University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Ann Zovein, MD

Ann Zovein, MD

Assistant Professor of Pediatrics; Investigator, Cardiovascular Research Institute, UCSF

Cancer Center Program Memberships

Hematopoietic Malignancies

Research Summary

The overall goal of my independent research program is to understand cell fate and identity changes during embryonic development, with the endothelial to hematopoietic fate transition in hemogenic endothelium as a model. Hemogenic endothelium is an example of specialized endothelial function with important clinical applications, where the first adult hematopoietic stem cells (HSC) emerge from hemogenic vascular sites during development. We aim to investigate the programs that govern the hemogenic process, and whether those programs can be activated in mature endothelium for HSC production. To accomplish this we have several lines of investigation within the laboratory that include understanding the basic cellular biology of the endothelial-to-hematopoietic transition, cellular engineering to convert mature endothelial cells that are readily available (such as umbilical cord vessels) for hematopoietic stem cell production, and mouse models to study vascular and hematopoietic development. In addition, we also investigate vascular regulation in the context of various clinical pathologies such as preeclampsia and HELLP syndrome, pediatric hemangioma, and alveolar capillary dysplasia.

Education

Boston University College of Engineering, Boston, MA, B.S., 05/1995, Biomedical Engineering
Boston University School of Medicine, Boston, MA, M.D., 05/1999, Medicine
UCLA Medical Center, Los Angeles, CA, 06/2002, Pediatric Residency
Department of Pediatrics, Division of Neonatology & Department of Molecular, Cell and Developmental Biology, UCLA, Los Angeles, CA, 06/2006, Neonatology Fellowship/ Pediatric Scientist Development Program
California Institute for Regenerative Medicine. Eli & Edythe Broad Stem Cell Research Center at UCLA, Los Angeles, CA, 06/2010, Clinical/Postdoctoral Fellowship

Honors & Awards

  • 1995
    Summa Cum Laude, B.S. Biomedical Engineering
  • 2000
    American Academy of Pediatrics Resident Scholarship and Research Grant
  • 2006
    Pediatric Academic Society Young Investigator’s Travel Award
  • 2006
    UCLA Department of Pediatrics, Pediatric Fellow Outstanding Research Award
  • 2008
    Developmental Vascular Biology Workshop Travel Award
  • 2010
    Burroughs Wellcome Fund Career Award for Medical Scientists
  • 2010
    UCSF Irene Perstein Award for Outstanding Junior Women Clinician Scientists
  • 2012
    NIH Director’s New Innovator Award
  • 2013
    CIRM New Faculty Physician Scientist Translational Research Award

