Wei Yan (biologist)

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Wei Yan
Born
Wei Yan

Liaoning, China
NationalityAmerican
EducationChina Medical University (MD)
University of Turku (PhD)
Baylor College of Medicine (Post-doc)
Known for
Scientific career
FieldsBiologist
Reproduction
RNA biology
Gene editing
InstitutionsBaylor College of Medicine
University of Nevada, Reno School of Medicine
David Geffen School of Medicine at UCLA
Doctoral advisorJorma Toppari
Websiteweiyanlab.com
This article uses Western name order when mentioning individuals.

Wei Yan is a Chinese-American reproductive biologist, currently Professor of Medicine at David Geffen School of Medicine at UCLA and Senior Investigator at The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center.[1] He is also University Foundation Professor[2] at University of Nevada, Reno, United States[3] and an Elected Fellow of the American Association for the Advancement of Science.[4] He is Director of National Center for Male Reproductive Epigenomics[5] and served as the editor-in-chief of the journal Biology of Reproduction.[6]

Biography[edit]

Wei Yan was born in Liaoning, China. He received his MD from China Medical University in 1990 and PhD from University of Turku, Finland in 2000.  He completed his post-doc training at Baylor College of Medicine, Houston, TX in 2004. He began his independent career as an Assistant Professor at the University of Nevada, Reno School of Medicine (UNR Med) in 2004. He rose through the ranks and became a full professor in 2013. He is currently Principal Investigator at The Lundquist Institute at Harbor-UCLA Medical Center and Professor of Medicine at David Geffen School of Medicine at UCLA. His research interests include genetic and epigenetic control of fertility, as well as epigenetic contribution of gametes (sperm and eggs) to fertilization, early embryonic development and adulthood health.[7] As a principal investigator, Dr. Yan has been continuously funded by grants from the NIH and various foundations, with a total of ~$17 million in direct cost. He also so far published >150 peer-reviewed research articles and book chapters in high-impact journals with >12,000 citations and a h-index of 63.[8]

Career and Research[edit]

After receiving his M.D., Dr. Yan became the Chief Examiner at Coroner office of the Institute of Forensic Science of Liaoning Province, Shenyang, China. While he enjoyed his work as an Examiner and developed better techniques for DNA extraction from crime scene samples, but he soon became fascinated with the research aspect and began to pursue a career in research. He enrolled in the Graduate program in the Department of Forensic Medicine at China Medical University while still working at the coroner's office. The next year he took the opportunity to leave China and work as a visiting scholar in the Department of Medical Genetics, at the University of Turku, Finland. He would stay at the University of Turku to finish in Ph.D. in March 2000 under the supervision of Drs. Jorma Toppari, Ilpo Hutaniemi and Martti Parvinen. After a short stint as a Postdoctoral Associate at University of Turku, he would travel to the United States to work with Dr. Martin M. Matzuk in the Department of Pathology at Baylor College of Medicine in Houston, Texas. It would be here at Baylor College of Medicine that we would get his first professional appointment as an Instructor in the Department of Pathology in 2003. One year later, Dr. Yan would get his first tenure-track Assistant Professorship in the Department of Physiology and Cell Biology at the University of Nevada School of Medicine in Reno Nevada. At UNR, Dr. Yan would go on to be an extremely productive researcher received multiple awards[9] and would climb the ranks to obtain the highest honor bestowed upon Professors; The University of Nevada, Reno Foundation Professor in 2020.[10] During this time he also served as the Editor-in-Chief of Biology or Reproduction, which is the official journal of the Society for the Study of Reproduction (SSR). Having achieved the highest honor at UNR, Dr. Yan would still go on to seek more challenges and moved to Los Angeles to take a Professor of Medicine appointment at the David Geffen School of Medicine at UCLA as well as a Senior Investigator position at The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center in Torrance, California.

