Ken Lau, Ph.D.

Assistant Professor

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Faculty Appointments
Assistant Professor of Cell and Developmental Biology
Ph.D., Proteomics and Bioinformatics , University of Toronto, Toronto, CanadaB.Sc., University of Toronto, Toronto, Canada
Office Address
2215 Garland Ave, MRB IV 10465J
Nashville, TN 37232
Research Description
Our lab develops and applies computational approaches to high content data generated by single-cell technologies to understand epithelial tissue function and organization. The intestinal epithelium is a single cell layer that separates the trillions of microbes in the gut lumen from the host’s body. The central goal of my lab is to understand how the inflammatory microenvironment, the so-called “niche”, signal to epithelial cells to alter their phenotypes. Microenvironmental signaling is exquisitely regulated to constrain and maintain a homeostatic state between epithelial cells, luminal microbes, and underlying immune cells. A disrupted balance leads to diseases such Inflammatory Bowel Disease and colorectal cancer. My lab is broadly interested in understanding how niche signals are integrated and interpreted to result in cell fate decisions, such as cellular decisions to differentiate into one cell type versus another. We utilize single approaches such as DISSECT-CyTOF (Simmons et al., 2015), multiplex imaging (MxIF) (McKinley et al., 2017), and single-cell RNA-seq to query single-cell states. We aim to unravel the degree of heterogeneity and plasticity of epithelial cell populations, such as cancer stem cells, in vivo, and to translate such knowledge into therapeutically tractable targets.
Research Keywords
single-cell, computational systems biology, inflammation, colorectal cancer, stem cells, epithelial biology, cell state specification, signal transduction
McKinley ET, Sui Y, Al-Kofahi Y, Millis BA, Tyska MJ, Roland JT, Santamaria-Pang A, Ohland CL, Jobin C, Franklin JL, Lau KS, Gerdes MJ, Coffey RJ. Optimized multiplex immunofluorescence single-cell analysis reveals tuft cell heterogeneity. JCI Insight [print-electronic]. 2017 Jun 6/2/2017; 2(11): PMID: 28570279, PMCID: PMC5453701, PII: 93487, DOI: 10.1172/jci.insight.93487, ISSN: 2379-3708.

Almohazey D, Lo YH, Vossler CV, Simmons AJ, Hsieh JJ, Bucar EB, Schumacher MA, Hamilton KE, Lau KS, Shroyer NF, Frey MR. The ErbB3 receptor tyrosine kinase negatively regulates Paneth cells by PI3K-dependent suppression of Atoh1. Cell Death Differ [print-electronic]. 2017 May; 24(5): 855-65. PMID: 28304405, PMCID: PMC5423110, PII: cdd201727, DOI: 10.1038/cdd.2017.27, ISSN: 1476-5403.

Simmons AJ, Lau KS. Deciphering tumor heterogeneity from FFPE tissues: Its promise and challenges. Mol Cell Oncol. 2017; 4(1): e1260191. PMID: 28197533, PMCID: PMC5286981, PII: 1260191, DOI: 10.1080/23723556.2016.1260191, ISSN: 2372-3556.

Simmons AJ, Scurrah CR, McKinley ET, Herring CA, Irish JM, Washington MK, Coffey RJ, Lau KS. Impaired coordination between signaling pathways is revealed in human colorectal cancer using single-cell mass cytometry of archival tissue blocks. Sci Signal. 2016 Oct 10/11/2016; 9(449): rs11. PMID: 27729552, PII: 9/449/rs11, DOI: 10.1126/scisignal.aah4413, ISSN: 1937-9145.

Gierut JJ, Wood LB, Lau KS, Lin YJ, Genetti C, Samatar AA, Lauffenburger DA, Haigis KM. Network-level effects of kinase inhibitors modulate TNF-a-induced apoptosis in the intestinal epithelium. Sci Signal. 2015 Dec 12/15/2015; 8(407): ra129. PMID: 26671150, PMCID: PMC4812576, PII: 8/407/ra129, DOI: 10.1126/scisignal.aac7235, ISSN: 1937-9145.

