Timothy Fields Laboratory
Timothy A. Fields, M.D., Ph.D.
Professor and Vice Chair for Research & Faculty Development
Director, MD-PhD Physician-Scientist Training Program
Division of Cancer & Developmental Biology; The Kidney Institute
M.D.: Duke University
Ph.D.: Duke University
Residency: Anatomic and Clinical Pathology, Duke University
Clinical Interests:
Kidney disease and solid organ transplantation
Basic Science Interests:
Our lab is focused on understanding the Wnt signaling pathways and their role in guiding differentiation and tumorigenesis. The Wnts are a family of extracellular signaling proteins that are critical for appropriate development, as they regulate behavior and cell fate decisions of stem cells and other progenitor cells. In addition, Wnt signaling can influence cell proliferation, differentiation, migration, and morphology in both adult and progenitor cells. Thus, it is not surprising that aberrant Wnt signaling can lead not only to morphogenetic defects in developing animals, but also to the development of proliferative diseases, including cancer.
The best characterized Wnt signaling pathway, referred to as the "canonical" Wnt pathway, controls the fate of cellular β-catenin, a multifunctional protein and transcriptional co-activator. Activation of canonical Wnt signaling results in β-catenin stabilization and its subsequent translocation into the nucleus. Once in the nucleus, accumulated β-catenin binds members of the TCF/LEF family and induces transcription of Wnt target genes. It is the stabilization of β-catenin and its nuclear accumulation that is commonly thought to account for the cellular outcomes that are elicited by canonical Wnts. However, we have found this simple model to be insufficient to explain the transcriptional and cellular changes stimulated by canonical Wnts and have observed that auxiliary pathways stimulated in parallel by canonical Wnts can modulate β-catenin-dependent transcriptional induction. We are focused on delineating the molecular components of these auxiliary pathways and the mechanisms by which they affect changes in gene transcription and cellular decisions. In addition, studies are underway to develop agents that interfere with Wnt signaling pathways to target proliferative diseases driven by Wnt. As model systems, we currently use pluripotent mesenchymal stem cells, which can self renew or differentiate along osteogenic, chondrogenic, myogenic, or adipogenic lineages, as well as cancer cell lines of varying aggressiveness. We are also in the process of building mouse models to study these phenomena. Our studies aim to bridge an understanding of the normal biology of Wnt signaling with an understanding how this signaling goes awry in developmental diseases and cancer.
Selected Publications:
- Almehmi A, Fields TA (2009). Cryoglobulinemic glomerulopathy compicating heliobacter pylori-associated gastric mucosa-associated lymphoid tissue lymphoma. Am J. Kidney Dis. Oct;54(4):770-4. Epub 2009 Jun 17.
- Rossol-Allison J, Stemmle LN, Swenson-Fields KI, Kelly P, Fields PE, McCall SJ, Casey PJ, Fields TA (2009). Rho GTPase active modulates Wnt3a/beta-catenin signaling. Cell Signal. Nov;21(11):1559-68. Epub 2009 May 29. Abstract
- Wang L, Gesty-Palmer D, Fields TA, Spurney RF (2009). Inhibition of WNT signaling by G protein-coupled receptor (GPCR) kinase 2 (GRK2). Mol Endocrinol. 2009 Sep;23(9):1455-65. Epub 2009 Jun 25. Abstract
Contact Us
Timothy A. Fields, MD, PhD
Professor and Vice Chair for Research & Faculty Development
Director, MD/PhD Physician-Scientist Training Program; Division of Cancer & Developmental Biology; The Kidney Institute
3901 Rainbow Boulevard
1123 Delp Pavilion, Mail Stop 3062
Kansas City, KS 66160
P: (913) 588-7169
F: (913) 945-6848
tfields@kumc.edu