Over his almost 30 years of research, Dr. Yan has made significant contributions to the field of Reproductive Biology and Epigenetic Inheritance in the following five areas:

Non-hormonal male contraceptives[edit]

Dr. Yan has been innovative in the contraceptives field with the novel idea of developing non-hormonal male contraceptives that disable sperm rather than killing them. His lab first put forward a novel idea for the development of non-hormonal male contraceptives: “Do not kill, but disable sperm”,[11][12] which led to the discovery of TRIPTONIDE, a natural compound purified from the Chinese herb Tripterygium Wilfordii Hook F. Triptonide acts as a reversible non-hormonal contraceptive agent in mice and monkeys, and established it as a drug candidate for “The Pill” for men.[13] This is the first and ONLY compound discovered in the past fifty years that has been tested on mice and monkeys and found to be efficient, reversible and safe.

Research on cellular and molecular mechanisms that control sperm production and male fertility[edit]

Dr. Yan’s lab first discovered the function of motile cilia in the reproductive tracts. In the male, motile ciliary beating functions as an agitator to maintain the constant suspension of immotile testicular sperm during their transit through the efferent ductules in men.[14][15] This work led to a novel concept that efferent ductal obstructions due to motile ciliopathy represent a new cause of male infertility, which has been validated in clinics. [16] This discovery has changed clinical practice in the diagnosis and treatment of obstructive azoospermia and idiopathic male infertility. In the female, motile cilia in the oviduct/Fallopian tube are essential for oocyte pickup and, therefore, fertility, but dispensable for embryo and sperm transport, which are mostly achieved through smooth muscle contraction.[17] This work solved the long-standing controversy about the role of cilia beating vs. muscle contraction in gamete/embryo transport.

Additionally, using a variety of gene knockout/genome editing technologies, his lab discovered many genetic networks that control the most fundamental cellular and molecular events in spermatogenesis, e.g., sperm connecting piece formation,[18] cytoplasmic removal,[19] global shortening of 3’UTRs,[20][21][22] and delayed translation/uncoupling of transcription and translation, and dynamic changes in poly(A) length and non-A contents.[23]

Discovery of novel small RNA species and their function in germ cells[edit]

As a young scientist, Dr. Yan was the first to discover mitochondrial genome-encoded small RNAs (mitosRNAs) [24] and endo-siRNAs in the male germline,[25] as well as meiotic sex chromosome inactivation (MSCI)-escaping X-linked miRNAs [26] and elucidated the functions of all during reproduction.[27][28][29]

Transgenerational Epigenetic Inheritance[edit]

Based on his work on sperm-borne small RNAs,[30][31][32] he put forward a novel hypothesis regarding the potential role of gamete small RNAs in epigenetic inheritance.[33] His study on the Kit paramutation mouse model first discovered that outcrossing promotes the correction of epimutations through epigenetic reprogramming, whereas intercrossing stabilizes the epimutations and enhances their transmission across multiple generations. Based on the accumulating data on inter- or trans-generational epigenetic inheritance, he and colleagues have come up with several inspiring hypotheses regarding the role of sperm small RNAs and their modifications in mediating epigenetic inheritance.[34][35] He established the first-ever National Center for Male Reproductive Epigenomics,[36] which is funded by an NCTRI P50 grant from the NICHD with a research focus on the molecular mechanism underlying epigenetic inheritance of lifestyle-induced metabolic syndrome in both humans and mice.[37]

Awards and Service[edit]

Dr. Yan has published >165 research articles, reviews and book chapters with >12,700 citations with h-index at 63 as of December 2023 according to Google Scholar.[38] Many of his publications appeared in high-impact journals, including Nature Genetics, Nature Cell Biology, Nature Reviews Genetics, Nature Communications, PNAS, Cell Research, Developmental Cell, Genome Biology, EMBO, and Development. His excellence in research has been recognized by a number of prestigious research awards, including the 2009 Society for the Study of Reproduction (SSR) Young Investigator Award, the 2012 American Society of Andrology (ASA) Young Andrologist Award, the 2013 Nevada Healthcare Hero Award for Research and Technology, the 2017 University of Nevada, Reno Outstanding Researcher Award, the 2018 SSR Research Award and the 2020 Nevada System of Higher Education Regents’ Research Award (mid-career).

