Kenneth Scott, Ph.D.
Assistant Professor of Molecular and Human Genetics
Assistant Professor, Program in Integrative Molecular and Biomedical Sciences
B.S., Texas State University, 1997
Ph.D., Baylor College of Medicine, 2005
Postdoc, Dana-Farber Cancer Institute, 2009
Cancer cells must acquire diverse biological capabilities during their transition through malignancy. These newfound characteristics accompany a highly unstable cancer genome. Chromosomal alterations, DNA mutations and aberrant epigenetic modifications coordinate to activate oncogenes and inactivate tumor suppressor genes, thereby serving as a driving force in tumorigenesis. Identification of such driver events remains a foundation for development of effective, targeted therapeutic agents against cancer. While today’s high-resolution technologies have enabled unprecedented definition of genomic aberrations across diverse human cancers, gene discovery efforts are hampered by the large number of potential candidates resulting from these analyses. When combined with genetic screens, genomics data can be quickly prioritized based on the functional activity of the candidates. Following these themes, my research utilizes oncogenomics-guided approaches coupled with genetic screens and downstream functional validation studies to identify new cancer genes and signaling pathways.
Recently, we described a gene discovery approach based on comparative genomic analyses of multiple tumor types (Scott et al., Nature 2009). The approach revealed a novel oncogene, Golgi Phosphoprotein 3 (GOLPH3), which was confirmed to be amplified in several solid tumor types. While its biological activity remains to be fully elucidated, GOLPH3 influences signaling through the Akt-mTOR pathway that plays a critical role in cell growth and cancer. Currently, we are using genetic and microscopy-based approaches to examine GOLPH3’s potential role in regulating the trafficking of signaling molecules upstream of the Akt-mTOR axis. We are also developing a mouse model to further explore GOLPH3’s biological function in vivo, and we hope to use this model to examine GOLPH3’s potential utility for cancer therapeutics.
Another major focus of my laboratory is tumor metastasis, which is the lethal feature of the majority of solid tumor cancers. Recently, we implemented an integrated genomics strategy to define a gene signature correlated with metastasis of melanoma. Functional screening of this signature identified a subset of genes whose over-expression enhances metastatic cell invasion. While initially discovered in the context of melanoma, these candidates also show progression-correlated expression in diverse non-melanoma tumor types and are proving prognostic in early stage cancers. Current work is focused on functionally validating individual candidates and elucidating their mode-of-action, and these efforts have already uncovered links to new and established metastasis pathways. My laboratory is also developing new metastasis gene discovery strategies for pancreatic cancer, which carries an exceptionally high mortality rate stemming from metastatic disease.
- Bonnen PE, Yarham JW, Besse A, Wu P, Faqeih EA, Al-Asmari AM, Saleh MA, Eyaid W, Hadeel A, He L, Smith F, Yau S, Simcox EM, Miwa S, Donti T, Abu-Amero KK, Wong LJ, Craigen WJ, Graham BH, Scott KL, McFarland R, Taylor RW (2013). Mutations in FBXL4 Cause Mitochondrial Encephalopathy and a Disorder of Mitochondrial DNA Maintenance. Am. J. Hum. Genet. 93(3): 471-81. PubMed PMID: 23993193
- Guo H, Gao M, Lu Y, Liang J, Lorenzi PL, Bai S, Hawke DH, Li J, Dogruluk T, Scott KL, Jonasch E, Mills GB, Ding Z (2013). Coordinate phosphorylation of multiple residues on single AKT1 and AKT2 molecules. Oncogene, in press. PubMed PMID: 23912456
- Wardwell-Ozgo J, Dogruluk T, Gifford A, Zhang Y, Heffernan TP, van Doorn R, Creighton CJ, Chin L, Scott KL (2013). HOXA1 drives melanoma tumor growth and metastasis and elicits an invasion gene expression signature that prognosticates clinical outcome. Oncogene, in press. PubMed PMID: 23435427.
- Liang H, Cheung LW, Li J, Ju Z, Yu S, Stemke-Hale K, Dogruluk T, Lu Y, Liu X, Gu C, Guo W, Scherer SE, Carter H, Westin SN, Dyer MD, Verhaak RG, Zhang F, Karchin R, Liu CG, Lu KH, Broaddus RR, Scott KL, Hennessy BT, Mills GB (2012). Whole-exome sequencing combined with functional genomics reveals novel candidate driver cancer genes in endometrial cancer. Genome Res. 22(11): 2120-9. PubMed PMID: 23028188
- Scott KL, Nogueira C, Heffernan TP, van Doorn R, Dhakal S, Hanna JA, Min C, Jaskelioff M, Xiao Y, Wu CJ, Cameron LA, Perry SR, Zeid R, Feinberg T, Kim M, Vande Woude G, Granter SR, Bosenberg M, Chu GC, Depinho RA, Rimm DL, Chin L (2011). Proinvasion metastasis drivers in early-stage melanoma are oncogenes. Cancer Cell 20(1): 92-103. PubMed PMID: 21741599
- Jiang Y, Scott KL, Kwak SJ, Chen R, Mardon G (2011). Sds22/PP1 links epithelial integrity and tumor suppression via regulation of myosin II and JNK signaling. Oncogene 30(29): 3248-60. PubMed PMID: 21399659
- Ding Z, Wu CJ, Chu GC, Xiao Y, Ho D, Zhang J, Perry SR, Labrot ES, Wu X, Lis R, Hoshida Y, Hiller D, Hu B, Jiang S, Zheng H, Stegh AH, Scott KL, Signoretti S, Bardeesy N, Wang YA, Hill DE, Golub TR, Stampfer MJ, Wong WH, Loda M, Mucci L, Chin L, DePinho RA (2011). SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression. Nature 470(7333): 269-73. PubMed PMID: 21289624
- Levy C, Khaled M, Iliopoulos D, Janas MM, Schubert S, Pinner S, Chen PH, Li S, Fletcher AL, Yokoyama S, Scott KL, Garraway LA, Song JS, Granter SR, Turley SJ, Fisher DE, Novina CD (2010). Intronic miR-211 assumes the tumor suppressive function of its host gene in melanoma. Mol. Cell 40(5): 841-9. PubMed PMID: 21109473
- Ying H, Zheng H, Scott K, Wiedemeyer R, Yan H, Lim C, Huang J, Dhakal S, Ivanova E, Xiao Y, Zhang H, Hu J, Stommel JM, Lee MA, Chen AJ, Paik JH, Segatto O, Brennan C, Elferink LA, Wang YA, Chin L, DePinho RA (2010). Mig-6 controls EGFR trafficking and suppresses gliomagenesis. Proc. Natl. Acad. Sci. U S A 107(15): 6912-7. PubMed PMID: 20351267
- Scott KL, Kabbarah O, Liang MC, Ivanova E, Anagnostou V, Wu J, Dhakal S, Wu M, Chen S, Feinberg T, Huang J, Saci A, Widlund HR, Fisher DE, Xiao Y, Rimm DL, Protopopov A, Wong KK, Chin L (2009). GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer. Nature 459(7250): 1085-90. PubMed PMID: 19553991
Kenneth L. Scott, Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, Rm. ABBR-R715
Mail Stop: BCM225
Houston, TX, 77030, U.S.A.