cell-free DNA (cfDNA), a broader term which describes DNA that is freely circulating in the bloodstream, but is not necessarily of tumor origin. Because ctDNA may reflect the entire tumor genome, it has gained traction for its potential clinical utility; "liquid biopsies" in the form of blood draws may be taken at various time points to monitor tumor progression throughout the treatment regimen.
The American Association for Cancer Research gives several annual awards for significant contributions to the field of cancer research.
Luis Alberto Diaz, Jr. is the Head of the Division of Solid Tumor Oncology in Memorial Sloan Kettering’s Department of Medicine.