Dr. Yan’s mentorship and leadership are as impressive as his research achievements. Dr. Yan has mentored six junior faculty members and trained 16 post-docs and 27 graduate students over the past 16 years. Dr. Yan served on the SSR Program Committee (2007, 2014, and 2016), the SSR Awards Committee (2015-2018), the BOR Board of Reviewing Editors (2009-2013), and as Biology of Reproduction (BOR) Associate Editor (2013-2017). Dr. Yan served as co-Editor-in-Chief of BOR (2017-2021). He is currently a Senior Editor of eLife (2022-) and the Deputy Editor-in-Chief of Andrology (2024-2028), the official journal of the American Society of Andrology (ASA) and the European Academy of Andrology (EAA).

Dr. Yan also serves on the Executive Committee of the North America Testis Workshop (NATW) and chaired the XXVI NATW in 2022. In addition, he served on the ASA Program Committee (2010-2014) and Nominating Committee (2012-2014). He was the program co-Chair for the 2019 ASA annual meeting. Dr. Yan is one of the Board of Directors of ASA (2022-2025).

To recognize his tremendous contributions to his institutions, academic societies and science in general, Dr. Yan was named the University of Nevada, Reno Foundation Professor,[39] the highest honor the University bestows upon its faculty in 2016. Dr. Yan was elected Fellow of the American Association for the Advancement of Science (AAAS) in 2017. He was also named the 2023 SSR Distinguished Fellow.

Awards and affiliations[edit]

Some of his awards include:

  • 2009 Society for the Study of Reproduction (SSR) Young Investigator Award[40]
  • 2012 American Society of Andrology (ASA) Young Andrologist Award[41]
  • 2013 Nevada Healthcare Hero Award for Research and Technology[42]
  • 2017 University of Nevada, Reno Outstanding Researcher Award[43]
  • 2018 SSR Research Award and the 2020 Nevada System of Higher Education Research Award[44]

He was elected Fellow of the American Association for the Advancement of Science (AAAS) in 2017.[4]

References[edit]

