Biomedical Research Education & Training
Faculty Member

Lau, Ken, PhD
Assistant Professor of Cell and Developmental Biology

Lab Url: http://www.mc.vanderbilt.edu/vumcdept/cellbio/laulab/

Phone Number: 615-936-6859

Email Address: ken.s.lau@vanderbilt.edu

Lau, Ken's picture
Academic history
PhD, University of Toronto
Postdoctoral Fellowship, Massachusetts General Hospital

Office Address   Mailing Address

2215 Garland Avenue, MRB IV 10475, Nashville TN 37232

2215 Garland Ave, MRB IV 10475 37232-0441


Research Keywords
inflammation, colorectal cancer, immunology, computational systems biology, stem cells, apoptosis, epithelial biology, cell specification, signal transduction

Research Specialty
In vivo single cell systems biology of intestinal diseases

Research Description
Goal
The central goal of my lab is to understand how inflammatory microenvironments affect epithelial cell behaviors in the context of human diseases, specifically, in inflammatory bowel diseases and colorectal cancer. Aberrant cell specification is now recognized to be a major factor in various intestinal diseases. For example, dysfunctional Goblet and Paneth cells in the intestine contribute to barrier defects, while progenitor-like colorectal cancer cells are prone to therapeutic resistance and metastasis. Devising ways to control these aberrant behaviors may lead to effective therapeutic strategies to combat these complex diseases. My lab is interested in understanding the signaling mechanisms that control the differentiating cell populations in the intestine (defined loosely as transit amplifying cells) as they become exposed to various in vivo environments. We want to characterize the degree of heterogeneity and plasticity in such populations, and to leverage such properties for reversing pathological behaviors.

Approach
In live tissues, cells must integrate dynamic mixtures of environmental cues through their signaling networks to arrive at response decisions. To understand the multivariate problem of how the microenvironment interacts with cells, we use multiplex and high throughput experimental approaches to characterize the network states (numbers and types of cells, secreted protein factors, intracellular signaling, and transcriptional changes, over time) within in vivo tissue. Our model system is the intestine of the laboratory mouse, whose state is controlled by interactions between the epithelium, immune system, and microbiota very much like in human. We use the collected datasets over different experimental conditions to build data-driven mathematical models to quantitatively describe environment-cell input/output relationships and how these relationships are integrated over time to derive cellular outcomes. Because cell populations in in vivo tissues are not homogeneous, we will focus on generating data from single cells using techniques derived from flow cytometry and microscopy.

Training
I received my training at Massachusetts General Hospital and MIT under joint supervision of Dr. Kevin Haigis (a mouse geneticist) and Dr. Douglas Lauffenburger (a bioengineer). There, I performed pioneering work on combining system-level signaling analyses and mouse models of intestinal diseases. I then further expanded these studies into looking at immune-epithelial cell interaction, and global signaling changes in mice with oncogenic mutations in the Ras proteins. Overall, I found that multivariate analyses are necessary for predicting signal-response relationships, whereas exploring single pathways one at a time is not predictive in vivo. I aim to foster a highly interdisciplinary and collaborative atmosphere in my lab, with a key focus on learning principles that will be translatable to human patients.

Publications
Lau, KS, Schrier, SB, Gierut, J, Lyons, J, Lauffenburger, DA, Haigis, KM. Network analysis of differential Ras isoform mutation effects on intestinal epithelial responses to TNF-a. Integr Biol (Camb), 5(11), 1355-65, 2013

Miraldi, ER, Sharfi, H, Friedline, RH, Johnson, H, Zhang, T, Lau, KS, Ko, HJ, Curran, TG, Haigis, KM, Yaffe, MB, Bonneau, R, Lauffenburger, DA, Kahn, BB, Kim, JK, Neel, BG, Saghatelian, A, White, FM. Molecular network analysis of phosphotyrosine and lipid metabolism in hepatic PTP1b deletion mice. Integr Biol (Camb), 5(7), 940-63, 2013

