Focus
The principal interest of Dr. Parvin’s laboratory is a tumor suppressor protein called BRCA1 (breast cancer-1), which plays an important role in breast cancer. As the name implies, this protein restrains cancerous changes in cells. BRCA1 is antagonistic to oncogenes, genes that turn on uncontrollable cell growth. When BRCA1 is mutated, it loses its ability to restrain cell growth, and the cell is driven into unbridled cancerous growth. There are several other tumor suppressor proteins, which are well known and quite important, but the unusual feature of BRCA1 is that it is specific to cancers of the breast and ovary. Dr. Parvin is studying BRCA1 at a fundamental level. He isolates key chemical reactions in the test tube and analyzes how BRCA1 changes those chemical reactions. Among women who have a familial history of breast cancer, about 40 percent carry the BRCA1 mutation, making it very important to learn as much as possible about this mechanism.
Background
A native of New Jersey, Dr. Parvin attended Haverford College in Pennsylvania and subsequently entered the M.D./Ph.D. program at the Mt. Sinai School of Medicine in New York City. During medical school, he “caught the research bug” and sought work in a number of laboratories, including Peter Palese’s lab at Mt. Sinai. Eventually, he made his way to the MIT Center for Cancer Research under the tutelage of Phillip A. Sharp. Sharp, who discovered some of the fundamental mechanisms of cell biology, was awarded the Nobel Prize in Medicine or Physiology in 1993, while Dr. Parvin was working in his lab. In 1995, Dr. Ramzi Cotran recruited Dr. Parvin to come to the Brigham and Women’s Hospital and start his own lab as an assistant professor in the Department of Pathology in the Division of Molecular Oncology. “Because Boston has the best research community anywhere,” Dr. Parvin recounts, “I worked very hard to stay in Boston.”
Research
Dr. Parvin has published a body of work on BRCA1 in top journals like Nature, the premiere journal for the basic sciences, Proceedings of the National Academy of Science, and Molecular and Cellular Biology, to name a few. Current work is focused on understanding how BRCA1 works. “What is the chemical reaction that BRCA1 prevents in cells?” Current thought is that if you inhibit BRCA1, a special organelle inside the cell termed the centrosome changes. The centrosome is responsible for organizing the chromosomes prior to cell division. “When centrosomes aren't working properly,” Dr. Parvin explains, “the DNA does not divide equally during cell division, and the daughter cells have massive mutations, extra chromosomes, and chromosomes that are fragmented and rejoined in weird ways.” Since centrosomes are found in every cell, however, it remains a mystery why the derangement in BRCA1 is associated only with breast and ovarian cancer.
Laboratory
Dr. Parvin’s lab is staffed by six Ph.D.’s, people who are focused on basic science with a view toward applying their research to problems in breast and prostate cancer, in addition to laboratory support staff. “We’ve always had very intelligent people working in our laboratory,” Dr. Parvin offers. “People who have made great strides in our basic understanding of BRCA1. One graduate student who stands out is Lea Starita, now a Ph.D. with the University of Seattle in Washington. She was working on the assumption that the function of BRCA1 is related to the activity of a particular enzyme. Her work changed the direction of our laboratory,” Dr. Parvin explains. “One of the joys of working in the lab is when people branch out in ways I would not have anticipated.”
Funding
Dr. Parvin’s lab derives support from several NIH grants, as well as other Federal grants. He is actively seeking funding sources for an expansion of his work in BRCA1, as well as for other areas in breast and prostate cancer.
Collaborations
Dr. Parvin collaborates with numerous other laboratories, both within the Longwood Medical Area and at the national and international level, including the Joslin Diabetes Center, the Dana Farber Cancer Institute, and laboratories at Brigham and Women’s Hospital. “All filled” as Dr. Parvin puts it, “with hundreds, no, thousands of scientists, all the best in the country. We all work together really nicely, independent of the walls.”
Importance of Being at the Brigham
When asked what he thinks is so special about working at the Brigham, Dr. Parvin points out its vast resources, both physical and intellectual. “That’s why I’m here, because there are so many people around here doing wonderful work. That’s what attracted me to the Brigham and Women’s Hospital and Harvard Medical School in general.” Although Dr. Parvin’s laboratory is principally involved in basic research, access to breast cancer patients who are being treated at the Brigham is very important for validating these findings in the real world of patients. “The Brigham has an excellent tissue bank for BRCA1 tumors,” Dr. Parvin comments. “Occasionally, we need to confirm that what is going on in the test tube is also happening in the patient. Alternatively, we may find something that is important for prognosis. For example, we may identify a subpopulation of patients more amenable to a certain treatment modality than other patients in the larger group.”
Future
The goal of Dr. Parvin’s work is to discover information that is directly applicable to potential new therapies.
Selected References
Anderson SF, Schlegel BP, Nakajima T, Wolpin ES, Parvin JD. BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA helicase A. Nature Genetics. 1998;19:254-256.
Starita LM, Machida Y, Sankaran S, Elias JE, Griffin K, Schlegel BP, Gygi SP, Parvin JD. BRCA1-dependent ubiquitination of gamma-tubulin regulates centrosome number. Mol Cell Biol. 2004;19:8457-8466.
Starita LM, Horwitz AA, Keogh M-C, Ishioka C, Parvin JD, Chiba N. BRCA1/BARD1 ubiquitinate phosphorylated RNA polymerase II. J Biol Chem. 2005;280:24498-24505.
This page was last modified on 7/7/2007
Send Feedback to: 
