| Email |
rander54@jhmi.edu |
| Phone |
(410) 955-3511 |
Related Websites
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Liver Cancer
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Robert A. Anders, M.D., Ph.D.
Primary Appointment in Pathology
My laboratory's interests focus on the basic processes that lead to liver cell death and division. We approach these questions through the use of both experimental models and examination of human tissues. A microarray screening method uncovered several candidate genes that seem to contribute to the development of hepatocellular carcinoma in the setting of end-stage hepatitis C viral cirrhosis (1,2). From these studies we have begun to focus on how the immune system can create an environment that contributes to liver cell growth and death. In particular, we wish to understand how the TNF alpha related superfamily members LIGHT and lymphotoxin can control liver cell death and division. It appears as though these cytokines and their receptors have a dominant control over liver cell survival. We use basic models to replicate immune mediated liver injury. Surprisingly, we have found that not all activated immune cells lead to liver damage. We have recently uncovered that activated hematopoietic cells also support liver growth. While we will continue to extend these basic mechanistic studies we are also developing new methods to explore human hepatocellular carcinogenesis.
Publications
Anders RA, Yerian L, Tretiakova M, Davison JM, Quigg R, Domer PH, Hoberg J, Hart J. cDNA microarray analysis of macroregenerative and dysplastic nodules in end stage Hepatitis C induced liver disease. American Journal of Pathology March 2003; 162:991-1000.
Yerian LM, Anders RA, Tretiakova M, Hart J. Caveolin and thrombospondin expression during hepatocellular carcinogenesis. American Journal of Surgical Pathology. March 2004;28(3):357-64 200. |
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| Email |
bbhagav@jhmi.edu |
| Phone |
(410) 614-5172 |
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Belur S. Bhagavan, M.D.
Primary Appointment in Pathology
My research efforts are essentially centered around clinicopathologic correlation studies of diagnostic challenges encountered in surgical pathology practice. The traditional gross and microscopic features are blended with information obtained from the more modern technologies of electron microscopy, immunohistochemistry, histochemistry, molecular biology, endoscopy and modern imaging techniqes in the correlative studies. My present interests are in the areas of adult and pediatric gastrointestinal diseases.
Publications
Slavin RE, Saeki K and Bhagavan BS. Segmental arterial mediolysis: A disease of the endothelial paracrine system and a precursor to fibromuscular dysplasia. A clinical pathologic study. Mod Pathol 8:287-294, 1995.
Howard TJ, Lewin KJ, Sted B, Bhagavan BS and Passaro Jr. E. Pancreaticpolypeptide immunoreactivity in gastrinoma: Relationship to intra abdominal location. Pancreas 11:350-356, 1995.
Abraham, S.C., Bhagavan, B.S., Lee, L.A., Rashid, A. and Wu, T.T. UpperGastrointestinal Tract Injury in Patients Receiving Kayexalate (SodiumPolystyrene Sulfonate) in Sorbitol: Clinical, Endoscopic and Histopathologic Findings. Amer.J.Surg. Path. 25: 637-644, 2001.
Dutta, S.K., Chung, K.Y., and Bhagavan, B.S. Thermal Injury of the Esophagus. New England Journal of Medicine, 339 (7): 480-481, 1998. |
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| Email |
jboitnot@jhmi.edu |
| Phone |
(410) 955-8377 |
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John K. Boitnott, M.D.
Primary Appointment in Pathology
Former Pathologist-in-Chief, Johns Hopkins Hospital
My principal area of interest is liver disease with an associated interest in disease of the biliary tract and pancreas. Most of my work involves collaborative clinico-pathologic studies. Areas in which there are now particularly good opportunities for such studies at Johns Hopkins include: liver transplants, bone marrow transplants, hepatic neoplasms, Budd-Chiari syndrome, sclerosing cholangitis, bile duct carcinomas and pancreatic carcinomas.
