Dr. Yanan Feng is a Senior Research Scientist working at Dr. Stanley N. Cohen’s lab in the Department of Genetics, Stanford University. She earned her PhD degree in the Cancer Biology Program from the Stanford University. For the past few years, her research has been focusing on the functions of a transcription elongation factor SUPT4H1 which is required for the transcription of the expanded nucleotide repeats. Such repeats are present and the cause of many genetic neurodegenerative diseases such as Huntington’s Disease and ALS. Through a high throughput screening which was done at Stanford by her and her colleagues, they discovered a few small molecule compounds which are able to interrupt the interaction between SUPT4H1 and its crucial partner SUPT5H. The interruption results in the defect of the transcription elongation function during RNA polymerase II mediated mRNA transcription. These compounds have the potential to be the therapeutic agents to the above-mentioned neurodegenerative diseases. From 2016 to 2019, she joined a start-up biotech company, Nuredis Inc, aiming to push the candidate compounds toward to clinical trials. In Nuredis, she set up the entire research facility and served as Director in Huntington’s Disease. She led the research team to optimize the lead compounds through Structure Activity Relationship (SAR) efforts and develop various assays for clinical applications. After returning to Stanford, she continues her interest in studying SUPT4H1 and its role in FMR1 gene transcription. The expanded CGG repeats at the 3’UTR of FMR1 is the cause of Fragile X syndrome, Fragile X-associated tremor/ataxia syndrome, and other ovarian problems.

Current Role at Stanford

Senior Research Scientist, Department of Genetics, Dr. Stanley N. Cohen's lab

Education & Certifications

  • Ph D, School of Medicine, Stanford University (2000)


  • Stanley N. CohenNing DENGYanan FengTzu-Hao ChengYun-Yun WuWen-Chieh Hsieh. "United States Patent US20180064744A1 Nucleoside agents for the reduction of the deleterious activity of extended nucleotide repeat containing genes", National Yang Ming Univ Leland Stanford Junior University, Mar 18, 2018
  • Stanley N. CohenDaniel RockAnnie ChangYanan FengLaszlo ZsakMaria Elisa Piccone. "United States Patent US20080176962A1 Methods and compositions for identifying cellular genes exploited by viral pathogens", Leland Stanford Junior University US, Jul 24, 2008
  • Stanley N. Cohen,Ning Deng,Yanan Feng,Tzu-Hao Cheng,Thomas W. Sun. "United States Patent US20200147069A1 Compounds for The Reduction of The Deleterious Activity of Extended Nucleotide Repeat Containing Genes", Leland Stanford Junior University, Jun 19, 0018

Work Experience

  • Director, Huntington’s Disease Research, Nuredis Inc (May 2017 - January 2019)

    Lead a research team for SAR drug discovery of Huntington’s Disease.
    -Develop and supervise high throughput assays for pipeline compounds validation.
    -Work with CROs for in vitro assay platforms of biomarker quantitation aiming for future clinical applications.


    Menlo Park, ca

All Publications

  • Spt4 selectively regulates the expression of C9orf72 sense and antisense mutant transcripts. Science Kramer, N. J., Carlomagno, Y., Zhang, Y., Almeida, S., Cook, C. N., Gendron, T. F., Prudencio, M., van Blitterswijk, M., Belzil, V., Couthouis, J., Paul, J. W., Goodman, L. D., Daughrity, L., Chew, J., Garrett, A., Pregent, L., Jansen-West, K., Tabassian, L. J., Rademakers, R., Boylan, K., Graff-Radford, N. R., Josephs, K. A., Parisi, J. E., Knopman, D. S., Petersen, R. C., Boeve, B. F., Deng, N., Feng, Y., Cheng, T., Dickson, D. W., Cohen, S. N., Bonini, N. M., Link, C. D., Gao, F., Petrucelli, L., Gitler, A. D. 2016; 353 (6300): 708-712


