Todd Nystul, PhD

Title(s)Professor, Anatomy
SchoolSchool of Medicine
Address513 Parnassus Avenue, HSW, #1326
San Francisco CA 94143
Phone415-970-6967
PronounsHe/Him/His
ORCID ORCID Icon0000-0002-6250-2394 Additional info
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    Collapse Overview 
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    Background:

    The follicular epithelium in the Drosophila ovary is an ideal model for the study of epithelial biology. It possesses many classical epithelial features, such as a columnar cell shape, apical/basal polarity, and canonical cell adhesion complexes, and yet is a relatively simple tissue and is highly tractable for molecular and cell biological analysis. Combined with the powerful genetic tools available in Drosophila, this allows us to address questions in epithelial stem cell and tissue biology with single-cell resolution in the natural, in vivo context.

    Major Goals: Our laboratory uses the Drosophila ovary as a model for studying the fundamental properties of epithelial stem cells, their associated niche, and the connection between epithelial stem cells and cancer. We are interested in questions such as:

    1. How is stem cell fate maintained within a dynamic epithelial tissue?
    2. What is the nature of the epithelial stem cell niche?
    3. What is the role of epithelial stem cells in normal reproductive physiology?
    4. Do stem cell defects underlie epithelial cancers and what can studies of epithelial stem cells teach us about the earliest steps in cancer formation?
    5. How are stem cell function and tissue homology affected by aging?

    Ongoing research:

    Identifying Stem Cells and their Niche

    Although adult stem cells are believed to reside in distinct microenvironments, or niches, that function to regulate stem cell behavior, niches have been hard to study because of the difficulty of precisely identifying the stem cells in most tissues. However, we have developed a set of criteria that facilitates reliable identification of the epithelial follicle stem cells (FSCs) in the Drosophila ovary and we are now mapping their interactions with neighboring cells to better understand the nature of the FSC niche. Surprisingly, we have found that the FSC niche appears much more dynamic than the few previously characterized niches. We are using lineage analysis to follow FSC behavior, track the patterns of FSC daughter cell migration and differentiation, and investigate relevant gene function.

    Epithelial Stem Cell Genetics

    The wnt/wingless, hedgehog, BMP and Notch signaling pathways are all important for FSC function and early epithelial development but little is known about where in the process these signals exert their effects or how they are coordinated to produce a functional, healthy epithelium. We are investigating the function of key signaling components at specific steps in early follicle formation to map the contributions of these pathways to FSC function and follicle formation. In addition, we are interested in the role that misregulation of signaling in the ovarian epithelial cells plays in ovarian cancer. We are now investigating the interaction between the wnt pathway and other putative ovarian cancer genes in follicle cells as well as screening for markers that identify pre-tumorous cells to better understand the early steps leading to hyperplasia. Through collaboration with our colleagues in the Center for Reproductive Sciences, we will be able to test whether gene interactions and markers that we identify in the fly ovary will also be present in mammalian model systems and human tissues. To identify additional genes that are required for proper FSC function, we screened through a collection of over 600 lines bearing lethal mutations. We have identified several mutants with a follicle stem cell phenotype including ones that accelerate the rate of stem cell loss; confer a “hyper-competitive” stem cell replacement phenotype; and/or cause over-proliferation, perhaps modeling a precancerous state.

    Epithelial Stem Cells and Oogenesis Oogenesis is well conserved from flies to mammals and studies of the Drosophila ovary have provided valuable insight into the process of female reproduction. Our work on the characterization of the follicle stem cells and their associated niche provides an opportunity to use the fly ovary as a model of follicle formation. By studying the lineage just downstream of the FSCs, we found that FSCs produce “pre-follicle cells” that are developmental intermediates between the FSCs and the polarized epithelium. Follicle formation begins when a newly formed germline cyst moves past the FSC niche and contacts these pre-follicle cells. We found that a Delta signal from the germline activates Notch in some pre-follicle cells, inducing them to migrate along the anterior fact of the cyst toward the opposite niche. Other pre-follicle cells that do not receive the signal instead migrate away from the niche toward the posterior, directly into the polarized epithelium. We are now studying how these and other cellular events lead to the formation of a new follicle during normal oogenesis.