Publications
Diehl AM, Boitnott JK, Herlong HF, Potter JJ, Van Duyn MA, Chandler E,Mezey E. Effect of parenteral amino acid supplementation in alcoholichepatitis. Hepatology 5:57-63, 1989.
Christensen WN, Boitnott JK, Kuhajda FP. Immunoperoxidase staining as adiagnostic aid for hepatocellular carcinoma. Mod Pathol 2:8-12, 1989.
Allison DC, Bose KK, Hruban RH, Piantadosi S, Dooley WC, Boitnott JK,Cameron JL. Pancreatic cancer cell DNA content correlates with long-termsurvival after pancreaticoduodenectomy. Ann Surg 214:648-656, 1991.
Ayuse T, Brienza N, Revelly JP, Boitnott JK, Robotham JL. The role ofnitric oxide in the porcine liver circulation under normal and endotoxemic conditions. J Appl Physiol 78:1319-1329, 1995. |
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| Email |
jeshlem@jhmi.edu |
| Phone |
(410) 955-3511 |
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James R. Eshleman, M.D., Ph.D.
Primary Appointment in Pathology; Secondary Appointment in Oncology
Member, Graduate Program in Pathobiology; Member, Graduate Program in Cellular and Molecular Medicine; Associate Director, Molecular Diagnostics Laboratory
Pancreatic cancer is the 10th leading cause of new cancers in the US, but the 3rd most common in cancer deaths. The 5-year survival of pancreatic cancer is currently less than 5%. Critical to improving these statistics is a full and detailed understanding of the gene mutations in pancreatic cancer, and familial predispositions. Towards this end, we recently performed full exomic sequencing for 24 pancreatic cancers and reported a new familial predisposition gene. Other ways to impact on this disease are early detection, molecular subclassification, and novel therapeutics.
My research laboratory is also involved in translational research in molecular diagnostics and basic science research on novel therapeutics. We have recently reported a novel method for point mutation detection, and are currently incorporating this strategy for early detection of pancreas cancer in collaboration with Drs. Michael Goggins Chris Gocke and Ralph Hruban.
I also have a significant interest in nucleic acid based novel therapeutics. Recently, we have developed a novel strategy to select against specific cell populations using "anti-gene padlocks." Anti-gene padlocks are oligonucleotides capable of reacting and intertwining with DNA followed by end-to-end ligation. We have demonstrated their activity in bacterial cells, where once bound and ligated, the padlock is inextricably attached. If the target is present in a bacterial cell's chromosome, the cell is killed. Experiments are currently underway to determine the critical features of anti-gene locks, the mechanism of cell death and whether this novel therapeutic can be used to target human cells in a similar fashion.
I also have special interests in Molecular Pathology.
Publications
Shi C, Eshleman SH, Jones D, Fukushima N, Hua L, Parker AR, Yeo CJ, Hruban RH, Goggins MG, and Eshleman JR. LigAmp for Sensitive Detection of Single Nucleotide Differences. Nature Methods, 1: 141-147, November, 2004.
Shi C, Parker AR, Hua L, Morrell CN, Lee SC, Bandaru W, Wu TC and Eshleman JR. Anti-gene padlocks kill bacterial cells based on their genotype. Submitted.
Shi C, Fukushima N, Abe T, Bian Y, Hua L, Wendelburg BJ, Yeo CJ, Hruban RH, Goggins MG, and Eshleman JR. Sensitive and quantitative detection of KRAS2 gene mutations in pancreatic duct juice differentiates patients with pancreatic cancer from chronic pancreatitis, potential for early detection. Cancer Biol Ther, 3/2008; 7:260-7.
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, and Kinzler KW. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 9/2008; 321:1801-6.
Shi C, Hong SM, Lim P, Kamiyama H, Khan M, Anders RA, Goggins M, Hruban RH, and Eshleman JR. KRAS2 mutations in human pancreatic acinar-ductal metaplastic lesions are limited to those with PanIN: Implications for the human pancreatic cancer cell of origin. Mol Cancer Res, 2/2009; 7:230-6 [NIHMS #89589].
