Howard Lipshitz

Last updated
Howard Lipshitz
Howard Lipshitz.jpg
Born (1955-10-30) October 30, 1955 (age 68)
CitizenshipUnited States, Canada
Education University of Natal
Yale University
Scientific career
FieldsGenetics, Developmental Biology, Genomics
Institutions
Doctoral advisor Douglas Kankel
Other academic advisors David Hogness

Howard David Lipshitz (born October 30, 1955) is an American and Canadian biologist who does genetic research on the fruit fly, Drosophila .

Contents

Early life and education

Lipshitz was born and raised in Durban, South Africa, where he attended the University of Natal (now the University of Kwazulu-Natal), obtaining a B.Sc. in Biological Sciences and Mathematical Statistics (1976) and a B.Sc.(Hons.) cum laude in Biological Sciences (1977). He completed his M. Phil. (1980) and Ph.D. (1983) degrees in Biology at Yale University with Douglas R. Kankel, working on Drosophila developmental neurogenetics. He then carried out postdoctoral research in the Biochemistry Department at Stanford University with David Hogness, where he defined the first long non-coding RNA, from the Bithorax complex of Drosophila. [1]

Career

In 1986 Lipshitz was appointed an Assistant Professor of Biology at the California Institute of Technology in Pasadena and promoted to Associate Professor in 1992. In 1995 he and his family moved to Toronto, where he held leadership positions at the Hospital for Sick Children's Research Institute (1996–2005) and at the University of Toronto, the latter as chair of its Department of Molecular Genetics (2005–2016). He served on the board of directors of the Society for Developmental Biology (2000–2006) and the Drosophila Board (2006–2009). He is one of the founders of the Rare Diseases Models and Mechanisms Network, Canada, [2] serving on its Scientific Advisory Committee since 2011. He was Associate Editor (2011–2016), then Senior Editor (2016–2020) of G3: Genes, Genomes, Genetics and in January 2021 was appointed Editor-in-Chief [3] of Genetics (journal). Both are peer-edited scientific journals published by the Genetics Society of America. He is a Fellow of the American Association for the Advancement of Science.

Research

Lipshitz studies embryonic development and post-transcriptional regulation of gene expression in Drosophila with a focus on mRNA translation, stability and localization during the Maternal to zygotic transition [4] and the role of RNA-binding proteins in this process. [5] [6] With collaborators he developed a panel of phage-displayed synthetic antibodies that recognize RNA-binding proteins [7] and has used these to carry out-genome-wide studies of their mechanisms, functions and binding specificity (e.g. [8] [9] [10] ). He also collaborates with scientists who study mammalian development, using Drosophila as a model in which to elucidate the molecular functions of evolutionarily conserved genes (e.g. [11] [12] [13] ). Lipshitz has edited several books, most notably the collected works of his late colleague at Caltech, Nobel Laureate Edward B. Lewis, in which he provided detailed historical and scientific commentary on Lewis' contributions. [14]

Awards and honors

Related Research Articles

<span class="mw-page-title-main">Blastulation</span> Sphere of cells formed during early embryonic development in animals

Blastulation is the stage in early animal embryonic development that produces the blastula. In mammalian development the blastula develops into the blastocyst with a differentiated inner cell mass and an outer trophectoderm. The blastula is a hollow sphere of cells known as blastomeres surrounding an inner fluid-filled cavity called the blastocoel. Embryonic development begins with a sperm fertilizing an egg cell to become a zygote, which undergoes many cleavages to develop into a ball of cells called a morula. Only when the blastocoel is formed does the early embryo become a blastula. The blastula precedes the formation of the gastrula in which the germ layers of the embryo form.

<span class="mw-page-title-main">Pseudogene</span> Functionless relative of a gene

Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Most arise as superfluous copies of functional genes, either directly by gene duplication or indirectly by reverse transcription of an mRNA transcript. Pseudogenes are usually identified when genome sequence analysis finds gene-like sequences that lack regulatory sequences needed for transcription or translation, or whose coding sequences are obviously defective due to frameshifts or premature stop codons. Pseudogenes are a type of junk DNA.

