Lawrence A. Quilliam, PhD

  The Quilliam lab is interested in delineating signal transduction pathways induced by growth-stimulatory factors, and in determining the mechanisms by which these pathways are aberrantly activated during the course of malignant transformation. Many of the genes that become mutated in human cancers encode for mitogenic signaling proteins. Characterization of the enzymes and protein-protein interactions involved in mitogenic signaling forms the basis for the rational design of novel anti-cancer therapeutics. Much of the focus of Dr. Quilliam’s research is centered on Ras family GTPases and the pathways they control. Ras proteins normally act as molecular switches to relay growth stimulatory signals but become constitutively activated in many cancers, leading to uncontrolled proliferation. The Ras onco-proteins are frequently mutated in pancreatic cancer, a malignancy with a dismal survival rate. Therefore, current lab efforts are addressing ways to combat Ras-induced transformation in pancreatic ductal adenocarcinoma cells through the simultaneous inhibition of pathways activated by Ras along with those, e.g. Yap/Taz transcriptional co-activators, that compensate for loss of Ras activity. Independently, mouse models have been developed to understand the molecular and biological roles of Rap1, one of over 30 Ras-related proteins. Rap1A and 1B contribute to leukocyte (myeloid) and endothelial cell pathologies and also impact tumor growth and metastasis. RAP1 knockout mice are being used to study these events.    

Small GTPase Rap1 Is Essential for Mouse Development and Formation of Functional Vasculature.
Chrzanowska-Wodnicka M; White GC 2nd; Quilliam LA; Whitehead KJ; PloS one 2015 Dec 29

Mammalian target of rapamycin complex 1 (mTORC1) enhances bortezomib-induced death in tuberous sclerosis complex (TSC)-null cells by a c-MYC-dependent induction of the unfolded protein response.
Babcock JT; Nguyen HB; He Y; Hendricks JW; Wek RC; Quilliam LA; The Journal of biological chemistry 2013 Apr 23

PI3-kinase ? promotes Rap1a-mediated activation of myeloid cell integrin a4ß1, leading to tumor inflammation and growth.
Schmid MC; Franco I; Kang SW; Hirsch E; Quilliam LA; Varner JA; PloS one 2013 Apr 2

LKB1 tumor suppressor regulates AMP kinase/mTOR-independent cell growth and proliferation via the phosphorylation of Yap.
Nguyen HB; Babcock JT; Wells CD; Quilliam LA; Oncogene 2012 Oct 1

Rap1a is a key regulator of fibroblast growth factor 2-induced angiogenesis and together with Rap1b controls human endothelial cell functions.
Yan J; Li F; Ingram DA; Quilliam LA; Molecular and cellular biology 2008 Jul 14

Org: Indiana University
Desc: Trustees' Teaching Award
Scope: University
Date: 2024-04-01

Org:
Desc: Trustees' Teaching Award
Scope: University
Date: 2008-05-01

Org:
Desc: Trustees' Teaching Award
Scope: University
Date: 2003-05-01