Jones S, Hruban RH, Kamiyama M, Borges M, Zhang X, Parsons DW, Cheng-Ho Lin J, Palmisano E, Brune K, Jaffee EM, Iacobuzio-Donahue CA, Maitra A, Parmigini G, Kern SE, Velculescu VE, Kinzler KW, Vogelstein B, Eshleman JR, Goggins M, and Klein AP. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science. 4/2009; 324:217.
Shi C, Chandrasekharan A, Thuluvath PJ, Karikari C, Argani P, Goggins M, Maitra A, and Eshleman JR. Ultrasensitive detection of KRAS2 mutations in bile and serum from patients with biliary tract carcinoma using LigAmp technology. J Molec Diagnostics. In Press. |
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| Email |
fgiardi@jhmi.edu |
| Phone |
(410) 955-2635 |
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Francis M. Giardiello, M.D.
Director, Division of Gastroenterology
Primary Appointment in Medicine, Division of Gastroenterology; Secondary Appointment in Pathology
My research has focused on the study of cancer and cancer chemoprevention in the gastrointestinal tract. This has included the investigation of the genetic basis of familial colorectal cancer and the use of genetic testing in the hereditary forms of colorectal cancer. I have had continuing interest in the study of the genotypic phenotypic correlations in the polyposis syndromes which include familial adenomatous polyposis, juvenile polyposis and Peutz-Jeghers syndrome.
Publications
Giardiello FM, Hamilton SR, Krush AJ, Booker SV, Jen J, Piantadosi S, Hylind LM, Celano P, Booker SV, Robinson CR, Offerhaus GJA. Evaluation of sulindac therapy for colonic and rectal adenornas in familial adenomatous polyposis. NEJM 1993; 328: 1313-16.
Giardiello FM, Brensinger JD, Luce MC, Peterson GM, Cayouette MC, Krush AJ, Booker SV, Bufill JA, Hamilton SR. Phenotype expression in adenomatous polyposis families with mutation in the 5' region of he adenormatous polyposis coli gene. Annal Internal Medicine 1997; 126: 514 -14.
Giardiello FM, Brensinger JD, Luce MC, Hylind LM, Bacon JQ, Booker SV, Parker RD, Hamilton SR. The use and interpretation of commercial APC gene testing for familial adenornatous polyposis. N. Engl J Med 1997; 336:823-7.
Giardiello FM, Brensinger JD, Tersmette A, Goodman SN, Johnson KA, Booker SV, Cruz-Curres M. Peterson GM, Offerhaus JGA, Peutz-Jeghers syndrome and high risk of cancer. Gastroenterology 2000;119:1447-53. |
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Michael G. Goggins, M.D.
Primary Appointment in Pathology; Secondary Appointments in Medicine, Oncology
Member, Graduate Program in Pathobiology
I am a gastroenterologist with a research laboratory dedicated to identifying translational opportunities in pancreatic cancer. Improving the prognosis of such a deadly disease will require advances in our ability to identify at-risk individuals, establish screening tests to identify earlier-stage disease, and to continue elucidating the biology of the disease. Currently, the laboratory is investigating the utility of detecting DNA methylation, DNA mutation and proteomic alterations to determine which markers are the most accurate markers of pancreatic cancer. We have also used gene expression data from microarrays and other sources as a way to identify markers of pancreatic cancer.
We are also pursuing proteomic approaches using protein chip technology and 2D gel electrophoresis to identify protein markers of pancreatic cancer that could be used for early diagnosis. We are also trying to identify genetic abnormalities that contribute to familial pancreatic cancer risk. We participate in a nationwide multicenter linkage study (PACGENE), the pancreatic cancer genetic epidemiology consortium to identify familial pancreatic cancer susceptibility genes. We are also characterizing genetic changes in familial pancreatic neoplasms to identify changes unique to these tumors. DNA methylation changes contribute to many of the biological properties of pancreatic cancer and we are determining why such changes occur during pancreatic cancer development and the biological significance of silencing genes by methylation in pancreatic neoplasia.