    An expanded hexanucleotide repeat in C9orf72 causes amyotrophic lateral sclerosis and frontotemporal dementia (c9FTD/ALS). Therapeutics are being developed to target RNAs containing the expanded repeat sequence (GGGGCC); however, this approach is complicated by the presence of antisense strand transcription of expanded GGCCCC repeats. We found that targeting the transcription elongation factor Spt4 selectively decreased production of both sense and antisense expanded transcripts, as well as their translated dipeptide repeat (DPR) products, and also mitigated degeneration in animal models. Knockdown of SUPT4H1, the human Spt4 ortholog, similarly decreased production of sense and antisense RNA foci, as well as DPR proteins, in patient cells. Therapeutic targeting of a single factor to eliminate c9FTD/ALS pathological features offers advantages over approaches that require targeting sense and antisense repeats separately.

    View details for DOI 10.1126/science.aaf7791

    View details for PubMedID 27516603

  • Effects on murine behavior and lifespan of selectively decreasing expression of mutant huntingtin allele by supt4h knockdown. PLoS genetics Cheng, H., Chern, Y., Chen, I., Liu, C., Li, S., Chun, S. J., Rigo, F., Bennett, C. F., Deng, N., Feng, Y., Lin, C., Yan, Y., Cohen, S. N., Cheng, T. 2015; 11 (3)


    Production of protein containing lengthy stretches of polyglutamine encoded by multiple repeats of the trinucleotide CAG is a hallmark of Huntington's disease (HD) and of a variety of other inherited degenerative neurological and neuromuscular disorders. Earlier work has shown that interference with production of the transcription elongation protein SUPT4H results in decreased cellular capacity to transcribe mutant huntingtin gene (Htt) alleles containing long CAG expansions, but has little effect on expression of genes containing short CAG stretches. zQ175 and R6/2 are genetically engineered mouse strains whose genomes contain human HTT alleles that include greatly expanded CAG repeats and which are used as animal models for HD. Here we show that reduction of SUPT4H expression in brains of zQ175 mice by intracerebroventricular bolus injection of antisense 2'-O-methoxyethyl oligonucleotides (ASOs) directed against Supt4h, or in R6/2 mice by deletion of one copy of the Supt4h gene, results in a decrease in mRNA and protein encoded specifically by mutant Htt alleles. We further show that reduction of SUPT4H in mouse brains is associated with decreased HTT protein aggregation, and in R6/2 mice, also with prolonged lifespan and delay of the motor impairment that normally develops in these animals. Our findings support the view that targeting of SUPT4H function may be useful as a therapeutic countermeasure against HD.

    View details for DOI 10.1371/journal.pgen.1005043

    View details for PubMedID 25760041

  • Upregulation of the Host SLC11A1 Gene by Clostridium difficile Toxin B Facilitates Glucosylation of Rho GTPases and Enhances Toxin Lethality INFECTION AND IMMUNITY Feng, Y., Cohen, S. N. 2013; 81 (8): 2724-2732


    Pseudomembranous enterocolitis associated with Clostridium difficile infection is an important cause of morbidity and mortality in patients being treated with antibiotics. Two closely related large protein toxins produced by C. difficile, TcdA and TcdB, which act identically but at different efficiencies to glucosylate low-molecular-weight Rho GTPases, underlie the microbe's pathogenicity. Using antisense RNA encoded by a library of human expressed sequence tags (ESTs), we randomly inactivated host chromosomal genes in HeLa cells and isolated clones that survived exposure to ordinarily lethal doses of TcdB. This phenotypic screening and subsequent analysis identified solute carrier family 11 member 1 (SLC11A1; formerly NRAMP1), a divalent cation transporter crucial to host defense against certain microbes, as an enhancer of TcdB lethality. Whereas SLC11A1 normally is poorly expressed in human cells of nonmyeloid lineage, TcdB increased SLC11A1 mRNA abundance in such cells through the actions of the RNA-binding protein HuR. We show that short hairpin RNA (shRNA) directed against SLC11A1 reduced TcdB glucosylation of small Rho GTPases and, consequently, toxin lethality. Consistent with the previously known role of SLC11A1 in cation transport, these effects were enhanced by elevation of Mn(2+) in media; conversely, they were decreased by treatment with a chelator of divalent cations. Our findings reveal an unsuspected role for SLC11A1 in determining C. difficile pathogenicity, demonstrate the novel ability of a bacterial toxin to increase its cytotoxicity, establish a mechanistic basis for these effects, and suggest a therapeutic approach to mitigate cell killing by C. difficile toxins A and B.

