Victor Velculescu

Last updated

Victor E. Velculescu
Dr. Vicotor Velculescu in his lab.tif
BornAugust 16, 1970
Bucharest, Romania
NationalityAmerican
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
FieldsGenomics, 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.

Contents

Early life and education

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]

Research

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]

Translational efforts

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.

Awards and honors

Related Research Articles

<span class="mw-page-title-main">Bioinformatics</span> Computational analysis of large, complex sets of biological data

Bioinformatics is an interdisciplinary field of science that develops methods and software tools for understanding biological data, especially when the data sets are large and complex. Bioinformatics uses biology, chemistry, physics, computer science, computer programming, information engineering, mathematics and statistics to analyze and interpret biological data. The subsequent process of analyzing and interpreting data is referred to as computational biology.

<span class="mw-page-title-main">CpG site</span> Region of often-methylated DNA with a cytosine followed by a guanine

The CpG sites or CG sites are regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5' → 3' direction. CpG sites occur with high frequency in genomic regions called CpG islands.

<span class="mw-page-title-main">Comparative genomics</span> Field of biological research

Comparative genomics is a branch of biological research that examines genome sequences across a spectrum of species, spanning from humans and mice to a diverse array of organisms from bacteria to chimpanzees. This large-scale holistic approach compares two or more genomes to discover the similarities and differences between the genomes and to study the biology of the individual genomes. Comparison of whole genome sequences provides a highly detailed view of how organisms are related to each other at the gene level. By comparing whole genome sequences, researchers gain insights into genetic relationships between organisms and study evolutionary changes. The major principle of comparative genomics is that common features of two organisms will often be encoded within the DNA that is evolutionarily conserved between them. Therefore, Comparative genomics provides a powerful tool for studying evolutionary changes among organisms, helping to identify genes that are conserved or common among species, as well as genes that give unique characteristics of each organism. Moreover, these studies can be performed at different levels of the genomes to obtain multiple perspectives about the organisms.

<span class="mw-page-title-main">Neoplasm</span> Tumor or other abnormal growth of tissue

A neoplasm is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, which may be called a tumour or tumor.

<span class="mw-page-title-main">Bert Vogelstein</span> American oncologist (born 1949)

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.

<span class="mw-page-title-main">Oncogenomics</span> Sub-field of genomics

Oncogenomics is a sub-field of genomics that characterizes cancer-associated genes. It focuses on genomic, epigenomic and transcript alterations in cancer.

The Cancer Genome Atlas (TCGA) is a project to catalogue the genomic alterations responsible for cancer using genome sequencing and bioinformatics. The overarching goal was to apply high-throughput genome analysis techniques to improve the ability to diagnose, treat, and prevent cancer through a better understanding of the genetic basis of the disease.

<span class="mw-page-title-main">MCC (gene)</span> Protein-coding gene in the species Homo sapiens

Colorectal mutant cancer protein is a protein that in humans is encoded by the MCC gene.

<span class="mw-page-title-main">CD248</span> Protein-coding gene in the species Homo sapiens

Endosialin is a protein that in humans is encoded by the CD248 gene.

<span class="mw-page-title-main">PLXDC1</span> Protein-coding gene in the species Homo sapiens

Plexin domain-containing protein 1 is a protein that in humans is encoded by the PLXDC1 gene.

Somatic evolution is the accumulation of mutations and epimutations in somatic cells during a lifetime, and the effects of those mutations and epimutations on the fitness of those cells. This evolutionary process has first been shown by the studies of Bert Vogelstein in colon cancer. Somatic evolution is important in the process of aging as well as the development of some diseases, including cancer.

<span class="mw-page-title-main">RNA-Seq</span> Lab technique in cellular biology

RNA-Seq is a technique that uses next-generation sequencing to reveal the presence and quantity of RNA molecules in a biological sample, providing a snapshot of gene expression in the sample, also known as transcriptome.

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.