The RNA-induced silencing complex, or RISC, is a multiprotein complex, specifically a ribonucleoprotein, which functions in gene silencing via a variety of pathways at the transcriptional and translational levels. Using single-stranded RNA (ssRNA) fragments, such as microRNA (miRNA), or double-stranded small interfering RNA (siRNA), the complex functions as a key tool in gene regulation. The single strand of RNA acts as a template for RISC to recognize complementary messenger RNA (mRNA) transcript. Once found, one of the proteins in RISC, Argonaute, activates and cleaves the mRNA. This process is called RNA interference (RNAi) and it is found in many eukaryotes; it is a key process in defense against viral infections, as it is triggered by the presence of double-stranded RNA (dsRNA).

Hox genes, a subset of homeobox genes, are a group of related genes that specify regions of the body plan of an embryo along the head-tail axis of animals. Hox proteins encode and specify the characteristics of 'position', ensuring that the correct structures form in the correct places of the body. For example, Hox genes in insects specify which appendages form on a segment, and Hox genes in vertebrates specify the types and shape of vertebrae that will form. In segmented animals, Hox proteins thus confer segmental or positional identity, but do not form the actual segments themselves.

Meiotic drive is a type of intragenomic conflict, whereby one or more loci within a genome will affect a manipulation of the meiotic process in such a way as to favor the transmission of one or more alleles over another, regardless of its phenotypic expression. More simply, meiotic drive is when one copy of a gene is passed on to offspring more than the expected 50% of the time. According to Buckler et al., "Meiotic drive is the subversion of meiosis so that particular genes are preferentially transmitted to the progeny. Meiotic drive generally causes the preferential segregation of small regions of the genome".

<i>Krüppel</i>

Krüppel is a gap gene in Drosophila melanogaster, located on the 2R chromosome, which encodes a zinc finger C2H2 transcription factor. Gap genes work together to establish the anterior-posterior segment patterning of the insect through regulation of the transcription factor encoding pair rule genes. These genes in turn regulate segment polarity genes. Krüppel means "cripple" in German, named for the crippled appearance of mutant larvae, who have failed to develop proper thoracic and anterior segments in the abdominal region. Mutants can also have abdominal mirror duplications.

Piwi-interacting RNA (piRNA) is the largest class of small non-coding RNA molecules expressed in animal cells. piRNAs form RNA-protein complexes through interactions with piwi-subfamily Argonaute proteins. These piRNA complexes are mostly involved in the epigenetic and post-transcriptional silencing of transposable elements and other spurious or repeat-derived transcripts, but can also be involved in the regulation of other genetic elements in germ line cells.

In developmental biology, midblastula or midblastula transition (MBT) occurs during the blastula stage of embryonic development in non-mammals. During this stage, the embryo is referred to as a blastula. The series of changes to the blastula that characterize the midblastula transition include activation of zygotic gene transcription, slowing of the cell cycle, increased asynchrony in cell division, and an increase in cell motility.

Gerald Mayer Rubin is an American biologist, notable for pioneering the use of transposable P elements in genetics, and for leading the public project to sequence the Drosophila melanogaster genome. Related to his genomics work, Rubin's lab is notable for development of genetic and genomics tools and studies of signal transduction and gene regulation. Rubin also serves as a vice president of the Howard Hughes Medical Institute and executive director of the Janelia Research Campus.

<span class="mw-page-title-main">RBM4</span> Protein-coding gene in the species Homo sapiens

RNA-binding protein 4 is a protein that in humans is encoded by the RBM4 gene.

Staufen is a protein product of a maternally expressed gene first identified in Drosophila melanogaster. The protein has been implicated in helping regulate genes important in determination of gradients that set up the anterior posterior axis such as bicoid and oskar. Staufen proteins, abbreviated Stau, are necessary for cell localization during the oogenesis and zygotic development. It is involved in targeting of the messenger RNA encoding these genes to the correct pole of the egg cell.

Maternal to zygotic transition (MZT), also known as embryonic genome activation, is the stage in embryonic development during which development comes under the exclusive control of the zygotic genome rather than the maternal (egg) genome. The egg contains stored maternal genetic material mRNA which controls embryo development until the onset of MZT. After MZT the diploid embryo takes over genetic control. This requires both zygotic genome activation (ZGA), and degradation of maternal products. This process is important because it is the first time that the new embryonic genome is utilized and the paternal and maternal genomes are used in combination. The zygotic genome now drives embryo development.

