Evers’s basic research, continuously funded by the NIH for the past 21, years
focuses on signaling pathways regulating colorectal cancer proliferation and
metastasis and mechanisms contributing to intestinal cell differentiation and
aging. His laboratory has identified key
components of the PI3K/Akt/mTOR pathway which play differential roles in
colorectal carcinogenesis and differentiation.
Activation of phosphatidylinositol 3-kinase (PI3K), a ubiquitous lipid
kinase composed of an 85 kDa regulatory subunit (p85) and a 110 kDa catalytic
subunit (p110) and its downstream effector protein, Akt, is associated with the
growth and progression of a number of cancers, including colorectal
cancer. Dr. Evers’s group hypothesizes
that colorectal cancer growth and progression are augmented by increased p85α
and Akt2 expression and that selective inhibition of PI3K/Akt components can
suppress colorectal cancer growth and metastasis and can sensitize resistant
colorectal cancers to chemotherapeutic agents.
Dr. Evers is the PI of an NIH MERIT award (R37 AG010885) which is
focused on a better understanding of the function of the gut peptide neurotensin
(NT) an important regulatory and trophic hormone localized to specialized
enteroendocrine cells (N cells) of the adult small bowel. Using the novel endocrine cell line model,
BON, investigators in Dr. Evers’s laboratory have identified the signaling
pathways responsible for NT secretion.
Current studies are also focused on the effects of NT associated with
aging and on the proliferation of various cancers. Dr. Evers is the PI of an R01 from NIDDK (R01
DK048498) which has led to the discovery of new pathways contributing to
intestinal cell differentiation. Current
studies are analyzing unique interactions of mTOR on other signaling proteins
such as the sirtuin family of proteins.
Finally, Dr. Evers is the PI for the UK GI Cancer SPORE planning grant
(P20) which represents a multidisciplinary effort to identify better treatment,
diagnostic and preventive strategies for GI cancers, a significant problem in
Kentucky. One project which is being
performed in collaboration with Dr. Tianyan Gao is focused on colorectal cancer
cell metabolism and effects of mTOR signaling.
- Wang QD, Zhou Y, Wang XF, Evers BM. p27Kip1 nuclear localization and cyclin-dependent kinase inhibitory activity are regulated by glycogen synthase kinase-3 in human colon cancer cells. Cell Death & Differentiation 15:908-919, 2008.
- Rychahou PG, Kang J, Gulhati P, Doan H, Chen AL, Xiao S, Chung DH, Evers BM. Akt2 overexpression plays a critical role in the establishment of colorectal cancer metastasis. Proceedings of the National Academy of Sciences 105:20315-20320, 2008.
- Gulhati P, Bowen KA, Liu J, Stevens PD, Rychahou PG, Chen M, Lee EY, Weiss HL, O’Connor KL, Gao T, Evers BM. mTORC1 and mTORC2 regulate EMT, motility and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways. Cancer Research 71:3246-3256, 2011.
- Zaytseva YY, Rychahou PG, Gulhati P, Elliott VA, Mustain WC, O’Connor KL, Morris AJ, Sunkara M, Weiss HL, Lee EY, Evers BM. Inhibition of fatty acid synthase attenuates CD44-associated signaling and reduces metastasis in colorectal cancer. Cancer Research 72:1504-1517, 2012.
- Li J, Song J, Cassidy M, Rychahou P, Starr M, Liu J, Li X, Epperly G, Weiss HL, Townsend C, Gao T, Evers BM. The PI3K p110α/Akt signaling negatively regulates secretion of the intestinal peptide neurotensin through interference of granule transport. Molecular Endocrinology 26:1380-1393, 2012.