Michael T. Lewis, Ph.D.
Baylor College of Medicine
B.S. Biology, College of William and Mary
Ph.D. Biology, University of California
1995-1998 - Post-doc. Biology, University of California
Post-doc. Physiology and Biophysics, University of Colorado
Our laboratory studies the developmental biology of the mammary gland as it relates to both normal breast function and breast cancer progression. Current laboratory research is centered on the role of hedgehog signal transduction in mammary gland development and breast cancer using the mouse as a model organism.
During embryonic development, the hedgehog signal transduction network mediates cell-cell communication and is required for normal organ formation. However, genetic mutation of hedgehog network genes can cause severe birth defects, basal cell carcinoma of the skin, and other tumors including lethal medulloblastomas of the brain.
Our work has demonstrated that loss-of-function mutations in two hedgehog network genes, Patched-1 (Ptc-1) and Gli-2, cause cancer-like lesions that closely resemble human ductal carcinoma in situ (DCIS). More recently, hedgehog signaling has been found to be required for functional differentiation of the gland at the onset of lactation.
The specific mechanism by which mutations in the hedgehog network lead to differentiation failure and mammary lesions is not known. Our data lead us to ask several fundamental questions, among which are: 1) Which genes in the hedgehog signaling network are required for different phases of mammary gland development. 2) In which tissue compartment(s) do these genes function? 3) What genes regulate, or are regulated by hedgehog signaling? 4) How does the hedgehog network interact with other hormone- and growth factor-dependent regulatory networks (e.g. estrogen, progesterone and TGFß-1)? And 5) Do hedgehog signaling disruptions lead to neoplasia in the human breast?