is a Japanese-American

molecular biologist Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...

and physician, famous for his discovery of the

hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...

endothelin Endothelins are peptides with receptors and effects in many body organs. Endothelin constricts blood vessels and raises blood pressure. The endothelins are normally kept in balance by other mechanisms, but when overexpressed, they contribute ...

and the

neuropeptide Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the ...

orexin Orexin (), also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. It exists in the forms of orexin-A and orexin-B. The most common form of narcolepsy, type 1, in which the individual experiences brief loss ...

, the absence of which is the cause of

narcolepsy Narcolepsy is a chronic neurological disorder that impairs the ability to regulate sleep–wake cycles, and specifically impacts REM (rapid eye movement) sleep. The symptoms of narcolepsy include excessive daytime sleepiness (EDS), sleep-r ...

. He is currently the Director of the International Institute for Integrative Sleep Medicine,

University of Tsukuba is a List of national universities in Japan, national research university located in Tsukuba, Ibaraki Prefecture, Ibaraki, Japan. The university has 28 college clusters and schools with around 16,500 students (as of 2014). The main Tsukuba ca ...

, and an adjunct professor at the Department of

Molecular Genetics Molecular genetics is a branch of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the st ...

University of Texas Southwestern Medical Center The University of Texas Southwestern Medical Center (UT Southwestern or UTSW) is a public academic health science center in Dallas, Texas. With approximately 23,000 employees, more than 3,000 full-time faculty, and nearly 4 million outpatient ...

Early life and education

Yanagisawa was born in Tokyo in 1960. His father was a surgeon and, thanks to his background in

electrical Electricity is the set of physical phenomena associated with the presence and motion of matter possessing an electric charge. Electricity is related to magnetism, both being part of the phenomenon of electromagnetism, as described by Maxwel ...

and

electronic engineering Electronic engineering is a sub-discipline of electrical engineering that emerged in the early 20th century and is distinguished by the additional use of active components such as semiconductor devices to amplify and control electric current flo ...

, an

electrophysiology Electrophysiology (from ee the Electron#Etymology, etymology of "electron" ; and ) is the branch of physiology that studies the electrical properties of biological cell (biology), cells and tissues. It involves measurements of voltage change ...

researcher. He graduated from

Musashi Junior and Senior High School is a private boys senior high school in Nerima, Tokyo, Japan. It is an affiliate of the Musashi University. History The school was founded by industrialist Nezu Kaichirō in 1922 as Musashi High School, and used a seven-year system. After the ...

in 1979, and entered the

to study medicine. After obtaining an MD in 1985, he pursued a PhD at the same institute, completing it 3 years later.

Career

Immediately after obtaining his PhD, Yanagisawa started his career as a

postdoctoral fellow A postdoctoral fellow, postdoctoral researcher, or simply postdoc, is a person professionally conducting research after the completion of their doctoral studies (typically a PhD). Postdocs most commonly, but not always, have a temporary academ ...

at the Department of

Pharmacology Pharmacology is the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur betwee ...

of the

. One year later, he became an assistant professor at the same department, and in 1991 moved to the

Kyoto University , or , is a National university, national research university in Kyoto, Japan. Founded in 1897, it is one of the former Imperial Universities and the second oldest university in Japan. The university has ten undergraduate faculties, eighteen gra ...

School of Medicine A medical school is a tertiary educational institution, professional school, or forms a part of such an institution, that teaches medicine, and awards a professional degree for physicians. Such medical degrees include the Bachelor of Medicine, ...

as an assistant professor at the Department of Pharmacology. Yanagisawa stayed at

Kyoto Kyoto ( or ; Japanese language, Japanese: , ''Kyōto'' ), officially , is the capital city of Kyoto Prefecture in the Kansai region of Japan's largest and most populous island of Honshu. , the city had a population of 1.46 million, making it t ...

only for one year, after which

Joseph L. Goldstein Joseph Leonard Goldstein ForMemRS (born April 18, 1940) is an American biochemist. He received the Nobel Prize in Physiology or Medicine in 1985, along with fellow University of Texas Southwestern researcher, Michael Brown, for their studies r ...

and

Michael Stuart Brown Michael Stuart Brown ForMemRS NAS AAA&S APS (born April 13, 1941) is an American geneticist and Nobel laureate. He was awarded the Nobel Prize in Physiology or Medicine with Joseph L. Goldstein in 1985 for describing the regulation of choles ...