    View details for DOI 10.1128/IAI.01177-12

    View details for Web of Science ID 000321622700008

    View details for PubMedID 23690404

    View details for PubMedCentralID PMC3719560

  • Identification of Cellular Genes Affecting the Infectivity of Foot-and-Mouth Disease Virus JOURNAL OF VIROLOGY Piccone, M. E., Feng, Y., Chang, A. C., Mosseri, R., Lu, Q., Kutish, G. F., Lu, Z., Burrage, T. G., Gooch, C., Rock, D. L., Cohen, S. N. 2009; 83 (13): 6681-6688


    Foot-and-mouth disease virus (FMDV) produces one of the most infectious of all livestock diseases, causing extensive economic loss in areas of breakout. Like other viral pathogens, FMDV recruits proteins encoded by host cell genes to accomplish the entry, replication, and release of infectious viral particles. To identify such host-encoded proteins, we employed an antisense RNA strategy and a lentivirus-based library containing approximately 40,000 human expressed sequence tags (ESTs) to randomly inactivate chromosomal genes in a bovine kidney cell line (LF-BK) that is highly susceptible to FMDV infection and then isolated clones that survived multiple rounds of exposure to the virus. Here, we report the identification of ESTs whose expression in antisense orientation limited host cell killing by FMDV and restricted viral propagation. The role of one such EST, that of ectonucleoside triphosphate diphosphohydrolase 6 (NTPDase6; also known as CD39L2), a membrane-associated ectonucleoside triphosphate diphosphohydrolase that previously was not suspected of involvement in the propagation of viral pathogens and which we now show is required for normal synthesis of FMDV RNA and proteins, is described in this report.

    View details for DOI 10.1128/JVI.01729-08

    View details for Web of Science ID 000267354100035

    View details for PubMedID 19369337

    View details for PubMedCentralID PMC2698527

  • Retention of core catalytic functions by a conserved minimal ribonuclease E peptide that lacks the domain required for tetramer formation JOURNAL OF BIOLOGICAL CHEMISTRY Caruthers, J. M., Feng, Y., McKay, D. B., Cohen, S. N. 2006; 281 (37): 27046-27051


    Ribonuclease E (RNase E) is a multifunctional endoribonuclease that has been evolutionarily conserved in both Gram-positive and Gram-negative bacteria. X-ray crystallography and biochemical studies have concluded that the Escherichia coli RNase E protein functions as a homotetramer formed by Zn linkage of dimers within a region extending from amino acid residues 416 through 529 of the 116-kDa protein. Using fragments of RNase E proteins from E. coli and Haemophilus influenzae, we show here that RNase E derivatives that are as short as 395 amino acid residues and that lack the Zn-link region shown previously to be essential for tetramer formation (i.e. amino acid residues 400-415) are catalytically active enzymes that retain the 5' to 3' scanning ability and cleavage site specificity characteristic of full-length RNase E and that also confer colony forming ability on rne null mutant bacteria. Further truncation leads to loss of these properties. Our results, which identify a minimal catalytically active RNase E sequence, indicate that contrary to current models, a tetrameric quaternary structure is not required for RNase E to carry out its core enzymatic functions.

