Faculty, Graduate Program
Professor and Director Center for Regenerative Medicine - TSRI, La Jolla, CA
Adjunct Professor Program in Stem Cells and Development - Sanford Burnham Medical Research Institute, La Jolla, CA
Adjunct Professor Department of Reproductive Medicine, School of Medicine, University of California, San Diego, CA
We focus on human pluripotent stem cells, the remarkable cultured cells that can become every cell type in the human body. Most of our research is on induced pluripotent stem cells (iPSCs), which we make from cells cultured from skin biopsies.
Since these stem cells are pluripotent, we as scientists need to be "pluripotent" too. We have a diverse group of stem cell research projects, ranging from the molecular (genomics and epigenetics) to the clinical (cell therapies).
Genomics and Epigenetics
On one end of the spectrum, we study the genomics and epigenetics of iPSCs, the fascinating symphony of changes in the DNA landscape as cells differentiate into beating heart cells or functioning nerve cells. These studies give us never-before-available access into the complex processes that occur during human embryonic development, and hints about the embryonic origins of mental illness. We are focusing on Fragile X syndrome, an inherited form of autism.
Parkinson's disease cell replacement therapy
On the other end of the spectrum, we are moving toward using iPSCs to treat Parkinson's disease (PD). This is a cell replacement therapy, in which cells are to be transplanted into the part of the brain that requires dopamine to function properly. Working with our clinical partner, Dr. Melissa Houser, who is Director of the Movement Disorder Center at Scripps Clinic, we have made iPSC lines from 8 Parkinson's patients, and have turned 3 of the lines so far into bona fide dopamine neurons, the cell type that dies duriing progression of the disease. We have confirmed that the cells function by studying their electrical activity (with colleague Pietro Sanna) and by reversing PD-like symptoms in a rat model of the disease. .
Multiple sclerosis therapy development
Another of our clinical paths is for treatment of multiple sclerosis (MS). We recently discovered a cell type derived from human pluripotent stem cells that reverses the clinical symptoms in a mouse model of MS. This program is not as advanced as the PD program, but we are following a path to developing a clinically relevant treatment.
We are using iPSCs from patients with Fragile X syndrome, an inherited form of autism, to understand the disease and identify drugs that might be used to treat it. This project uses high throughput screening, the technique used by pharmaceutical companies to find drugs.
Drugs often work differently in different people. A drug that works in African Americans, for example, might be toxic to people with a different genetic ancestry. We are generating an ethnically diverse bank of iPSCs that we plan to provide to pharmaceutical drug developers so they may be able to predict the effects of a drug in different populations before testing it in people.
The Stem Cell Zoo
Some highly endangered species will inevitably become extinct in our lifetimes if we do not take extraordinary measures to save them. One of these approaches is to make iPSCs from endangered animals, like the Northern White Rhino, a species that has only 7 animals left. Working with the San Diego Zoo's Conservation Research Institute, we are generating iPSCs from endangered species, in the hope that some day these cells can be used to repopulate the species.
B.S., Molecular Biology, University of Washington, Seattle, Washington, 1972
Ph.D., Developmental Neurobiology, University of Oregon, Eugene, Oregon, 1979
2004-2007 Co-Director, Stem Cell Center Burnham Institute for Medical Research - La Jolla, CA
1997-2001 Senior Director - Incyte Genomics - Palo Alto, CA
1995-1997 Senior Research Fellow - Molecular Dynamics - Sunnyvale, CA
1989-1995 Senior Scientist - GenPharm International, Inc. Mountain View, CA
1987-1989 Staff Scientist - Hana Biologics, Inc. - Alameda, CA
2009 - Marie and Jimmy Mayer Award for Melanoma Research
2009, 2010 - Esther O'Keefe Foundation Award for Stem Cell Research
2008, 2009 - Millipore Foundation Stem Cell Research Award
2007 - Burnham Institute for medical Research Leadership Award
2006 - Korean Society of Developmental Biology, Commendation
2006 - San Diego Chapter of Clinical Research Professionals, Educational Award
Melanocytes derived from transgene-free human induced pluripotent stem cells.
Jones JC, Sabatini K, Liao X, Tran HT, Lynch CL, Morey RE, Glenn-Pratola V, Boscolo FS, Yang Q, Parast MM, Liu Y, Peterson SE, Laurent LC, Loring JF, Wang YC.
J Invest Dermatol. 2013 Mar 20. doi: 10.1038/jid.2013.139. [Epub ahead of print] No abstract available.
PMID: 23514962 [PubMed - as supplied by publisher]
Conversion of human fibroblasts to angioblast-like progenitor cells.