    Collapse Research 
    Collapse Research Activities and Funding
    Cell Fate Decisions in Epithelial Stem Cell Lineages
    NIH R35GM136348Jul 1, 2020 - May 31, 2025
    Role: Principal Investigator
    Regulation of Epithelial Plasticity
    NIH R01GM116384Jul 1, 2015 - Jun 30, 2019
    Role: Co-Principal Investigator
    Models for studying of the role of stem cell competition in field cancerization
    NIH R21CA164404Mar 1, 2012 - Feb 28, 2015
    Role: Principal Investigator
    Modeling epithelial stem cell competition in a dynamic drosophila ovarian niche
    NIH R01GM097158Jul 1, 2011 - Jun 30, 2020
    Role: Principal Investigator

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    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help. to make corrections and additions.
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    1. A High-Throughput Method for Quantifying Drosophila Fecundity. Toxics. 2024 Sep 9; 12(9):658. Gomez GA, Gonzalez GS, Oke OA, Luo LJ, Duong DJ, Esquerra ER, Zimmerman ZT, Capponi CS, Fung FJ, Nystul NT. .
      View in: Publisher Site   Mentions:
    2. A high-throughput method for quantifying Drosophila fecundity. bioRxiv. 2024 Mar 30. Gomez A, Gonzalez S, Oke A, Luo J, Duong JB, Esquerra RM, Zimmerman T, Capponi S, Fung JC, Nystul TG. PMID: 38585877; PMCID: PMC10996622.
      View in: PubMed   Mentions:
    3. Single-cell RNA sequencing identifies eggplant as a regulator of germ cell development in Drosophila. EMBO Rep. 2023 Oct 09; 24(10):e56475. Sun Z, Nystul TG, Zhong G. PMID: 37603128; PMCID: PMC10561367.
      View in: PubMed   Mentions: 2     Fields:    Translation:AnimalsCells
    4. Intracellular pH dynamics regulates intestinal stem cell lineage specification. Nat Commun. 2023 06 23; 14(1):3745. Liu Y, Reyes E, Castillo-Azofeifa D, Klein OD, Nystul T, Barber DL. PMID: 37353491; PMCID: PMC10290085.
      View in: PubMed   Mentions: 2     Fields:    Translation:AnimalsCells
    5. A DLG1-ARHGAP31-CDC42 axis is essential for the intestinal stem cell response to fluctuating niche Wnt signaling. Cell Stem Cell. 2023 02 02; 30(2):188-206.e6. Castillo-Azofeifa D, Wald T, Reyes EA, Gallagher A, Schanin J, Vlachos S, Lamarche-Vane N, Bomidi C, Blutt S, Estes MK, Nystul T, Klein OD. PMID: 36640764; PMCID: PMC9922544.
      View in: PubMed   Mentions: 3     Fields:    Translation:AnimalsCells
    6. Preparation of Drosophila Ovarioles for Single-Cell RNA Sequencing. Methods Mol Biol. 2023; 2626:323-333. Meyer N, Peralta J, Nystul T. PMID: 36715913; PMCID: PMC11105965.
      View in: PubMed   Mentions:    Fields:    Translation:AnimalsCells
    7. Fly Cell Atlas: A single-nucleus transcriptomic atlas of the adult fruit fly. Science. 2022 03 04; 375(6584):eabk2432. Li H, Janssens J, De Waegeneer M, Kolluru SS, Davie K, Gardeux V, Saelens W, David FPA, Brbic M, Spanier K, Leskovec J, McLaughlin CN, Xie Q, Jones RC, Brueckner K, Shim J, Tattikota SG, Schnorrer F, Rust K, Nystul TG, Carvalho-Santos Z, Ribeiro C, Pal S, Mahadevaraju S, Przytycka TM, Allen AM, Goodwin SF, Berry CW, Fuller MT, White-Cooper H, Matunis EL, DiNardo S, Galenza A, O'Brien LE, Dow JAT, FCA Consortium§, Jasper H, Oliver B, Perrimon N, Deplancke B, Quake SR, Luo L, Aerts S, Agarwal D, Ahmed-Braimah Y, Arbeitman M, Ariss MM, Augsburger J, Ayush K, Baker CC, Banisch T, Birker K, Bodmer R, Bolival B, Brantley SE, Brill JA, Brown NC, Buehner NA, Cai XT, Cardoso-Figueiredo R, Casares F, Chang A, Clandinin