April Pyle, Ph.D.

Laboratory Address:
615 Charles E. Young Dr. South
Los Angeles , CA 90095

Work Address:
615 Charles E. Young Dr. South
Los Angeles , CA 90095

Affiliations
Affiliations
Associate Professor, Microbiology, Immunology & Molecular Genetics
Member, CTSI, Cell & Developmental Biology GPB Home Area, Center for Duchenne Muscular Dystrophy, Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, JCCC Cancer and Stem Cell Biology Program Area
Research Interests
Human pluripotent stem cells (hPSCs) have enormous potential for use in regenerative medicine, in patient-specific screening and as a model for understanding human development. HPSCs encompass both human embryonic stem cells (hESCs) derived from the inner cell mass of the blastocyst, and human induced pluripotent stem cells (hiPSCs), which are derived from reprogramming somatic cells back to the pluripotent state. HiPSCs derived from patients with genetic diseases can be used as a human cellular model of the disease, thus enabling mechanistic studies and pre-clinical drug screening. However there are many critical hurdles that preclude the translation of hPSCs clinical potential into practice including poor survival and self-renewal upon dissociation, potential for genetic instability and tumorigenesis, and inefficient differentiation. Our laboratory interests have centered on identifying regulators of these three key processes in hPSCs. Elucidating the regulatory mechanisms controlling survival/self-renewal, stability and differentiation will improve our understanding of regulation of the pluripotent state and provide inroads into use of these cells in regenerative medicine. A main focus of the lab is interested in understanding the role of intrinsic and extrinsic signals involved in directing muscle differentiation from hPSCs as well as development of a novel reprogramming platform for muscle differentiation. This will improve our basic understanding of human muscle specification and could provide regenerative approaches for treatments of muscle disorders including muscular dystrophy.
Biography

Dr. Pyle received her Ph.D. from the University of Tennessee in 2002 and completed her postdoctoral fellowship work with Peter Donovan in 2006 at Johns Hopkins University. She is currently an Associate Professor in the Department of Microbiology, Immunology and Molecular Genetics at UCLA and a member of the Eli and Edythe Broad Stem Cell Center, the Center for Duchenne Muscular Dystrophy and the Jonsson Comprehensive Cancer Center at UCLA. Dr. Pyle's lab uses multi-disciplinary approaches to study human pluripotent stem cell biology and differentiation of these cells for use in regenerative medicine. Dr. Pyle's lab studies both basic aspects of stem cell biology as well as more translational aspects of human pluripotent stem cell differentiation towards skeletal muscle for use in therapeutic approaches for patients with muscular dystrophy.

Publications
Young CS, Hicks MR, Ermolova NV, Nakano H, Jan M, Younesi S, Karumbayaram S, Kumagai-Cresse C, Wang D, Zack JA, Kohn DB, Nakano A, Nelson SF, Miceli MC, Spencer MJ*, Pyle AD*. *co-corresponding A Single CRISPR-Cas9 Deletion Strategy that Targets the Majority of DMD Patients Restores Dystrophin Function in hiPSC-Derived Muscle Cells. Cell Stem Cell 2016; 18: 1-8.
Lee Patrick C, Truong Brian, Vega-Crespo Agustin, Gilmore W Blake, Hermann Kip, Angarita Stephanie Ak, Tang Jonathan K, Chang Katherine M, Wininger Austin E, Lam Alex K, Schoenberg Benjamen E, Cederbaum Stephen D, Pyle April D, Byrne James A, Lipshutz Gerald S Restoring Ureagenesis in Hepatocytes by CRISPR/Cas9-mediated Genomic Addition to Arginase-deficient Induced Pluripotent Stem Cells. Molecular therapy. Nucleic acids. 2016; 5(11): e394.
Young Courtney S, Pyle April D Exon Skipping Therapy. Cell. 2016; 167(5): 1144.
