Focus
A principal focus of Dr. Charles Dimitroff's laboratory, established in 2003, is to understand how and why cancer cells metastasize, or spread, to distant sites. The central idea of Dr. Dimitroff's work is that tumor cells use the same kinds of surface molecules that normal blood leukocytes (white cells) use to stick to blood vessels and creep into the tissues, where, in the case of cancer cells, they set up shop and grow into a metastatic tumor. In most forms of human cancer, it is the metastatic tumors that ultimately kill the patient, making metastasis one of the most important issues in cancer research.
Dr. Dimitroff's scientific team is particularly interested in understanding this process in prostate cancer, which has a strong tendency to metastasize to the bone.
Background
A graduate of Columbia University, Dr. Dimitroff received his doctoral training at the Roswell Park Cancer Institute in upstate New York where he studied tumor biology and obtained a Ph.D. In 1999, he was recruited to Brigham and Women's Hospital as a postdoctoral fellow by Dr. Robert Sackstein of the Department of Dermatology who was investigating why stem cells migrate or ‘home’ to bone marrow. As Dr. Dimitroff transitioned into an independent investigator within that department, he continued to work on problems related to tumor metastasis and cell migration to bone.
Research
One of Dr. Dimitroff's key discoveries is the existence of a factor, or molecule, present on the surface of prostate tumor cells that causes them to ‘traffic’ or enter the bone. The molecule responsible for this ‘homing’ factor, called a cell adhesion molecule, is a cell surface glycoprotein called PSGL-1. Dr. Dimitroff explains that “prostate tumor cells, which characteristically metastasize to bone, bind to the endothelial cells that line bone marrow blood vessels through a protein found on the surface of the endothelial cells called E-selectin. To our surprise,” Dr. Dimitroff explains, “we found that the E selectin-binding form of P-selectin glycoprotein ligand-1 (PSGL-1) is expressed on the human bone-metastatic prostate tumor MDA PCa 2b cell line. Interestingly, we also found that human prostate tumor cells derived from bone, lymph node, and brain metastases expressed another leukocyte E-selectin ligand, E-selectin ligand-1 (ESL-1). These findings suggest that prostate cancer cells co-opt some of the tricks that are used by white cells, cells of the immune system, to recognize and home to the tissues in which they eventually form metastases.” This important discovery, published in Cancer Research in 2005, launched Dr. Dimitroff's career as an independent scientist and enabled him to gain funding support from the National Institutes of Health and the American Cancer Society. Other areas of active investigation in Dr. Dimitroff's laboratory include the identification of other ‘homing’ molecules present on the surface of circulating cells and their role in inflammation.
Laboratory
The laboratory's progress depends on a team of highly trained and dedicated scientific researchers. Dr. Madeliene Gainers, a research fellow who received a medical degree from the University of Pittsburgh, is working to identify a novel skin-homing receptor on the surface of inflammatory lymphocytes. Dr. Steven R. Barthel, a research fellow who received his Ph.D. from the University of Wisconsin-Madison, is elucidating the role of PSGL-1 and carbohydrate moieties in the metastasis of prostate tumor cells. A dedicated teacher, Dr. Dimitroff fosters a didactic environment in the laboratory and is actively seeking new participants in this work of varying levels of experience including undergraduate interns, medical students, graduate students, and postdoctoral fellows. “I'm particularly looking for a student wishing to go to graduate school or medical school,” explains Dr. Dimitroff, “because they have the interest and drive to overcome some of the problems they may face in the lab and they have the intellectual ability to grasp some of the biological concepts that tend to be difficult, especially when I talk about carbohydrates and how they relate to the structure of adhesion molecules, a scenario that is not typically taught.”
Funding
The bulk of Dr. Dimitroff ’s funding is from the Federal government through the National Institutes of Health.
Collaborations
Dr. Dimitroff and his colleagues enjoy numerous local, national, and international collaborations, and have relied heavily on the Dana Farber/Harvard Specialized Histopathology Services Laboratory, which is based in the pathology department at Brigham and Women’s Hospital.
Importance of Being at the Brigham
Working in the hospital environment where patients are treated surgically has been vital to Dr. Dimitroff's work. Since the inception of his laboratory, Dr. Dimitroff has established more than a dozen collaborative projects both within and outside the Brigham and Women's Hospital. “What makes being at the Brigham important to me,” he explains, “is that I have access to pathologists who can help me read prostate cancer slides, as well as orthopedic surgeons who can help me obtain the bone marrow samples I need to do my work.”
Future
The translational aspect of Dr. Dimitroff's work is the hope that once fully characterized and tested in humans, these ‘homing’ molecules can be blocked by a simple compound without side effects, which would serve as an adjunct to conventional established therapies to prevent the deadly spread of prostate cancer.
Selected reference
Dimitroff CJ, Descheny L, Trujillo N, Kim R, Nguyen V, Huang W, Pienta KJ, Kutok JL, Rubin MA. Identification of leukocyte E-selectin ligands, P-selectin glycoprotein ligand-1 and E-selectin ligand-1, on human metastatic prostate tumor cells. Cancer Res. 2005;65:5750-5760.
This page was last modified on 7/7/2007
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