Johns Hopkins Center
Our Center is focused on identifying the genetic alterations responsible for human tumorigenesis and exploiting this knowledge to manage patients with cancer.
• BS, Philadelphia College of Pharmacy and Science
• PhD, The Johns Hopkins University School of Medicine
• Postdoctoral Fellow in Oncology, The Johns Hopkins School of Medicine
I am a medical oncologist and an expert in the treatment of colorectal and pancreatic cancers. My research focuses on the diagnostic and therapeutic applications of cancer genomics.
BS, University of Michigan, 1993
MD, University of Michigan, 1998
Residency, Internal Medicine, Johns Hopkins Medical Institute, 2001
Fellowship, Medical Oncology, Johns Hopkins Medical Institute, 2004
The Brain Cancer Biology and Therapy Laboratory’s goals are to develop and improve new therapies for brain and other cancers. We have developed more accurate in vivo and in vitro models of brain cancer for these preclinical studies. We also carefully study the molecular, pathological and genetic basis of gliomas, medulloblastoma and other nervous system malignancies to better understand how to improve the therapies we are developing in the laboratory. The first clinical trial from our work has opened for the treatment of newly diagnosed high-grade gliomas using a repurposed drug that disrupts tubulin formation and oncogenic signaling. We are also developing new therapies for clinical trials based on drug combination, activation of apoptosis, or using immune mediate targeting of solid tumors.
MD, Emory University, Atlanta, Georgia, 1994
PhD, human genetics, Emory University, Atlanta, Georgia, 1994
MS, biomedical engineering, Penn State University, University Park, Pennsylvania, 1984
BChE, chemical engineering, University of Delaware, Newark, Delaware, 1982
Professor of Neurosurgery and Oncology (with Tenure) at Johns Hopkins University, 2008
Director, Division of Neurosurgery Research, Johns Hopkins University, 2006
Inaugural Recipient of the Irving J. Sherman Professorship in Neurosurgery Research, 2004
Tenure Awarded (clinical and basic science), Duke University Medical Center, Durham, North Carolina, 2002
Laboratory Director, Brain Cancer Biology and Therapy Laboratory, 1997
Research Program Coordinator
MD, PhD student
MD, PhD student
Cancer is a genetic disease, and from all the differences between cancer and normal cells it is the genetic alterations present in the cancer cells that unequivocally distinguish them from the normal cells. Such genetic alterations provide exquisite specificity as biomarkers and pinpoint targets for the development of therapeutics. Our group has focused on: a) applying genome-wide approaches, such as high-throughput, massively parallel sequencing, for the identification of genetic changes on specific genes involved in the development and progression of cancer; and b) using this knowledge for the development of clinically applicable methods for early diagnostics, companion diagnostics, monitoring of disease, and therapeutics for cancer.
BS, Aristotle University of Thessaloniki, Thessaloniki, Greece
MS, University of Houston
PhD, University of Texas Health Science Center at Houston
Fogerty Fellowship, National Institutes on Aging, NIH
Postdoctoral Fellowship in Oncology, Johns Hopkins School of Medicine
Hypoxia, a consequence of tumor cells outgrowing their blood supply, and subsequent angiogenesis are two of the hallmarks of rapidly growing solid tumors. My group has been exploiting these unique pathological features for developing novel therapeutic approaches. One example is the development of C. novyi-NT, an attenuated strain of the anaerobic bacterium Clostridium novyi. The hypoxic tumor compartment poses challenges for both chemo and radiation therapies as hypoxia diminishes the therapeutic effects of chemotherapeutic agents and radiation. Conversely, this tumor compartment, hypoxic and immune-privileged, provides a unique niche for anaerobic bacteria to grow. We therefore generated C. novyi-NT, which has shown substantial therapeutic effects in experimental tumor models. A human Phase I trial and several canine trials are currently being conducted.
PhD, University of Pittsburgh
MD, Beijing Second Medical University
Senior Research Specialist
Research Technician III
Research Technician II
Research in the Ludwig Center at Johns Hopkins University is founded on the tenet that cancer is fundamentally due to a defect the cancer cell's genetic instructions. We have therefore focused our efforts on the identification of genes specifically mutated in human cancer. As a result of these efforts, we were the first group to sequence the exome in any human cancer, and eventually we would sequence 98 of the first 104 cancer exomes sequenced worldwide.
Our Center was paramount in defining many major cancer genes, including APC/β-catenin, FBXW, PIK3CA, IDH1/2, ARID1A/2, ATRX/DAXX and CIC/FUBP1. The identification of these mutated cancer genes provided important insights into the biology of cancer, suggested new therapeutic approaches and provided potentially clinically useful markers for cancer. This latter application is another major focus of our group.
Our Center was the first to demonstrate that the detection of mutated cancer genes in stool, plasma and other clinical samples could be used to monitor disease and detect human tumors at a stage when they were still curable. Our ultimate goal is that mutated cancer genes will be routinely used to detect cancer at early, curable stages. To help achieve this goal, we continue to develop innovative assays for detecting cancer gene mutations in clinical samples.
