HOME

TheInfoList



OR:

Robb Krumlauf is an American
developmental biologist Developmental biology is the study of the process by which animals and plants grow and develop. Developmental biology also encompasses the biology of regeneration, asexual reproduction, metamorphosis, and the growth and differentiation of stem ...
. He is best known for researching the Hox family of
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
s. He is most interested in understanding the role of the
Hox gene 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 co ...
s in the hindbrain and their role in areas of animal development, such as craniofacial development. Krumlauf worked with a variety of renowned scientists in the field of developmental biology throughout his time researching Hox genes.


Early life and education

Robb was born in Ohio and raised in Ohio and New York. He graduated from
Vanderbilt University Vanderbilt University (informally Vandy or VU) is a private research university in Nashville, Tennessee. Founded in 1873, it was named in honor of shipping and rail magnate Cornelius Vanderbilt, who provided the school its initial $1-million ...
in 1970 with a degree in
chemical engineering Chemical engineering is an engineering field which deals with the study of operation and design of chemical plants as well as methods of improving production. Chemical engineers develop economical commercial processes to convert raw materials in ...
. He later went to
The Ohio State University The Ohio State University, commonly called Ohio State or OSU, is a public land-grant research university in Columbus, Ohio. A member of the University System of Ohio, it has been ranked by major institutional rankings among the best public ...
and received his PhD in developmental biology in 1979. He has since gone on to be a researcher and professor.


Career

After Krumlauf had completed his formal education, he was hired at Beatson Institute for Cancer Research along with the
Fox Chase Cancer Center Fox Chase Cancer Center is a National Cancer Institute-designated Comprehensive Cancer Center research facility and hospital located in the Fox Chase section of Philadelphia, Pennsylvania, United States. The main facilities of the center are loc ...
. In 1985, he moved to London to work at what is now known as the
Francis Crick Institute The Francis Crick Institute (formerly the UK Centre for Medical Research and Innovation) is a biomedical research centre in London, which was established in 2010 and opened in 2016. The institute is a partnership between Cancer Research UK, Im ...
. This institution is one of the most well-known biomedical research centers in the world. At the turn of the millennium, Krumlauf came back to the United States and resided in Missouri. He has since taken on three occupations and has been a professor at the
University of Kansas The University of Kansas (KU) is a public research university with its main campus in Lawrence, Kansas, United States, and several satellite campuses, research and educational centers, medical centers, and classes across the state of Kansas. Tw ...
, the
University of Kansas School of Medicine The University of Kansas School of Medicine is a public medical school located on the University of Kansas Medical Center campuses in Kansas City, Kansas, and also Salina, Kansas, and Wichita, Kansas. The Kansas City campus is co-located with t ...
, and the University of Missouri at Kansas Dental School. He is now the director of the
Stowers Institute for Medical Research The Stowers Institute for Medical Research is a biomedical research organization that conducts basic research on genes and proteins that control fundamental processes in living cells to analyze diseases and find keys to their causes, treatment, ...
.