Simmons AJ, Banerjee A, McKinley ET, Scurrah CR, Herring CA, Gewin LS, Masuzaki R, Karp SJ, Franklin JL, Gerdes MJ, Irish JM, Coffey RJ, Lau KS. Cytometry-based single-cell analysis of intact epithelial signaling reveals MAPK activation divergent from TNF-a-induced apoptosis in vivo. Mol. Syst. Biol. 2015 Oct; 11(10): 835. PMID: 26519361, PMCID: PMC4631206, ISSN: 1744-4292.

Lyons J, Herring CA, Banerjee A, Simmons AJ, Lau KS. Multiscale analysis of the murine intestine for modeling human diseases. Integr Biol (Camb). 2015 Jul; 7(7): 740-57. PMID: 26040649, PMCID: PMC4569017, DOI: 10.1039/c5ib00030k, ISSN: 1757-9708.

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) [print-electronic]. 2013 Nov; 5(11): 1355-65. PMID: 24084984, PMCID: PMC3966991, DOI: 10.1039/c3ib40062j, ISSN: 1757-9708.

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) [print-electronic]. 2013 Jul 7/24/2013; 5(7): 940-63. PMID: 23685806, PMCID: PMC3759823, DOI: 10.1039/c3ib40013a, ISSN: 1757-9708.

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 [print-electronic]. 2012; 10(9): e1001393. PMID: 23055830, PMCID: PMC3463506, PII: PBIOLOGY-D-12-01984, DOI: 10.1371/journal.pbio.1001393, ISSN: 1545-7885.

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 [print-electronic]. 2012; 7(7): e41343. PMID: 22815993, PMCID: PMC3399817, PII: PONE-D-12-03440, DOI: 10.1371/journal.pone.0041343, ISSN: 1932-6203.

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. 2011; 4(165): ra16. PMID: 21427409, PMCID: PMC3963028, PII: 4/165/ra16, DOI: 10.1126/scisignal.2001338, ISSN: 1937-9145.

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. 2011; 2: 334. PMID: 21629267, PMCID: PMC3133923, PII: ncomms1333, DOI: 10.1038/ncomms1333, ISSN: 2041-1723.

Dennis JW, Lau KS, Demetriou M, Nabi IR. Adaptive regulation at the cell surface by N-glycosylation. Traffic [print-electronic]. 2009 Nov; 10(11): 1569-78. PMID: 19761541, PII: TRA981, DOI: 10.1111/j.1600-0854.2009.00981.x, ISSN: 1600-0854.

Lau KS, Haigis KM. Non-redundancy within the RAS oncogene family: insights into mutational disparities in cancer. Mol. Cells [print-electronic]. 2009 Oct 10/31/2009; 28(4): 315-20. PMID: 19812895, PMCID: PMC3976423, DOI: 10.1007/s10059-009-0143-7, ISSN: 0219-1032.

Lau KS, Dennis JW. N-Glycans in cancer progression. Glycobiology [print-electronic]. 2008 Oct; 18(10): 750-60. PMID: 18701722, PII: cwn071, DOI: 10.1093/glycob/cwn071, ISSN: 1460-2423.

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. 2008 Aug 8/15/2008; 68(16): 6688-97. PMID: 18701493, PII: 68/16/6688, DOI: 10.1158/0008-5472.CAN-07-6833, ISSN: 1538-7445.

Lau KS, Khan S, Dennis JW. Genome-scale identification of UDP-GlcNAc-dependent pathways. Proteomics. 2008 Aug; 8(16): 3294-302. PMID: 18646010, DOI: 10.1002/pmic.200800208, ISSN: 1615-9861.

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. 2008 Feb; 44(2): ix-xiv. PMID: 18422490, PII: 000112757, DOI: 10.2144/000112757, ISSN: 0736-6205.

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. 2007 Oct 10/15/2007; 67(20): 9771-80. PMID: 17942907, PII: 67/20/9771, DOI: 10.1158/0008-5472.CAN-06-4580, ISSN: 0008-5472.

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. 2007 Apr 4/6/2007; 129(1): 123-34. PMID: 17418791, PII: S0092-8674(07)00315-7, DOI: 10.1016/j.cell.2007.01.049, ISSN: 0092-8674.

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 [print-electronic]. 2003; 4(4): R25. PMID: 12702206, PMCID: PMC154576, ISSN: 1474-760X.

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. 2002.