<span class="mw-page-title-main">Cancer epigenetics</span> Field of study in cancer research

Cancer epigenetics is the study of epigenetic modifications to the DNA of cancer cells that do not involve a change in the nucleotide sequence, but instead involve a change in the way the genetic code is expressed. Epigenetic mechanisms are necessary to maintain normal sequences of tissue specific gene expression and are crucial for normal development. They may be just as important, if not even more important, than genetic mutations in a cell's transformation to cancer. The disturbance of epigenetic processes in cancers, can lead to a loss of expression of genes that occurs about 10 times more frequently by transcription silencing than by mutations. As Vogelstein et al. points out, in a colorectal cancer there are usually about 3 to 6 driver mutations and 33 to 66 hitchhiker or passenger mutations. However, in colon tumors compared to adjacent normal-appearing colonic mucosa, there are about 600 to 800 heavily methylated CpG islands in the promoters of genes in the tumors while these CpG islands are not methylated in the adjacent mucosa. Manipulation of epigenetic alterations holds great promise for cancer prevention, detection, and therapy. In different types of cancer, a variety of epigenetic mechanisms can be perturbed, such as the silencing of tumor suppressor genes and activation of oncogenes by altered CpG island methylation patterns, histone modifications, and dysregulation of DNA binding proteins. There are several medications which have epigenetic impact, that are now used in a number of these diseases.

Single-cell sequencing examines the nucleic acid sequence information from individual cells with optimized next-generation sequencing technologies, providing a higher resolution of cellular differences and a better understanding of the function of an individual cell in the context of its microenvironment. For example, in cancer, sequencing the DNA of individual cells can give information about mutations carried by small populations of cells. In development, sequencing the RNAs expressed by individual cells can give insight into the existence and behavior of different cell types. In microbial systems, a population of the same species can appear genetically clonal. Still, single-cell sequencing of RNA or epigenetic modifications can reveal cell-to-cell variability that may help populations rapidly adapt to survive in changing environments.

Saurabh Saha is an American biotech entrepreneur.

<span class="mw-page-title-main">Circulating tumor DNA</span> Tumor-derived fragmented DNA in the bloodstream

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.

Luis Alberto Diaz, Jr. is the Head of the Division of Solid Tumor Oncology in Memorial Sloan Kettering’s Department of Medicine.