Research

Krumlauf researched Hox gene complexes in both mice and ''
Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many s ...
'' in 1989. The complexes in both species were compared in order to determine if the gene complexes between these two species may have arisen from a common ancestor. The data shows alignment of these complexes and comparable relative position of genes. This research demonstrates the relationship between
Homeobox genes A homeobox is a Nucleic acid sequence, DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. For instance, mutations in a homeobox may change large-scale anatomical ...
in ''Drosophila'' (insects) and mice (metazoans). Krumlauf examined Hox-2
gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. ...
dependence on the differentiation pathway in 1991. The study shows Hox-2 gene expression has a clear reliance on the
endoderm Endoderm is the innermost of the three primary germ layers in the very early embryo. The other two layers are the ectoderm (outside layer) and mesoderm (middle layer). Cells migrating inward along the archenteron form the inner layer of the gast ...
pathway the cells follow, which suggests a dependence on Hox-2 expression on the type and degree of differentiation in different cells. This publication also solidified the importance of
retinoic acid Retinoic acid (used simplified here for all-''trans''-retinoic acid) is a metabolite of vitamin A1 (all-''trans''- retinol) that mediates the functions of vitamin A1 required for growth and development. All-''trans''-retinoic acid is required in ...
on Hox-2 expression. In 1996, Krumlauf researched the abnormal migration of
motor neuron A motor neuron (or motoneuron or efferent neuron) is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly or indirectly ...
s in mice that lack Hoxb-1. In this study, Krumlauf knew that the vertebrate hindbrain segments into
rhombomere In the vertebrate embryo, a rhombomere is a transiently divided segment of the developing neural tube, within the hindbrain region (a neuromere) in the area that will eventually become the rhombencephalon. The rhombomeres appear as a series of s ...
s, and that this was responsible for controlling the arrangement of motor neurons in the
hindbrain The hindbrain or rhombencephalon or lower brain is a developmental categorization of portions of the central nervous system in vertebrates. It includes the medulla, pons, and cerebellum. Together they support vital bodily processes. Metencep ...
. His research with mutant mouse embryos found that the absence of Hoxb-1 lead to changes in rhombomere 4 (r4) identity. This mutation causes a difference in migration patterns in r4, which demonstrates that Hoxb-1 is plays a role in the regulation of migratory properties of motor neurons present in the hindbrain. Krumlauf has manipulated the expression of Hox genes in many ways throughout his career in order to observe variations in development amongst certain animals. For example, in 2013, Krumlauf and his team configured mutant animals with a double-mutant cluster of HoxA-HoxB genes in their neural crest cells. In these mutant animals, they observed a bone that resembled the
dentary In anatomy, the mandible, lower jaw or jawbone is the largest, strongest and lowest bone in the human facial skeleton. It forms the lower jaw and holds the lower teeth in place. The mandible sits beneath the maxilla. It is the only movable bone ...
along with an attachment of neo-muscle. This helped Krumlauf to determine the HoxB genes are able to enhance a
phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological prop ...
that was directly caused by the deletion of a HoxA cluster. This helped the research group to assess the cooperation between different clusters of Hox genes. Through the use of mutant clusters of HoxA-HoxB genes, Krumlauf and his team were able to visualize how the suppression of one of the Hox genes, with amplification of another type of Hox genes, can be critical in the proper development of an animal. The example shown in this study was the variation in craniofacial development when certain Hox genes are suppressed. In 2014, Krumlauf examined Hox gene expression in comparison to hindbrain segmentation.
Gnathostomes Gnathostomata (; from Greek: (') "jaw" + (') "mouth") are the jawed vertebrates. Gnathostome diversity comprises roughly 60,000 species, which accounts for 99% of all living vertebrates, including humans. In addition to opposing jaws, living ...
were used in this research in an attempt to determine how primitive the relationship between Hox gene expression and segmentation of the hindbrain is. The data concluded that there is clear correlation between Hox expression and hindbrain segmentation. The use of gnathostomes shows this trait to be ancient, with origin at the base of vertebrates. Krumlauf is best known for his progression in the field of animal developmental biology and his progression on the current understanding of Hox genes. Hox genes are known for laying out the basic body structures of a wide variety of animals. Hox genes control a variety of regulatory interactions in the hindbrain which leads to segmentation in animals. /sup> After many years of research on the importance of Hox genes through manipulation trials, Krumlauf studied the variations of Hox genes between
vertebrate Vertebrates () comprise all animal taxon, taxa within the subphylum Vertebrata () (chordates with vertebral column, backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the ...
s and
invertebrate Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordate ...
s in 2017. He notes that Hox gene expression was found in even the most primitive vertebrates, such as the
sea lamprey The sea lamprey (''Petromyzon marinus'') is a parasitic lamprey native to the Northern Hemisphere. It is sometimes referred to as the "vampire fish". Description The sea lamprey has an eel-like body without paired fins. Its mouth is jawless, ...
. This Hox gene expression has been maintained across
phylogenetically In biology, phylogenetics (; from Greek φυλή/ φῦλον [] "tribe, clan, race", and wikt:γενετικός, γενετικός [] "origin, source, birth") is the study of the evolutionary history and relationships among or within groups o ...
dissimilar vertebrates. However, this is not the case for invertebrates. Krumlauf studied the Hox genes present in
chordate A chordate () is an animal of the phylum Chordata (). All chordates possess, at some point during their larval or adult stages, five synapomorphies, or primary physical characteristics, that distinguish them from all the other taxa. These five ...
s and found these invertebrates to lack hindbrain segmentation. He did find that chordates still had conserved some of the aspects of the Hox gene network. This includes things such as the use of
retinoic acid Retinoic acid (used simplified here for all-''trans''-retinoic acid) is a metabolite of vitamin A1 (all-''trans''- retinol) that mediates the functions of vitamin A1 required for growth and development. All-''trans''-retinoic acid is required in ...
in establishing Hox-gene domains. Krumlauf’s publications can be used to better understand the role of Hox genes within many species of animals. His research has also helped to express the importance of suppression and regulation of individual Hox genes.


