# Ira Herskowitz
**Ira Herskowitz** (1946–2003) was an American molecular geneticist who worked out how baker's yeast, *Saccharomyces cerevisiae*, switches mating type, and how yeast cells divide asymmetrically, and who spent his career at the [University of California, San Francisco](https://www.edgepedia.org/university-of-california-san-francisco), as the Herzstein Professor of Genetics.[1](https://www.macfound.org/fellows/class-of-1987/ira-herskowitz) His genetic analysis of mating-type interconversion led to the cassette model, in which one copy of a gene is replaced by another, and his laboratory went on to define the regulatory logic of yeast cell types and the mechanics of asymmetric cell division.[1](https://www.macfound.org/fellows/class-of-1987/ira-herskowitz) • [2](https://www.cell.com/cell/fulltext/S0092-8674(03)00510-5) According to *The Scientist*, he died on April 28, 2003, of pancreatic cancer at his home in San Francisco, at age 56.[3](https://www.the-scientist.com/ira-herskowitz-dies-51712) • [4](https://www.nytimes.com/2003/05/03/us/ira-herskowitz-a-top-geneticist-dies-at-56.html)
| Fact | Detail |
|---|---|
| Field | Molecular genetics of *Saccharomyces cerevisiae*; mating-type switching, cell differentiation, asymmetric cell division[2](https://www.cell.com/cell/fulltext/S0092-8674(03)00510-5) |
| Training | B.S. Caltech 1967; Ph.D. MIT 1971, thesis on gene control in bacteriophage lambda[5](http://hdl.handle.net/1721.1/12632) |
| Career | University of Oregon (from 1971); UCSF faculty from 1981–1982 until his death in 2003[2](https://www.cell.com/cell/fulltext/S0092-8674(03)00510-5) • [1](https://www.macfound.org/fellows/class-of-1987/ira-herskowitz) |
| Signature work | "Mechanisms of asymmetric cell division: Two Bs or not two Bs, that is the question" (Cell, 1992); "A regulatory hierarchy for cell specialization in yeast" (Nature, 1989); ["Genetic control of bud site selection in yeast by a set of gene products that constitute a morphogenetic pathway"](https://doi.org/10.1016/0092-8674(91)90015-q), *Cell*, 1991 |
| Leadership | Chaired UCSF Department of Biochemistry and Biophysics 1990–1995; co-directed the Program in Human Genetics from 1997[3](https://www.the-scientist.com/ira-herskowitz-dies-51712) |
| Honors | NAS (1986), MacArthur Fellowship (1987), Thomas Hunt Morgan Medal (2002), Institute of Medicine (2002), Lewis S. Rosenstiel Award (2003)[1](https://www.macfound.org/fellows/class-of-1987/ira-herskowitz) |
| Death | April 28, 2003, pancreatic cancer, age 56[3](https://www.the-scientist.com/ira-herskowitz-dies-51712) |
## Education and early career
Ira was born in 1946 in Brooklyn; his father was a *Drosophila* geneticist.[2](https://www.cell.com/cell/fulltext/S0092-8674(03)00510-5) As a Caltech undergraduate, from which he graduated in 1967, Herskowitz joined a bacteriophage research project with Robert Edgar and [Jonathan King](https://www.edgepedia.org/jonathan-king), where, according to the Genetics Society of America, he developed a passion for experimental genetics.[6](https://doi.org/10.1093/genetics/164.2.419)
His 1971 MIT doctoral thesis in biology was titled "Control of late genes, early genes, the cI gene, and replication in bacteriophage lambda."[5](http://hdl.handle.net/1721.1/12632) In that last year of graduate school he accepted an assistant professorship in the [University of Oregon](https://www.edgepedia.org/university-of-oregon)'s Institute of Molecular Biology, deferring his arrival to spend a year at MIT with [David Botstein](https://www.edgepedia.org/david-botstein) preparing to move onto yeast.[2](https://www.cell.com/cell/fulltext/S0092-8674(03)00510-5) After a 1979 sabbatical at UC San Francisco, he joined the UCSF faculty; the Cell memorial places the move in 1981, while the MacArthur Foundation record gives 1982, and he remained at UCSF for the rest of his life.[6](https://doi.org/10.1093/genetics/164.2.419) • [2](https://www.cell.com/cell/fulltext/S0092-8674(03)00510-5) • [1](https://www.macfound.org/fellows/class-of-1987/ira-herskowitz)