Albert Erives is a developmental geneticist who studies transcriptional enhancers underlying animal development and diseases of development (cancers). Erives also proposed the pacRNA model for the dual origin of the genetic code and universal homochirality. He is known for work at the intersection of genetics, evolution, developmental biology, and gene regulation. He has worked at the California Institute of Technology, University of California, Berkeley, and Dartmouth College, and is an associate professor at the University of Iowa.

In molecular biology mir-430 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

Norbert Perrimon is a French geneticist and developmental biologist. He is the James Stillman Professor of Developmental Biology in the Department of Genetics at Harvard Medical School, an Investigator at the Howard Hughes Medical Institute, and an Associate of the Broad Institute. He is known for developing a number of techniques for used in genetic research with Drosophila melanogaster, as well as specific substantive contributions to signal transduction, developmental biology and physiology.

<span class="mw-page-title-main">Alexander F. Schier</span> Swiss biologist

Alexander F. Schier is a Professor of Cell Biology and the Director of the Biozentrum University of Basel, Switzerland.

<i>Homeotic protein bicoid</i> Protein-coding gene in the species Drosophila melanogaster

Homeotic protein bicoid is encoded by the bcd maternal effect gene in Drosophilia. Homeotic protein bicoid concentration gradient patterns the anterior-posterior (A-P) axis during Drosophila embryogenesis. Bicoid was the first protein demonstrated to act as a morphogen. Although bicoid is important for the development of Drosophila and other higher dipterans, it is absent from most other insects, where its role is accomplished by other genes.

Ruth Lehmann is a developmental and cell biologist. She is the Director of the Whitehead Institute for Biomedical Research. She previously was affiliated with the New York University School of Medicine, where she was the Director of the Skirball Institute of Biomolecular Medicine, the Laura and Isaac Perlmutter Professor of Cell Biology, and the Chair of the Department of Cell Biology. Her research focuses on germ cells and embryogenesis.

<span class="mw-page-title-main">Smaug (protein)</span> RNA-binding protein in Drosophila

Smaug is a RNA-binding protein in Drosophila that helps in maternal to zygotic transition (MZT). The protein is named after the fictional character Smaug, the dragon in J.R.R. Tolkien's 1937 novel The Hobbit. The MZT ends with the midblastula transition (MBT), which is defined as the first developmental event in Drosophila that depends on zygotic mRNA. In Drosophila, the initial developmental events are controlled by maternal mRNAs like Hsp83, nanos, string, Pgc, and cyclin B mRNA. Degradation of these mRNAs, which is expected to terminate maternal control and enable zygotic control of embryogenesis, happens at interphase of nuclear division cycle 14. During this transition smaug protein targets the maternal mRNA for destruction using miRs. Thus activating the zygotic genes. Smaug is expected to play a role in expression of three miRNAs – miR-3, miR-6, miR-309 and miR-286 during MZT in Drosophila. Among them smaug dependent expression of miR-309 is needed for destabilization of 410 maternal mRNAs. In smaug mutants almost 85% of maternal mRNA is found to be stable. Smaug also binds to 3′ untranslated region (UTR) elements known as SMG response elements (SREs) on nanos mRNA and represses its expression by recruiting a protein called Cup(an eIF4E-binding protein that blocks the binding of eIF4G to eIF4E). There after it recruits deadenylation complex CCR4-Not on to the nanos mRNA which leads to deadenylation and subsequent decay of the mRNA. It is also found to be involved in degradation and repression of maternal Hsp83 mRNA by recruiting CCR4/POP2/NOT deadenylase to the mRNA. The human Smaug protein homologs are SAMD4A and SAMD4B.

Antonio Jesus Giraldez is a Spanish developmental biologist and RNA researcher at Yale University School of Medicine, where he serves as chair of the department of genetics and Fergus F. Wallace Professor of Genetics. He is also affiliated with the Yale Cancer Center and the Yale Stem Cell Center.

