The URL for our Divisional Web site is http://pathology2.jhu.edu/department/divisions/gi/index.cfm

Brat DJ, Hahn SA, Griffin CA, Kern SE, Hruban RH. Structural basis of molecular genetic deletions: integration of classical cytogenic and molecular analyses in pancreatic adenocarcinoma. Am J Pathol 150:383-391, 1997.

Fujii H, Inagaki M, Kasai, Miyokawa N, Toshihiko Y, Gabrielson E, Hruban RH. Genetic progression and heterogeneity in intraductal papillary-mucinous neoplasms of the pancreas. Am J Pathol 151:1447-1454, 1997.

Christine A. Iacobuzio-Donahue, Anirban Maitra, Grace L. Shen-Ong, Tjarda van Heek, Raheela Ashfaq, Renee Meyer, Kimberly Walter, Karin Berg, Michael A. Hollingsworth, John L. Cameron, Charles J. Yeo, Scott E. Kern, Michael Goggins, and Ralph H. Hruban Discovery of Novel Tumor Markers of Pancreatic Cancer using Global Gene Expression Technology. Am J Pathol 2002 160: 1239-1249.

Susan C. Abraham, David S. Klimstra, Robb E. Wilentz, Charles J. Yeo, Kevin Conlon, Murray Brennan, John L. Cameron, Tsung-Teh Wu, and Ralph H. Hruban Solid-Pseudopapillary Tumors of the Pancreas Are Genetically Distinct from Pancreatic Ductal Adenocarcinomas and Almost Always Harbor ß-catenin Mutations. Am J Pathol 2002 160: 1361-1369.

Director, Division of Gastrointestinal and Liver Pathology
Deputy Director for Fund and Program Development, Department of Pathology
Primary Appointment in Pathology; Secondary Appointment in Oncology

Belur S. Bhagavan, M.B., B.S._

410-614-5172

bbhagav@jhmi.edu

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.

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. Pancreatic polypeptide immunoreactivity in gastrinoma: Relationship to intraabdominal location. Pancreas 11:350-356, 1995.

Abraham, S.C., Bhagavan, B.S., Lee, L.A., Rashid, A. and Wu, T.T. Upper Gastrointestinal Tract Injury in Patients Receiving Kayexalate (Sodium Polystyrene 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.

Primary Appointment in Pathology

John K. Boitnott, M.D._

410-955-8377

jboitnot@jhmi.edu

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.

Diehl AM, Boitnott JK, Herlong HF, Potter JJ, Van Duyn MA, Chandler E, Mezey E. Effect of parenteral amino acid supplementation in alcoholic hepatitis. Hepatology 5:57-63, 1989.

Christensen WN, Boitnott JK, Kuhajda FP. Immunoperoxidase staining as a diagnostic 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-term survival after pancreaticoduodenectomy. Ann Surg 214:648-656, 1991.

Ayuse T, Brienza N, Revelly JP, Boitnott JK, Robotham JL. The role of nitric oxide in the porcine liver circulation under normal and endotoxemic conditions. J Appl Physiol 78:1319-1329, 1995.

Primary Appointment in Pathology
Former Pathologist-in-Chief, Johns Hopkins Hospital

James Eshleman, M.D., Ph.D._

410-955-3511

*** none ***

Colorectal cancer is the second leading cause of cancer deaths in the US. Many cases of colon cancer occur in the setting of the familial cancer syndrome, Hereditary Non-Polyposis Colon Cancer (HNPCC). In these cancers, defects in a DNA repair system, mismatch repair, profoundly increase the mutation rate of these cells, thereby accelerating carcinogenesis and causing microsatellite instability. We have been investigating colon cancers, which do not possess defects in mismatch repair, and find that these microsatellite stable cancer cells commonly possess increases in their spontaneous mutation rates. We are currently investigating the mechanism for this, and preliminary data points to defects in the DNA repair of oxidative damage. We use hprt as a reporter gene to examine the types of spontaneous mutations which arise in these colon cancer cell lines. This analysis will help identify the different DNA repair systems, in which defects contribute to colon cancer carcinogenesis.

Dr. Eshleman's laboratory is also involved in translational research in molecular diagnostics and basic science research on novel therapeutics. He and Dr. Kathy Murphy recently developed several novel methods to perform DNA sequencing of multiple PCR products simultaneously and to perform combined PCR and sequencing in single reactions. He has also been doing research on DNA based novel therapeutics. Recently, he and Dr. Tony Parker have developed a novel strategy to select against specific cell populations using 'anti-gene locks'. Anti-gene locks are oligonucleotides capable of reacting and intertwining with DNA followed by end-to-end ligation. They have demonstrated their activity in bacterial cells, where once bound and ligated, the structure is inextricable. If the target is present on episomal DNA, the episome is eliminated, while if the target is in the 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.

