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Victor E. Velculescu, M.D., Ph.D.

Photo of Dr. Victor E. Velculescu, M.D., Ph.D.

Co-Director of Cancer Biology

Professor of Oncology

Research Interests: Cancer Genomics

Contact for Research Inquiries

1550 Orleans Street
Koch Cancer Research Building
Baltimore, MD 21287 map
Phone: 410-955-7033
Fax: 410-502-5742

Email me

Background

Dr. Velculescu is Co-Director of Cancer Biology and Professor of Oncology and Pathology at the Johns Hopkins University Kimmel Cancer Center.  His research interests are focused on genomic analyses of human cancer and using such information to understand the underlying biology of cancer and to identify new diagnostic and therapeutic approaches.

Dr. Velculescu is internationally known for his genomic discoveries in human cancer.  He developed SAGE (serial analysis of gene expression) and used this method to perform the first transcriptome analysis in eukaryotic cells.  Subsequently, he developed Digital Karyotyping for analysis of structural genomic alterations and together with his colleagues performed the first sequence analysis of the coding genome in human cancers, including breast, colorectal, brain, pancreatic, and ovarian cancers.  These analyses identified a variety of genes not previously known to be involved in neoplasia, including PIK3CA gene as one of the most highly mutated genes in human cancer.  More recently, his group has developed PARE (personalized analysis of rearranged ends) for non-invasive liquid biopsy approaches for tumor detection and monitoring.  These discoveries provide insights into the mechanistic features and pathways underlying human cancer and provide new opportunities for individualized diagnostic and therapeutic approaches. 

Dr. Velculescu completed his B.S. at Stanford University and his M.D., Ph.D., and postdoctoral fellowship in Oncology at Johns Hopkins University.  Dr. Velculescu is a member of the Board of Directors of AACR, has served as a member of scientific advisory boards of Basser Research Center at University of Pennsylvania, the Starr Cancer Consortium, Quintiles, Helicos Biosciences, Inostics, and SoftGenetics, and is a co-founder of Personal Genome Diagnostics.  He is the recipient of several awards for his work including the Grand Prize Winner of the Amersham/Pharmacia & Science Young Scientist Prize (1999), Judson Daland Prize of the American Philosophical Society (2008), the European Association of Cancer Research and Carcinogenesis Young Investigator Award (2008), the AACR Award for Outstanding Achievement in Cancer Research (2009), the Paul Marks Prize for Cancer Research (2011), and the AACR Team Science Awards for Pancreatic (2013) and Brain Cancer Research (2014).

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Titles

  • Co-Director of Cancer Biology
  • Professor of Oncology
  • Professor of Pathology

Education

Degrees

  • B.S., Stanford University (California) (1992)
  • Ph.D., Johns Hopkins University (Maryland) (1999)
  • M.D., Johns Hopkins University School of Medicine (Maryland) (1999)

Additional Training

Postdoctoral fellowship, Johns Hopkins University Kimmel Cancer Center, Baltimore, Maryland, 2001, Oncology

Research & Publications

Research Summary

It is now widely accepted that cancer is a disease mediated by alterations in specific genes. The last decade has witnessed a dramatic increase in our understanding of the genomic characteristics of human cancer. In my laboratory we began these studies through a systematic analysis of gene families in human cancer, identifying PIK3CA as one of the most commonly mutated cancer genes. We extended these approaches with colleagues at JHU and other institutions to perform the first analyses of cancer genomes in breast, colorectal, pancreas, brain and other cancers. These efforts revealed the genomic landscape of human cancers, identifying new therapeutic targets such as mutant IDH genes in brain cancers and dysregulation of chromatin remodeling as a major mechanism of tumorigenesis. These analyses were spurred through novel genomic approaches we developed, including SAGE, Digital Karyotyping, and high throughput sequencing methods. 

Despite the progress that has been made, much remains to be discovered in understanding the dynamic changes that occur in cancer genomes during therapy, resistance and progression, and using this information for early detection and intervention. My group currently focuses on identifying genetic alterations in cancer affecting sensitivity and resistance to targeted therapies, and connecting such changes to key clinical characteristics and novel therapeutic approaches. We have recently developed methods that allow non-invasive characterization of cancer, including the PARE method that provided the first whole genome analysis of tumor DNA in the circulation of cancer patients. These analyses provide a window into real-time genomic analyses of cancer patients and provide new avenues for personalized diagnostic and therapeutic intervention.

