Ken Lau, Ph.D.

Associate Professor

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Faculty Appointments
Associate Professor of Cell & Developmental Biology Associate Professor of Surgery
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
Brubaker DK, Kumar MP, Chiswick EL, Gregg C, Starchenko A, Vega PN, Southard-Smith AN, Simmons AJ, Scoville EA, Coburn LA, Wilson KT, Lau KS, Lauffenburger DA. An interspecies translation model implicates integrin signaling in infliximab-resistant inflammatory bowel disease. Sci Signal. 2020 Aug 8/4/2020; 13(643): PMID: 32753478, PII: 13/643/eaay3258, DOI: 10.1126/scisignal.aay3258, ISSN: 1937-9145.

Southard-Smith AN, Simmons AJ, Chen B, Jones AL, Ramirez Solano MA, Vega PN, Scurrah CR, Zhao Y, Brenan MJ, Xuan J, Shrubsole MJ, Porter EB, Chen X, Brenan CJH, Liu Q, Quigley LNM, Lau KS. Dual indexed library design enables compatibility of in-Drop single-cell RNA-sequencing with exAMP chemistry sequencing platforms. BMC Genomics. 2020 Jul 7/2/2020; 21(1): 456. PMID: 32616006, PMCID: PMC7331155, PII: 10.1186/s12864-020-06843-0, DOI: 10.1186/s12864-020-06843-0, ISSN: 1471-2164.

Yang X, Graff SM, Heiser CN, Ho KH, Chen B, Simmons AJ, Southard-Smith AN, David G, Jacobson DA, Kaverina I, Wright CVE, Lau KS, Gu G. Coregulator Sin3a Promotes Postnatal Murine ß-Cell Fitness by Regulating Genes in Ca2+ Homeostasis, Cell Survival, Vesicle Biosynthesis, Glucose Metabolism, and Stress Response. Diabetes [print-electronic]. 2020 Jun; 69(6): 1219-31. PMID: 32245798, PMCID: PMC7243292, PII: db19-0721, DOI: 10.2337/db19-0721, ISSN: 1939-327X.

Islam M, Chen B, Spraggins JM, Kelly RT, Lau KS. Use of Single-Cell -Omic Technologies to Study the Gastrointestinal Tract and Diseases, From Single Cell Identities to Patient Features. Gastroenterology [print-electronic]. 2020 May 5/14/2020; PMID: 32417404, PII: S0016-5085(20)30656-9, DOI: 10.1053/j.gastro.2020.04.073, ISSN: 1528-0012.

Heiser CN, Lau KS. A Quantitative Framework for Evaluating Single-Cell Data Structure Preservation by Dimensionality Reduction Techniques. Cell Rep. 2020 May 5/5/2020; 31(5): 107576. PMID: 32375029, PMCID: PMC7305633, PII: S2211-1247(20)30525-8, DOI: 10.1016/j.celrep.2020.107576, ISSN: 2211-1247.

Rozenblatt-Rosen O, Regev A, Oberdoerffer P, Nawy T, Hupalowska A, Rood JE, Ashenberg O, Cerami E, Coffey RJ, Demir E, Ding L, Esplin ED, Ford JM, Goecks J, Ghosh S, Gray JW, Guinney J, Hanlon SE, Hughes SK, Hwang ES, Iacobuzio-Donahue CA, Jané-Valbuena J, Johnson BE, Lau KS, Lively T, Mazzilli SA, Pe'er D, Santagata S, Shalek AK, Schapiro D, Snyder MP, Sorger PK, Spira AE, Srivastava S, Tan K, West RB, Williams EH, . The Human Tumor Atlas Network: Charting Tumor Transitions across Space and Time at Single-Cell Resolution. Cell. 2020 Apr 4/16/2020; 181(2): 236-49. PMID: 32302568, PMCID: PMC7376497, PII: S0092-8674(20)30346-9, DOI: 10.1016/j.cell.2020.03.053, ISSN: 1097-4172.

Liu Q, Sheng Q, Ping J, Ramirez MA, Lau KS, Coffey RJ, Shyr Y. ScRNABatchQC: multi-samples quality control for single cell RNA-seq data. Bioinformatics. 2019 Dec 12/15/2019; 35(24): 5306-8. PMID: 31373345, PMCID: PMC6954654, PII: 5542946, DOI: 10.1093/bioinformatics/btz601, ISSN: 1367-4811.