Publications
Koopmann J, Buckhultz P, Brown DA, Zahurak M, Sato N, Fukushima N, Sokoll L, Chan D, Yeo CJ, Hruban RH, Breit S, Kinzler K, Vogelstein B, Goggins M. Serum Macrophage Inhibitory Cytokine 1 as a marker of Pancreatic and other Periampullary cancers. Clin Cancer Res 2004;10:2386-92.
Sato N, Maehara N, Su GH, Goggins M. Effects of 5-Aza-2'-deoxycytidine on matrix metalloproteinase expression and pancreatic cancer cell invasiveness. J Natl Cancer Institute 2003:95:327-30.
Sato N, Fukushima N, Anirban Maitra, Matsubayashi M, Yeo CJ, Cameron JL, Hruban R, Goggins M. Discovery of novel targets for aberrant methylation in pancreatic carcinoma using high-throughput microarrays. Cancer Res:2003;633735-42.
Sato N, Ueki T., Fukushima N, Iacobuzio-Donahue CA, Yeo CJ, Cameron JL, Hruban RH, Goggins M. Aberrant Methylation of CpG Islands in Intraductal Papillary Mucinous Neoplasms of the Pancreas Increases with Histological Grade. Gastroenterology 2002; 123;365-72.
Rosty C, Christa L, Kuzdzal S, Baldwin WM, Zahurak ML, Carnot F, Chan DW, Canto M, Lillemoe KD, Cameron JL, Yeo CJ, Hruban RH, Goggins M. Identification of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein I as a biomarker for pancreatic ductal adenocarcinoma by proteinbiochip technology. Cancer Res. 2002 Mar 15;62(6):1868-75. |
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Christine A. Iacobuzio-Donahue, M.D., Ph.D.
Primary Appointment in Pathology; Secondary Appointment in Oncology
My research efforts are focused upon the molecular biology and genetics associated with lethal cancer metastasis. To support my research, I instituted the Johns Hopkins Gastrointestinal Cancer Rapid Medical Donation Program (GICRMDP) in 2003. This unique program allows patients with terminal, metastatic cancer to agree to undergo a rapid autopsy for research purposes. These tissues are then analyzed by my laboratory using a variety of high-throughput methods including whole genome high-density SNP arrays, gene sequencing and oligonucleotide microarrays in an effort to identify novel areas of homozygous deletion and/or genetic alteration specifically associated with cancer metastasis. Candidate genes identified are further evaluated using a variety of in vivo mouse models to explore their functional relationship to tumor progression, invasion and metastasis.
Publications
C.A. Iacobuzio-Donahue, B. Ryu, R.H. Hruban, S.E. Kern. Exploring the host desmoplastic response to pancreatic carcinoma: Gene expression of stromal and neoplastic cells at the site of primary invasion. American Journal of Pathology 2002, 160:91-99.
C.A.Iacobuzio-Donahue, R. Ashfaq, A. Maitra, N.V. Adsay, G.L. Shen-Ong, K.Berg, M.A. Hollingsworth, C.J.Yeo, S.E.Kern, M.G. Goggins, R.H.Hruban. Highly Expressed Genes in Pancreatic Ductal Adenocarcinomas: A Comprehensive Characterization and Comparison of the Transcription Profiles Obtained from Three Major Technologies. Cancer Res 2003 63:8614-22.
C.A. Iacobuzio-Donahue, Jason Song, Giovanni Parmiagiani, Charles J. Yeo, Ralph H. Hruban, Scott E. Kern. Missense mutations of MADH4: Characterization of the mutational hotspot and functional consequences in human tumors. Clin Cancer Res. 2004 10:1597-604.
C.A. Iacobuzio-Donahue, M.S. van der Heijden, M.R. Baumgartner, W.J. Troup, J.R. Romm, K. Doheny, E.W.Pugh, C.J.Yeo, M.G.Goggins, R.H.Hruban, S.E.Kern. Large Scale Allelotype of Pancreaticobiliary Carcinoma Provides Quantitative Estimates of Genome-Wide Allelic Loss. Cancer Res 2004 64:871-5.