Kurian L, Sancho-Martinez I, Nivet E, Aguirre A, Moon K, Pendaries C, Volle-Challier C, Bono F, Herbert JM, Pulecio J, Xia Y, Li M, Montserrat N, Ruiz S, Dubova I, Rodriguez C, Denli AM, Boscolo FS, Thiagarajan RD, Gage FH, Loring JF, Laurent LC, Izpisua Belmonte JC.
Nat Methods. 2013 Jan;10(1):77-83. doi: 10.1038/nmeth.2255. Epub 2012 Dec 2.
PMID: 23202434 [PubMed - in process]
Ethnically diverse pluripotent stem cells for drug development.
Fakunle ES, Loring JF.
Trends Mol Med. 2012 Dec;18(12):709-16. doi: 10.1016/j.molmed.2012.10.007. Epub 2012 Nov 9.
PMID: 23142148 [PubMed - in process]
The functions of microRNAs in pluripotency and reprogramming.
Leonardo TR, Schultheisz HL, Loring JF, Laurent LC.
Nat Cell Biol. 2012 Nov;14(11):1114-21. doi: 10.1038/ncb2613.
PMID: 23131918 [PubMed - in process]
Equally potent? Does cellular reprogramming justify the abandonment of human embryonic stem cells?
Nazor KL, Loring JF, Laurent LC.
EMBO Rep. 2012 Oct;13(10):890-4. doi: 10.1038/embor.2012.134. Epub 2012 Sep 18. No abstract available.
PMID: 22986548 [PubMed - in process]
Full-length mRNA-Seq from single-cell levels of RNA and individual circulating tumor cells.
Ramsköld D, Luo S, Wang YC, Li R, Deng Q, Faridani OR, Daniels GA, Khrebtukova I, Loring JF, Laurent LC, Schroth GP, Sandberg R.
Nat Biotechnol. 2012 Aug;30(8):777-82.
PMID: 22820318 [PubMed - in process]
Recurrent variations in DNA methylation in human pluripotent stem cells and their differentiated derivatives.
Nazor KL, Altun G, Lynch C, Tran H, Harness JV, Slavin I, Garitaonandia I, Müller FJ, Wang YC, Boscolo FS, Fakunle E, Dumevska B, Lee S, Park HS, Olee T, D'Lima DD, Semechkin R, Parast MM, Galat V, Laslett AL, Schmidt U, Keirstead HS, Loring JF, Laurent LC.
Cell Stem Cell. 2012 May 4;10(5):620-34. doi: 10.1016/j.stem.2012.02.013.
PMID: 22560082 [PubMed - indexed for MEDLINE]
Highly parallel genome-wide expression analysis of single mammalian cells.
Fan JB, Chen J, April CS, Fisher JS, Klotzle B, Bibikova M, Kaper F, Ronaghi M, Linnarsson S, Ota T, Chien J, Laurent LC, Loring JF, Nisperos SV, Chen GY, Zhong JF.
PLoS One. 2012;7(2):e30794. doi: 10.1371/journal.pone.0030794. Epub 2012 Feb 8. Erratum in: PLoS One. 2012;7(2). doi: 10.1371/annotation/3f0ddf41-2e7a-4b56-93c2-2731f2890b19. Loring, Jeanne F [added].
PMID: 22347404 [PubMed - indexed for MEDLINE]
Teratoma generation in the testis capsule.
Peterson SE, Tran HT, Garitaonandia I, Han S, Nickey KS, Leonardo T, Laurent LC, Loring JF.
J Vis Exp. 2011 Nov 7;(57):e3177. doi: 10.3791/3177.
PMID: 22158256 [PubMed - indexed for MEDLINE]
Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile X syndrome.
Sheridan SD, Theriault KM, Reis SA, Zhou F, Madison JM, Daheron L, Loring JF, Haggarty SJ.
PLoS One. 2011;6(10):e26203. doi: 10.1371/journal.pone.0026203. Epub 2011 Oct 12.
PMID: 22022567 [PubMed - indexed for MEDLINE]
Specific lectin biomarkers for isolation of human pluripotent stem cells identified through array-based glycomic analysis.
Wang YC, Nakagawa M, Garitaonandia I, Slavin I, Altun G, Lacharite RM, Nazor KL, Tran HT, Lynch CL, Leonardo TR, Liu Y, Peterson SE, Laurent LC, Yamanaka S, Loring JF.
Cell Res. 2011 Nov;21(11):1551-63. doi: 10.1038/cr.2011.148. Epub 2011 Sep 6.
PMID: 21894191 [PubMed - indexed for MEDLINE]
Induced pluripotent stem cells from highly endangered species.
