Junying Yuan
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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 medical school of Harvard University and is located in the Longwood Medical and Academic Area, Longwood Medical Area in Boston, Massachusetts. Founded in 1782, HMS is the third oldest medical school in the Un ...
, 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 di ...
. Early in her career, she contributed significant findings to the discovery and characterization of
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
. 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, Shanghainese: , Standard Chinese pronunciation: is a direct-administered municipality and the most populous urban area in China. The city is located on the Chinese shoreline on the southern estuary of the Yangtze River, with the ...
, 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, while her uncle, Yuan Chengye, was a professor and an academician of the
Chinese Academy of Sciences The Chinese Academy of Sciences (CAS; ) is the national academy for natural sciences and the highest consultancy for science and technology of the People's Republic of China. It is the world's largest research organization, with 106 research i ...
. Junying Yuan attended
Fudan University Fudan University (FDU) is a public university, national public university in Yangpu, Shanghai, Yangpu, Shanghai, China. It is affiliated with the Ministry of Education (China), Ministry of Education and is co-funded with the Shanghai Municipal ...
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 Social movement, sociopolitical movement in the China, People's Republic of China (PRC). It was launched by Mao Zedong in 1966 and lasted until his de ...
. She was among the first wave of students to attempt the newly revived
National Higher Education Entrance Examination The Nationwide Unified Examination for Admissions to General Universities and Colleges (), commonly abbreviated as the Gaokao (), is the annual nationally coordinated undergraduate admission exam in mainland China, held in early June. Despite the ...
in 1977, coming in first of all students who attempted it in Shanghai. She completed her
bachelor's A bachelor's degree (from Medieval Latin ''baccalaureus'') or baccalaureate (from Modern Latin ''baccalaureatus'') is an undergraduate degree awarded by colleges and universities upon completion of a course of study lasting three to six years ( ...
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, a ...
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 Ph.D. in
Neuroscience Neuroscience is the scientific study of the nervous system (the brain, spinal cord, and peripheral nervous system), its functions, and its disorders. It is a multidisciplinary science that combines physiology, anatomy, molecular biology, ...
(1989) at
Harvard University Harvard University is a Private university, private Ivy League research university in Cambridge, Massachusetts, United States. Founded in 1636 and named for its first benefactor, the History of the Puritans in North America, Puritan clergyma ...
under the supervision of
MIT The Massachusetts Institute of Technology (MIT) is a private research university in Cambridge, Massachusetts, United States. Established in 1861, MIT has played a significant role in the development of many areas of modern technology and sc ...
professor H. Robert Horvitz, where she endeavored to elucidate the molecular mechanisms behind programmed cell death in the
nematode The nematodes ( or ; ; ), roundworms or eelworms constitute the phylum Nematoda. Species in the phylum inhabit a broad range of environments. Most species are free-living, feeding on microorganisms, but many are parasitic. Parasitic worms (h ...
''
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 Hybrid word, blend of the Greek ''caeno-'' (recent), ''r ...
''. 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'' ( ...
, 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 proteolytically cleaves other proteins, such as the precursors of the inflammatory cytokines interleukin 1β and interleukin 18 as well as the pyroptosis ...
.


Career

Junying Yuan established an independent lab at Harvard-affiliated
Massachusetts General Hospital Massachusetts General Hospital (Mass General or MGH) is a teaching hospital located in the West End neighborhood of Boston, Massachusetts. It is the original and largest clinical education and research facility of Harvard Medical School/Harvar ...
in 1989, immediately upon completion of her Ph.D. 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 cyste ...
s in mediating
mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...
ian
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
. 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 The Nobel Prize in Chemistry () is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outst ...
won by her Ph.D. supervisor, Robert Horvitz. 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 an ...
at
Harvard Medical School Harvard Medical School (HMS) is the medical school of Harvard University and is located in the Longwood Medical and Academic Area, Longwood Medical Area in Boston, Massachusetts. Founded in 1782, HMS is the third oldest medical school in the Un ...
'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 proteolytically cleaves other proteins, such as the precursors of the inflammatory cytokines interleukin 1β and interleukin 18 as well as the pyroptosis ...
-driven
inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
. 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. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who is ...
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 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 Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...
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, necroptosis, and PANoptosis Some of th ...
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—in the United States—Lou Gehrig's disease (LGD), is a rare, Terminal illness, terminal neurodegenerative disease, neurodegenerative disorder that results i ...
(ALS),
Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
,
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...
,
psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by patches of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small localized patches to complete b ...
, 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, fever, abdominal distension, and weight loss. Complications outside of the ...
.


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 (The Academy) 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 other ...
*2010 Fellow of the
American Association for the Advancement of Science The American Association for the Advancement of Science (AAAS) is a United States–based international nonprofit with the stated mission of promoting cooperation among scientists, defending scientific freedom, encouraging scientific responsib ...
*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, NGO, 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 ...


References


External links


Harvard Medical School Investigator Page

Curriculum Vitae

Google Scholar ProfilePublications
{{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 21st-century Chinese science writers Writers from Shanghai American women academics 21st-century American women