Barrett J. Rollins, MD, PhD
Linde Family Professor of Medicine, Harvard Medical School
Office phone: 617-632-3896
Preferred contact method: email
View Physician Profile
Area of ResearchControl of Leukocyte Migration by Chemokines
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA 02215
After graduating from Amherst College, Dr. Rollins received his MD in 1979 and PhD in 1980 from Case Western Reserve University. He completed his internship and residency in internal medicine at Beth Israel Hospital, Boston. He then served a clinical fellowship in medical oncology at DFCI and a postdoctoral research fellowship with Dr. Charles Stiles. Since joining DFCI in 1989, Dr. Rollins has worked in the area of white blood cell trafficking and the interactions between inflammation and cancer.
- Association of American Physicians, 2004
- American Society for Clinical Investigation, 1996
- Scholar, Leukemia Society of America, 1995
ResearchControl of Leukocyte Migration by Chemokines
White blood cells are the first line of host defense against invaders from without (e.g., microbial pathogens) or within (e.g., tumors). To be effective, leukocytes must engage in complex trafficking patterns. Some travel to the site of the initial breach to fight the invasion nonspecifically. Others sample the invasion site and carry bits of information back to lymph nodes where they initiate an immune response that directs the migration of effector cells back to the invasion site. We now know that these movements are controlled by a family of small secreted proteins called chemokines.
One approach our laboratory takes to understanding chemokines is to study one in detail, namely monocyte chemoattractant protein-1 (MCP-1). We have dissected the molecular determinants of its function by structure-activity analyses and have attempted to understand its physiology using genetically modified mice. For example, studies in MCP-1-deficient mice show that this chemokine is essential for monocyte recruitment in inflammation, including diseases with inflammatory components such as atherosclerosis.
We have also discovered that MCP-1 is required for the development of type 2 T helper cell-polarized immune responses, that is, those that fight parasites and are involved in allergies. Current efforts are directed toward understanding the molecular basis for this effect. We are also interested in the interface between chemokines and cancer. Chemokines can stimulate leukocytes to engage in host antitumor activity, but some chemokines can affect tumor cells directly. Recently, we demonstrated that ambient chemokines stimulate anti-apoptotic responses in tumor cells. In fact, some tumors secrete chemokines that act in an autocrine manner to inhibit apoptosis - a powerful and direct mechanism whereby inflammation can promote cancer.
Finally, a new area of research involves the Langerhans cell histiocytoses, a family of diseases in which chemokine abnormalities may play a role in determining patterns of organ involvement. We have demonstrated that pathologic Langerhans cells aberrantly express chemokine receptors in a manner that could explain patterns of tissue involvement in the histiocytoses.
Cell Cycle Control
In addition to leukocyte trafficking, our laboratory studies cell cycle control. In particular, we have demonstrated that cyclin C, an understudied regulator of the cell cycle, combines with cdk3 to promote exit from the G0 state by phosphorylation of pRb, the product of the retinoblastoma susceptibility gene. These new insights into the G0 resting state may have important implications for cancer treatment.
- Fleming MD, Pinkus JL, Alexander SW, Fournier MV, Tam C, Loda M, Sallan SE, Nichols KE, Carpentieri DF, Pinkus GS, Rollins BJ. Coincident expression of the chemokine receptors CCR6 and CCR7 by pathologic Langerhans cells in Langerhans cell histiocytosis. Blood 2003;101:2473-5.
- Soejima K, Fang W, Rollins BJ. DNA methyltransferase 3b contributes to oncogenic transformation induced by SV40 T antigen and activated ras. Oncogene 2003;22:4723-33.
- Kleine-Lowinski K, Rheinwald JG, Fichorova R, Anderson DJ, Basile J, Münger K, Daly CM, Rösl F, Rollins BJ. Selective suppression of monocyte chemoattractant protein-1 (MCP-1) expression by human papillomavirus E6 and E7 oncoproteins in human cervical epithelial and epidermal cells. Int J Cancer 2003;107:407-15.
- Ren S, Rollins BJ. Cyclin C/Cdk3 promotes Rb-dependent G0 exit. Cell 2004;117:239-51.
- Conti I, Rollins BJ. CCL2 (monocyte chemoattractant protein-1) and cancer. Semin Cancer Biol 2004;14:149-54.
- Ren, Shengjun, PhD
- Xuguang, Chen, PhD
- Mrigank, Srivastava, PhD
- Gayane, Badalian, MD, PhD
- David, Nelson, PhD