    View details for DOI 10.1074/jbc.M602467200

    View details for Web of Science ID 000240397700031

    View details for PubMedID 16854990

  • Phenotype-based identification of host genes required for replication of African swine fever virus JOURNAL OF VIROLOGY Chang, A. C., Zsak, L., Feng, Y., Mosseri, R., Lu, Q., Kowalski, P., Zsak, A., Burrage, T. G., Neilan, J. G., Kutish, G. F., Lu, Z., Laegreid, W., Rock, D. L., Cohen, S. N. 2006; 80 (17): 8705-8717


    African swine fever virus (ASFV) produces a fatal acute hemorrhagic fever in domesticated pigs that potentially is a worldwide economic threat. Using an expressed sequence tag (EST) library-based antisense method of random gene inactivation and a phenotypic screen for limitation of ASFV replication in cultured human cells, we identified six host genes whose cellular functions are required by ASFV. These included three loci, BAT3 (HLA-B-associated transcript 3), C1qTNF (C1q and tumor necrosis factor-related protein 6), and TOM40 (translocase of outer mitochondrial membrane 40), for which antisense expression from a tetracycline-regulated promoter resulted in reversible inhibition of ASFV production by >99%. The effects of antisense transcription of the BAT3 EST and also of expression in the sense orientation of this EST, which encodes amino acid residues 450 to 518 of the mature BAT3 protein, were investigated more extensively. Sense expression of the BAT3 peptide, which appears to reversibly interfere with BAT3 function by a dominant negative mechanism, resulted in decreased synthesis of viral DNA and proteins early after ASFV infection, altered transcription of apoptosis-related genes as determined by cDNA microarray analysis, and increased cellular sensitivity to staurosporine-induced apoptosis. Antisense transcription of BAT3 reduced ASFV production without affecting abundance of the virus macromolecules we assayed. Our results, which demonstrate the utility of EST-based functional screens for the detection of host genes exploited by pathogenic viruses, reveal a novel collection of cellular genes previously not known to be required for ASFV infection.

    View details for DOI 10.1128/JVI.00475-06

    View details for Web of Science ID 000239934500038

    View details for PubMedID 16912318

    View details for PubMedCentralID PMC1563864

  • RraA: a protein inhibitor of RNase E activity that globally modulates RNA abundance in E. coli CELL Lee, K. S., Zhan, X. M., Gao, J. J., Ji, Q., Feng, Y. A., Meganathan, R., Cohen, S. N., Georgiou, G. 2003; 114 (5): 623-634


    Ribonuclease E (RNase E) has a key role in mRNA degradation and the processing of catalytic and structural RNAs in E. coli. We report the discovery of an evolutionarily conserved 17.4 kDa protein, here named RraA (regulator of ribonuclease activity A) that binds to RNase E and inhibits RNase E endonucleolytic cleavages without altering cleavage site specificity or interacting detectably with substrate RNAs. Overexpression of RraA circumvents the effects of an autoregulatory mechanism that normally maintains the RNase E cellular level within a narrow range, resulting in the genome-wide accumulation of RNase E-targeted transcripts. While not required for RraA action, the C-terminal RNase E region that serves as a scaffold for formation of a multiprotein degradosome complex modulates the inhibition of RNase E catalytic activity by RraA. Our results reveal a possible mechanism for the dynamic regulation of RNA decay and processing by inhibitory RNase binding proteins.

    View details for Web of Science ID 000185193100011

    View details for PubMedID 13678585

  • The catalytic domain of RNase E shows inherent 3 ' to 5 ' directionality in cleavage site selection PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Feng, Y. A., Vickers, T. A., Cohen, S. N. 2002; 99 (23): 14746-14751