Thakore-Shah K, Koleilat T, Jan M, John A, Pyle AD. REST/NRSF Knockdown Alters Survival, Lineage Differentiation and Signaling in Human Embryonic Stem Cells. Plos One 2015; 10(12): .
Hicks M, Pyle A. The Path from Pluripotency to Skeletal Muscle: Developmental Myogenesis Guides the Way. Cell Stem Cell 2015; 17(3): 255-7.
Hou Shuang, Choi Jin-sil, Chen Kuan-Ju, Zhang Yang, Peng Jinliang, Garcia Mitch A, Yu Jue-Hua, Thakore-Shah Kaushali, Ro Tracy, Chen Jie-Fu, Peyda Parham, Fan Guoping, Pyle April D, Wang Hao, Tseng Hsian-Rong Supramolecular nanosubstrate-mediated delivery for reprogramming and transdifferentiation of mammalian cells. Small (Weinheim an der Bergstrasse, Germany). 2015; 11(21): 2499-504.
Peng Jinliang, Garcia Mitch André, Choi Jin-sil, Zhao Libo, Chen Kuan-Ju, Bernstein James R, Peyda Parham, Hsiao Yu-Sheng, Liu Katherine W, Lin Wei-Yu, Pyle April D, Wang Hao, Hou Shuang, Tseng Hsian-Rong Molecular recognition enables nanosubstrate-mediated delivery of gene-encapsulated nanoparticles with high efficiency. ACS nano. 2014; 8(5): 4621-9.
Awe Jason P, Lee Patrick C, Ramathal Cyril, Vega-Crespo Agustin, Durruthy-Durruthy Jens, Cooper Aaron, Karumbayaram Saravanan, Lowry William E, Clark Amander T, Zack Jerome A, Sebastiano Vittorio, Kohn Donald B, Pyle April D, Martin Martin G, Lipshutz Gerald S, Phelps Patricia E, Pera Renee A Reijo, Byrne James A Generation and characterization of transgene-free human induced pluripotent stem cells and conversion to putative clinical-grade status. Stem cell research & therapy. 2013; 4(4): 87.
Yanes Rolando E, Tarn Derrick, Hwang Angela A, Ferris Daniel P, Sherman Sean P, Thomas Courtney R, Lu Jie, Pyle April D, Zink Jeffrey I, Tamanoi Fuyuhiko Involvement of lysosomal exocytosis in the excretion of mesoporous silica nanoparticles and enhancement of the drug delivery effect by exocytosis inhibition. Small (Weinheim an der Bergstrasse, Germany). 2013; 9(5): 697-704.
Palomares Karina, Vigant Frederic, Van Handel Ben, Pernet Olivier, Chikere Kelechi, Hong Patrick, Sherman Sean P, Patterson Michaela, An Dong Sung, Lowry William E, Mikkola Hanna K A, Morizono Kouki, Pyle April D, Lee Benhur Nipah virus envelope-pseudotyped lentiviruses efficiently target ephrinB2-positive stem cell populations in vitro and bypass the liver sink when administered in vivo. Journal of virology. 2013; 87(4): 2094-108.
Sherman Sean P, Pyle April D Small molecule screening with laser cytometry can be used to identify pro-survival molecules in human embryonic stem cells. PloS one. 2013; 8(1): e54948.
Jonas Steven J, Alva Jackelyn A, Richardson Wade, Sherman Sean P, Galic Zoran, Pyle April D, Dunn Bruce A spatially and chemically defined platform for the uniform growth of human pluripotent stem cells. Materials science & engineering. C, Materials for biological applications. 2013; 33(1): 234-41.
Karumbayaram Saravanan, Lee Peiyee, Azghadi Soheila F, Cooper Aaron R, Patterson Michaela, Kohn Donald B, Pyle April, Clark Amander, Byrne James, Zack Jerome A, Plath Kathrin, Lowry William E From skin biopsy to neurons through a pluripotent intermediate under Good Manufacturing Practice protocols. Stem cells translational medicine. 2012; 1(1): 36-43.
