Hal K. Berman

My laboratory investigates the basic cellular pathways and processes that maintain proper growth and differentiation in tissues under the control of sex hormones.  We develop vitro models originating from normal primary human cells derived from patient biopsies to address basic questions in both breast and ovarian carcinogenesis.

Research Synopsis

My laboratory investigates the basic cellular pathways and processes that maintain proper growth and differentiation in tissues under the control of sex hormones. To better under the earliest of events that foster premalignant phenotypes through deregulation of these pathways, we develop and employ in vitro models that originate from normal primary human cells freshly isolated from patient biopsies. Studies in human mammary and fallopian tubal epithelia and progenitor cells allow us to address basic questions in both breast and ovarian carcinogenesis.

Our breast cancer studies focus on the consequences of loss of function of BRCA1/2 in normal mammary cells. Mutations in BRCA1 are a major known cause of familial breast and ovarian cancers. Unfortunately, tumours that form in BRCA1 mutation carriers grow quickly, show aggressive behavior, and are uncommonly diagnosed at early stage. Our inability to detect, diagnose, and treat these tumours at an early point in time is, in part, due to a lack of understanding of events that occur shortly after the function of BRCA1 goes awry. Our studies seek to understand these “early events” in BRCA1-associated breast cancer by studying human breast cells donated from volunteers with and without BRCA1 mutations. Our preliminary findings uncover new knowledge about how BRCA1 works and how mutations in BRCA1 may lead to familial breast cancer. Our research seeks to deepen our understanding of familial breast and ovarian cancer and provide candidate biomarkers to detect tumours early and predict risk for future tumour formation in familial carcinogenesis.

There is a growing body of evidence that many, if not most, ovarian cancers may arise in the fallopian tube (i.e. "the fallopian tube hypothesis"). Risk for ovarian cancer arising from the fallopian tube can be genetically inherited (i.e. mutations in BRCA1/2) and can be related to the number of menstrual cycles in a woman's lifetime. Biologically, the changes that confer risk of cancer formation within the fallopian tube are poorly understood. We seek to apply our expertise in modeling of human breast cancer toward the development of new laboratory models to study the origins of ovarian cancer. Our approach involves isolation and study of epithelial cells derived from the fallopian tube of human volunteers, both with and without mutations in BRCA1/2. Using this approach, we have identified molecular alterations associated with the menstrual cycle that may place fallopian tubal cells at risk for early cancer development. Future studies seek to determine if modulation of these pathways may prevent cancer initiation by maintaining fallopian tube cellular homeostasis.