TR, Crasta S, Desplan C, Detweiler AM, Dhakan DB, Donà E, Engert S, Floc'hlay S, George N, González-Segarra AJ, Groves AK, Gumbin S, Guo Y, Harris DE, Heifetz Y, Holtz SL, Horns F, Hudry B, Hung RJ, Jan YN, Jaszczak JS, Jefferis GSXE, Karkanias J, Karr TL, Katheder NS, Kezos J, Kim AA, Kim SK, Kockel L, Konstantinides N, Kornberg TB, Krause HM, Labott AT, Laturney M, Lehmann R, Leinwand S, Li J, Li JSS, Li K, Li K, Li L, Li T, Litovchenko M, Liu HH, Liu Y, Lu TC, Manning J, Mase A, Matera-Vatnick M, Matias NR, McDonough-Goldstein CE, McGeever A, McLachlan AD, Moreno-Roman P, Neff N, Neville M, Ngo S, Nielsen T, O'Brien CE, Osumi-Sutherland D, Özel MN, Papatheodorou I, Petkovic M, Pilgrim C, Pisco AO, Reisenman C, Sanders EN, Dos Santos G, Scott K, Sherlekar A, Shiu P, Sims D, Sit RV, Slaidina M, Smith HE, Sterne G, Su YH, Sutton D, Tamayo M, Tan M, Tastekin I, Treiber C, Vacek D, Vogler G, Waddell S, Wang W, Wilson RI, Wolfner MF, Wong YE, Xie A, Xu J, Yamamoto S, Yan J, Yao Z, Yoda K, Zhu R, Zinzen RP. PMID: 35239393; PMCID: PMC8944923.
      View in: PubMed   Mentions: 203     Fields:    Translation:AnimalsCells
    8. Distinct roles of Bendless in regulating FSC niche competition and daughter cell differentiation. Development. 2021 11 15; 148(22). Tatapudy S, Peralta J, Nystul T. PMID: 35020878; PMCID: PMC8645206.
      View in: PubMed   Mentions: 1     Fields:    Translation:AnimalsCells
    9. Author Correction: A single-cell atlas and lineage analysis of the adult Drosophila ovary. Nat Commun. 2021 Oct 06; 12(1):5951. Rust K, Byrnes LE, Yu KS, Park JS, Sneddon JB, Tward AD, Nystul TG. PMID: 34615857; PMCID: PMC8494928.
      View in: PubMed   Mentions:    Fields:    
    10. A single-cell atlas and lineage analysis of the adult Drosophila ovary. Nat Commun. 2020 11 06; 11(1):5628. Rust K, Byrnes LE, Yu KS, Park JS, Sneddon JB, Tward AD, Nystul TG. PMID: 33159074; PMCID: PMC7648648.
      View in: PubMed   Mentions: 48     Fields:    Translation:Animals
    11. Signal transduction in the early Drosophila follicle stem cell lineage. Curr Opin Insect Sci. 2020 02; 37:39-48. Rust K, Nystul T. PMID: 32087562; PMCID: PMC7155752.
      View in: PubMed   Mentions: 9     Fields:    Translation:AnimalsCells
    12. The follicle epithelium in the Drosophila ovary is maintained by a small number of stem cells. Elife. 2019 12 18; 8. Fadiga J, Nystul TG. PMID: 31850843; PMCID: PMC6946398.
      View in: PubMed   Mentions: 18     Fields:    Translation:AnimalsCells
    13. Drosophila anion exchanger 2 is required for proper ovary development and oogenesis. Dev Biol. 2019 08 15; 452(2):127-133. Benitez M, Tatapudy S, Liu Y, Barber DL, Nystul TG. PMID: 31071312; PMCID: PMC6592727.
      View in: PubMed   Mentions: 8     Fields:    Translation:Animals
    14. Wingless promotes EGFR signaling in follicle stem cells to maintain self-renewal. Development. 2018 12 05; 145(23). Kim-Yip RP, Nystul TG. PMID: 30389852; PMCID: PMC6288384.
      View in: PubMed   Mentions: 11     Fields:    Translation:AnimalsCells
    15. Cell fate decisions: emerging roles for metabolic signals and cell morphology. EMBO Rep. 2017 12; 18(12):2105-2118. Tatapudy S, Aloisio F, Barber D, Nystul T. PMID: 29158350; PMCID: PMC5709733.
      View in: PubMed   Mentions: 47     Fields:    Translation:Cells
    16. Methods for Imaging Intracellular pH of the Follicle Stem Cell Lineage in Live Drosophila Ovarian Tissue. J Vis Exp. 2017 09 26; (127). Tatapudy S, Benitez M, Nystul T. PMID: 28994781; PMCID: PMC5752337.