, both 1985

Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine () is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, acco ...

laureates and famous for their research in

cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

, recruited him to the

(UTSW). He began as an

associate professor Associate professor is an academic title with two principal meanings: in the North American system and that of the ''Commonwealth system''. In the ''North American system'', used in the United States and many other countries, it is a position ...

at the Department of

Molecular genetics Molecular genetics is a branch of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the st ...

, was promoted to

full professor Professor (commonly abbreviated as Prof.) is an academic rank at universities and other post-secondary education and research institutions in most countries. Literally, ''professor'' derives from Latin as a 'person who professes'. Professors ...

in 1996, and endowed with the Patrick E. Haggerty Distinguished Chair in Basic Biomedical Science in 1998. Between 2001 and 2006, he had his own project under the

Japan Science and Technology Agency The Japan Science and Technology Agency (JST; Japanese: 科学技術振興機構) is a Japanese government agency which aims to build infrastructure that supports knowledge creation and dissemination in Japan. It is one of the National Research an ...

ERATO (Exploratory Research for Advanced Technology) scheme, focusing on discovering

endogenous Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell. For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...

ligands In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's ...

for

orphan receptor In biochemistry, an orphan receptor is a protein that has a similar structure to other identified receptors but whose endogenous ligand has not yet been identified. If a ligand for an orphan receptor is later discovered, the receptor is referred ...

s. He returned to Japan in 2012 to found and direct the International Institute for Integrative Sleep Medicine at the University of Tsukuba, which was established under the World Premier International Research Center Initiative by Japan's

Ministry of Education, Culture, Sports, Science and Technology The , also known as MEXT, is one of the eleven ministries of Japan that compose part of the executive branch of the government of Japan. History The Meiji period, Meiji government created the first Ministry of Education in 1871. In January 2001 ...

. Two years later, he switched to part-time at UTSW as an

adjunct professor An adjunct professor is a type of academic appointment in higher education who does not work at the establishment full-time. The terms of this appointment and the job security of the tenure vary in different parts of the world, but the term is gen ...

. Yanagisawa was also an investigator at the

Howard Hughes Medical Institute The Howard Hughes Medical Institute (HHMI) is an American non-profit medical research organization headquartered in Chevy Chase, Maryland with additional facilities in Ashburn, Virginia. It was founded in 1953 by Howard Hughes, an American busin ...

during his time working full-time at UTSW.

Research

Yanagisawa is most well known for his discovery of the

and the

. Early 1980s saw the revelation that

nitric oxide Nitric oxide (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...

was the substance

endothelial cell The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and th ...

s produce to relax the

smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...

around

blood vessel Blood vessels are the tubular structures of a circulatory system that transport blood throughout many Animal, animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the Tissue (biology), tissues of a Body (bi ...

s, which causes

vasodilation Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel wa ...

and increased blood flow. This led to the speculation of and hunt for the inverse, an endothelium-derived

vasoconstricting Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...

substance. During his PhD study, Yanagisawa's supervisor, Tomoh Masaki, agreed to let him try to isolate the substance. This study became his PhD thesis, and he published his finding it 1988, naming the substance "endothelin" and reporting its peptide sequence. He then published a number of reports on the function and regulation of endothelin, including working with Takeshi Sakurai to identify the

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

for endothelin. He kept studying endothelin after moving to the

(UTSW) in the United States, for example discovering one of the mechanisms to activate endothelin and that a mutation in endothelin receptor can cause

Hirschsprung's disease Hirschsprung's disease (HD or HSCR) is a birth defect in which nerves are missing from parts of the intestine. The most prominent symptom is constipation. Other symptoms may include vomiting, abdominal pain, diarrhea and slow growth. Most child ...

. Eventually, his interest in endothelin diminished and Yanagisawa switched his focus to

s, which are receptors whose

have yet to be identified, particularly orphan

G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related ...

s (GPCRs). In 1998, again teaming up with Takeshi Sakurai, who has moved to the United States as a

at UTSW, Yanagisawa connected two orphan GPCRs with a family of

s as their ligands. They named it "

" after the

Greek Greek may refer to: Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group *Greek language, a branch of the Indo-European language family **Proto-Greek language, the assumed last common ancestor of all kno ...

word for appetite, since the neuropeptide was found exclusively in the

hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...