  1. ^ "The Lundquist Institute Adds Six Exceptional Researchers to its Investigator Ranks | The Lundquist Institute". lundquist.org. Retrieved 2022-02-14.
  2. ^ "2016 Foundation Professors announced". University of Nevada, Reno. Retrieved 2021-11-06.
  3. ^ "Wei Yan". unr.edu. Retrieved December 21, 2017.
  4. ^ a b "Two faculty members named AAAS Fellows". unr.edu. Retrieved November 21, 2017.
  5. ^ "National Center for Male Reproductive Epigenomics". National Center for Reproductive Epigenomics. Retrieved 2022-02-14.
  6. ^ Yan, Wei; Clarke, Hugh (2017-07-01). "A New Chapter for Biology of Reproduction". Biology of Reproduction. 97 (1): 1. doi:10.1093/biolre/iox091. ISSN 0006-3363. PMID 28859289.
  7. ^ "Welcome to the Yan lab!". The Yan Lab. Retrieved 2022-02-14.
  8. ^ "Wei Yan".
  9. ^ "Health and reproductive biology: a research record of paradigm-shifting discoveries". University of Nevada, Reno. Retrieved 2022-02-15.
  10. ^ "Foundation Professor Award | Faculty Affairs | Office of the Provost and Executive Vice President". University of Nevada, Reno. Retrieved 2022-02-15.
  11. ^ Yan, Wei (10 July 2009). "Male infertility caused by spermiogenic defects: Lessons from gene knockouts". Molecular and Cellular Endocrinology. 306 (1–2): 24–32. doi:10.1016/j.mce.2009.03.003. PMC 5438260. PMID 19481682.
  12. ^ Nickels, Logan; Yan, Wei (January 2024). "Nonhormonal Male Contraceptive Development—Strategies for Progress". Pharmacological Reviews. 76 (1): 37–48. doi:10.1124/pharmrev.122.000787. PMC 10759220. PMID 38101934.
  13. ^ Chang, Zongliang; Qin, Weibing; Zheng, Huili; Schegg, Kathleen; Han, Lu; Liu, Xiaohua; Wang, Yue; Wang, Zhuqing; McSwiggin, Hayden; Peng, Hongying; Yuan, Shuiqiao; Wu, Jiabao; Wang, Yongxia; Zhu, Shenghui; Jiang, Yanjia; Nie, Hua; Tang, Yuan; Zhou, Yu; Hitchcock, Michael J. M.; Tang, Yunge; Yan, Wei (23 February 2021). "Triptonide is a reversible non-hormonal male contraceptive agent in mice and non-human primates". Nature Communications. 12 (1): 1253. Bibcode:2021NatCo..12.1253C. doi:10.1038/s41467-021-21517-5.
  14. ^ Yuan, Shuiqiao; Liu, Yue; Peng, Hongying; Tang, Chong; Hennig, Grant W.; Wang, Zhuqing; Wang, Li; Yu, Tian; Klukovich, Rachel; Zhang, Ying; Zheng, Huili; Xu, Chen; Wu, Jingwen; Hess, Rex A.; Yan, Wei (26 February 2019). "Motile cilia of the male reproductive system require miR-34/miR-449 for development and function to generate luminal turbulence". Proceedings of the National Academy of Sciences. 116 (9): 3584–3593. Bibcode:2019PNAS..116.3584Y. doi:10.1073/pnas.1817018116. PMC 6397547. PMID 30659149.
  15. ^ Wu, Jingwen; Bao, Jianqiang; Kim, Minkyung; Yuan, Shuiqiao; Tang, Chong; Zheng, Huili; Mastick, Grant S.; Xu, Chen; Yan, Wei (15 July 2014). "Two miRNA clusters, miR-34b/c and miR-449 , are essential for normal brain development, motile ciliogenesis, and spermatogenesis". Proceedings of the National Academy of Sciences. 111 (28): E2851-7. Bibcode:2014PNAS..111E2851W. doi:10.1073/pnas.1407777111. PMC 4104921. PMID 24982181.
  16. ^ Rosenfeld, Cheryl S. (2019-02-26). "Male reproductive tract cilia beat to a different drummer". Proceedings of the National Academy of Sciences. 116 (9): 3361–3363. Bibcode:2019PNAS..116.3361R. doi:10.1073/pnas.1900112116. ISSN 0027-8424. PMC 6397526. PMID 30692268.
  17. ^ Yuan, Shuiqiao; Wang, Zhuqing; Peng, Hongying; Ward, Sean M.; Hennig, Grant W.; Zheng, Huili; Yan, Wei (June 2021). "Oviductal motile cilia are essential for oocyte pickup but dispensable for sperm and embryo transport". Proceedings of the National Academy of Sciences. 118 (22). Bibcode:2021PNAS..11802940Y. doi:10.1073/pnas.2102940118. PMC 8179221. PMID 34039711.
