Boris
Pasche, MD, PhD
Assistant Professor
Department of Hematology Oncology
To Contact Dr. Pasche:
phone: 312-695-0320
e-mail: b-pasche@northwestern.edu
Dr. Pasche's website
PubMed
Reference Lookup
Research Interests
Dr. Pasche’s research work focuses on the role of Transforming
Growth Factor Beta (TGF-b ) in cancer development and progression. TGF-b signaling
and growth-inhibition are mediated by the type I TGF-b receptor (Tb R-I).
In a search for mutations of this receptor, a polymorphic allele has been
discovered, Tb R-I(6A), that has a deletion of three alanines from a nine-alanine
stretch. To investigate the possible association of this mutant allele with
neoplasms, a case-control study was designed to determine the relative frequency
of this allele in patients with various malignancies. There were 123 of 851
(14.6%) Tb R-I(6A) heterozygotes among cases and 78 of 735 (10.6%) heterozygotes
among controls (p<0.02, Fisher’s exact test). Further, a higher than
expected number of Tb R-I(6A) homozygotes was observed among cases (9 out
of 851) whereas there were no Tb R-I(6A) homozygotes among 735 controls of
similar ethnic background (p< 0.01, Fisher’s exact test). A subset
analysis revealed the presence of four Tb R-I(6A) homozygotes among 112 patients
with colon cancer (p< 0.01, Fisher’s exact test). Signal transduction
of Tb R-I and Tb R-I(6A) was assessed in stably transfected cell lines by
means of TGF-b growth-inhibition assays. Tb R-I(6A) cells were less effectively
inhibited by TGF-b than Tb R-I cells (p< 0.01). Using the Smad4-specific
DNA binding element reporter gene construct, pSBE4, other investigators have
recently corroborated these findings.