Lab Website: Institute for Computational Medicine

Clinical Trials

Learn more about clinical trials at the Johns Hopkins Kimmel Cancer Center.

Selected Publications

View all on Pubmed

  1. Wang TL, Maierhofer C, Speicher MR, Lengauer C, Vogelstein B, Kinzler KW, Velculescu VE. Digital karyotyping. PNAS 99:16156-16161, 2002
  2. Bardelli A, Parsons DW, Silliman N, Ptak J, Szabo S, Saha S, Markowitz S, Willson JK, Parmigiani G, Kinzler KW, Vogelstein B, Velculescu VE. Mutational analysis of the tyrosine kinome. Science 300:949, 2003
  3. Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE. High Frequency of Mutations of the PIK3CA Gene in Human Cancers. Science, 304(5670): 554, 2004.
  4. Samuels Y, Diaz LA Jr, Schmidt-Kittler O, Cummins JM, Delong L, Cheong I, Rago C, Huso DL, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE. Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell 2005;7:561-73.
  5. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber T, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE. The Consensus Coding Sequences of Human Breast and Colorectal Cancers. Science. 314(5797):268-74, 2006.
  6. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW. An integrated genomic analysis of human glioblastoma multiforme. Science. 321(5897):1807-12, 2008. PMCID: PMC2820389
  7. Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, Hong SM, Fu B, Lin MT, Calhoun ES, Kamiyama M, Walter K, Nikolskaya T, Nikolsky Y, Hartigan J, Smith DR, Hidalgo M, Leach SD, Klein AP, Jaffee EM, Goggins M, Maitra A, Iacobuzio-Donahue C, Eshleman JR, Kern SE, Hruban RH, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 321(5897):1801-6, 2008. PMCID: PMC2848990.
  8. Leary RJ, Kinde I, Diehl F, Schmidt K, Clouser C, Duncan C, Antipova A, Lee C, McKernan K, de la Vega, F, Kinzler KW, Vogelstein B, Diaz LA Jr, Velculescu VE. Development of Personalized Tumor Biomarkers Using Massively Parallel Sequencing. Science TM, 2: 20ra14, 2010. PMCID: PMC2858564.
  9. Parsons DW, Li M, Zhang X, Jones S, Leary RJ, Lin JC, Boca SM, Carter H, Samayoa J, Bettegowda C, Gallia GL, Jallo GI, Binder ZA, Nikolsky Y, Hartigan J, Smith DR, Gerhard DS, Fults DW, VandenBerg S, Berger MS, Marie SK, Shinjo SM, Clara C, Phillips PC, Minturn JE, Biegel JA, Judkins AR, Resnick AC, Storm PB, Curran T, He Y, Rasheed BA, Friedman HS, Keir ST, McLendon R, Northcott PA, Taylor MD, Burger PC, Riggins GJ, Karchin R, Parmigiani G, Bigner DD, Yan H, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE. The genetic landscape of the childhood cancer medulloblastoma. Science 331: 435-439, 2010. PMCID: PMC3110744.
  10. Sausen M, Leary RJ, Jones S, Wu J, Reynolds CP, Liu X, Blackford A, Parmigiani G, Diaz LA Jr, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE, Hogarty MD. Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma. Nature Genetics. 45: 12-17, 2012. PMCID: PMC3557959.
  11. Leary RJ, Sausen M, Kinde I, Papadopoulos N, Carpten JD, Craig D, O'Shaughnessy J, Kinzler KW, Parmigiani G, Vogelstein B, Diaz LA Jr, Velculescu VE. Detection of chromosomal alterations in the circulation of cancer patients with whole-genome sequencing. Science TM. 4:162ra154, 2012. PMCID: PMC3641759.
  12. Haber DA, Velculescu VE. Blood-Based Analyses of Cancer: Circulating Tumor Cells and Circulating Tumor DNA. Cancer Discovery. 2014 Jun;4(6):650-61. PubMed PMID: 24801577.

Academic Affiliations & Courses

Graduate Program Affiliation

Program in Human Genetics

Cellular and Molecular Medicine Program

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