Diehl, F., Schmidt, K., Choti, M.A., Romans, K., Goodman, S., Li, M., Thornton, K., Agrawal, N., Sokoll, L., Szabo, S.A., Kinzler, K.W., Vogelstein, B. and Diaz Jr., L.A. Circulating mutant DNA to assess tumor dynamics. Nature Medicine 9: 985-990, 2008.
Parsons, D.W., Jones, S., Zhang, X., Lin, J.C., Leary, R.J., Angenendt, P., Mankoo, P., Carter, H., Siu, I.M., Gallia, G.L., Olivi, A., McLendon, R., Rasheed, B.A., Keir, S., Nikolskaya, T., Nikolsky, Y., Busam, D.A., Tekleab, H., Diaz, L.A. Jr, Hartigan, J., Smith, D.R., Strausberg, R.L., Marie, S.K., Shinjo, S.M., Yan, H., Riggins, G.J., Bigner, D.D., Karchin, R., Papadopoulos, N., Parmigiani, G., Vogelstein, B., Velculescu, V.E. and Kinzler K.W. An Integrated Genomic Analysis of Human Glioblastoma Multiforme. Science 26: 1807-1812 2008.
Jones, S., Zhang, X., Parsons, D.W., Lin, J.C., Leary, R.J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., Hong, S.M., Fu, B., Lin, M.T., Calhoun, E.S., Kamiyama, M., Walter, K., Nikolskaya, T., Nikolsky, Y., Hartigan, J., Smith, D.R., Hidalgo, M., Leach, S.D., Klein, A.P., Jaffee, E.M., Goggins, M., Maitra, A., Iacobuzio-Donahue, C., Eshleman, J.R., Kern, S.E., Hruban, R.H., Karchin, R., Papadopoulos, N., Parmigiani, G., Vogelstein, B., Velculescu, V.E. and Kinzler, K.W. Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses. Science 321: 1801-1806, 2008.
Yun, J., Rago, C., Cheong, I., Pagliarini, R., Angenendt, P., Rajagopalan, H., Schmidt, K., Wilson, J.K.V., Markowitz, S., Zhou, S., Diaz Jr. L.A., Velculescu, V.E., Lengauer, C., Kinzler, K.W., Vogelstein, B., Papadopoulos, N. Glucose Deprivation Contributes to the Development of KRAS Pathway Mutations in Tumor Cells. Science 325: 1555-1559, 2009.
He, Y., Wu, J., Dressman, D.C., Iacobuzio-Donahue, C., Markowitz, S.D., Velculescu, V.E., Diaz Jr., L.A., Kinzler, K.W., Vogelstein, B. and Papadopoulos, N. Heteroplasmic mitochondrial DNA mutations in normal and tumor cells. Nature 464:610-614, 2010. PMCID: PMC3176451
Jones, S., Wang, T.L., Shih,I.M., Mao, T.L., Nakayama, K., Roden, R., Glas, R., Slamon, D., Diaz, L.A. Jr., Vogelstein, B., Kinzler, K.W., Velculescu, V.E. and Papadopoulos, N. Frequent Mutations of Chromatin Remodeling Gene ARID1A in Ovarian Clear Cell Carcinoma. Science 363: 1532-1543, 2010.
Jiao, Y., Shi, C., Edil, B.H., de Wilde, R.F., Klimstra, D.S., Maitra, A., Schulick, R.D., Tang, L.H., Wolfgang, C.L., Choti, M.A., Velculescu, V.E., Diaz, L.A. Jr., Vogelstein, B., Kinzler, K.W., Hruban, R.H. and Papadopoulos, N. DAXX/ATRX, MEN1, and mTOR Pathway Genes Are Frequently Altered in Pancreatic Neuroendocrine Tumors. Science 331:1199-1203, 2011.
Bettegowda, C., Agrawal, N., Jiao, Y., Sausen, M., Wood, L.D., Hruban, R.H., Rodriguez, F.J., Cahill, D.P., McLendon, R., Riggins, G., Velculescu, V.E., Oba-Shinjo, S.M., Marie, S.K.N, Vogelstein, B., Bigner, D., Yan, H., Papadopoulos, N., Kinzler, K.W. Mutations in CIC and FUBP1 contribute to human oligodendrogliomas. Science 333: 1453-1455, 2011.
Diaz, L.A. Jr., Williams, R.T., Wu., J., Kinde, I., Hecht, J.R., Berlin, J., Allen, B., Bozic, I., Reiter, J.G., Nowak, M.A., Kinzler, K.W., Oliner, K.S. and Vogelstein, B. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 486: 537-540, 2012.
Kinde, I., Bettegowda, C., Wang, Y., Wu, J., Agrawal, N., Shih, IeM., Kurman, R., Dao, F., Levine, D.A., Giuntoli, R., Roden, R., Eshleman, J.R., Carvalho, J.P., Marie, S.K., Papadopoulos, N., Kinzler, K.W., Vogelstein, B. and Diaz, L.A. Jr. Evaluation of DNA from the papanicolaou test detect ovarian and endometrial cancers. Sci. Transl. Med. 5: 167ra4, 2013.