Lau, KS, Cortez-Retamozo, V, Philips, SR, Pittet, MJ, Lauffenburger, DA, Haigis, KM. Multi-scale in vivo systems analysis reveals the influence of immune cells on TNF-a-induced apoptosis in the intestinal epithelium. PLoS Biol, 10(9), e1001393, 2012

Lau, KS, Zhang, T, Kendall, KR, Lauffenburger, D, Gray, NS, Haigis, KM. BAY61-3606 affects the viability of colon cancer cells in a genotype-directed manner. PLoS One, 7(7), e41343, 2012

Lau, KS, Juchheim, AM, Cavaliere, KR, Philips, SR, Lauffenburger, DA, Haigis, KM. In vivo systems analysis identifies spatial and temporal aspects of the modulation of TNF-a-induced apoptosis and proliferation by MAPKs. Sci Signal, 4(165), ra16, 2011

Mkhikian, H, Grigorian, A, Li, CF, Chen, HL, Newton, B, Zhou, RW, Beeton, C, Torossian, S, Tatarian, GG, Lee, SU, Lau, K, Walker, E, Siminovitch, KA, Chandy, KG, Yu, Z, Dennis, JW, Demetriou, M. Genetics and the environment converge to dysregulate N-glycosylation in multiple sclerosis. Nat Commun, 2, 334, 2011

Dennis, JW, Lau, KS, Demetriou, M, Nabi, IR. Adaptive regulation at the cell surface by N-glycosylation. Traffic, 10(11), 1569-78, 2009

Lau, KS, Haigis, KM. Non-redundancy within the RAS oncogene family: insights into mutational disparities in cancer. Mol Cells, 28(4), 315-20, 2009

Beheshti Zavareh, R, Lau, KS, Hurren, R, Datti, A, Ashline, DJ, Gronda, M, Cheung, P, Simpson, CD, Liu, W, Wasylishen, AR, Boutros, PC, Shi, H, Vengopal, A, Jurisica, I, Penn, LZ, Reinhold, VN, Ezzat, S, Wrana, J, Rose, DR, Schachter, H, Dennis, JW, Schimmer, AD. Inhibition of the sodium/potassium ATPase impairs N-glycan expression and function. Cancer Res, 68(16), 6688-97, 2008

Katz, D, Ito, E, Lau, KS, Mocanu, JD, Bastianutto, C, Schimmer, AD, Liu, FF. Increased efficiency for performing colony formation assays in 96-well plates: novel applications to combination therapies and high-throughput screening. Biotechniques, 44(2), ix-xiv, 2008

Lau, KS, Dennis, JW. N-Glycans in cancer progression. Glycobiology, 18(10), 750-60, 2008

Lau, KS, Khan, S, Dennis, JW. Genome-scale identification of UDP-GlcNAc-dependent pathways. Proteomics, 8(16), 3294-302, 2008

Lau, KS, Partridge, EA, Grigorian, A, Silvescu, CI, Reinhold, VN, Demetriou, M, Dennis, JW. Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation. Cell, 129(1), 123-34, 2007

Mendelsohn, R, Cheung, P, Berger, L, Partridge, E, Lau, K, Datti, A, Pawling, J, Dennis, JW. Complex N-glycan and metabolic control in tumor cells. Cancer Res, 67(20), 9771-80, 2007

Cheung, J, Estivill, X, Khaja, R, MacDonald, JR, Lau, K, Tsui, LC, Scherer, SW. Genome-wide detection of segmental duplications and potential assembly errors in the human genome sequence. Genome Biol, 4(4), R25, 2003

Lau, KS, Mantas, M, Chass, GA, Ferretti, FH, Estrada M, Zamarbide G, Csizmadia, IG. . Ab initio and DFT conformational analysis of selected flavones: 5,7-dihydroxyflavone (chrysin) and 7,8-dihydroxyflavone. Can J Chem, 7(80), 845-855, 2002


Postdoctoral Position Available
N/A

Postdoctoral Position Details
N/A

Updated Date
10/24/2013