Harold M. Weintraub

Harold M. "Hal" Weintraub was an American scientist who lived from 1945 until his death in 1995 from an aggressive brain tumor. Only 49 years old, Weintraub left behind a legacy of research.^[1][2][3]

Early life and education

Born on June 2, 1945 in Newark, New Jersey, Weintraub's childhood revolved around sports, including basketball, an activity he would continue to particularly relish throughout his adult life. Weintraub was also the pitcher for an all-city high school baseball team, and a football fullback.^[4]

Weintraub attended Harvard College, obtaining his bachelor's degree in 1967.^[4] He then proceeded to the University of Pennsylvania, where he earned his M.D. and Ph.D. in 1972.^[4] Weintraub performed his Ph.D. dissertation research in the laboratory of Howard Holtzer,^[5] studying red blood cell development and production (erythropoeisis) in chicken embryos. This work included the study of cell cycle kinetics, hemoglobin synthesis, and the control of cell division.^[6] The effects of bromodeoxyuridine on cell differentiation (conversion of a primitive cell into a more specialized cell) were also analyzed.^[7] While still only a graduate student, Weintraub's early work contributed significantly to the fields of developmental and cellular biology, yielding numerous peer-reviewed publications and setting the stage for the next chapter in his research explorations.^[1]

Research achievements

During his abbreviated career, Weintraub was the author of more than 130 scientific articles, most of which were in top-tier, peer-reviewed journals, including the "Big 3" basic science journals: Cell, Science, and Nature.^[8] Weintraub was a member of the National Academy of Sciences,^[9] and served as editorial advisor for numerous journals.^[4]

Weintraub spent approximately a year at the Medical Research Council in Cambridge, England, doing a postdoctoral fellowship in the laboratories of Sydney Brenner and Francis Crick. There, his studies of the nucleosome — a basic unit of DNA packaging — showed that its structure was altered when genes were actively transcribed.^[1] Weintraub returned to the United States, and between the years 1973-1977 was an Assistant Professor at Princeton University.^[10] His research at Princeton, which would continue during his years in Seattle, applied enzymatic and traditional biochemical isolation/separation techniques to clarify the relationship between the physical structure of genes and their expression (the process by which DNA is transcribed into messenger RNA, and eventually into protein.)^[11] Another avenue of research in Weintraub's lab studied the effects of oncoviruses on cellular gene expression.^[12]

In 1978, Weintraub joined the Fred Hutchinson Cancer Research Center (FHCRC), established in 1971 as an independent affiliate of the University of Washington (UW), Seattle. He was a founding member of the Basic Sciences Division, and professor of genetics at UW. As described in an essay by Marc Kirschner, one of his former colleagues at Princeton, "When most of us left [Princeton] in the late 1970s, Hal, typically concerned more with research opportunity than with glamour, went to a young research institution where the practice of science would be paramount."^[2] Weintraub remained at "the Hutch" (the nickname for FHCRC) until his death in 1995. In addition, from 1990-1995 Weintraub was a Howard Hughes Medical Institute Investigator.^[13]

While at FHCRC, Weintraub continued and extended his prior studies of chromatin structure and function.^{[14][15][16][17]} Another of his contributions was developing the technique of using antisense RNA to create specific mutant phenotypes in vertebrate organisms.^[18][19] Perhaps the work for which Weintraub is best known was his laboratory's discovery and characterization of "myoD", the first master regulatory gene. When expressed, the myoD gene produces a protein referred to as MyoD (or MyoD1), which can bind certain DNA sequences, stop cell division, and elicit an entire program of muscle cell differentiation. In a series of sequential experiments, Weintraub and his students showed that myoD was able to convert fibroblasts (connective tissue cells) into myoblasts (skeletal muscle cells).^[20][21] Later studies by the same group of investigators at FHCRC further characterized the structural and functional characteristics of myoD and its nuclear-localized protein product,^[22][23] which were found to be present in organisms as diverse as nematode worms, frogs, mice, and humans.^[24] During the final years of his life, Weintraub's work used myoD to delve broadly and deeply into the areas of regulatory proteins, gene expression, and the molecular control of cell differentiation.^{[25][26][27][28][29][30][31]} As part of this work, his lab pioneered a molecular biology technique known as the Selection And Amplification Binding (SAAB) assay, which is used to find the DNA-binding sites for proteins.^[32]

Biotechnology Involvement

Along with chemist Peter Dervan of Caltech and developmental biologist Doug Melton of Harvard, Weintraub was one of three core scientific advisors to Michael L. Riordan, founder of Gilead Sciences, helping to establish the company’s scientific vision at its founding during the late 1980s.