Dr. Eshleman also has special interests in Molecular Pathology and Transfusion Medicine.

Eshleman JR, Lang EZ, Bowerfind GK, Parsons R, Vogelstein B, Willson JKV, Veigl M, Sedwick WD, and Markowitz S. Increased mutation rate at the hprt locus accompanies microsatellite instability in colon cancer. Oncogene 10:33-37, 1995.

Eshleman JR, Donover PS, Littman SJ, Swinler SE, Li GM, Lutterbaugh JD, Willson JKV, Sedwick WD, Markowitz SD, and Veigl ML. Increased transversions in a novel mutator colon cancer. Oncogene, 16:1125-1130, 1998.

Oliver DH, Thompson RE, Griffin CA, and Eshleman JR. Use of Single Nucleotide Polymorphisms (SNP) and Real-Time PCR for Bone Marrow Engraftment Analysis. The Journal of Molecular Diagnostics, 2:202-208, 2000.

Murphy KM and Eshleman JR. Simultaneous Sequencing of Multiple PCR Products and Combined PCR with Cycle Sequencing in Single Reactions. American Journal of Pathology, Jul; 161(1):27-33, 2002.

Primary Appointment in Pathology; Secondary Appointment in Oncology
Member, Graduate Program in Pathobiology; Member, Graduate Program in Cellular and Molecular Medicine

Francis M. Giardiello, M.D._

410-955-2635

*** none ***

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.

Giardiello FM, Hamilton SR, Krush AJ, Booker SV, Jen J, Piantadosi S, Hylind LM, Celano P, Booker SV, Robinson CR, Offerhaust 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

Director, Division of Gastroenterology
Primary Appointment in the Division of Gastroenterology, Department of Medicine; Secondary Appointment in Pathology

Michael S. Goggins, MB, BCH, BAO_

410-955-3511

mgoggins@jhmi.edu

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, much of the laboratory's focus is studying DNA methylation alterations in pancreatic cancer particularly their biological correlations and potential as tumor markers. We are also exploring the utility of applying expression data from SAGE for pancreatic-specific expression arrays.

We are also pursuing proteomic approaches using protein chip technology 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.

You can visit the lab's Web site at http://pathology.jhu.edu/gogginslab

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 protein biochip technology. Cancer Res. 2002 Mar 15;62(6):1868-75.

Tascilar M, Skinner HG, Rosty C, Sohn T, Wilentz RE, Offerhaus GJ, Adsay V, Abrams RA, Cameron JL, Kern SE, Yeo CJ, Hruban RH, Goggins M. The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma. Clin Cancer Res. 2001 Dec;7(12):4115-21.

Sato N, Rosty C, Jansen M, Fukushima N, Ueki T, Yeo CJ, Cameron JL, Iacobuzio-Donahue CA, Hruban RH, Goggins M. STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas. Am J Pathol. 2001 Dec;159(6):2017-22.

Ueki T, Toyota M, Skinner H, Walter KM, Yeo CJ, Issa JP, Hruban RH, Goggins M. Identification and characterization of differentially methylated CpG islands in pancreatic carcinoma. Cancer Res. 2001 Dec 1;61(23):8540-6.

Primary Appointment in Pathology; Secondary Appointments in Medicine, Oncology

Christine A. Iacobuzio-Donahue, MD, PhD_

410-955-3511

ciacobu@jhmi.edu

Currently, my research efforts are focused on the global gene expression patterns of pancreatic carcinoma, using technologies such as cDNA microarrays and oligonucleotide arrays, as well as high throughput genome screening using microsatellite markers to scan for novel areas of homozygous deletion in pancreatic cancer. These investigations have not only provided insight into the biology of pancreatic cancer, but have also identified several candidate tumor markers of pancreatic cancer that are currently under investigation. I am also involved in a collaborative effort to develop novel small molecules to target potentially important signaling pathways identified in pancreatic cancers. In addition to my research activities, I have a strong diagnostic interest in colorectal and pancreatic pathology.

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, A. Maitra, G. L. Shen-Ong, T. van Heek , R. Ashfaq, R. Meyer, K. Walter, K. Berg, M. A. Hollingsworth, J. L. Cameron, C. J. Yeo, S. E. Kern, M. Goggins, and R. H. Hruban. Discovery of Novel Tumor Markers of Pancreatic Cancer using Global Gene Expression Technology. Americal Journal of Pathology 2002, 160:1239-1249.