Additional publications

"Patterning the vertebrate neuraxis" (1996) This publication examines segmentation and long-range signaling from organizing centers to interpret the role these principles play in the patterning of a vertebrate
neuraxis The neuraxis or sometimes neuroaxis is the axis of the central nervous system. It denotes the direction in which the central nervous system lies. During embryological development, the neuraxis is bent by various flexures, contributing to the ma ...
. "Organization of the Fugu rubripes Hox clusters: evidence for continuing evolution of vertebrate Hox complexes" (1997) This investigation seeks to observe the Hox clusters present in a
teleost Teleostei (; Greek ''teleios'' "complete" + ''osteon'' "bone"), members of which are known as teleosts ), is, by far, the largest infraclass in the class Actinopterygii, the ray-finned fishes, containing 96% of all extant species of fish. Tel ...
fish,
Fugu rubripes ''Takifugu rubripes'', commonly known as the Japanese puffer, Tiger puffer, or torafugu ( ja, 虎河豚), is a pufferfish in the genus ''Takifugu''. It is distinguished by a very small genome that has been fully sequenced because of its use as a m ...
. Four different Hox complexes were discovered within Fugu rubripes. The data shows the Hox clusters in Fugu to be widely variant with respect to length. At least nine genes in the Hox complex has been lost in Fugu when compared to present mammalian complexes. This data demonstrates that gene loss of prototypical Hox clusters is a defining feature in both
tetrapod Tetrapods (; ) are four-limb (anatomy), limbed vertebrate animals constituting the superclass Tetrapoda (). It includes extant taxon, extant and extinct amphibians, sauropsids (reptiles, including dinosaurs and therefore birds) and synapsids (p ...
and fish evolution. "'Shocking' developments in chick embryology: electroporation and in ovo gene expression" (1999) This paper focuses on new approaches to the analysis of
gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. ...
through the use of
electroporation Electroporation, or electropermeabilization, is a microbiology technique in which an electrical field is applied to cells in order to increase the permeability of the cell membrane, allowing chemicals, drugs, electrode arrays or DNA to be introdu ...
. This work focuses on the protocol for electroporation, how it can be applied to differing organisms, and the future experiments that could be conducted through the use of electroporation.


Awards and honors

* 1975   NIH Pre-Doctoral Fellow * 1979   NATO/NSF Postdoctoral Fellow * 1982   NIH Postdoctoral Fellow * 2003   American Academy of Arts & Science Member * 2007   American Association for Advancement of Science Fellow * 2016   National Academy of Sciences Member * 2018   Edwin G. Conklin Medal Recipient


References

{{DEFAULTSORT:Krumlauf, Robb Vanderbilt University alumni Ohio State University alumni 21st-century American biologists Living people University of Kansas faculty 21st-century American educators University of Missouri faculty Year of birth missing (living people) Stowers Institute for Medical Research people