L.S. Nichols, R. Ashfaq, C.A. Iacobuzio-Donahue. Claudin 4 Protein Expression in Primary and Metastatic Pancreatic Cancer: Support for use as a Therapeutic Target. Am J Clin Pathol 2004 121:226-230. |
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| Email |
Ejaffee1@jhmi.edu |
| Phone |
(410) 955-2957 |
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Elizabeth Jaffee, M.D.
Primary Appointment in Oncology; Secondary Appointments in Pathology and Pharmacology
Member, Graduate Program in Cellular and Molecular Medicine; Member, Graduate Program in Immunology; Member, Graduate Program in Pharmacology and Molecular Science
The laboratory's overall goal is to develop vaccine strategies that can induce specific antitumor immunity potent enough to cure cancer. The laboratory focuses predominantly on two diseases: breast cancer and pancreatic cancer. One major project is the evaluation of new antigen-specific vaccine approaches for the treatment and prevention of cancer in the HER-2/neu transgenic mouse model of breast cancer. These mice overexpress the proto-oncogene under the MMTV promoter in normal mammary tissue and subsequently develop focal mammary tumors. This model has several advantages over previous models used to develop vaccine approaches. First, this model provides an endogenously expressed antigen to target that is expressed both by normal tissue and the tumor, thereby allowing for the development of vaccines for prevention as well as treatment. Second, endogenous tumors develop in 100% of mice, thereby allowing for the testing of vaccines for the treatment of naturally developing tumors. Third, these transgenic mice demonstrate peripheral tolerance to the HER-2/neu gene product which appears to be similar to the tumor tolerance observed in humans. The laboratory is currently using this model to identify vaccine strategies that can ultimately be tested in patients with cancer, particularly breast and pancreatic cancers. A second major project is the identification of human tumor antigens recognized by T cells that have been isolated from vaccinated individuals. We have recently identified mesothelin as a relevant pancreatic tumor antigen recognized by patients treated with a pancreatic cancer vaccine. A third major project is the analysis of antitumor immune responses in patients enrolled on vaccine studies that my colleagues and I are conducting. We have completed an allogeneic GM-CSF secreting pancreatic vaccine phase 1 study and are currently analyzing several immune parameters in patients enrolled in this study. We are currently conducting two phase II studies in metastatic cancer patients and patients following pancreaticoduodenectomy.
Publications
Reilly RT, Gottlieb MBC, Ercolini AM, Machiels J-PH, Kane CE, Okoye FI, Muller WJ, Dixon KH, and Jaffee EM. HER-2/neu Is a Tumor Rejection Target in Tolerized HER-2/neu Transgenic Mice1. Cancer Research 60, 3569-3576, 2000.
Reilly RT, Machiels J-P H, Emens LA, Ercolini AM, Okoye FI, Lei RY, Weintraub D, Jaffee EM. The Collaboration of Both Humoral and Cellular HER-2/neu-targeted Immune Responses Is Required for the Complete Eradication of HER-2/neu-expressing Tumors1. Cancer Research 61, 880-883, 2001.
Machiels J-PH, Reilly RT, Emens LA, Ercolini AM, Lei RY, Weintraub D, Okoye FI, Jaffee EM. Cyclophosphamide, Doxorubicin, and Paclitaxel Enhanced the Antitumor Immune Response of Granulocyte/Macrophage-Colony Stimulating Factor-secreting Whole-Cell Vaccines in HER-2/neu Tolerized Mice. Cancer Research 61, 3689-3697, 2001.
