Junying Yuan (, born October 3, 1958) is the
Elizabeth D. Hay Professor of Cell Biology at
Harvard Medical School
Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consi ...
,
best known for her work in
cell death
Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as dis ...
. Early in her career, she contributed significant findings to the discovery and characterization of
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
.
More recently, she was responsible for the discovery of the programmed form of necrotic cell death known as
necroptosis
Necroptosis is a programmed form of necrosis, or inflammatory cell death. Conventionally, necrosis is associated with unprogrammed cell death resulting from cellular damage or infiltration by pathogens, in contrast to orderly, programmed cell dea ...
.
Education and early career
Yuan was born in
Shanghai
Shanghai (; , , Standard Mandarin pronunciation: ) is one of the four direct-administered municipalities of the People's Republic of China (PRC). The city is located on the southern estuary of the Yangtze River, with the Huangpu River flow ...
, her maternal grandfather was the scholar and translator Li Qingya (李青崖), and her paternal grandfather, Yuan Kaiji (袁开基), was a famous professor of organic chemistry. Her parents were both medical professors at
Fudan University Shanghai Medical College
The Shanghai Medical College of Fudan University, formerly the independent Shanghai Medical University, is one of the oldest and most prestigious medical schools in China. Clinical medicine of the Shanghai Medical College of Fudan University is c ...
, while her uncle,
Yuan Chengye, was a professor and an academician of the
Chinese Academy of Sciences
The Chinese Academy of Sciences (CAS); ), known by Academia Sinica in English until the 1980s, is the national academy of the People's Republic of China for natural sciences. It has historical origins in the Academia Sinica during the Republ ...
. Junying Yuan attended
Fudan University
Fudan University () is a national public research university in Shanghai, China. Fudan is a member of the C9 League, Project 985, Project 211, and the Double First Class University identified by the Ministry of Education of China. It is als ...
following the revival of higher education after its suspension under the
Cultural Revolution
The Cultural Revolution, formally known as the Great Proletarian Cultural Revolution, was a sociopolitical movement in the People's Republic of China (PRC) launched by Mao Zedong in 1966, and lasting until his death in 1976. Its stated goal ...
. She was among the first wave of students to attempt the newly revived
National Higher Education Entrance Examination
The National College Entrance Examination (NCEE), commonly known as the gaokao (), is a standardized college entrance exam held annually in mainland China. It is required for entrance into almost all higher education institutions at the underg ...
in 1977, coming in first of all students who attempted it in Shanghai. She completed her
Bachelors
A bachelor is a man who is not and has never been married.Bachelors are, in Pitt & al.'s phrasing, "men who live independently, outside of their parents' home and other institutional settings, who are neither married nor cohabitating". ().
Etymo ...
in
Biochemistry
Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...
in 1982, and was subsequently one of the first students admitted to doctoral study in the United States through the
China-U.S. Biochemistry Examination and Application (CUSBEA) program, coming in second out of the 25,000 who attempted the CUSBEA in its first year.
In the United States, she completed her
PhD in
Neuroscience
Neuroscience is the scientific study of the nervous system (the brain, spinal cord, and peripheral nervous system), its functions and disorders. It is a multidisciplinary science that combines physiology, anatomy, molecular biology, development ...
(1989) at
Harvard University
Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...
under the supervision of
MIT
The Massachusetts Institute of Technology (MIT) is a private land-grant research university in Cambridge, Massachusetts. Established in 1861, MIT has played a key role in the development of modern technology and science, and is one of the m ...
professor
H. Robert Horvitz
Howard Robert Horvitz ForMemRS NAS AAA&S APS NAM (born May 8, 1947) is an American biologist best known for his research on the nematode worm ''Caenorhabditis elegans'', for which he was awarded the 2002 Nobel Prize in Physiology or Medicine, t ...
, where she endeavored to elucidate the molecular mechanisms behind programmed cell death in the
nematode
The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-Parasitism, parasitic nematodes also known as eelworms. They are a diverse animal phylum inhab ...
''
Caenorhabditis elegans
''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (ro ...
''. She identified the proteins ced-3 and ced-4 as drivers behind programmed cell death in
C. elegans
''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...
, and subsequently identified the mammalian homologue of ced-3 known as interleukin-1 beta-converting enzyme(ICE), later called
caspase-1
Caspase-1/Interleukin-1 converting enzyme (ICE) is an evolutionarily conserved enzyme that proteolysis, proteolytically cleaves other proteins, such as the Protein precursor, precursors of the inflammatory cytokines Interleukin 1 beta, interleuki ...
.
[
]
Career
Junying Yuan established an independent lab at Harvard-affiliated Massachusetts General Hospital
Massachusetts General Hospital (Mass General or MGH) is the original and largest teaching hospital of Harvard Medical School located in the West End neighborhood of Boston, Massachusetts. It is the third oldest general hospital in the United Stat ...
in 1989, immediately upon completion of her PhD.[ Her initial efforts were directed towards providing evidence for the functional role of ]caspase
Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cystei ...
s in mediating mammal
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
ian apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
. Her independent work at this stage provided the first insights into molecular mechanisms in mammalian apoptosis, which contributed significantly to the Nobel Prize in Chemistry
)
, image = Nobel Prize.png
, alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "M ...
won by her PhD supervisor, Robert Horvitz
Howard Robert Horvitz ForMemRS NAS AAA&S APS NAM (born May 8, 1947) is an American biologist best known for his research on the nematode worm ''Caenorhabditis elegans'', for which he was awarded the 2002 Nobel Prize in Physiology or Medicine, t ...