      View in: PubMed   Mentions: 1     Fields:    Translation:AnimalsCells
    17. Methods for Imaging Intracellular pH of the Follicle Stem Cell Lineage in Live Drosophila Ovarian Tissue. Journal of Visualized Experiments. 2017 Sep 26; (127). Tatapudy TS, Benitez BM, Nystul NT. .
      View in: Publisher Site   Mentions:
    18. Neutral Competition for Drosophila Follicle and Cyst Stem Cell Niches Requires Vesicle Trafficking Genes. Genetics. 2017 07; 206(3):1417-1428. Cook MS, Cazin C, Amoyel M, Yamamoto S, Bach E, Nystul T. PMID: 28512187; PMCID: PMC5500140.
      View in: PubMed   Mentions: 8     Fields:    Translation:AnimalsCells
    19. Phosphorylated Groucho delays differentiation in the follicle stem cell lineage by providing a molecular memory of EGFR signaling in the niche. Development. 2016 12 15; 143(24):4631-4642. Johnston MJ, Bar-Cohen S, Paroush Z, Nystul TG. PMID: 27836963; PMCID: PMC5201033.
      View in: PubMed   Mentions: 17     Fields:    Translation:AnimalsCells
    20. Increased intracellular pH is necessary for adult epithelial and embryonic stem cell differentiation. J Cell Biol. 2016 Nov 07; 215(3):345-355. Ulmschneider B, Grillo-Hill BK, Benitez M, Azimova DR, Barber DL, Nystul TG. PMID: 27821494; PMCID: PMC5100294.
      View in: PubMed   Mentions: 41     Fields:    Translation:AnimalsCells
    21. A Pak-regulated cell intercalation event leading to a novel radial cell polarity is involved in positioning of the follicle stem cell niche in the Drosophila ovary. Development. 2015 Jan 01; 142(1):82-91. Vlachos S, Jangam S, Conder R, Chou M, Nystul T, Harden N. PMID: 25516970; PMCID: PMC6514404.
      View in: PubMed   Mentions: 10     Fields:    Translation:AnimalsCells
    22. EGFR signaling promotes self-renewal through the establishment of cell polarity in Drosophila follicle stem cells. Elife. 2014 Dec 01; 3. Castanieto A, Johnston MJ, Nystul TG. PMID: 25437306; PMCID: PMC4298699.
      View in: PubMed   Mentions: 32     Fields:    Translation:AnimalsCells
    23. Enhancer-trap flippase lines for clonal analysis in the Drosophila ovary. G3 (Bethesda). 2014 Jul 14; 4(9):1693-9. Huang P, Sahai-Hernandez P, Bohm RA, Welch WP, Zhang B, Nystul T. PMID: 25024257; PMCID: PMC4169162.
      View in: PubMed   Mentions: 8     Fields:    Translation:AnimalsCells
    24. Basolateral junction proteins regulate competition for the follicle stem cell niche in the Drosophila ovary. PLoS One. 2014; 9(7):e101085. Kronen MR, Schoenfelder KP, Klein AM, Nystul TG. PMID: 24991805; PMCID: PMC4084627.
      View in: PubMed   Mentions: 18     Fields:    Translation:AnimalsCells
    25. A dynamic population of stromal cells contributes to the follicle stem cell niche in the Drosophila ovary. Development. 2013 Nov; 140(22):4490-8. Sahai-Hernandez P, Nystul TG. PMID: 24131631; PMCID: PMC3817939.
      View in: PubMed   Mentions: 56     Fields:    Translation:AnimalsCells
    26. Advanced Techniques for Cell Lineage Labelling in Drosophila. eLS. 2012 Mar 15. Hafezi HY, Nystul NT. .
      View in: Publisher Site   Mentions:
    27. Drosophila models of epithelial stem cells and their niches. Wiley Interdiscip Rev Dev Biol. 2012 May-Jun; 1(3):447-57. Sahai-Hernandez P, Castanieto A, Nystul TG. PMID: 23801493; PMCID: PMC4924536.
      View in: PubMed   Mentions: 29     Fields:    Translation:AnimalsCells