Jaffee EM, Hruban RH, Biedrzycki B, Laheru D, Schepers K, Sauter PR, Goemann M, Coleman J, Grochow L, Donehower RC, Lillemoe KD, O'Reilly S, Abrams RA, Pardoll DM, Cameron JL, Yeo CJ. Novel Allogeneic Granulocyte-Macrophage Colony-Stimulating Factor-Secreting Tumor Vaccine for Pancreatic Cancer: A Phase I Trial of Safety and Immune Activation. Journal of Clinical Oncology 19 (1), 145-156, 2001.
Thomas AM, Santarsiero LM, Lutz ER, Armstrong TD, Chen Y-C, Huang L-Q, Laheru DA, Goggins M, Hruban RH, Jaffee EM. Mesothelin Specific CD8+ T Cell Responses Provide Human Evidence of In Vivo Cross-Priming by Antigen Presenting Cells in Vaccinated Pancreatic Cancer Patients. J Exp Med., 200(3):297-306, 2004. |
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| Email |
skern1@jhmi.edu |
| Phone |
(410) 614-3314 |
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Scott E. Kern, M.D.
Primary Appointment in Oncology; Secondary Appointment in Pathology
Member, Graduate Program in Cellular and Molecular Medicine; Member, Graduate Program in Human Genetics and Molecular Biology; Member, Graduate Program in Pathobiology
I am a cancer geneticist and gastrointestinal pathologist interested in clonal genetic changes in neoplasia. This has included genetic alterations in colorectal and pancreatic carcinoma, their association with pathological characteristics and prognosis, cloning of the DCC and DPC4 genes, localization of the BRCA2 gene, the cause of familial pancreatic cancer, the DNA-binding characteristics of p53 and DPC4, and gene expression profiling.
Publications
Kern SE, Kinzler KW, Bruskin A, Jarosz D, Friedman P, Prives C, Vogelstein B.Identification of p53 as a sequence-specific DNA-binding protein. Science252:1708-11, 1991.
Hahn SA, Schutte M, Hoque ATMS, Moskaluk CA, da Costa LT, Rozenblum E,Weinstein CL, Fischer A, Yeo CJ, Hruban RH, Kern SE. DPC4, a candidatetumor-suppressor gene at human chromosome 18q21.1. Science 271:350-353,1996.
Ryu B, Jones J, Hollingsworth MA, Hruban RH, Kern SE. Invasion-specificgenes in malignancy: SAGE comparisons of primary and passaged cancers. CancerRes 2001; 61:1833-1838.
Schutte M, DaCosta LT, Hahn SA, Moskaluk C, Hoque ATMS, Rozenblum E,Weinstein CL, Bittner M, Meltzer PS, Trent JM, Yeo CJ, Hruban RH, Kern SE.Identification by representational difference analysis of a homozygousdeletion in pancreatic carcinoma that lies within the BRCA2 region. Proc Natl Acad Sci 92:5950-5954, 1995. |
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| Email |
aklein1@jhmi.edu |
| Phone |
(410) 614-3314 |
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Alison Klein, Ph.D., M.H.S.
Primary Appointment in Oncology; Secondary Appointment in Pathology
My research involves understanding why pancreatic cancer clusters in some families. I am the Director of the National Familial Pancreas Tumor Registry at Johns Hopkins, a registry with over 1400 pancreatic cancer kindreds. It is by studying these families that I hope to learn about the genetic and environmental factors involved in the development of pancreatic cancer, so that we can one day reduce the burden of the disease. My work involves collaborations with Drs. Hruban, Goggins and Maitra.
Publications
Klein AP, Brune, KA , Petersen GM, Goggins M., Tersmette, AC, Offerhaus GJA, Griffin CA, Cameron JL, Yeo CJ, Kern S, Hruban RH. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Research, 2004 64:2634-2638
Klein AP, Beaty TH, Bailey-Wilson JE., Brune KA, Hruban RH, Petersen GM. Evidence for a Major Gene Influencing Risk of Pancreatic Cancer. Genetic Epidemiology. 2002; 23 133-149.