  18. ^ Yuan, Shuiqiao; Stratton, Clifford J.; Bao, Jianqiang; Zheng, Huili; Bhetwal, Bhupal P.; Yanagimachi, Ryuzo; Yan, Wei (3 February 2015). "Spata6 is required for normal assembly of the sperm connecting piece and tight head–tail conjunction". Proceedings of the National Academy of Sciences. 112 (5): E430-9. Bibcode:2015PNAS..112E.430Y. doi:10.1073/pnas.1424648112. PMC 4321249. PMID 25605924.
  19. ^ Zheng, Huili; Stratton, Clifford J.; Morozumi, Kazuto; Jin, Jingling; Yanagimachi, Ryuzo; Yan, Wei (17 April 2007). "Lack of Spem1 causes aberrant cytoplasm removal, sperm deformation, and male infertility". Proceedings of the National Academy of Sciences. 104 (16): 6852–6857. Bibcode:2007PNAS..104.6852Z. doi:10.1073/pnas.0701669104. PMC 1871874. PMID 17426145.
  20. ^ Tang, Chong; Klukovich, Rachel; Peng, Hongying; Wang, Zhuqing; Yu, Tian; Zhang, Ying; Zheng, Huili; Klungland, Arne; Yan, Wei (9 January 2018). "ALKBH5-dependent m6A demethylation controls splicing and stability of long 3′-UTR mRNAs in male germ cells". Proceedings of the National Academy of Sciences. 115 (2): E325–E333. doi:10.1073/pnas.1717794115. PMC 5777073. PMID 29279410.
  21. ^ Bao, Jianqiang; Vitting-Seerup, Kristoffer; Waage, Johannes; Tang, Chong; Ge, Ying; Porse, Bo T.; Yan, Wei (5 May 2016). "UPF2-Dependent Nonsense-Mediated mRNA Decay Pathway Is Essential for Spermatogenesis by Selectively Eliminating Longer 3'UTR Transcripts". PLOS Genetics. 12 (5): e1005863. doi:10.1371/journal.pgen.1005863. PMC 4858225.
  22. ^ Zhang, Ying; Tang, Chong; Yu, Tian; Zhang, Ruirui; Zheng, Huili; Yan, Wei (December 2017). "MicroRNAs control mRNA fate by compartmentalization based on 3′ UTR length in male germ cells". Genome Biology. 18 (1): 105. doi:10.1186/s13059-017-1243-x. PMC 5471846. PMID 28615029.
  23. ^ Guo, Mei; Luo, Chunhai; Wang, Zhuqing; Chen, Sheng; Morris, Dayton; Ruan, Fengying; Chen, Zhichao; Yang, Linfeng; Wei, Xiongyi; Wu, Chuanwen; Luo, Bei; Lv, Zhou; Huang, Jin; Zhang, Dong; Yu, Cong; Gao, Qiang; Wang, Hongqi; Zhang, Ying; Sun, Fei; Yan, Wei; Tang, Chong (15 June 2022). "Uncoupling transcription and translation through miRNA-dependent poly(A) length control in haploid male germ cells". Development. 149 (12). doi:10.1242/dev.199573. PMC 9270972.
  24. ^ Ro, Seungil; Ma, Hsiu-Yen; Park, Chanjae; Ortogero, Nicole; Song, Rui; Hennig, Grant W; Zheng, Huili; Lin, Yung-Ming; Moro, Loredana; Hsieh, Jer-Tsong; Yan, Wei (June 2013). "The mitochondrial genome encodes abundant small noncoding RNAs". Cell Research. 23 (6): 759–774. doi:10.1038/cr.2013.37. PMC 3674384. PMID 23478297.
  25. ^ Song, Rui; Hennig, Grant W.; Wu, Qiuxia; Jose, Charlie; Zheng, Huili; Yan, Wei (9 August 2011). "Male germ cells express abundant endogenous siRNAs". Proceedings of the National Academy of Sciences. 108 (32): 13159–13164. Bibcode:2011PNAS..10813159S. doi:10.1073/pnas.1108567108. PMC 3156200. PMID 21788498.
  26. ^ Song, Rui; Ro, Seungil; Michaels, Jason D; Park, Chanjae; McCarrey, John R; Yan, Wei (April 2009). "Many X-linked microRNAs escape meiotic sex chromosome inactivation". Nature Genetics. 41 (4): 488–493. doi:10.1038/ng.338. PMC 2723799. PMID 19305411.
  27. ^ Wu, Qiuxia; Song, Rui; Ortogero, Nicole; Zheng, Huili; Evanoff, Ryan; Small, Chris L.; Griswold, Michael D.; Namekawa, Satoshi H.; Royo, Helene; Turner, James M.; Yan, Wei (July 2012). "The RNase III Enzyme DROSHA Is Essential for MicroRNA Production and Spermatogenesis". Journal of Biological Chemistry. 287 (30): 25173–25190. doi:10.1074/jbc.M112.362053. PMC 3408133. PMID 22665486.
