The HBP1 Gene and Wnt Signaling: A Twisted Tale of Breast and Colon
Dr. Amy Yee received her A.B degree in biochemistry from the University of California at Berkeley and her Ph.D. in biochemistry the University of California at Davis (mentor: Prof. Mark McNamee, acetylcholine receptor function). She was an American Cancer Society Postdoctoral Scholar at the Rockefeller University in New York (mentor Prof. Joseph Nevins, E2F transcription factor). She then moved to the Dept. of Biochemistry at Tufts University School of Medicine in Boston, where she is now a full Professor of Developmental, Molecular and Chemical Biology. She did the biochemistry of the E2F transcription factor as a postdoc and in her own lab, but developed a new focus on the HBP1 transcription factor and Wnt signaling. In the past 10-15 years, her lab has developed basic science projects with clinical emphases in the areas of breast cancer, epilepsy, and recently colitis and colon cancer. Each project has a biochemistry-clinician working team to develop the respective emphases. She has been the recipient of junior faculty awards from the American Cancer Society, established investigator award from the American Heart Association and a Zucker award from my peers at Tufts in recognition of research excellence. NIH, DOD, Komen, AICR and other grants have supported the work in the lab. She has served on numerous NIG and DOD panels as a reviewer and have mentored numerous bachelor’s, master’s and PhD level students to future success in science and medicine. She is the current president of AACR-Boston, Inc., the local affiliate of AACR.
One goal of the Yee lab is to understand triple negative breast cancer (TNBC) progression and to advance new diagnostic and therapeutic strategies at the pre-clinical level. The Yee Lab has previously shown that reductions or mutations of the HBP1 gene are associated with a decreased relapse-free survival. We focus upon the HBP1 gene in the context of a novel Wnt and EGFR signaling metabolic signaling networks. The Yee Lab use pre-clinical models that recapitulate aspects of human breast cancer to dissect mechanisms and to evaluate new therapeutic strategies. The Yee Lab is investigating: 1) Mechanisms of a Wnt/EGFR/HBP1 metabolic reprogramming towards therapeutics and developing non-invasive MRI-based markers. 2) Potential of the green tea compound EGCG as a collaborative chemotherapeutic agent for TNBC, an aggressive subtype. 3) Etiology of brain metastases, which are an increasingly devastating consequence of metastatic breast cancer, and of tumor-associated seizures, a frequent clinical consequence.
A second project uses lessons learned in breast cancer to focus on colitis. Using expertise on Wnt signaling, cancer biology and capitalizing on a serendipitous observation in the HBP1 KO, mice, the Yee Lab is investigating the role of the HBP1 and Wnt signaling in colitis and colitis-associated colorectal cancer (CAC). The Yee Lab discovered that the HBP1 KO mice exhibit the full spectrum from colitis to CAC, which is an exceedingly complex cancer due to extensive inflammation and immune system dysfunction. There are few genetic models of CAC, hampering the necessary detailed mechanistic elaboration necessary for discovering new therapeutic strategies and new biomarkers that may predict whether colitis may develop into full-blown CAC.