Klein AP, Hruban RH, Brune, KA, Petersen, GM, Goggins, M. Familial Pancreatic Cancer. The Cancer Journal. 2001; 7 266-273 |
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| Email |
amaitra1@jhmi.edu |
| Phone |
(410) 955-3511 |
Related Websites
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Pancreas Cancer
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Anirban Maitra, M.B.B.S.
Primary Appointment in Pathology; Secondary Appointments in Oncology and in the McKusick-Nathans Institute for Genetic Medicine
Pancreatic cancer accounts for 31,000 cancer-related deaths each year in the United States, and currently available conventional chemo-radiation therapies have been unable to significantly ameliorate the prognosis of this terrible disease. The major focus of my laboratory is the development of potent targeted therapies for pancreatic cancer. In particular, we are studying the role of aberrantly activated developmental signaling pathways, such as the Hedgehog and Notch pathways, as potential therapeutic targets in pancreatic cancer. To facilitate these studies, we have developed a unique repertoire of human pancreatic cancer xenografts and low-passage cell lines that permit both ex vivo and in vivo validation of novel small molecule and antibody-based treatment strategies. In addition, we are working with established genetic mouse models of pancreatic preneoplasia and invasive cancer as a platform for biomarker discovery and therapeutic targeting. The study of pancreatic cancer genetics, particularly novel oncogenes and tumor suppressor genes that may form substrates for targeted therapies, is also an area of active interest. Lastly, my laboratory is also pursuing the development of nanoparticle-based targeted drug and gene delivery to pancreatic cancer.
Publications
Berman DM*, Karhadkar SS*, Maitra A*, et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature.2003; 425:846-51 (*equal contribution)
Miyamoto Y, Maitra A, Ghosh B, et al. Notch mediates TGF alpha-inducedchanges in epithelial differentiation during pancreatic tumorigenesis. CancerCell. 2003; 3:565-76
Nowak NJ, Gaile D, Conroy JM, McQuaid D, Cowell J, Carter R, Goggins MG, Hruban RH, Maitra A. Genome-wide aberrations in pancreatic adenocarcinoma. Cancer Genet Cytogenet. 2005;161:36-50.
Hustinx SR, Hruban RH, Leoni LM, Iacobuzio-Donahue C, Cameron JL, Yeo CJ, Brown PN, Argani P, Ashfaq R, Fukushima N, Goggins M, Kern SE, Maitra A. Homozygous deletion of the MTAP gene in invasive adenocarcinoma of the pancreas and in periampullary cancer: a potential new target for therapy. Cancer Biol Ther. 2005;4:83-6
Maitra A, Fukushima N, Takaori K, Hruban RH. Precursors to invasive pancreatic cancer. Adv Anat Pathol. 2005;12:81-91 |
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Elizabeth A. Montgomery, M.D.
Primary Appointment in Pathology
My research efforts are clinicopathologic studies of well-characterized and novel entities encountered in surgical pathology using both conventional light microscopy and newer techniques. Specific interests include several topics in gastrointestinal pathology, especially Barrett esophagus. I look forward to additional clinicopathological work using newer technology. I also have a strong interest in soft tissue pathology and recent studies have been of telomeres in translocation-associated sarcomas compared to chromosome unstable types.
Publications
Montgomery E, Bronner M, Goldblum J, Greenson J, Haber M, Hart J, Lamps L, Lauwers G, Lazenby A, Lewin D, Robert M, Toledano A, Shyr Y, Washington K. Diagnostic reproducibility of dysplasia in Barrett esophagus (BE): Are affirmation. Human Pathology 2001; 32: 368-78.
Montgomery E, Goldblum J, Greenson JK, et al. Dysplasia as a predictive marker for invasive carcinoma in Barrett's esophagus; A follow-up study basedon 138 cases from a diagnostic variability study. Human Pathology 2001; 32:379-388.
