Christine Iacobuzio-Donahue obtained her bachelor’s degree in Biology from Adelphi University in Garden City NY in 1991, and both her M.D. and Ph.D. degrees from Boston University School of Medicine in 1998. Her Ph.D. was earned from the Department of Pathology at Boston University where she studied the roles of the proteolytic enzymes, in particular cathepsins B and D, in colorectal tumorigenesis and progression. Upon graduation, she moved to Baltimore where she completed a residency in Anatomic Pathology at The Johns Hopkins Hospital, the final year of which she served as one of two appointed Chief Residents. Her training also includes a postdoctoral fellowship in Gastrointestinal Oncology in the lab of Dr. Scott Kern M.D., a renowned pancreatic cancer researcher and pioneer in the field of pancreatic cancer genetics, and a Gastrointestinal/Liver Pathology fellowship at Johns Hopkins. At the end of her training she had authored or co-authored 27 peer-reviewed publications including first author papers in The American Journal of Pathology, Cancer Research, and The Journal of Biological Chemistry. Dr. Iacobuzio joined the full-time Pathology faculty at Johns Hopkins in 2003 as an Instructor, was promoted later in 2003 to an Assistant Professor of Pathology and Oncology, and to Associate Professor in February 2007. She is also an affiliate faculty member of the Center for Epigenetic Studies.
Dr. Iacobuzio is the Principal Investigator of an NIH funded laboratory whose focus is the molecular genetics of gastrointestinal cancers, with a focus on pancreatic and colorectal cancer. Her lab was among the first to demonstrate the genomic features of pancreatic cancer (Cancer Res 64:871) and has elucidated many of the molecular features of pancreatic cancer at the genetic level. For example, she has shown that loss of Dpc4 protein expression is strongly correlated with deletions of the DPC4 gene in pancreatic cancer (Cancer Res 60:2002), and based on this finding demonstrated the frequency of DPC4 inactivation in variant forms of pancreatic cancer (Am J Pathol 157:755, Am J Surg Pathol 24:1544). She was also the first to identify and characterize of the mutation cluster region in the SMAD4/DPC4 tumor suppressor gene (Clin Cancer Res 10:1597), and because of its clinical implications for diagnosis this article was selected as the cover article in the issue of Clinical Cancer Research in which it was published. She was among the first to report the expression profiles of pancreatic cancer using the three major profiling technologies (serial analysis of gene expression, oligonucleotide microarrays and cDNA microarrays), and to draw conclusions of the reproducibility of each method in identifying changes in gene expression with biologic significance (Cancer Biol Ther 3:1254, Am J Pathol 160:1239, Am J Pathol 162:1151, Cancer Res 63:8614). She has validated the protein expression of several of the biomarkers identified by these studies in pancreatic cancer tissues (Cancer Epidemiol Biomarkers Prev 13:487, Am J Clin Pathol 118:52, Clin Cancer Res 7:3862, Am J Clin Pathol 2004; 121:226), and her work has formed the basis for ongoing clinical trials to therapeutically target or image pancreatic cancer (Mol Imaging 6:131, Cancer Immun. 7:20). She was among was the first to characterize the “expression architecture” of infiltrating pancreatic cancers, defining the cell compartments in which genes are overexpressed and thereby demonstrating that infiltrating pancreatic cancers undergo robust changes in gene expression associated with cell-cell and cell-matrix contacts. Related to these studies, she characterized the expression profiles of the desmoplastic stroma associated with infiltrating pancreatic carcinomas, and showed that desmoplastic stroma can be further compartmentalized into juxtatumoral stroma, the putative site of tumor-stromal interactions, and the pan-stromal compartment (Am J Pathol 160:91). She extended this finding to infiltrating breast cancers, and her findings were also selected as the cover article for the journal Cancer Research (Cancer Res 62:5351). More recently, her studies of the juxtatumoral compartment associated with infiltrating neoplasms of the pancreas indicate that gene expression of the juxtatumoral compartment is related to the infiltrating nature of the neoplasm and not the organ site (Cancer Biol Ther 4:302), and that stromal gene expression of pancreatic cancer is a predictor of patient outcome (J Clin Oncol 25:319). This work not only adds to our understanding of the fundamental biology of pancreatic cancer, but also provides several new avenues for new treatments targeting cell-cell interactions.