Alva Jackelyn A, Lee Grace E, Escobar Erika E, Pyle April D Phosphatase and tensin homolog regulates the pluripotent state and lineage fate choice in human embryonic stem cells. Stem cells (Dayton, Ohio). 2011; 29(12): 1952-62.
Sherman Sean P, Alva Jackelyn A, Thakore-Shah Kaushali, Pyle April D Human pluripotent stem cells: the development of high-content screening strategies. Methods in molecular biology (Clifton, N.J.). 2011; 767(1): 283-95.
Le Belle Janel E, Orozco Nicolas M, Paucar Andres A, Saxe Jonathan P, Mottahedeh Jack, Pyle April D, Wu Hong, Kornblum Harley I Proliferative neural stem cells have high endogenous ROS levels that regulate self-renewal and neurogenesis in a PI3K/Akt-dependant manner. Cell stem cell. 2011; 8(1): 59-71.
Tchieu Jason, Kuoy Edward, Chin Mark H, Trinh Hung, Patterson Michaela, Sherman Sean P, Aimiuwu Otaren, Lindgren Anne, Hakimian Shahrad, Zack Jerome A, Clark Amander T, Pyle April D, Lowry William E, Plath Kathrin Female human iPSCs retain an inactive X chromosome. Cell stem cell. 2010; 7(3): 329-42.
Tseng Han-Ching, Arasteh Aida, Paranjpe Avina, Teruel Antonia, Yang Wendy, Behel Armin, Alva Jackelyn A, Walter Gina, Head Christian, Ishikawa Tomo-o, Herschman Harvey R, Cacalano Nicholas, Pyle April D, Park No-Hee, Jewett Anahid Increased lysis of stem cells but not their differentiated cells by natural killer cells; de-differentiation or reprogramming activates NK cells. PloS one. 2010; 5(7): e11590.
Kamei Ken-ichiro, Ohashi Minori, Gschweng Eric, Ho Quinn, Suh Jane, Tang Jinghua, For Yu Zeta Tak, Clark Amander T, Pyle April D, Teitell Michael A, Lee Ki-Bum, Witte Owen N, Tseng Hsian-Rong Microfluidic image cytometry for quantitative single-cell profiling of human pluripotent stem cells in chemically defined conditions. Lab on a chip. 2010; 10(9): 1113-9.
Chin Mark H, Mason Mike J, Xie Wei, Volinia Stefano, Singer Mike, Peterson Cory, Ambartsumyan Gayane, Aimiuwu Otaren, Richter Laura, Zhang Jin, Khvorostov Ivan, Ott Vanessa, Grunstein Michael, Lavon Neta, Benvenisty Nissim, Croce Carlo M, Clark Amander T, Baxter Tim, Pyle April D, Teitell Mike A, Pelegrini Matteo, Plath Kathrin, Lowry William E Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell stem cell. 2009; 5(1): 111-23.
Zeng Weihua, de Greef Jessica C, Chen Yen-Yun, Chien Richard, Kong Xiangduo, Gregson Heather C, Winokur Sara T, Pyle April, Robertson Keith D, Schmiesing John A, Kimonis Virginia E, Balog Judit, Frants Rune R, Ball Alexander R, Lock Leslie F, Donovan Peter J, van der Maarel Silvère M, Yokomori Kyoko Specific loss of histone H3 lysine 9 trimethylation and HP1gamma/cohesin binding at D4Z4 repeats is associated with facioscapulohumeral dystrophy (FSHD). PLoS genetics. 2009; 5(7): e1000559.
Damoiseaux Robert, Sherman Sean P, Alva Jackelyn A, Peterson Cory, Pyle April D Integrated chemical genomics reveals modifiers of survival in human embryonic stem cells. Stem cells (Dayton, Ohio). 2009; 27(3): 533-42.