Montgomery E, Wilentz R, Argani P, Hruban RH, Fisher C, Kern SE, Lengauer C. Analysis of Anaphase Figures in Routine Histologic Sections Distinguishes Chromosomally Unstable From Chromosomally Stable Malignancies. Cancer Biology and Therapy 2003;3:248-52
Montgomery E, Argani P, Hicks JL, DeMarzo AM and Meeker AK. In situ analysis of telomere lengths in translocation associated and non-translocation associated sarcomas. Am J Pathol 2004; 164: 1523-1529.
Hansel DE, Dhara S, Huang RC, Ashfaq R, Deasel M, Shimada Y, Bernstein HS, Harmon J, Brock M, Forastiere A, Washington MK, Maitra A, Montgomery E. CDC2/CDK1 Expression in Esophageal Adenocarcinoma and Precursor Lesions Serves as a Diagnostic and Cancer Progression Marker and Potential Novel Drug Target. Am J Surg Pathol. In press [2005]. |
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| Email |
mtorben@jhmi.edu |
| Phone |
(443) 287-4730 |
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Michael S. Torbenson, M.D.
Primary Appointment in Pathology
I am interested in liver and gastrointestinal disease as well as transplant pathology. Currently, my research is focused on viral hepatitis and I am investigating the prevalence and significance of occult hepatitis B infections (HBsAg negative, HBV DNA positive). I am also interested in primary hepatocellular neoplasms and am involved in a variety of clinicopathological studies. I also have a long-standing interest in archaeology and the history of medicine.
Publications
Torbenson M, Wang J, Nichols L, Jain A, Fung J, Nalesnik MA. Occult nonhematopoietic malignancies present at autopsy in solid organ transplant patients who died within 100 days. Transplantation 2001; 71 (1):64-70.
Minervini MI, Torbenson M, Scantlebury V, Vivas C, Jordan M, Shapiro R, Randhawa P. Acute renal allograft rejection with severe tubulitis (Banff 1997grade 1B). American Journal of Surgical Pathology, 2000 24(4):553-8.
Torbenson M, Wang J, Nichols L, Randhawa P, Nalesnik MA. Renal cortical neoplasms in long term survivors of solid organ transplantation.Transplantation. 2000 15;69(5):864-8.
Torbenson M, Kelly R, Erlen J, Cropcho L, Moraca M, Beiler B, Rao KN,Virji M. Lash's: A bitter medicine: Biochemical analysis of a historical proprietary medicine. Historical Archaeology 2000, 34(2):56-64. |
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| Email |
vogelbe@welch.jhmi.edu |
| Phone |
(410) 955-0548 |
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Bert Vogelstein, M.D.
Primary Appointment in Oncology; Secondary Appointment in Pathology; Joint Appointment in Molecular Biology and Genetics
Member, Graduate Program in Cellular and Molecular Medicine; Member, Graduate Program in Human Genetics and Molecular Biology; Member, Graduate Program in Pharmacology and Molecular Sciences
It has become clear over the last decade that cancer is, in essence, a genetic disease. The study of colorectal tumorigenesis has provided particularly cogent evidence of the influence of genes on cancer, and has illuminated the following principles. First, human tumors represent the expansion of a single transformed cell. Second, the initiation of this process and the expansion of the transformed cell are due to mutations in specific oncogenes and tumor suppressor genes. Third, these mutations occur in a preferred order as the tumor progresses from benign to malignant stages. Fourth, mutations in the same genes can occur either through inherited or somatic pathways. Fifth, naturally-occurring mutations in these genes can provide critical clues to their biochemical and physiologic functions. Sixth, most cancers are genetically unstable, with the elevated mutation rates facilitating development of the multiple mutations required for malignancy. Our current research is directed to further understanding the genes and pathways underlying colorectal tumorigenesis and to the development of new approaches for the management of patients with this disease.
Publications
Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 61:759-767, 1990.
Kinzler KW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell 87:159-170, 1996.
Lengauer, C., Kinzler, K.W., and Vogelstein, B. Genetic instabilities in human cancers. Nature 396: 643 649, 1998.
Vogelstein, B. and Kinzler, K.W. Cancer genes and the pathways they control. Nature Medicine 10: 789-799, 2004. |
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