Metastatic disease is the most common cause of death for patients with pancreatic cancer, but little is known about pancreatic cancer progression. To address this important deficiency in research, Dr. Iacobuzio established the Gastrointestinal Rapid Medical Donation Program to enable patients with terminal gastrointestinal cancer to consent to a rapid autopsy. Since creation of the program in February 2003, 102 rapid autopsies have been coordinated by Dr. Iacobuzio thus establishing her as a leader in this important area of research. The importance of the Medical Donation Program created by Dr. Iacobuzio has been recognized at the national level in a medical news report that was featured on CNN, in the New York Times, and in Forbes Magazine. The impact of this program in its first five years has been far reaching. Utilizing this unique resource, her lab had demonstrated the technical methods and frequency by which cell lines and xenografts can be generated from postmortem tissues (Cancer Biol Ther 4:548), that the genetic and epigenetic features of these samples are reflective of the tissues from which they are derived (Cancer Biol Ther. 6:1546), and the gene expression associated with disease progression (IJCEP 1:32, Clin Cancer Res 14:412). This resource has also formed the basis of a multi-collaborator effort to sequence the pancreatic cancer genome that was recently published in the journal Science (Science 321:1801), the scale of which is unparalleled for any tumor type thus far. Based on this program, her lab has also shown that pretreatment levels of deoxycytidine kinase are highly predictive of survival following Gemcitabine treatment, and that levels of dCK do not change even after clinical resistance has been documented (Clin Cancer Res 12:2492). Most recently, her lab has made the striking discovery that genetic inactivation of the DPC4 and TP53 tumor suppressor genes in primary pancreatic cancers (at diagnosis) are strongly correlated with metastatic disease that ultimately lead to treatment failure and death, whereas primary carcinomas of patients that contained an intact DPC4 gene died of complications related to locally advanced pancreatic cancer and not lethal metastasis (Journal of Clinical Oncology 2009). The implications of this finding are profound as it suggests that pancreatic cancers are represented by two different biologic phenotypes, and that a determination of these genetic features at diagnosis may have value in therapeutic decisions.
While pancreatic cancer metastasis is a major focus of her laboratory, Dr. Iacobuzio has also been highly prolific in the field of colorectal neoplasia. She has described the role of loss of imprinting of the IGF2 gene in colorectal carcinogenesis in the Min mouse model (Science 307:1976), and the mechanisms by which loss of imprinting of IGF2 lead to enhanced proliferation at the cellular level (PNAS 104:20926). Dr. Iacobuzio has also served as a critical collaborator in studies describing thymidylate synthase amplification as a mechanism for resistance to 5-flourouracil in patients with metastatic colon cancer (PNAS 2004 101:3089), the role of microsatellite instability in colorectal cancers (Int J Cancer 116:914, Am J Clin Pathol 126:564), and the characterization of telomere length abnormalities in colorectal neoplasms (Clin Cancer Res 10:3317), among others.
In addition to her abundance of research endeavors, Dr. Iacobuzio is an attending gastrointestinal pathologist at The Johns Hopkins Hospital and an expert in the pathology of colorectal neoplasia. She is perhaps best known for her role as co-editor of the diagnostic textbook Gastrointestinal and Liver Pathology in the Foundations in Diagnostic Pathology series, and has contributed chapters to a variety of publications including Pathology of the Gastrointestinal Tract, Liver, Biliary Tract and Pancreas (Eds. Odze, Goldblum and Crawford) and the forthcoming 8th edition of Robbins and Cotran’s Pathologic Basis of Disease. She has been invited to speak nationally and internationally (including invited talks in England, Germany, Italy and Japan). She serves as a Senior Editor for the International Journal of Clinical and Experimental Pathology (www.ijcep.com), as well as a reviewer for numerous journals including Cancer Research and PNAS. Above all else, she strives to be a mentor and role model to undergraduates, graduate and medical students, residents and junior faculty as they transition to independent careers in the medical sciences.