References

  1. Lipshitz, H D; Peattie, D A; Hogness, D S (1 May 1987). "Novel transcripts from the Ultrabithorax domain of the bithorax complex". Genes & Development. 1 (3): 307–322. doi: 10.1101/gad.1.3.307 . PMID   3119423.
  2. Boycott, Kym M.; Campeau, Philippe M.; Howley, Heather E.; Pavlidis, Paul; Rogic, Sanja; Oriel, Christine; Berman, Jason N.; Hamilton, Robert M.; Hicks, Geoffrey G.; Lipshitz, Howard D.; Masson, Jean-Yves; Shoubridge, Eric. A.; Junker, Anne; Leroux, Michel R.; McMaster, Christopher R.; Michaud, Jaques L.; Turvey, Stuart E.; Dyment, David; Innes, A. Micheil; van Karnebeek, Clara D.; Lehman, Anna; Cohn, Ronald D.; MacDonald, Ian M.; Rachubinski, Richard A.; Frosk, Patrick; Vandersteen, Anthony; Wozniak, Richard W.; Pena, Izabella A.; Wen, Xiao-Yan; Lacaze-Masmonteil, Thierry; Rankin, Catharine; Hieter, Philip (February 2020). "The Canadian Rare Diseases Models and Mechanisms (RDMM) Network: Connecting Understudied Genes to Model Organisms". The American Journal of Human Genetics. 106 (2): 143–152. doi:10.1016/j.ajhg.2020.01.009. PMC   7010971 . PMID   32032513.
  3. "Genetics Society of America announces Howard Lipshitz as new Editor in Chief of GENETICS". Genes to Genomes. 30 September 2020.
  4. Vastenhouw, Nadine L.; Cao, Wen Xi; Lipshitz, Howard D. (1 June 2019). "The maternal-to-zygotic transition revisited". Development. 146 (11): dev161471. doi: 10.1242/dev.161471 . PMID   31189646. S2CID   189816312.
  5. Cao, Wen Xi; Kabelitz, Sarah; Gupta, Meera; Yeung, Eyan; Lin, Sichun; Rammelt, Christiane; Ihling, Christian; Pekovic, Filip; Low, Timothy C.H.; Siddiqui, Najeeb U.; Cheng, Matthew H.K.; Angers, Stephane; Smibert, Craig A.; Wühr, Martin; Wahle, Elmar; Lipshitz, Howard D. (June 2020). "Precise Temporal Regulation of Post-transcriptional Repressors Is Required for an Orderly Drosophila Maternal-to-Zygotic Transition". Cell Reports. 31 (12): 107783. doi:10.1016/j.celrep.2020.107783. PMC   7372737 . PMID   32579915.
  6. Tadros, Wael; Goldman, Aaron L.; Babak, Tomas; Menzies, Fiona; Vardy, Leah; Orr-Weaver, Terry; Hughes, Timothy R.; Westwood, J. Timothy; Smibert, Craig A.; Lipshitz, Howard D. (January 2007). "SMAUG Is a Major Regulator of Maternal mRNA Destabilization in Drosophila and Its Translation Is Activated by the PAN GU Kinase". Developmental Cell. 12 (1): 143–155. doi: 10.1016/j.devcel.2006.10.005 . PMID   17199047.
  7. Na, Hong; Laver, John D.; Jeon, Jouhyun; Singh, Fateh; Ancevicius, Kristin; Fan, Yujie; Cao, Wen Xi; Nie, Kun; Yang, Zhenglin; Luo, Hua; Wang, Miranda; Rissland, Olivia; Westwood, J. Timothy; Kim, Philip M.; Smibert, Craig A.; Lipshitz, Howard D.; Sidhu, Sachdev S. (April 2016). "A high-throughput pipeline for the production of synthetic antibodies for analysis of ribonucleoprotein complexes". RNA. 22 (4): 636–655. doi:10.1261/rna.055186.115. PMC   4793217 . PMID   26847261.
  8. Laver, John D.; Li, Xiao; Ancevicius, Kristin; Westwood, J. Timothy; Smibert, Craig A.; Morris, Quaid D.; Lipshitz, Howard D. (November 2013). "Genome-wide analysis of Staufen-associated mRNAs identifies secondary structures that confer target specificity". Nucleic Acids Research. 41 (20): 9438–9460. doi:10.1093/nar/gkt702. PMC   3814352 . PMID   23945942.