Min J, Vega PN, Engevik AC, Williams JA, Yang Q, Patterson LM, Simmons AJ, Bliton RJ, Betts JW, Lau KS, Magness ST, Goldenring JR, Choi E. Heterogeneity and dynamics of active Kras-induced dysplastic lineages from mouse corpus stomach. Nat Commun. 2019 Dec 12/5/2019; 10(1): 5549. PMID: 31804471, PMCID: PMC6895174, PII: 10.1038/s41467-019-13479-6, DOI: 10.1038/s41467-019-13479-6, ISSN: 2041-1723.

Vasaikar S, Huang C, Wang X, Petyuk VA, Savage SR, Wen B, Dou Y, Zhang Y, Shi Z, Arshad OA, Gritsenko MA, Zimmerman LJ, McDermott JE, Clauss TR, Moore RJ, Zhao R, Monroe ME, Wang YT, Chambers MC, Slebos RJC, Lau KS, Mo Q, Ding L, Ellis M, Thiagarajan M, Kinsinger CR, Rodriguez H, Smith RD, Rodland KD, Liebler DC, Liu T, Zhang B, . Proteogenomic Analysis of Human Colon Cancer Reveals New Therapeutic Opportunities. Cell [print-electronic]. 2019 May 5/2/2019; 177(4): 1035-1049.e19. PMID: 31031003, PII: S0092-8674(19)30292-2, DOI: 10.1016/j.cell.2019.03.030, ISSN: 1097-4172.

Howard AM, LaFever KS, Fenix AM, Scurrah CR, Lau KS, Burnette DT, Bhave G, Ferrell N, Page-McCaw A. DSS-induced damage to basement membranes is repaired by matrix replacement and crosslinking. J. Cell. Sci [print-electronic]. 2019 Mar 3/5/2019; PMID: 30837285, PII: jcs.226860, DOI: 10.1242/jcs.226860, ISSN: 1477-9137.

Manolopoulou M, Matlock BK, Nlandu Khodo S, Simmons AJ, Lau KS, Phillips-Mignemi M, Ivanova A, Alford CE, Flaherty DK, Gewin LS. Novel kidney dissociation protocol and image-based flow cytometry facilitate improved analysis of injured proximal tubules. Am. J. Physiol. Renal Physiol [print-electronic]. 2019 Feb 2/13/2019; PMID: 30759021, DOI: 10.1152/ajprenal.00354.2018, ISSN: 1522-1466.

Foegeding NJ, Raghunathan K, Campbell AM, Kim SW, Lau KS, Kenworthy AK, Cover TL, Ohi MD. Intracellular degradation of Helicobacter pylori VacA toxin as a determinant of gastric epithelial cell viability. Infect. Immun [print-electronic]. 2019 Jan 1/28/2019; PMID: 30692181, PII: IAI.00783-18, DOI: 10.1128/IAI.00783-18, ISSN: 1098-5522.

Vega PN, Lau KS, Goldenring JR. Not All Insults Are Created Equal for Awakening Dormant Stem Cell Abilities [editorial]. Cell Mol Gastroenterol Hepatol [print-electronic]. 2019 Jan 1/7/2019; PMID: 30629924, PII: S2352-345X(18)30178-4, DOI: 10.1016/j.jcmgh.2018.12.003, ISSN: 2352-345X.

Liu J, Banerjee A, Herring CA, Attalla J, Hu R, Xu Y, Shao Q, Simmons AJ, Dadi PK, Wang S, Jacobson DA, Liu B, Hodges E, Lau KS, Gu G. Neurog3-Independent Methylation Is the Earliest Detectable Mark Distinguishing Pancreatic Progenitor Identity. Dev. Cell. 2019 Jan 1/7/2019; 48(1): 49-63.e7. PMID: 30620902, PMCID: PMC6327977, PII: S1534-5807(18)31032-3, DOI: 10.1016/j.devcel.2018.11.048, ISSN: 1878-1551.

