Wei Yan | |
---|---|
Born | Wei Yan Liaoning, China |
Nationality | American |
Education | China Medical University (MD) University of Turku (PhD) Baylor College of Medicine (Post-doc) |
Known for |
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Scientific career | |
Fields | Biologist Reproduction RNA biology Gene editing |
Institutions | Baylor College of Medicine University of Nevada, Reno School of Medicine David Geffen School of Medicine at UCLA |
Doctoral advisor | Jorma Toppari |
Website | weiyanlab |
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]
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]
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:
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.
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]
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]
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]
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.
Some of his awards include:
He was elected Fellow of the American Association for the Advancement of Science (AAAS) in 2017. [4]
Genomic imprinting is an epigenetic phenomenon that causes genes to be expressed or not, depending on whether they are inherited from the female or male parent. Genes can also be partially imprinted. Partial imprinting occurs when alleles from both parents are differently expressed rather than complete expression and complete suppression of one parent's allele. Forms of genomic imprinting have been demonstrated in fungi, plants and animals. In 2014, there were about 150 imprinted genes known in mice and about half that in humans. As of 2019, 260 imprinted genes have been reported in mice and 228 in humans.
A spermatozoon is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote.
In biology, epigenetics is the study of heritable traits, or a stable change of cell function, that happen without changes to the DNA sequence. The Greek prefix epi- in epigenetics implies features that are "on top of" or "in addition to" the traditional genetic mechanism of inheritance. Epigenetics usually involves a change that is not erased by cell division, and affects the regulation of gene expression. Such effects on cellular and physiological phenotypic traits may result from environmental factors, or be part of normal development. They can lead to cancer.
Reproductive technology encompasses all current and anticipated uses of technology in human and animal reproduction, including assisted reproductive technology (ART), contraception and others. It is also termed Assisted Reproductive Technology, where it entails an array of appliances and procedures that enable the realization of safe, improved and healthier reproduction. While this is not true of all people, for an array of married couples, the ability to have children is vital. But through the technology, infertile couples have been provided with options that would allow them to conceive children.
In biology, the epigenome of an organism is the collection of chemical changes to its DNA and histone proteins that affects when, where, and how the DNA is expressed; these changes can be passed down to an organism's offspring via transgenerational stranded epigenetic inheritance. Changes to the epigenome can result in changes to the structure of chromatin and changes to the function of the genome.
Tripterygium wilfordii, or léi gōng téng (Mandarin), sometimes called thunder god vine but more properly translated thunder duke vine, is a vine used in traditional Chinese medicine.
Male contraceptives, also known as male birth control, are methods of preventing pregnancy by interrupting the function of sperm. The main forms of male contraception available today are condoms, vasectomy, and withdrawal, which together represented 20% of global contraceptive use in 2019. New forms of male contraception are in clinical and preclinical stages of research and development, but as of 2024, none have reached regulatory approval for widespread use.
Human fertilization is the union of an egg and sperm, occurring primarily in the ampulla of the fallopian tube. The result of this union leads to the production of a fertilized egg called a zygote, initiating embryonic development. Scientists discovered the dynamics of human fertilization in the 19th century.
Male infertility refers to a sexually mature male's inability to impregnate a fertile female. In humans, it accounts for 40–50% of infertility. It affects approximately 7% of all men. Male infertility is commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity. More recently, advance sperm analyses that examine intracellular sperm components are being developed.
Decapacitation factor (DF) is composed of sperm surface-associated proteins which modulate the fertilizing ability of spermatozoa. Decapacitation is a reversible process that converts fertile, capacitated sperm to less-fertile uncapacitated sperm. This activity is achieved by interaction between cholesterol, phospholipids and fibronectin-like substances and delivered via small vesicles in seminal plasma. DF prevents onset of capacitation. Many DFs are released in secretions from the epididymis and accessory organs of the male reproductive system. However, some DFs have been identified that are located on the acrosome of sperm. Normally, capacitation is initiated through the loss of DF before the spermatozoa can perform the acrosomal reaction. Physiologically decapacitation will inhibit the acrosomal reaction as DFs reassociate onto the sperm surface. For example, one way this can be achieved is through spermatozoal membrane stabilization by maintaining physiological cholesterol/phospholipid ratio.
Azoospermia factor (AZF) is one of several proteins or their genes, which are coded from the AZF region on the human male Y chromosome. Deletions in this region are associated with inability to produce sperm. Subregions within the AZF region are AZFa, AZFb and AZFc. AZF microdeletions are one of the major causes of male infertility for azoospermia and severe oligozoospermia males. AZF is the term used by the HUGO Gene Nomenclature Committee.