  9. Laver, John D; Li, Xiao; Ray, Debashish; Cook, Kate B; Hahn, Noah A; Nabeel-Shah, Syed; Kekis, Mariana; Luo, Hua; Marsolais, Alexander J; Fung, Karen YY; Hughes, Timothy R; Westwood, J Timothy; Sidhu, Sachdev S; Morris, Quaid; Lipshitz, Howard D; Smibert, Craig A (December 2015). "Brain tumor is a sequence-specific RNA-binding protein that directs maternal mRNA clearance during the Drosophila maternal-to-zygotic transition". Genome Biology. 16 (1): 94. doi: 10.1186/s13059-015-0659-4 . PMC   4460960 . PMID   25962635.
  10. Laver, John D.; Ly, Jimmy; Winn, Allison K.; Karaiskakis, Angelo; Lin, Sichun; Nie, Kun; Benic, Giulia; Jaberi-Lashkari, Nima; Cao, Wen Xi; Khademi, Alireza; Westwood, J. Timothy; Sidhu, Sachdev S.; Morris, Quaid; Angers, Stephane; Smibert, Craig A.; Lipshitz, Howard D. (March 2020). "The RNA-Binding Protein Rasputin/G3BP Enhances the Stability and Translation of Its Target mRNAs". Cell Reports. 30 (10): 3353–3367.e7. doi: 10.1016/j.celrep.2020.02.066 . PMID   32160542.
  11. Cohen, Brenda; Bashirullah, Arash; Dagnino, Lina; Campbell, Christine; Fisher, William W.; Leow, Ching Ching; Whiting, Elisabeth; Ryan, David; Zinyk, Dawn; Boulianne, Gabrielle; Hui, Chi-chung; Gallic, Brenda; Phillips, Robert A.; Lipshitz, Howard D.; Egan, Sean E. (July 1997). "Fringe boundaries coincide with Notch-dependent patterning centres in mammals and alter Notch-dependent development in Drosophila". Nature Genetics. 16 (3): 283–288. doi:10.1038/ng0797-283. PMID   9207795. S2CID   28033622.
  12. Sing, Angela; Pannell, Dylan; Karaiskakis, Angelo; Sturgeon, Kendra; Djabali, Malek; Ellis, James; Lipshitz, Howard D.; Cordes, Sabine P. (September 2009). "A Vertebrate Polycomb Response Element Governs Segmentation of the Posterior Hindbrain". Cell. 138 (5): 885–897. doi: 10.1016/j.cell.2009.08.020 . PMID   19737517. S2CID   8103493.
  13. Amadei, Gianluca; Zander, Mark A.; Yang, Guang; Dumelie, Jason G.; Vessey, John P.; Lipshitz, Howard D.; Smibert, Craig A.; Kaplan, David R.; Miller, Freda D. (25 November 2015). "A Smaug2-Based Translational Repression Complex Determines the Balance between Precursor Maintenance versus Differentiation during Mammalian Neurogenesis". The Journal of Neuroscience. 35 (47): 15666–15681. doi:10.1523/JNEUROSCI.2172-15.2015. PMC   6705466 . PMID   26609159.
  14. Lipshitz, Howard D., ed. (2007). Genes, Development and Cancer: The Life and Work of Edward B. Lewis (2 ed.). Dordrecht, Netherlands: Springer Netherlands. ISBN   978-1-4020-6343-5.
  15. 1 2 3 "The Maternal-to-Zygotic Transition, Volume 113". The Maternal-to-Zygotic Transition, Volume 113. Elsevier.
  16. "Profile - The Helen Hay Whitney Foundation". The Helen Hay Whitney Foundation.
  17. "Howard D. Lipshitz - Searle Scholars Program". Searle Scholars Program.
  18. "Elected Fellows". American Association for the Advancement of Science.
  19. "Lipshitz Biography 202102" (PDF). University of Toronto.
  20. "Honorary Staff - People - School of Biomedical Sciences, HKU". Honorary Staff - People - School of Biomedical Sciences, HKU. The University of Hong Kong.
  21. "Lipshitz CV 20210623" (PDF). University of Toronto.
  22. "Trustees, Administration, Faculty" (PDF). California Institute of Technology.