Death and Legacy

Weintraub died on March 28, 1995 in Seattle, Washington, as a result of complications from glioblastoma multiforme, a very aggressive and fast-growing brain tumor.^[10] He had only been diagnosed six months beforehand, undergoing neurosurgery in an attempt to curb its spread.^[3] Weintraub was survived by his wife and two sons.^[2] In the years that followed, several items were created in his memory:

• the Fred Hutch Weintraub and Groudine Fund: “established to foster intellectual exchange through the promotion of programs for graduate students, fellows and visiting scholars.”^[33]

• the Weintraub meeting, held annually since 1997, is a two-day symposium serving as a reunion for Weintraub's former graduate students, postdoctoral fellows, and scientific collaborators.^[34]

• the Harold M. Weintraub Graduate Student Award, initiated at FHCRC in 2000, occurs annually, honoring Weintraub and his commitment to innovative science, and recognizing outstanding achievement during graduate studies in the biological sciences. Students are nominated by their department/program chairperson, and submit their CV, a one-page description of their thesis work, and a recommendation letter from their research mentor. Those accepted participate in a one-day symposium, giving presentations and interacting with other students and faculty. A selection committee made up of FHCRC faculty and students select up to twelve awardees from those nominated, on the basis of quality, originality, and significance of their work, as well as to represent a broad range of research topics.^[33]