P. Argani, C. Iacobuzio-Donahue, B. Ryu, C. Rosty, M. Goggins, R.E. Wilentz, S.R. Murugesan, M. Kaushal, S.D. Leach, E. Jaffee, C.J. Yeo, J.L. Cameron, S.E. Kern, R.H. Hruban. Mesothelin is Overexpressed in the Vast Majority of Adenocarcinomas of the Pancreas: Identification of a New Pancreatic Cancer Marker by Serial Analysis of Gene Expression (SAGE). Clinical Cancer Research 2001, 7:3862-3868.

Primary Appointment in Pathology

Elizabeth M. Jaffee, M.D._

410-955-2957

*** none ***

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. 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 just completed an allogeneic GM-CSF secreting pancreatic vaccine phase 1 study and are currently analyzing several immune parameters in patients enrolled in this study.

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.

Primary Appointment in Oncology; Secondary Appointment in Pathology, Pharmacology
Member, Graduate Program in Immunology; Member, Graduate Program in Cellular and Molecular Medicine; Member, Graduate Program in Pharmacology and Molecular Science

Scott E. Kern, M.D._

410-614-3314

skern1@jhmi.edu

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.

Kern SE, Kinzler KW, Bruskin A, Jarosz D, Friedman P, Prives C, Vogelstein B. Identification of p53 as a sequence-specific DNA-binding protein. Science 252:1708-11, 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 candidate tumor-suppressor gene at human chromosome 18q21.1. Science 271:350-353,1996.

Ryu B, Jones J, Hollingsworth MA, Hruban RH, Kern SE. Invasion-specific genes in malignancy: SAGE comparisons of primary and passaged cancers. Cancer Res 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 homozygous deletion in pancreatic carcinoma that lies within the BRCA2 region. Proc Natl Acad Sci 92:5950-5954, 1995.

Primary Appointment in Oncology; Secondary Appointment in Pathology
Member, Graduate Program in Pathobiology; Member, Graduate Program in Cellular and Molecular Medicine; Member, Graduate Program in Human Genetics

Anirban Maitra, M.D._

410-955-3511

amaitra1@jhmi.edu

The major thrust of my research involves characterizing genomic, transcriptomic and proteomic abnormalities in cancers of the biliary tree (gallbladder cancer and cholangiocarcinomas). The information gleaned from these studies is critical for developing potent "mechanism-based" therapies and identification of novel biomarkers for early detection of these lethal cancers.

The Biliary Cancer Web Site can be viewed at http://pathology.jhu.edu/gallbladder.

I also collaborate extensively with colleagues both within and outside the Gastrointestinal/Liver Pathology Division on basic and translational aspects of pancreatic cancer research. Ongoing work in my laboratory has focused on the role of aberrant activation of developmental signaling pathways (e.g., the Hedgehog signaling pathway) in pancreato-biliary tumorigenesis. We have established a unique repository of human pancreatic and biliary cancer xenografts and low-passage cell lines, which have allowed us to characterize the role of these aberrant signaling pathways in cancer, including their therapeutic targeting using small molecule inhibitors.

In addition, my laboratory is actively pursuing novel technological aspects of cancer diagnosis and therapy, such as custom-designed, high-throughput sequencing microarrays (gene chips) for mutation detection, and the development of nanoparticle-based targeted drug and gene delivery to cancer cells.

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-induced changes in epithelial differentiation during pancreatic tumorigenesis. Cancer Cell. 2003; 3:565-76

Hansel DE, Rahman A, Hidalgo M, et al. Identification of novel cellular targets in biliary tract cancers using global gene expression technology. Am J Pathol. 2003; 163:217-29.

Primary Appointment in Pathology; Secondary Appointment in McKusick-Nathans Institute for Genetic Medicine

Elizabeth A. Montgomery, M.D._

410-955-3511

emontgom@jhmi.edu

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. A recent multicenter study concerns standardization of histologic grading of dysplasia in Barrett esophagus and collaborative work with gastroenterologists focuses on chemoprevention in such patients. 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 sarcomas with myofibroblastic differentiation.

You can visit the Barrett's Esophagus Web site at http://pathology2.jhu.edu/beweb/.

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): A reaffirmation. 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 based on 138 cases from a diagnostic variability study. Human Pathology 2001; 32: 379-388.

Montgomery EA, Fisher C. Myofibroblastic differentiation in malignant fibrous hystiocytoma (pleomorphic myofibrosarcoma): a clinicopathologic study. Histopathology 2001; 38: 99-509.