Conway Anne E, Lindgren Anne, Galic Zoran, Pyle April D, Wu Hong, Zack Jerome A, Pelligrini Matteo, Teitell Michael A, Clark Amander T A self-renewal program controls the expansion of genetically unstable cancer stem cells in pluripotent stem cell-derived tumors. Stem cells (Dayton, Ohio). 2009; 27(1): 18-28.
Wu Hao, Kim Kevin J, Mehta Kshama, Paxia Salvatore, Sundstrom Andrew, Anantharaman Thomas, Kuraishy Ali I, Doan Tri, Ghosh Jayati, Pyle April D, Clark Amander, Lowry William, Fan Guoping, Baxter Tim, Mishra Bud, Sun Yi, Teitell Michael A Copy number variant analysis of human embryonic stem cells. Stem cells (Dayton, Ohio). 2008; 26(6): 1484-9.
Hohenstein Kristi A, Pyle April D, Chern Jing Yi, Lock Leslie F, Donovan Peter J Nucleofection mediates high-efficiency stable gene knockdown and transgene expression in human embryonic stem cells. Stem cells (Dayton, Ohio). 2008; 26(6): 1436-43.
Dravid Gautam, Ye Zhaohui, Hammond Holly, Chen Guibin, Pyle April, Donovan Peter, Yu Xiaobing, Cheng Linzhao Defining the role of Wnt/beta-catenin signaling in the survival, proliferation, and self-renewal of human embryonic stem cells. Stem cells (Dayton, Ohio). 2006; 23(10): 1489-501.
Pyle April D, Lock Leslie F, Donovan Peter J Neurotrophins mediate human embryonic stem cell survival. Nature biotechnology. 2006; 24(3): 344-50.
Fenderson Bruce A, De Miguel Maria P, Pyle April D, Donovan Peter J Staining embryonic stem cells using monoclonal antibodies to stage-specific embryonic antigens. Methods in molecular biology (Clifton, N.J.). 2006; 325(3): 207-24.
Russell Liane B, Hunsicker Patricia R, Kerley Marilyn, Pyle April, Saxton Arnold M Etoposide exposure during male mouse pachytene has complex effects on crossing-over and causes nondisjunction. Mutation research. 2004; 565(1): 61-77.
Sharan Shyam K, Pyle April, Coppola Vincenzo, Babus Janice, Swaminathan Srividya, Benedict Jamie, Swing Deborah, Martin Betty K, Tessarollo Lino, Evans Janice P, Flaws Jodi A, Handel Mary Ann BRCA2 deficiency in mice leads to meiotic impairment and infertility. Development (Cambridge, England). 2004; 131(1): 131-42.
Pyle April D, Donovan Peter J, Lock Leslie F Chipping away at 'stemness'. Genome biology. 2004; 5(8): 235.
Pyle April, Handel Mary Ann Meiosis in male PL/J mice: a genetic model for gametic aneuploidy. Molecular reproduction and development. 2003; 64(4): 471-81.
Eaker Shannon, Cobb John, Pyle April, Handel Mary Ann Meiotic prophase abnormalities and metaphase cell death in MLH1-deficient mouse spermatocytes: insights into regulation of spermatogenic progress. Developmental biology. 2002; 249(1): 85-95.
Xi Haibin, Fujiwara Wakana, Gonzalez Karen, Jan Majib, Liebscher Simone, Van Handel Ben, Schenke-Layland Katja, Pyle April D In Vivo Human Somitogenesis Guides Somite Development from hPSCs. Cell reports. 2017; 18(6): 1573-1585.
Young Courtney S, Mokhonova Ekaterina, Quinonez Marbella, Pyle April D, Spencer Melissa J Creation of a Novel Humanized Dystrophic Mouse Model of Duchenne Muscular Dystrophy and Application of a CRISPR/Cas9 Gene Editing Therapy. Journal of neuromuscular diseases. 2017; 4(2): 139-145.