References

1. ↑ 1.0 1.1 1.2 Axel, Richard; Maniatis, Thomas (1995). "Harold Weintraub (1945-1995)". Cell 81: 317–318. doi:10.1016/0092-8674(95)90382-8. 
2. ↑ 2.0 2.1 2.2 Kirschner, Marc (1995). "In memory of Harold Weintraub". Mol Biol Cell 6: 757–758. doi:10.1091/mbc.6.7.757. 
3. ↑ 3.0 3.1 Alberts, B (1995). "Harold M. Weintraub (1945-1995)". Nature 375: 19. doi:10.1038/375019a0. 
4. ↑ 4.0 4.1 4.2 4.3 Beers, Carole (April 1, 1995). "Dr. Harold Weintraub loved genes and jeans". The Seattle Times. Retrieved 11 November 2014. 
5. ↑ "Howard Holtzer, Ph.D. (deceased)". University of Pennsylvania - School of Medicine - Howard Holtzer, Ph.D. University of Pennsylvania. Retrieved 25 November 2014. 
6. ↑ Weintraub, H; Campbell Gle, M; Holtzer, H (1971). "Primitive erythropoiesis in early chick embryogenesis. I. Cell cycle kinetics and control of cell division". J Cell Biol 50: 652–668. doi:10.1083/jcb.50.3.652. 
7. ↑ Weintraub, H; Campbell, GL; Holtzer, H (1972). "Identification of a developmental program using bromodeoxyuridine". J Mol Biol 70: 337–350. doi:10.1016/0022-2836(72)90543-8. 
8. ↑ "Pub Med Search for Weintraub H*[Author]". Pub Med: National Center for Biotechnology Information: National Library of Medicine: National Institutes of Health. Retrieved November 26, 2014. 
9. ↑ "Harold Weintraub". National Academy of Sciences: Member Directory. Retrieved 22 January 2015. 
10. ↑ 10.0 10.1 Saxon, Wolfgang (March 31, 1995). "Harold Weintraub, 49, biologist who studied cell development". New York Times. Retrieved November 11, 2014. 
11. ↑ Weintraub, H; Groudine, M (1976). "Chromosomal subunits in active genes have an altered conformation". Science 193: 848–856. doi:10.1126/science.948749. 
12. ↑ Groudine, M; Weintraub, H (1975). "Rous sarcoma virus activates embryonic globin genes in chick fibroblasts". Proc Natl Acad Sci USA 72: 4464–4468. doi:10.1073/pnas.72.11.4464. 
13. ↑ "Our Scientists". Howard Hughes Medical Institute. Retrieved 18 January 2015. 
14. ↑ Riley, D; Weintraub, H (1979). "Conservative segregation of parental histones during replication in the presence of cycloheximide". Proc Natl Acad Sci USA 76: 328–332. doi:10.1073/pnas.76.1.328. 
15. ↑ Weisbrod, S; Weintraub, H (1979). "Isolation of a subclass of nuclear proteins responsible for conferring a DNAse I-sensitive structure on globin chromatin". Proc Natl Acad Sci USA 76: 630–634. doi:10.1073/pnas.76.2.630. 
16. ↑ Seidman, MM; Levine, AJ; Weintraub, H (1979). "The asymmetric segregation of parental nucleosomes during chromosome replication". Cell 18: 439–49. doi:10.1016/0092-8674(79)90063-1. 
17. ↑ Weisbrod, S; Groudine, M; Weintraub, H (1980). "Interaction of HMG 14 and 17 with actively transcribed genes". Cell 19: 289–301. doi:10.1016/0092-8674(80)90410-9. 
18. ↑ Harland, R; Weintraub, H (1985). "Translation of mRNA injected into Xenopus oocytes is specifically inhibited by antisense RNA". J Cell Biol 101: 1094–1099. doi:10.1083/jcb.101.3.1094. 
19. ↑ Weintraub, HM (1990). "Antisense RNA and DNA". Sci Am 262: 40–46. doi:10.1038/scientificamerican0190-40. 
20. ↑ Lassar, AB; Paterson, BM; Weintraub, H (1986). "Transfection of a DNA locus that mediates the conversion of 10T1/2 fibroblasts to myoblasts". Cell 47: 649–656. doi:10.1016/0092-8674(86)90507-6. PMID 2430720. 
21. ↑ Tapscott, SJ; Davis, RL; Thayer, MJ; Cheng, PF; Weintraub, H; Lassar, AB (1988). "MyoD1: a nuclear phosphoprotein requiring a Myc homology region to convert fibroblasts to myoblasts". Science 242: 405–411. doi:10.1126/science.3175662. PMID 3175662. 
22. ↑ Thayer, MJ; Tapscott, SJ; Davis, RL; Wright, WE; Lassar, AB; Weintraub, H (1989). "Positive autoregulation of the myogenic determination gene MyoD1". Cell 58: 241–248. doi:10.1016/0092-8674(89)90838-6. 
23. ↑ Lassar, AB; Buskin, JN; Lockshon, D; Davis, RL; Apone, S; Hauschka, SD; Weintraub, H (1989). "MyoD is a sequence-specific DNA binding protein requiring a region of myc homology to bind to the muscle creatine kinase enhancer". Cell 58: 823–831. doi:10.1016/0092-8674(89)90935-5. 
24. ↑ Krause, M; Fire, A; White-Harrison, S; Weintraub, H; Tapscott, S. "Functional conservation of nematode and vertebrate myogenic regulatory factors". J Cell Sci Suppl 16: 111-115. 
25. ↑ Lassar, AB; Thayer, MJ; Overell, RW; Weintraub, H (1989). "Transformation by activated ras or fos prevents myogenesis by inhibiting expression of MyoD1". Cell 58: 659–667. doi:10.1016/0092-8674(89)90101-3. 
26. ↑ Sassoon, D; Lyons, G; Wright, WE; Lin, V; Lassar, A; Weintraub, H; Buckingham, M (1989). "Expression of two myogenic regulatory factors myogenin and MyoD1 during mouse embryogenesis". Nature 341: 303–307. doi:10.1038/341303a0. 
27. ↑ Benezra, R; Davis, RL; Lockshon, D; Turner, DL; Weintraub, H (1990). "The protein Id: a negative regulator of helix-loop-helix DNA binding proteins". Cell 61: 49–59. doi:10.1016/0092-8674(90)90214-y. 
28. ↑ Weintraub, H; Hauschka, S; Tapscott, SJ (1991). "The MCK enhancer contains a p53 responsive element". Proc Natl Acad Sci USA 88: 4570–4571. doi:10.1073/pnas.88.11.4570. 
29. ↑ Bengal, E; Ransone, L; Scharfmann, R; Dwarki, VJ; Tapscott, SJ; Weintraub, H; Verma, IM (1992). "Functional antagonism between c-Jun and MyoD proteins: a direct physical association". Cell 68: 507–519. doi:10.1016/0092-8674(92)90187-h. PMID 1310896. 
30. ↑ Turner, DL; Weintraub, H (1994). "Expression of achaete-scute homolog 3 in Xenopus embryos converts ectodermal cells to a neural fate". Genes Dev 8: 1434–1447. doi:10.1101/gad.8.12.1434. 
31. ↑ Zhuang, Y; Soriano, P; Weintraub, H (1994). "The helix-loop-helix gene E2A is required for B cell formation". Cell 79: 875–884. doi:10.1016/0092-8674(94)90076-0. 
32. ↑ Blackwell, KT; Weintraub, H (1990). "Differences and similarities in DNA-binding preferences of MyoD and E2A protein complexes revealed by binding site selection". Science 250: 1104–1110. doi:10.1126/science.2174572. 
33. ↑ 33.0 33.1 "Weintraub Graduate Student Award". Fred Hutchinson Cancer Research Center: Basic Sciences Division. Retrieved 21 January 2015. 
34. ↑ "Center hosts 15th Weintraub reunion meeting Nov. 4, 5". Fred Hutchinson Cancer Research Center: Hutch News. Retrieved November 28, 2014.