.
In 1996, Yuan moved her lab to the Department of Cell Biology
Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living and ...
at Harvard Medical School
Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consi ...
's Longwood campus, where she continued her investigation into cell death. Her work delved further into programmed cell death and revealed a wide cohort of proteins involved in the regulation and consequences of apoptosis. Some notable work includes her discovery that BID cleavage by caspase-8
Caspase-8 is a caspase protein, encoded by the ''CASP8'' gene. It most likely acts upon caspase-3.
''CASP8'' orthologs have been identified in numerous mammals for which complete genome data are available. These unique orthologs are also present ...
mediates mitochondrial damage in apoptosis, and her discovery of caspase-11's role in regulating caspase-1
Caspase-1/Interleukin-1 converting enzyme (ICE) is an evolutionarily conserved enzyme that proteolysis, proteolytically cleaves other proteins, such as the Protein precursor, precursors of the inflammatory cytokines Interleukin 1 beta, interleuki ...
-driven inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
.
In 2005, Yuan's group discovered a non-apoptotic form of programmed necrotic
Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...
cell death, which they termed "necroptosis
Necroptosis is a programmed form of necrosis, or inflammatory cell death. Conventionally, necrosis is associated with unprogrammed cell death resulting from cellular damage or infiltration by pathogens, in contrast to orderly, programmed cell dea ...
".[ Other groups first observed that the stimulation of Fas/]TNFR
The tumor necrosis factor receptor superfamily (TNFRSF) is a protein superfamily of cytokine receptors characterized by the ability to bind tumor necrosis factors (TNFs) via an extracellular cysteine-rich domain. With the exception of nerve growth ...
family of death-domain receptors(DR) activated a canonical apoptotic pathway; however, in many cell types, not only did caspase inhibition fail to inhibit cell death, as would be expected of canonical apoptosis, but stimulated cells experienced a form of cell death that more closely resembled necrosis than apoptosis. Yuan's group conducted a chemical screen that identified a small molecule capable of inhibiting DR-driven cell death, necrostatin-1, and demonstrated necroptosis' role in ischemic neuronal injury, thereby positing a potential role for necrostatin-1 in stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
treatment. Her group then identified RIPK1
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions in a variety of cellular pathways related to both cell survival and death. In terms of cell death, RIPK1 plays a role in apoptosis and necroptosis. Some of the cell survival p ...
as the target for necrostatin-1, thus implicating it as a key player in necroptosis.
Yuan went on to identify and characterize members of the signaling network responsible for regulating necroptosis, and continues to elucidate the mechanisms of necroptosis while exploring its potential as a target of therapeutic intervention. Necrosis was previously considered to be a form of passive cell death, forced in response to stress. This belief had driven an aversion towards developing therapeutic applications targeting necrosis. In demonstrating a form of programmed necrosis, Yuan's work revealed new avenues of treatment for an ever-increasing cohort of diseases where necroptosis is implicated. , small-molecule inhibitors of RIPK1 have advanced beyond Phase I human clinical trials for the treatment of various inflammatory and neurodegenerative diseases, including amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...
(ALS), Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
, rheumatoid arthritis
Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...
, psoriasis
Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...
, and Crohn's disease
Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...
.
Awards and Fellowships
*1985-1989 Ryan Fellowship
*1994 Wilson S. Stone Memorial Award
*1996-1999 American Heart Established Investigator
*1999 SCBA Outstanding Young Investigator Award[
*2002 Innovator Award for Breast Cancer Research
*2002 Merit Award, National Institute of Aging][
*2003 BBS Mentoring Award, Harvard Medical School][
*2005 ]National Institutes of Health Director's Pioneer Award
National Institutes of Health Director's Pioneer Award is a research initiative first announced in 2004 designed to support individual scientists' biomedical research. The focus is specifically on "pioneering" research that is highly innovative ...
*2006 International Cell Death Society Award
*2007 Fellow of the American Academy of Arts and Sciences
The American Academy of Arts and Sciences (abbreviation: AAA&S) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, and ...
*2010 Fellow of the American Association for the Advancement of Science
The American Association for the Advancement of Science (AAAS) is an American international non-profit organization with the stated goals of promoting cooperation among scientists, defending scientific freedom, encouraging scientific respons ...
*2013 Agilent Technologies Thought Leader Award
*2017 Member of the National Academy of Sciences
The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nati ...
References
External links
Harvard Medical School Investigator Page
Curriculum Vitae
Google Scholar Profile
Publications
{{DEFAULTSORT:Yuan, Junying
1958 births
Living people
American women biologists
American people of Chinese descent
Fellows of the American Academy of Arts and Sciences
Fellows of the American Association for the Advancement of Science
Fudan University alumni
Harvard Medical School alumni
Massachusetts Institute of Technology alumni
Harvard Medical School faculty
Physicians of Massachusetts General Hospital
Educators from Shanghai
Biologists from Shanghai
Chinese women biologists
Members of the United States National Academy of Sciences
Physicians from Shanghai
Chinese science writers
Writers from Shanghai
American women academics
21st-century American women