## Mating-type switching and the cassette model
Yeast can change mating type as often as every generation by a site-specific recombination event that replaces one MAT allele with DNA sequences encoding the opposite allele.[7](https://doi.org/10.1146/annurev.genet.32.1.561) Herskowitz's genetic experiments suggested a novel cassette-insertion mechanism for this interconversion, and the Cold Spring Harbor yeast group demonstrated that the switch occurs by recombination initiated at a DNA double-strand break.[2](https://www.cell.com/cell/fulltext/S0092-8674(03)00510-5) The MacArthur Foundation describes the cassette model as a major conceptual breakthrough in the genetic basis of cell differentiation.[1](https://www.macfound.org/fellows/class-of-1987/ira-herskowitz) Study of the switching process went on to yield insights into the control of cell lineage, silencing of gene expression, formation of heterochromatin, and the molecular events of double-strand-break-induced recombination.[7](https://doi.org/10.1146/annurev.genet.32.1.561) David Botstein judged the mating-type switching work one of the great advances in understanding regulatory systems in eukaryotes.[3](https://www.the-scientist.com/ira-herskowitz-dies-51712)
## Representative work
**The STE12 papers.** Work in Molecular and Cellular Biology in 1987 ([doi:10.1128/mcb.7.10.3818](https://doi.org/10.1128/mcb.7.10.3818)) showed that the STE12 gene of *Saccharomyces cerevisiae* is necessary for RNA synthesis from two sets of cell-type-specific genes, cloned STE12 by complementation of the mating defect of ste12 cells, and showed that the STE12 transcript is repressed 5- to 10-fold in a/alpha diploid cells, so the STE12 product promotes mating-gene expression in haploids and is repressed in diploids.[8](https://doi.org/10.1128/mcb.7.10.3818)
**The 1989 Nature review.** "A regulatory hierarchy for cell specialization in yeast" ([doi:10.1038/342749a0](https://doi.org/10.1038/342749a0)) established that the specialized gene sets determining yeast cell types are controlled by combinations of DNA-binding proteins, some present only in certain cell types and others in all cell types, and that final differentiation requires an inductive signal triggering both gene transcription and cell-cycle arrest.[9](https://doi.org/10.1038/342749a0)
**The 1992 Cell review.** "Mechanisms of asymmetric cell division: Two Bs or not two Bs, that is the question" ([doi:10.1016/0092-8674(92)90468-r](https://doi.org/10.1016/0092-8674(92)90468-r)), published in January 1992, framed the general problem of how one mother cell produces two different daughters, and carries 529 citations in the publisher's record.[10](https://doi.org/10.1016/0092-8674(92)90468-r) According to Herskowitz's obituary, his own studies at UCSF showed that in yeast a particular mRNA distributed to one progeny cell initiates the developmental program of asymmetric cell division.[11](https://doi.org/10.1038/424384a)
## Later UCSF work
At UCSF, Herskowitz's laboratory studied the life cycle of *Saccharomyces cerevisiae* as a prototypic eukaryotic cell, with genetics as its specialty alongside biochemistry and molecular biology, supported in part by NIH grants GM59256, GM59466, and GM48052.