Selected Publications

  1. Zape JP, Lizama CO, Cautivo KM, Zovein AC. Cell cycle dynamics and complement expression distinguishes mature haematopoietic subsets arising from hemogenic endothelium. Cell Cycle. 2017 Aug 18; 1-13.
    View on PubMed
  2. Jiang X, Hawkins JS, Lee J, Lizama CO, Bos FL, Zape JP, Ghatpande P, Peng Y, Louie J, Lagna G, Zovein AC, Hata A. Let-7 microRNA-dependent control of leukotriene signaling regulates the transition of hematopoietic niche in mice. Nat Commun. 2017 Jul 25; 8(1):128.
    View on PubMed
  3. Emmerson E, May AJ, Nathan S, Cruz-Pacheco N, Lizama CO, Maliskova L, Zovein AC, Shen Y, Muench MO, Knox SM. SOX2 regulates acinar cell development in the salivary gland. Elife. 2017 Jun 17; 6.
    View on PubMed
  4. Schmitt CE, Morales BM, Schmitz EMH, Hawkins JS, Lizama CO, Zape JP, Hsiao EC, Zovein AC. Fluorescent tagged episomals for stoichiometric induced pluripotent stem cell reprogramming. Stem Cell Res Ther. 2017 Jun 05; 8(1):132.
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  5. Ponder KL, Bárcena A, Bos FL, Gormley M, Zhou Y, Ona K, Kapidzic M, Zovein AC, Fisher SJ. Preeclampsia and Inflammatory Preterm Labor Alter the Human Placental Hematopoietic Niche. Reprod Sci. 2016 Sep; 23(9):1179-92.
    View on PubMed
  6. Bos FL, Hawkins JS, Zovein AC. Single-cell resolution of morphological changes in hemogenic endothelium. Development. 2015 Aug 01; 142(15):2719-24.
    View on PubMed
  7. Lizama CO, Hawkins JS, Schmitt CE, Bos FL, Zape JP, Cautivo KM, Borges Pinto H, Rhyner AM, Yu H, Donohoe ME, Wythe JD, Zovein AC. Repression of arterial genes in hemogenic endothelium is sufficient for haematopoietic fate acquisition. Nat Commun. 2015 Jul 23; 6:7739.
    View on PubMed
  8. Zovein AC, Forsberg EC. Hematopoietic development at high altitude: blood stem cells put to the test. Development. 2015 May 15; 142(10):1728-32.
    View on PubMed
  9. Koh FM, Lizama CO, Wong P, Hawkins JS, Zovein AC, Ramalho-Santos M. Emergence of hematopoietic stem and progenitor cells involves a Chd1-dependent increase in total nascent transcription. Proc Natl Acad Sci U S A. 2015 Apr 07; 112(14):E1734-43.
    View on PubMed
  10. Schmitt CE, Lizama CO, Zovein AC. From transplantation to transgenics: mouse models of developmental hematopoiesis. Exp Hematol. 2014 Aug; 42(8):707-16.
    View on PubMed
  11. Lizama CO, Zovein AC. Polarizing pathways: balancing endothelial polarity, permeability, and lumen formation. Exp Cell Res. 2013 May 15; 319(9):1247-54.
    View on PubMed
  12. Cristofaro B, Shi Y, Faria M, Suchting S, Leroyer AS, Trindade A, Duarte A, Zovein AC, Iruela-Arispe ML, Nih LR, Kubis N, Henrion D, Loufrani L, Todiras M, Schleifenbaum J, Gollasch M, Zhuang ZW, Simons M, Eichmann A, le Noble F. Dll4-Notch signaling determines the formation of native arterial collateral networks and arterial function in mouse ischemia models. Development. 2013 Apr; 140(8):1720-9.
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  13. Hofmann JJ, Briot A, Enciso J, Zovein AC, Ren S, Zhang ZW, Radtke F, Simons M, Wang Y, Iruela-Arispe ML. Endothelial deletion of murine Jag1 leads to valve calcification and congenital heart defects associated with Alagille syndrome. Development. 2012 Dec 01; 139(23):4449-60.
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  14. Zape JP, Zovein AC. Hemogenic endothelium: origins, regulation, and implications for vascular biology. Semin Cell Dev Biol. 2011 Dec; 22(9):1036-47.
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  15. Hofmann JJ, Zovein AC, Koh H, Radtke F, Weinmaster G, Iruela-Arispe ML. Jagged1 in the portal vein mesenchyme regulates intrahepatic bile duct development: insights into Alagille syndrome. Development. 2010 Dec; 137(23):4061-72.
    View on PubMed
  16. Zovein AC, Turlo KA, Ponec RM, Lynch MR, Chen KC, Hofmann JJ, Cox TC, Gasson JC, Iruela-Arispe ML. Vascular remodeling of the vitelline artery initiates extravascular emergence of hematopoietic clusters. Blood. 2010 Nov 04; 116(18):3435-44.
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  17. Zovein AC, Luque A, Turlo KA, Hofmann JJ, Yee KM, Becker MS, Fassler R, Mellman I, Lane TF, Iruela-Arispe ML. Beta1 integrin establishes endothelial cell polarity and arteriolar lumen formation via a Par3-dependent mechanism. Dev Cell. 2010 Jan 19; 18(1):39-51.
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  18. Zovein AC, Iruela-Arispe ML. Time to cut the cord: placental HSCs grow up. Cell Stem Cell. 2009 Oct 02; 5(4):351-2.
    View on PubMed
  19. Zovein AC, Hofmann JJ, Lynch M, French WJ, Turlo KA, Yang Y, Becker MS, Zanetta L, Dejana E, Gasson JC, Tallquist MD, Iruela-Arispe ML. Fate tracing reveals the endothelial origin of hematopoietic stem cells. Cell Stem Cell. 2008 Dec 04; 3(6):625-36.
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  20. Monvoisin A, Alva JA, Hofmann JJ, Zovein AC, Lane TF, Iruela-Arispe ML. VE-cadherin-CreERT2 transgenic mouse: a model for inducible recombination in the endothelium. Dev Dyn. 2006 Dec; 235(12):3413-22.
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