    RNase E, a multifunctional endoribonuclease of Escherichia coli, attacks substrates at highly specific sites. By using synthetic oligoribonucleotides containing repeats of identical target sequences protected from cleavage by 2'-O-methylated nucleotide substitutions at specific positions, we investigated how RNase E identifies its cleavage sites. We found that the RNase E catalytic domain (i.e., N-Rne) binds selectively to 5'-monophosphate RNA termini but has an inherent mode of cleavage in the 3' to 5' direction. Target sequences made uncleavable by the introduction of 2'-O-methyl-modified nucleotides bind to RNase E and impede cleavages at normally susceptible sites located 5' to, but not 3' to, the protected target. Our results indicate that RNase E can identify cleavage sites by a 3' to 5' "scanning" mechanism and imply that anchoring of the enzyme to the 5'-monophosphorylated end of these substrates orients the enzyme for directional cleavages that occur in a processive or quasiprocessive mode. In contrast, we find that RNase G, which has extensive structural homology with and size similarity to N-Rne, and can functionally complement RNase E gene deletions when overexpressed, has a nondirectional and distributive mode of action.

    View details for DOI 10.1073/pnas.202590899

    View details for Web of Science ID 000179224800027

    View details for PubMedID 12417756

    View details for PubMedCentralID PMC137490

  • Escherichia coli poly(A)-binding proteins that interact with components of degradosomes or impede RNA decay mediated by polynucleotide phosphorylase and RNase E JOURNAL OF BIOLOGICAL CHEMISTRY Feng, Y., Huang, H. J., Liao, J., Cohen, S. N. 2001; 276 (34): 31651-31656


    The multifunctional ribonuclease RNase E and the 3'-exonuclease polynucleotide phosphorylase (PNPase) are major components of an Escherichia coli ribonucleolytic "machine" that has been termed the RNA degradosome. Previous work has shown that poly(A) additions to the 3' ends of RNA substrates affect RNA degradation by both of these enzymes. To better understand the mechanism(s) by which poly(A) tails can modulate ribonuclease action, we used selective binding in 1 m salt to identify E. coli proteins that interact at high affinity with poly(A) tracts. We report here that CspE, a member of a family of RNA-binding "cold shock" proteins, and S1, an essential component of the 30 S ribosomal subunit, are poly(A)-binding proteins that interact functionally and physically, respectively, with degradosome ribonucleases. We show that purified CspE impedes poly(A)-mediated 3' to 5' exonucleolytic decay by PNPase by interfering with its digestion through the poly(A) tail and also inhibits both internal cleavage and poly(A) tail removal by RNase E. The ribosomal protein S1, which is known to interact with sequences at the 5' ends of mRNA molecules during the initiation of translation, can bind to both RNase E and PNPase, but in contrast to CspE, did not affect the ribonucleolytic actions of these enzymes. Our findings raise the prospect that E. coli proteins that bind to poly(A) tails may link the functions of degradosomes and ribosomes.

    View details for Web of Science ID 000170613500026

    View details for PubMedID 11390393

  • Unpaired terminal nucleotides and 5 ' monophosphorylation govern 3 ' polyadenylation by Escherichia coli poly(A) polymerase I PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Feng, Y. N., Cohen, S. N. 2000; 97 (12): 6415-6420


    In bacteria, most mRNAs and certain regulatory RNAs are rapidly turned over, whereas mature tRNA and ribosomal RNA are highly stable. The selective susceptibility of unstable Escherichia coli RNAs to 3' polyadenylation by the pcnB gene product, poly(A) polymerase I (PAP I), in vivo is a key factor in their rapid degradation by 3' to 5' exonucleases. Using highly purified His-tagged recombinant PAP I, we show that differential adenylation of RNA substrates by PAP I occurs in vitro and that this capability resides in PAP I itself rather than in any ancillary protein(s). Surprisingly, the efficiency of 3' polyadenylation is affected by substrate structure at both termini; single-strand segments at either the 5' or 3' end of RNA molecules and monophosphorylation at an unpaired 5' terminus dramatically increase the rate and length of 3' poly(A) tail additions by PAP I. Our results provide a mechanistic basis for the susceptibility of certain RNAs to 3' polyadenylation. They also suggest a model of "programmed" RNA decay in which endonucleolytically generated RNA fragments containing single-stranded monophosphorylated 5' termini are targeted for poly(A) addition and further degradation.

    View details for Web of Science ID 000087526300035

    View details for PubMedID 10823925