RNA activation (RNAa) is a small RNA-guided and Argonaute (Ago)-dependent gene regulation phenomenon in which promoter-targeted short double-stranded RNAs (dsRNAs) induce target gene expression at the transcriptional/epigenetic level. RNAa was first reported in a 2006 PNAS paper by Li et al. who also coined the term "RNAa" as a contrast to RNA interference (RNAi) to describe such gene activation phenomenon. dsRNAs that trigger RNAa have been termed small activating RNA (saRNA). Since the initial discovery of RNAa in human cells, many other groups have made similar observations in different mammalian species including human, non-human primates, rat and mice, plant and C. elegans, suggesting that RNAa is an evolutionarily conserved mechanism of gene regulation.
Glyceraldehyde-3-phosphate dehydrogenase, spermatogenic or glyceraldehyde-3-phosphate dehydrogenase, testis-specific is an enzyme that in humans is encoded by the GAPDHS gene.
Gonocytes are the precursors of spermatogonia that differentiate in the testis from primordial germ cells around week 7 of embryonic development and exist up until the postnatal period, when they become spermatogonia. Despite some uses of the term to refer to the precursors of oogonia, it was generally restricted to male germ cells. Germ cells operate as vehicles of inheritance by transferring genetic and epigenetic information from one generation to the next. Male fertility is centered around continual spermatogonia which is dependent upon a high stem cell population. Thus, the function and quality of a differentiated sperm cell is dependent upon the capacity of its originating spermatogonial stem cell (SSC).
Ming-Ming Zhou is an American scientist whose specification is structural and chemical biology, NMR spectroscopy, and drug design. He is the Dr. Harold and Golden Lamport Professor and Chairman of the Department of Pharmacological Sciences. He is also the co-director of the Drug Discovery Institute at the Icahn School of Medicine at Mount Sinai and Mount Sinai Health System in New York City, as well as Professor of Sciences. Zhou is an elected fellow of the American Association for the Advancement of Science.
Transgenerational epigenetic inheritance is the transmission of epigenetic markers and modifications from one generation to multiple subsequent generations without altering the primary structure of DNA. Thus, the regulation of genes via epigenetic mechanisms can be heritable; the amount of transcripts and proteins produced can be altered by inherited epigenetic changes. In order for epigenetic marks to be heritable, however, they must occur in the gametes in animals, but since plants lack a definitive germline and can propagate, epigenetic marks in any tissue can be heritable.
Cancer epigenetics is the study of epigenetic modifications to the DNA of cancer cells that do not involve a change in the nucleotide sequence, but instead involve a change in the way the genetic code is expressed. Epigenetic mechanisms are necessary to maintain normal sequences of tissue specific gene expression and are crucial for normal development. They may be just as important, if not even more important, than genetic mutations in a cell's transformation to cancer. The disturbance of epigenetic processes in cancers, can lead to a loss of expression of genes that occurs about 10 times more frequently by transcription silencing than by mutations. As Vogelstein et al. points out, in a colorectal cancer there are usually about 3 to 6 driver mutations and 33 to 66 hitchhiker or passenger mutations. However, in colon tumors compared to adjacent normal-appearing colonic mucosa, there are about 600 to 800 heavily methylated CpG islands in the promoters of genes in the tumors while these CpG islands are not methylated in the adjacent mucosa. Manipulation of epigenetic alterations holds great promise for cancer prevention, detection, and therapy. In different types of cancer, a variety of epigenetic mechanisms can be perturbed, such as the silencing of tumor suppressor genes and activation of oncogenes by altered CpG island methylation patterns, histone modifications, and dysregulation of DNA binding proteins. There are several medications which have epigenetic impact, that are now used in a number of these diseases.
Epigenetics of anxiety and stress–related disorders is the field studying the relationship between epigenetic modifications of genes and anxiety and stress-related disorders, including mental health disorders such as generalized anxiety disorder (GAD), post-traumatic stress disorder, obsessive-compulsive disorder (OCD), and more. These changes can lead to transgenerational stress inheritance.
The Society for the Study of Reproduction (SSR) is an international not-for-profit professional society for scientists working in the fields of reproduction, fertility and development. The Society focuses on reproduction in both people and animals, including research from the areas of medicine, agriculture and basic biology. It is credited with being the first organization to focus on "the full panoply of reproductive phenomena" and is listed as a major professional association publishing reproductive research and a major organization in American animal agriculture. The Society includes members from at least 50 countries worldwide. The official peer-reviewed scientific journal for SSR is Biology of Reproduction.
Triptonide is a chemical compound found in Tripterygium wilfordii, a plant used in traditional Chinese medicine. A 2021 trial in mice and monkeys suggested that triptonide may offer a reversible male contraceptive.
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