    28. Regulation of epithelial stem cell replacement and follicle formation in the Drosophila ovary. Genetics. 2010 Feb; 184(2):503-15. Nystul T, Spradling A. PMID: 19948890; PMCID: PMC2828728.
      View in: PubMed   Mentions: 61     Fields:    Translation:AnimalsCells
    29. Stem cells and their niches: integrated units that maintain Drosophila tissues. Cold Spring Harb Symp Quant Biol. 2008; 73:49-57. Spradling AC, Nystul T, Lighthouse D, Morris L, Fox D, Cox R, Tootle T, Frederick R, Skora A. PMID: 19022764.
      View in: PubMed   Mentions: 35     Fields:    Translation:AnimalsCells
    30. An epithelial niche in the Drosophila ovary undergoes long-range stem cell replacement. Cell Stem Cell. 2007 Sep 13; 1(3):277-85. Nystul T, Spradling A. PMID: 18371362.
      View in: PubMed   Mentions: 105     Fields:    Translation:AnimalsCells
    31. The carnegie protein trap library: a versatile tool for Drosophila developmental studies. Genetics. 2007 Mar; 175(3):1505-31. Buszczak M, Paterno S, Lighthouse D, Bachman J, Planck J, Owen S, Skora AD, Nystul TG, Ohlstein B, Allen A, Wilhelm JE, Murphy TD, Levis RW, Matunis E, Srivali N, Hoskins RA, Spradling AC. PMID: 17194782; PMCID: PMC1840051.
      View in: PubMed   Mentions: 324     Fields:    Translation:AnimalsCells
    32. Breaking out of the mold: diversity within adult stem cells and their niches. Curr Opin Genet Dev. 2006 Oct; 16(5):463-8. Nystul TG, Spradling AC. PMID: 16919446.
      View in: PubMed   Mentions: 21     Fields:    Translation:HumansAnimalsCells
    33. Multiple types of niche control stem cells in drosophila adults. Developmental Biology. 2006 Jul 1; 295(1):329. Spradling SA, Ohlstein OB, Buszczak BM, Nystul NT, Morris ML, Decotto DE. .
      View in: Publisher Site   Mentions:
    34. Buying time in suspended animation. Sci Am. 2005 Jun; 292(6):48-55. Roth MB, Nystul T. PMID: 15934652.
      View in: PubMed   Mentions: 19     Fields:    Translation:HumansAnimals
    35. Carbon monoxide-induced suspended animation protects against hypoxic damage in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2004 Jun 15; 101(24):9133-6. Nystul TG, Roth MB. PMID: 15184665; PMCID: PMC428485.
      View in: PubMed   Mentions: 30     Fields:    Translation:Animals
    36. Suspended animation in C. elegans requires the spindle checkpoint. Science. 2003 Nov 07; 302(5647):1038-41. Nystul TG, Goldmark JP, Padilla PA, Roth MB. PMID: 14605367.
      View in: PubMed   Mentions: 52     Fields:    Translation:AnimalsCells
    37. Dephosphorylation of cell cycle-regulated proteins correlates with anoxia-induced suspended animation in Caenorhabditis elegans. Mol Biol Cell. 2002 May; 13(5):1473-83. Padilla PA, Nystul TG, Zager RA, Johnson AC, Roth MB. PMID: 12006646; PMCID: PMC111120.
      View in: PubMed   Mentions: 70     Fields:    Translation:AnimalsCells
    38. Giardia lamblia expresses a proteobacterial-like DnaK homolog. Mol Biol Evol. 2001 Apr; 18(4):530-41. Morrison HG, Roger AJ, Nystul TG, Gillin FD, Sogin ML. PMID: 11264404.
      View in: PubMed   Mentions: 7     Fields:    Translation:HumansAnimalsCells
    39. Novel protein-disulfide isomerases from the early-diverging protist Giardia lamblia. J Biol Chem. 1999 Oct 15; 274(42):29805-11. Knodler LA, Noiva R, Mehta K, McCaffery JM, Aley SB, Svärd SG, Nystul TG, Reiner DS, Silberman JD, Gillin FD. PMID: 10514458.
      View in: PubMed   Mentions: 21     Fields:    Translation:AnimalsCells
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