Ph.D. Biophysics, UC San Francisco, 2000
B.S. Biochemistry, Brown University, 1994
Variation between long-diverged fungal species. Fungi specialize to their environment in amazing ways. When a fungal species from one niche differs radically from its relatives elsewhere, we would love to know the mechanism at play. In many cases the underlying adaptive alleles are a mystery, especially if they arose long ago. The main roadblock to date has been that most experimental tools in evolutionary genetics research are only applicable to comparison across strains, not species. Ongoing work in the lab is devoted to breaking through this limitation. We have developed a novel approach to map the genetic basis of differences between distantly related species. Our strategy is designed to reveal the nucleotide-level variants that a given fungus has used to adapt to its environment over evolutionary time. We have just completed a pilot project focused on thermotolerance in Saccharomyces yeast as a test case, and are excited about extending the method to many other eukaryotes.
Mapping genotype to phenotype in fungi. Most fungal genomes are poorly annotated, so we have no idea of the genetic architecture for many fungal traits of industrial and biomedical relevance. In published work, our lab has used variation across wild populations to find the molecular basis of morphology traits in the model fungi Saccharomyces and Neurospora; we have also developed genomic screening approaches to annotate candidate virulence islands in the plant pathogen Zymoseptoria and lipid metabolism genes in the oleaginous yeast Rhodosporidium. Our next project, now in progress, is focused on strain variation in virulence and stress resistance traits in the human pathogen Coccidioides.
Polygenic evolution. In many cases, adaptation may be the result of multiple, subtly acting variants that work together to give rise to a new phenotype. Our lab has pushed the envelope of methods to detect cases of this type of polygenic evolution. In recent published studies we have used Saccharomyces yeast as a test case, and ongoing work is focused on Cryptococcus.
Weiss CV, Roop JI, Hackley RK, Chuong JN, Grigoriev IV, Arkin AP, Skerker JM, Brem RB. Genetic dissection of an ancient divergence in yeast thermotolerance. Nature Genetics, in press, 2018.
Hill RZ, Hoffman B, Morita T, Campos SM, Lumpkin EA, Brem RB, Bautista DM. The signaling lipid sphingosine-1-phosphate regulates mechanical pain. eLife 7:e33285, 2018.
Coradetti ST, Pinel D, Geiselman G, Ito M, Mondo S, Reilly MC, Cheng YF, Bauer S, Grigoriev I, Gladden JM, Simmons BA, Brem RB, Arkin AP, Skerker JM. Functional genomics of lipid metabolism in the oleaginous yeast Rhodosporidium toruloides. eLife 7:e32110, 2018. Featured article, eLife Digest.
Bay RA, Rose N, Barrett R, Bernatchez L, Ghalambour CK, Lasky JR, Brem RB, Palumbi SR, Ralph P. Predicting evolutionary responses to contemporary environmental change using population genomic data. American Naturalist 189(5):463-473, 2017.
Cross-phenotype association tests uncover genes mediating nutrient response in Drosophila. Nelson CS, Beck JN, Wilson KA, Pilcher ER, Kapahi P, Brem RB. BMC Genomics 17(1):867, 2016.
Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes skn-1, ire-1, and xbp-1. Mark KA, Dumas KJ, Bhaumik D, Schilling B, Davis S, Oron TR, Sorensen DJ, Lucanic M, Brem RB, Melov S, Ramanathan A, Gibson BW, Lithgow GJ. Cell Reports 17(5):1226-1237.
The role of transcription factors at antisense-expressing gene pairs in yeast. Mostovoy Y, Thiemicke A, Hsu TY, Brem RB. Genome Biology and Evolution 8(6):1748-61, 2016.
Polygenic evolution of a sugar specialization tradeoff in yeast. Roop JI, Chung KC, Brem RB. Nature 530(7590):336-9, 2016. Featured article in Cell Systems, March 2016 issue.
