Boris Pasche, MD, PhD, FACP
Year elected: 2007
Current membership category: Senior
Director, Comprehensive Cancer Center and Chair, Department of Cancer Biology
Wake Forest Baptist Medical Center
1, Medical Blvd
Winston-Salem, NC 27157-1082
United States of America
Phone: 336-716-7971
Facsimile: 336-716-0293
Email: bpasche@wakehealth.edu

Biographical statement

Studies of twins indicate that approximately 27% of breast cancers and 35% of colorectal cancers are inherited. High-penetrance tumor susceptibility genes only account for a small fraction of these common cancers. The remainder of the unexplained familial risk is presumably due to other high penetrance genes but polygenic mechanisms and low penetrance tumor susceptibility genes are likely to account for a greater proportion of familial breast and colorectal cancers. In a search for mutations of the type I TGF-β receptor (TGFBR1) we have identified a common variant, TGFBR1*6A, which has a deletion of three GCG triplets coding for alanine within a nine alanine (9A) repeat of TGFBR1 signal sequence. In normal epithelial cells TGFBR1*6A mediates TGF-β growth inhibitory signals less effectively than TGFBR1 and in cancer cells it may switch growth-inhibitory signals into growth-stimulatory signals. This important allele is emerging as a common breast and colon cancer susceptibility allele. Using a novel mouse model of Tgfbr1 haploinsufficiency we have shown that constitutively decreased Tgfbr1 signaling is a potent modifier of colorectal cancer in mice and humans. This led to the identification of TGFBR1 haplotypes associated with colorectal cancer and non-small cell lung cancer risk. We have also pioneered the use of amplitude-modulated electromagnetic field as a novel therapeutic approach in oncology. Our lab focuses on the role of the Transforming Growth Factor Beta (TGF-β) pathway in cancer development and progression with a focus on naturally-occurring variants such as TGFBR1*6A and constitutively decreased expression of TGFBR1. We are developing novel in vitro and in vivo models of radiofrequency electromagnetic fields exposure to assess the mechanism of action of amplitude-modulated electromagnetic fields in cancer.

Institutional affiliations

Wake Forest University School of Medicine (Primary)

Specialties

Internal Medicine