Montgomery E, Goldblum JR, Fisher C. Myofibrosarcoma: A clinicopathologic study. Am J Surg Pathol 2001; 25: 219-228.

Primary Appointment in Pathology

Michael S. Torbenson, M.D._

410-955-7402

mtorben@jhmi.edu

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.

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 1997 grade 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.

Primary Appointment in Pathology

Bert Vogelstein, M.D._

410-955-8877

vogelbe@jhmi.edu

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.

Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 61:759-767, 1990.

El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B. WAF1, a potential mediator of p53 tumor suppression. Cell 75:817-825, 1993.

Kinzler KW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell 87:159-170, 1996.

Cahill DP, Lengauer C, Yu J, Riggins GJ, Wilson JKV, Markowitz SD, Kinzler KW, Vogelstein B. Mutations of mitotic checkpoint genes in human cancers. Nature 392:300-303, 1998.

Primary Appointment in Oncology; Secondary Appointment in Pathology
Joint Appointment in Molecular Biology and Genetics
Member, Graduate Program in Pharmacology and Molecular Sciences; Member, Graduate Program in Cellular and Molecular Medicine; Member, Graduate Program in Human Genetics and Molecular Biology

Young Y. Wang, M.D., M.Med._

410-502-7875

*** none ***

Detecting cancer early using serum cancer biomarker remains to be a challenging task for many cancers. My current research involves identifying new cancer biomarkers using proteomics approach and evaluating their clinically utility for the early detection, diagnosis, and prognosis of cancer. I am also interested in the development of non-isotopic immunoassays for cancer biomarkers. In collaboration with Dr. Francis P. Kuhajda of the Department of Pathology, we have developed enzyme linked immunosorbent assay (ELISA) for fatty acid synthase (FAS). Elevated levels of FAS were observed in cancer patient blood. To identify the FAS circulating forms and understanding its role in cancer diagnosis is another research interest.

Wang Y, Kuhajda FP, Sokoll LJ, Chan DW. Two-site ELISA for the quantitative determination of fatty acid synthase. Clinica Chimica Acta, 2001, 304:107-115.

Wang YY, Kuhajda FP, Li JN, Pizer ES, Han WF, Sokoll LJ. Chan DW. Fatty acid synthase (FAS) expression in human breast cancer cell culture supernatants and in breast cancer patients. Cancer Lett, 2001, 167:99-104.

Wang YY, Kuhajda FP, Cheng P, Chee WY, Li T, Sokoll LJ, Chan DW. A new model ELISA, based on two monoclonal antibodies, for quantification of fatty acid synthase. J Immunoassay and immunochemistry, 2002, 23:279-292.

Li J, Zhang Z., Rosenzweig J., Wang Y., Chan D.W. Proteomics and bioinformatics approaches for identification of serum biomarkers to detect breast cancer. Clin Chem, 2002 (in press.)

Primary Appointment in Pathology

John H. Yardley, M.D._

410-502-3047

jyardley@jhmi.edu

Inflammatory diseases of the intestines in their various manifestations are a long-standing interest. Studies are commonly done with clinical colleagues. Publications have been concerned with collagenous and lymphocytic colitis, focusing on their similarities and differences, and on colitis-related neoplasia. Disorders of malabsorption, esophagitis, and gastritis are also major interests.

Kelly KJ, Lazenby AJ, Rowe PC, Yardley JH, Perman JA, Sampson HA. Eosinophilic esophagitis attributed to gastroesophageal reflux: Improvement with an amino acid based formula. Gastroenterology 109:1503-1512, 1995.

Yardley JH. Malabsorption disorders. In: Ming SC, Goldman H (eds.) Pathology of the gastrointestinal tract. Baltimore, Williams and Wilkins, 1998, Chapter 31, 2nd edition. pages 755-799.

Yardley JH, Hendrix TR. Gastritis, duodenitis, and associated ulcerative lesions. In: Yamada T, Alpers DH, Owyang C, Powell DW and Silverstein FE. (Ed.s) Textbook of Gastroenterology. Lippincott, Philadelphia. Chapter 66, 3rd Edition, 1998.

Yardley JH, Hendrix TR. Pathology and Pathophysiology of the Upper Gastrointestinal Tract. Gastroenterology Teaching Project, Unit GTP 003, The American Gastroenterological Association. Published by Milner-Fenwick, Inc., Timonium, MD, 2002.

Primary Appointment in Pathology
Former Baxley Professor and Director of Pathology
Member, Graduate Program in Cellular and Molecular Medicine