Katewa SD, Akagi K, Bose N, Rakshit K, Camarella T, Zheng X, Hall D, Davies S, Nelson C, Brem RB, Ramanathan A, Sehgal A, Giebultowicz JM, Kapahi P. Peripheral Circadian Clocks Mediate Dietary Restriction-Dependent Changes in Lifespan and Fat Metabolism in Drosophila. Cell Metabolism 23(1):143-54, 2016.
McCormick M, … Brem RB, … Kennedy BK. A comprehensive analysis of replicative lifespan in 4,698 single-gene deletion strains uncovers novel mechanisms of aging. Cell Metabolism 22(5):895-906, 2015.
Morita T, McClain SP, Batia LM, Pellegrino M, Wilson SR, Kienzler MA, Lyman K, Olsen ASB, Wong JF, Brem RB, Bautista DM. HTR7 is a transducer of serotonergic acute and chronic itch. Neuron 87(1):124-38, 2015.
Kellner R, Bhattacharyya A, Poppe S, Hsu TY, Brem RB, Stukenbrock E. Transcriptome sequencing at early-stage infection of the wheat pathogen Z. tritici reveals chromosome differences in transcription patterns and host-specific gene expression. Genome Biology and Evolution 6(6):1353-65, 2014.
Ellison CE, Kowbel D, Glass NL, Taylor JW, Brem RB. Discovering functions of unannotated genes from a transcriptome survey of wild fungal isolates. mBio 5(2):e01046-13, 2014.
Schraiber JG, Mostovoy Y, Hsu TY, Brem RB. Inferring pathway evolutionary histories from transcriptional profiling data. PLoS Computational Biology 9(10):e1003255, 2013.
Palma-Guerrero J, Hall CR, Kowbel D, Welch J, Taylor JW, Brem RB, Glass NL. Genome-wide association identifies novel loci involved in fungal communication. PLoS Genetics 9(8):e1003669, 2013.
Lee HN, Mostovoy Y, Hsu TY, Chang A, Brem RB. Divergence of iron metabolism in wild Malaysian yeast. G3: Genes|Genomes|Genetics 3(12):2187-94, 2013.
Roop JI, Brem RB. Rare variants in hypermutable genes underlie common morphology and growth traits in wild S. paradoxus yeasts. Genetics 195(2):513-525, 2013. Cover article, July 2014 issue; featured paper, October 2013 issue highlights.
Yoon OK, Hsu TY, Im JH, Brem RB. Genetics and regulatory impact of alternative polyadenylation in human B-lymphoblastoid cells. PLoS Genetics 8(8):e1002882, 2012.
Martin HC, Roop JI, Schraiber JG, Hsu TY, Brem RB. Evolution of a membrane protein regulon in Saccharomyces. Molecular Biology and Evolution, 29(7):1747-1756, 2012.
Denby CM, Im JH, Yu RC, Pesce CG, Brem RB. Negative feedback confers mutational robustness in yeast transcription factor regulation. PNAS 109(10):3874-8, 2012.
Zhu J, Sova P, Xu Q, Dombek KM, Xu EY, Vu H, Tu Z, Brem RB, Bumgarner RE, Schadt EE. Stitching together multiple data dimensions reveals interacting metabolic and transcriptomic networks that modulate cell regulation. PLoS Biology 10(4):e1001301, 2012.
Ellison CE, Hall C, Kowbel D, Welch J, Brem RB, Glass NG, Taylor JW. Population genomics and local adaptation in wild isolates of a model microbial eukaryote. PNAS 108(7):2831-6, 2011. Faculty of 1000 Must Read/Recommended Paper.
Lee HN, Magwene PM, Brem RB. Natural variation in CDC28 underlies morphological phenotypes in an environmental yeast isolate. Genetics 188(3):723-30, 2011.
Bullard JH, Mostovoy J, Dudoit S, Brem RB. Polygenic and directional regulatory evolution across pathways in Saccharomyces. PNAS 107(11):5058-5063, 2010.
Yoon OK, Brem RB. Non-canonical transcript forms in yeast and their regulation during environmental stress. RNA 16(6):1256-67, 2010. Faculty of 1000 Recommended Paper.