References

  1. ↑ "Author Details: Victor Velculescu". Scopus .
  2. ↑ Victor Velculescu's publications in Google Scholar
  3. ↑ "Românul care vrea să pună frână celei mai grele boli a omenirii: cancerul. Decoperirea sa va revoluționa medicina". Stirileprotv.ro (in Romanian). December 1, 2017. Retrieved January 1, 2020.
  4. 1 2 "Pharmacia Prize". Science. 1999. ISSN   0036-8075 . Retrieved January 1, 2020.
  5. ↑ ""Doamna Drăculescu" ține în mână destinele Greciei! Vezi cum a ajuns o româncă de succes sefa misiunii FMI!" ["Mrs. Drăculescu" is holding Greece's destinies! See how a successful Romanian has become the head of the IMF mission!]. cancan.ro (in Romanian). July 22, 2015. Retrieved January 1, 2020.
  6. ↑ "Background: Victor Velculescu". The World Technology Network. 2005. Retrieved January 1, 2020.
  7. ↑ Velculescu VE, Zhang L, Vogelstein B, Kinzler KW (October 1995). "Serial analysis of gene expression". Science. 270 (5235): 484–7. Bibcode:1995Sci...270..484V. doi:10.1126/science.270.5235.484. PMID   7570003. S2CID   16281846.
  8. ↑ Velculescu VE, Zhang L, Zhou W, Vogelstein J, et al. (January 1997). "Characterization of the yeast transcriptome". Cell. 88 (2): 243–51. doi: 10.1016/s0092-8674(00)81845-0 . PMID   9008165. S2CID   11430660.
  9. ↑ Mardis ER (2008). "Next-generation DNA sequencing methods". Annual Review of Genomics and Human Genetics. 9: 387–402. doi:10.1146/annurev.genom.9.081307.164359. PMID   18576944. S2CID   2484571.
  10. ↑ Wang TL, Maierhofer C, Speicher MR, Lengauer C, et al. (December 2002). "Digital karyotyping". Proceedings of the National Academy of Sciences of the United States of America. 99 (25): 16156–61. Bibcode:2002PNAS...9916156W. doi: 10.1073/pnas.202610899 . PMC   138581 . PMID   12461184.
  11. ↑ Ding L, Wendl MC, Koboldt DC, Mardis ER (October 2010). "Analysis of next-generation genomic data in cancer: accomplishments and challenges". Human Molecular Genetics. 19 (R2): R188–96. doi:10.1093/hmg/ddq391. PMC   2953747 . PMID   20843826.
  12. ↑ Haber DA, Velculescu VE (June 2014). "Blood-based analyses of cancer: circulating tumor cells and circulating tumor DNA". Cancer Discovery. 4 (6): 650–61. doi:10.1158/2159-8290.CD-13-1014. PMC   4433544 . PMID   24801577.
  13. ↑ Bardelli A, Parsons DW, Silliman N, Ptak J, et al. (May 2003). "Mutational analysis of the tyrosine kinome in colorectal cancers". Science. 300 (5621): 949. doi:10.1126/science.1082596. PMID   12738854. S2CID   85934154.
  14. ↑ Samuels Y, Wang Z, Bardelli A, Silliman N, et al. (April 2004). "High frequency of mutations of the PIK3CA gene in human cancers". Science. 304 (5670). New York, N.Y.: 554. doi:10.1126/science.1096502. PMID   15016963. S2CID   10147415.
  15. ↑ Sjöblom T, Jones S, Wood LD, Parsons DW, et al. (October 2006). "The consensus coding sequences of human breast and colorectal cancers". Science. 314 (5797). New York, N.Y.: 268–74. Bibcode:2006Sci...314..268S. doi:10.1126/science.1133427. PMID   16959974. S2CID   15764172.
  16. 1 2 "Cancer genetics, Variations on a theme". The Economist. September 7, 2006.
  17. ↑ Wood LD, Parsons DW, Jones S, Lin J, et al. (November 2007). "The genomic landscapes of human breast and colorectal cancers". Science. 318 (5853). New York, N.Y.: 1108–13. Bibcode:2007Sci...318.1108W. doi:10.1126/science.1145720. PMID   17932254. S2CID   7586573.
  18. 1 2 Parsons DW, Jones S, Zhang X, Lin JC, et al. (September 2008). "An integrated genomic analysis of human glioblastoma multiforme". Science. 321 (5897). New York, N.Y.: 1807–12. Bibcode:2008Sci...321.1807P. doi:10.1126/science.1164382. PMC   2820389 . PMID   18772396.
  19. 1 2 Jones S, Zhang X, Parsons DW, Lin JC, et al. (September 2008). "Core signaling pathways in human pancreatic cancers revealed by global genomic analyses". Science. 321 (5897): 1801–6. Bibcode:2008Sci...321.1801J. doi:10.1126/science.1164368. PMC   2848990 . PMID   18772397.
  20. ↑ Parsons DW, Li M, Zhang X, Jones S, et al. (January 2011). "The genetic landscape of the childhood cancer medulloblastoma". Science. 331 (6016). New York, N.Y.: 435–9. Bibcode:2011Sci...331..435P. doi:10.1126/science.1198056. PMC   3110744 . PMID   21163964.
  21. ↑ Fox M (December 16, 2010). "Gene Scan Shows Childhood Brain is Different". Reuters.
  22. ↑ Sausen M, Leary RJ, Jones S, Wu J, et al. (January 2013). "Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma". Nature Genetics. 45 (1): 12–7. doi:10.1038/ng.2493. PMC   3557959 . PMID   23202128.
  23. ↑ "PopSci's 2nd Annual Brilliant 10". Popular Science. August 4, 2003.
  24. ↑ "Victor E. Velculescu, M.D., Ph.D." Pew's Scholars Directory. The Pew Charitable Trust. Archived from the original on July 20, 2012.
  25. ↑ "The Sir William Osler Young Investigator Award". Interurban Clinical Club.
  26. ↑ "Carcinogenesis Award Winners". Oxford University Press.
  27. ↑ "AACR Award for Outstanding Achievement in Cancer Research Recipients". American Association for Cancer Research (AACR).
  28. ↑ "Victor Velculescu". Judson Daland Prize for Outstanding Achievement in Patient-oriented Clinical Investigation. The American Philosophical Society. 2007. Archived from the original on July 20, 2012.
  29. ↑ "Paul Marks Prize Honors Young Investigators for Promising Cancer Research". Memorial Sloan Kettering Cancer Center. March 2012.
  30. 1 2 "AACR Team Science Award Recipients". American Association for Cancer Research (AACR).
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