  28. ^ Bao, J; Zhang, Y; Schuster, A S; Ortogero, N; Nilsson, E E; Skinner, M K; Yan, W (May 2014). "Conditional inactivation of Miwi2 reveals that MIWI2 is only essential for prospermatogonial development in mice". Cell Death & Differentiation. 21 (5): 783–796. doi:10.1038/cdd.2014.5. PMC 3978311.
  29. ^ Ro, Seungil; Park, Chanjae; Young, David; Sanders, Kenton M.; Yan, Wei (September 2007). "Tissue-dependent paired expression of miRNAs". Nucleic Acids Research. 35 (17): 5944–5953. doi:10.1093/nar/gkm641. PMC 2034466. PMID 17726050.
  30. ^ Song, Rui; Hennig, Grant W.; Wu, Qiuxia; Jose, Charlie; Zheng, Huili; Yan, Wei (9 August 2011). "Male germ cells express abundant endogenous siRNAs". Proceedings of the National Academy of Sciences. 108 (32): 13159–13164. Bibcode:2011PNAS..10813159S. doi:10.1073/pnas.1108567108. PMC 3156200. PMID 21788498.
  31. ^ Yuan, Shuiqiao; Schuster, Andrew; Tang, Chong; Yu, Tian; Ortogero, Nicole; Bao, Jianqiang; Zheng, Huili; Yan, Wei (1 January 2015). "Sperm-borne miRNAs and endo-siRNAs are important for fertilization and preimplantation embryonic development". Development. doi:10.1242/dev.131755. PMC 4760322. PMID 26718009.
  32. ^ Bao, Jianqiang; Yuan, Shuiqiao; Maestas, Ashley; Bhetwal, Bhupal P.; Schuster, Andrew; Yan, Wei (October 2013). "Stk31 is dispensable for embryonic development and spermatogenesis in mice". Molecular Reproduction and Development. 80 (10): 786. doi:10.1002/mrd.22225. PMC 5441557. PMID 23929668.
  33. ^ Yan, Wei (December 2014). "Potential roles of noncoding RNAs in environmental epigenetic transgenerational inheritance". Molecular and Cellular Endocrinology. 398 (1–2): 24–30. doi:10.1016/j.mce.2014.09.008. PMC 4262681.
  34. ^ Chen, Qi; Yan, Wei; Duan, Enkui (December 2016). "Epigenetic inheritance of acquired traits through sperm RNAs and sperm RNA modifications". Nature Reviews Genetics. 17 (12): 733–743. doi:10.1038/nrg.2016.106. PMC 5441558. PMID 27694809.
  35. ^ Zhang, Yunfang; Zhang, Xudong; Shi, Junchao; Tuorto, Francesca; Li, Xin; Liu, Yusheng; Liebers, Reinhard; Zhang, Liwen; Qu, Yongcun; Qian, Jingjing; Pahima, Maya; Liu, Ying; Yan, Menghong; Cao, Zhonghong; Lei, Xiaohua; Cao, Yujing; Peng, Hongying; Liu, Shichao; Wang, Yue; Zheng, Huili; Woolsey, Rebekah; Quilici, David; Zhai, Qiwei; Li, Lei; Zhou, Tong; Yan, Wei; Lyko, Frank; Zhang, Ying; Zhou, Qi; Duan, Enkui; Chen, Qi (May 2018). "Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs". Nature Cell Biology. 20 (5): 535–540. doi:10.1038/s41556-018-0087-2. PMID 29695786. S2CID 19089262.
  36. ^ Epigenomics, National Center for Reproductive. "National Center for Reproductive Epigenomics". National Center for Reproductive Epigenomics.
  37. ^ Wang, Hetan; Wang, Zhuqing; Zhou, Tong; Morris, Dayton; Chen, Sheng; Li, Musheng; Wang, Yue; Zheng, Huili; Fu, Weineng; Yan, Wei (May 2023). "Small RNA shuffling between murine sperm and their cytoplasmic droplets during epididymal maturation". Developmental Cell. 58 (9): 779–790.e4. doi:10.1016/j.devcel.2023.03.010. PMID 37023748. S2CID 257992816.
  38. ^ "Wei Yan".
  39. ^ "2016 Foundation Professors announced". University of Nevada, Reno. Retrieved 2021-11-06.
  40. ^ "SSR Awards - Society for the Study of Reproduction". community.ssr.org.
  41. ^ "Young Andrologist Award | American Society of Andrology".
  42. ^ Nevada Business Mag (2013-09-03). "Nevada Healthcare Heroes 2013". Nevadabusiness.com. Retrieved 2021-11-07. {{cite web}}: |author= has generic name (help)
  43. ^ "Health and reproductive biology: a research record of paradigm-shifting discoveries". University of Nevada, Reno.
  44. ^ "2017 AAAS Fellows Recognized for Advancing Science | American Association for the Advancement of Science". www.aaas.org.

External links[edit]

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