Scurrah CR, Simmons AJ, Lau KS. Single-Cell Mass Cytometry of Archived Human Epithelial Tissue for Decoding Cancer Signaling Pathways. Methods Mol. Biol. 2019; 1884: 215-29. PMID: 30465206, DOI: 10.1007/978-1-4939-8885-3_15, ISSN: 1940-6029.

Chen B, Herring CA, Lau KS. PyNVR: Investigating factors affecting feature selection from scRNA-seq data for lineage reconstruction. Bioinformatics [print-electronic]. 2018 Nov 11/16/2018; PMID: 30445607, PII: 5184958, DOI: 10.1093/bioinformatics/bty950, ISSN: 1367-4811.

Liu Q, Herring CA, Sheng Q, Ping J, Simmons AJ, Chen B, Banerjee A, Li W, Gu G, Coffey RJ, Shyr Y, Lau KS. Quantitative assessment of cell population diversity in single-cell landscapes. PLoS Biol. 2018 Oct; 16(10): e2006687. PMID: 30346945, PMCID: PMC6211764, PII: pbio.2006687, DOI: 10.1371/journal.pbio.2006687, ISSN: 1545-7885.

Banerjee A, McKinley ET, von Moltke J, Coffey RJ, Lau KS. Interpreting heterogeneity in intestinal tuft cell structure and function. J. Clin. Invest [print-electronic]. 2018 May 5/1/2018; 128(5): 1711-9. PMID: 29714721, PMCID: PMC5919882, PII: 120330, DOI: 10.1172/JCI120330, ISSN: 1558-8238.

Herring CA, Banerjee A, McKinley ET, Simmons AJ, Ping J, Roland JT, Franklin JL, Liu Q, Gerdes MJ, Coffey RJ, Lau KS. Unsupervised Trajectory Analysis of Single-Cell RNA-Seq and Imaging Data Reveals Alternative Tuft Cell Origins in the Gut. Cell Syst [print-electronic]. 2018 Jan 1/24/2018; 6(1): 37-51.e9. PMID: 29153838, PMCID: PMC5799016, PII: S2405-4712(17)30449-0, DOI: 10.1016/j.cels.2017.10.012, ISSN: 2405-4712.

Herring CA, Chen B, McKinley ET, Lau KS. Single-Cell Computational Strategies for Lineage Reconstruction in Tissue Systems. Cell Mol Gastroenterol Hepatol. 2018; 5(4): 539-48. PMID: 29713661, PMCID: PMC5924749, PII: S2352-345X(18)30031-6, DOI: 10.1016/j.jcmgh.2018.01.023, ISSN: 2352-345X.

Maseda D, Banerjee A, Johnson EM, Washington MK, Kim H, Lau KS, Crofford LJ. MPGES-1-Mediated Production of PGE2 and EP4 Receptor Sensing Regulate T Cell Colonic Inflammation. Front Immunol. 2018; 9: 2954. PMID: 30619314, PMCID: PMC6302013, DOI: 10.3389/fimmu.2018.02954, ISSN: 1664-3224.

Kim SW, Ehrman J, Ahn MR, Kondo J, Lopez AAM, Oh YS, Kim XH, Crawley SW, Goldenring JR, Tyska MJ, Rericha EC, Lau KS. Shear stress induces noncanonical autophagy in intestinal epithelial monolayers. Mol. Biol. Cell [print-electronic]. 2017 Nov 11/1/2017; 28(22): 3043-56. PMID: 28855375, PMCID: PMC5662261, PII: mbc.E17-01-0021, DOI: 10.1091/mbc.E17-01-0021, ISSN: 1939-4586.

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.

Available Postdoctoral Position Details
Posted: 12/6/2018

An immediate opening for a postdoctoral position exists at Vanderbilt University School of Medicine. The project is to examine the role of stem cells in metastasis using orthotopic mouse models of colon cancer with unique reporters embedded. Individuals with experience in mouse models, colonoscopy, lineage mapping, and immunofluorescence microscopy are encouraged to apply. The Lau lab collaborates closely with the Coffey lab, and the individual will be immersed in an interdisciplinary environment with training opportunities in single-cell resolution multiplex immunofluorescence, smFISH, and single-cell RNA-seq, organoids, and computational data science techniques. Funding is secure, along with a highly competitive salary and fringe benefits. Those interested should contact Ken Lau at with a CV and cover letter.