[12](https://web.archive.org/web/20150219032612/http:/biochemistry.ucsf.edu/labs/herskowitz/index.html) According to his memorial article in *Cell*, his group's questions extended to bud-site selection, cell polarity, crosstalk between signaling pathways, sporulation, and mechanisms of resistance to the anticancer drug cisplatin; he later spearheaded pharmacogenomics work on membrane transporters and drug response.[2](https://www.cell.com/cell/fulltext/S0092-8674(03)00510-5) The New York Times described him as a pioneer in the effort to learn how genetic differences among people influence the effectiveness of drugs.[4](https://www.nytimes.com/2003/05/03/us/ira-herskowitz-a-top-geneticist-dies-at-56.html) His work also reached signal transduction, cell-cycle progression, polarized growth, chromatin, meiosis, gene expression, and RNA localization.[11](https://doi.org/10.1038/424384a)
## Honors and recognition
Herskowitz was elected to the National Academy of Sciences in 1986 and received a MacArthur Fellowship in the class of 1987.[1](https://www.macfound.org/fellows/class-of-1987/ira-herskowitz) The Rosenstiel Award credited him with discovering the molecular basis for cellular differentiation in yeast and the molecular mechanisms that control yeast cell division.[13](https://www.ucsf.edu/news/2003/04/97064/renowed-yeast-and-human-geneticist-ucsf-receives-major-research-honor)
## Death and legacy
Herskowitz died at home in San Francisco on April 28, 2003, of pancreatic cancer, at 56.[3](https://www.the-scientist.com/ira-herskowitz-dies-51712) At UCSF he had revamped the genetics program, chaired the Department of Biochemistry and [Biophysics](https://www.edgepedia.org/biophysics) from 1990 to 1995, and co-directed the Program in Human Genetics from 1997.[3](https://www.the-scientist.com/ira-herskowitz-dies-51712) David Botstein's memorial article, "Ira Herskowitz: 1946–2003," appeared in *Genetics* in February 2004 (volume 166, pages 653–660).[14](https://pmc.ncbi.nlm.nih.gov/articles/PMC1470729/)
## References
1. [Ira Herskowitz, MacArthur Foundation](https://www.macfound.org/fellows/class-of-1987/ira-herskowitz)
2. https://www.cell.com/cell/fulltext/S0092-8674(03)00510-5
3. [Ira Herskowitz dies, The Scientist](https://www.the-scientist.com/ira-herskowitz-dies-51712)
4. [Ira Herskowitz, a Top Geneticist, Dies at 56, The New York Times](https://www.nytimes.com/2003/05/03/us/ira-herskowitz-a-top-geneticist-dies-at-56.html)
5. [Control of late genes, early genes, the cI gene, and replication in bacteriophage lambda, MIT dissertation record](http://hdl.handle.net/1721.1/12632)
6. [The 2002 Thomas Hunt Morgan Medal, Ira Herskowitz, Genetics](https://doi.org/10.1093/genetics/164.2.419)
7. [Mating-type gene switching in Saccharomyces cerevisiae, Annual Review of Genetics](https://doi.org/10.1146/annurev.genet.32.1.561)
8. [Regulation by the yeast mating-type locus of STE12, Mol. Cell. Biol. (1987)](https://doi.org/10.1128/mcb.7.10.3818)
9. [A regulatory hierarchy for cell specialization in yeast, Nature 342, 749–757 (1989)](https://doi.org/10.1038/342749a0)
10. https://doi.org/10.1016/0092-8674(92)90468-r
11. [Ira Herskowitz (1946–2003), Nature](https://doi.org/10.1038/424384a)
12. [Herskowitz Lab Home (archived)](https://web.archive.org/web/20150219032612/http:/biochemistry.ucsf.edu/labs/herskowitz/index.html)
13. [Renowned yeast and human geneticist at UCSF receives major research honor, UCSF](https://www.ucsf.edu/news/2003/04/97064/renowed-yeast-and-human-geneticist-ucsf-receives-major-research-honor)
14. [Ira Herskowitz: 1946–2003, Genetics (2004)](https://pmc.ncbi.nlm.nih.gov/articles/PMC1470729/)
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*Topic: Encyclopedia › Life and health › Life and health scientists › Life scientists › Researchers in genetics, genomics, and genome engineering › Functional genomics and gene regulation*
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