The theme of our research is the identification and evaluation of genetic determinants of chromosome segregation using budding yeast as a model organism. Our goal is to identify and understand the function of genes whose loss results in genome instability in budding yeast, and to evaluate these as potential contributors to genome instability observed in other organisms. Currently, we are engaged in projects aimed at understanding kinetochore proteins operating in spindle checkpoint control, as well as chromosomal proteins important for the establishment or maintenance of sister chromatid cohesion. In addition, we are taking advantage of the yeast knockout strain sets to study chromosome transmission at a genomic level in several strategies. In one, we are embarking on a project to define a set of genetic interactions among nonessential genes (that is, genes which are not themselves individually required for cell viability). A product of this effort will be a "genetic interaction map" documenting lethality, or markedly decreased fitness, of double mutant combinations. This work will reveal functional relationships important in evolution, will augment the definition of pathways, and will serve to predict functional activities of unstudied genes.

Research Interests:

• DNA replication/repair and sister chromatid cohesion
• Genetic variation and genome evolution
• Synthetic lethal interaction analysis
• Genetic interaction map of yeast

Educational Activities:

• Preceptor: Predoctoral Training Program in Human Genetics
• Lecturer, Fundamentals of Genetics. Graduate course. Topics: Introduction to Genetics, and Meiosis & Recombination in Tetrad Analysis. Since 1997
• Instructor, Method and Logic. Graduate course. Since 1997
• Lecturer, Advanced Topics in Human Genetics. Graduate course. Topic: Human disease gene identification. Since 1993
• Organizer, Cold Spring Harbor Fall Course "Gene Isolation: Advanced Methods in Positional Cloning" 1997 - 2000

Publications:

Hanna JS, E Kroll, P Hieter, F Spencer. Budding yeast CTF4 and CTF18 are required for sister chromatid cohesion. Mol Cell Biol 21:3144-3158 (2001).

Warren C, M Brady, J Hanna, R Johnston, KG Hardwick, and F Spencer. Distinct chromosome segregation roles for spindle checkpoint proteins. Mol Biol Cell 13:3029-3041 (2002).

Warren CD, DM Eckley, MS Lee, JS Hanna, A Hughes, B Peyser, C Jie, R Irizarry, and F Spencer. S phase checkpoint genes safeguard high fidelity sister chromatid cohesion. Mol Biol Cell 15: 1724-1735 (2004).

Wu Z, RA Irizarry, R Gentleman, F Martinez-Murillo, and FA Spencer. A model based background adjustment for oligonucleotide expression arrays. J Am Stat Assoc 468:909-917 (2004).

Pan X, DS Yuan, D Xiang, X Wang, S Sookhai-Mahadeo, JS Bader, PA Hieter, F Spencer, JD Boeke. A robust toolkit for functional profiling of the yeast genome. Mol Cell 16: 487-496 (2004).

Kastenmayer JP, MS Lee, AL Hong, FA Spencer, MA Basrai. The C-terminal half of Mad1p mediates spindle checkpoint function, chromosome transmission fidelity, and CEN association. Genetics, in press (2005).

Irizarry RA, Warren D, Spencer F, Kim IF, Biswal S, Frank BC, Gabrielson E, Garcia JG, Geoghegan J, Germino G, Griffin C, Hilmer SC, Hoffman E, Jedlicka AE, Kawasaki E, Martinez-Murillo F, Morsberger L, Lee H, Petersen D, Quackenbush J, Scott A, Wilson M, Yang Y, Ye SQ, Yu W. Multiple-laboratory comparison of microarray platforms. Nat Methods 2: 345-50 (2005).