, a brain region that regulates appetite, and because

mice A mouse (: mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...

consumed more food after receiving a dose of orexin. Another group at

The Scripps Research Institute Scripps Research is a nonprofit American medical research facility that focuses on research and education in the biomedical sciences. Headquartered in San Diego, California, the institute has over 170 laboratories employing 2,100 scientists, tec ...

(now

Scripps Research Scripps Research is a nonprofit American medical research facility that focuses on research and education in the biomedical sciences. Headquartered in San Diego, California, the institute has over 170 laboratories employing 2,100 scientists, tec ...

) made the same discovery in the same year, and named the neuropeptide "hypocretin". Today, "hypocretin" (or ''HCRT'') is used to refer to the

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

and

transcript Transcript may refer to: * Transcript (biology), a molecule of RNA transcribed from DNA * Transcript (education), a copy of a student's permanent academic record * Transcript (law), a written record of spoken language in court proceedings * Transc ...

, while "orexin" is used to refer to the

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

. Yanagisawa and his team then

knocked out A knockout (abbreviated to KO or K.O.) is a fight-ending, winning criterion in several full-contact combat sports, such as boxing, kickboxing, Muay Thai, mixed martial arts, karate, some forms of taekwondo and other sports involving striking, a ...

the orexin

in mice, hoping to see the animal eating less. Instead, they observed behavior similar to the human condition of

, whose cause at the time was still unknown. The association between orexin and narcolepsy was definitively established not long afterwards in 2000. Since then, his research has mostly focused on studying

sleep Sleep is a state of reduced mental and physical activity in which consciousness is altered and certain Sensory nervous system, sensory activity is inhibited. During sleep, there is a marked decrease in muscle activity and interactions with th ...

and orphan receptors. For example, he uncovered the functions of GPR7 (NPBW1) and GPR8 (NPBW2), GPR41 (FFA3), and GPR103 (QRFPR). More recently, using an unbiased

forward genetics Forward genetics is a molecular genetics approach of determining the genetic basis responsible for a phenotype. Forward genetics provides an unbiased approach because it relies heavily on identifying the genes or genetic factors that cause a partic ...

approach, which randomly introduced

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

s in mice and then observed their electrocardiogram and

electromyogram Electromyography (EMG) is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph to produce a record called an electromyogram. An electromyo ...

, Yanagisawa and his team reported the role of

KIAA0999 KIAA0999 protein is a protein that in humans is encoded by the ''SIK3'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcri ...

(encoded by the ''Sik3'' gene) and NALCN (encoded by the ''Nalcn'' gene) in regulating sleep. His team also identified the

phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

and

dephosphorylation In biochemistry, dephosphorylation is the removal of a phosphate () group from an organic compound by hydrolysis. It is a reversible post-translational modification. Dephosphorylation and its counterpart, phosphorylation, activate and deactivate e ...

of 80 proteins as a major regulation mechanism of the

sleep cycle The sleep cycle is an oscillation between the slow-wave and REM (paradoxical) phases of sleep. It is sometimes called the ultradian sleep cycle, sleep–dream cycle, or REM-NREM cycle, to distinguish it from the circadian alternation between ...

in mice.

Honors and awards

Personal life

Yanagisawa is married, and is a

Baptist Baptists are a Christian denomination, denomination within Protestant Christianity distinguished by baptizing only professing Christian believers (believer's baptism) and doing so by complete Immersion baptism, immersion. Baptist churches ge ...

Christian A Christian () is a person who follows or adheres to Christianity, a Monotheism, monotheistic Abrahamic religion based on the life and teachings of Jesus in Christianity, Jesus Christ. Christians form the largest religious community in the wo ...

since his second year of PhD. He plays the flute.

References

{{DEFAULTSORT:Yanagisawa, Masashi 1960 births Living people 21st-century Japanese biologists American biologists Academic staff of the University of Tsukuba Academic staff of Kyoto University University of Texas Southwestern Medical Center faculty Scientists from Tokyo University of Tsukuba alumni Persons of Cultural Merit Recipients of the Medal with Purple Ribbon Japanese emigrants to the United States American academics of Japanese descent American scientists of Asian descent Members of the United States National Academy of Sciences Japanese molecular biologists