Ben-Nun IF, Montague SC, Houck ML, Tran HT, Garitaonandia I, Leonardo TR, Wang YC, Charter SJ, Laurent LC, Ryder OA, Loring JF.
Nat Methods. 2011 Sep 4;8(10):829-31. doi: 10.1038/nmeth.1706.
PMID: 21892153 [PubMed - indexed for MEDLINE]
Evidence that gene activation and silencing during stem cell differentiation requires a transcriptionally paused intermediate state.
Golob JL, Kumar RM, Guenther MG, Pabon LM, Pratt GA, Loring JF, Laurent LC, Young RA, Murry CE.
PLoS One. 2011;6(8):e22416. doi: 10.1371/journal.pone.0022416. Epub 2011 Aug 19.
PMID: 21886766 [PubMed - indexed for MEDLINE]
Normal human pluripotent stem cell lines exhibit pervasive mosaic aneuploidy.
Peterson SE, Westra JW, Rehen SK, Young H, Bushman DM, Paczkowski CM, Yung YC, Lynch CL, Tran HT, Nickey KS, Wang YC, Laurent LC, Loring JF, Carpenter MK, Chun J.
PLoS One. 2011;6(8):e23018. doi: 10.1371/journal.pone.0023018. Epub 2011 Aug 16.
PMID: 21857983 [PubMed - indexed for MEDLINE]
Basic approaches to gene expression analysis of stem cells by microarrays.
Schuldt B, Lin Q, Müller FJ, Loring J.
Methods Mol Biol. 2011;767:269-82. doi: 10.1007/978-1-61779-201-4_20.
PMID: 21822882 [PubMed - indexed for MEDLINE]
FISH analysis of human pluripotent stem cells.
Peterson SE, Chun J, Loring J.
Methods Mol Biol. 2011;767:191-200. doi: 10.1007/978-1-61779-201-4_14.
PMID: 21822876 [PubMed - indexed for MEDLINE]
Chromatin insulator elements block transgene silencing in engineered human embryonic stem cell lines at a defined chromosome 13 locus.
Macarthur CC, Xue H, Van Hoof D, Lieu PT, Dudas M, Fontes A, Swistowski A, Touboul T, Seerke R, Laurent LC, Loring JF, German MS, Zeng X, Rao MS, Lakshmipathy U, Chesnut JD, Liu Y.
Stem Cells Dev. 2012 Jan 20;21(2):191-205. doi: 10.1089/scd.2011.0163. Epub 2011 Aug 4.
PMID: 21699412 [PubMed - indexed for MEDLINE]
Muller, F.J., Schuldt, B.M., Williams, R., Mason, D., Altun, G., Papapetrou, E.P., Danner, S., Goldmann, J.E., Herbst, A., Schmidt, N.O., Aldenhoff, J.B., Laurent, L.C., Loring, J.F., 2011. A bioinformatic assay for pluripotency in human cells. Nat Methods. 2011 Apr;8(4):315-7. Epub 2011 Mar 6
PMID:21378979[PubMed - indexed for MEDLINE]
Laurent, L.C., Ulitsky, I., Slavin, I., Tran, H., Schork, A., Morey, R., Lynch, C., Harness, J.V., Lee, S., Barrero, M.J., Ku, S., Martynova, M., Semechkin, R., Galat, V., Gottesfeld, J., Izpisua Belmonte, J.C., Murry, C., Keirstead, H.S., Park, H.S., Schmidt, U., Laslett, A.L., Muller, F.J., Nievergelt, C.M., Shamir, R., Loring, J.F., 2011. Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture. Cell Stem Cell. 2011 Jan 7;8(1):106-18
PMID: 21211785 [PubMed - in process]
Harness, J.V., Turovets, N.A., Seiler, M.J., Nistor, G., Altun, G., Agapova, L.S., Ferguson, D., Laurent, L.C., Loring, J.F., Keirstead, H.S., 2011. Equivalence of conventionally-derived and parthenote-derived human embryonic stem cells. PLoS One 6, e14499. PMID: 21249129 [PubMed - in process] - Free PMC Article
Guang-Hui Liu,Keiichiro Suzuki, Jing Qu, Ignacio Sancho-Martinez, Fei Yi, Mo Li, Sachin Kumar, Emmanuel Nivet, Jessica Kim, Rupa Devi Soligalla, Ilir Dubova, April Goebl, Nongluk Plongthongkum, Ho-Lim Fung, Kun Zhang, Jeanne F. Loring, Louise C. Laurent, and Juan Carlos Izpisua Belmonte. Targeted Gene Correction of Laminopathy-Associated LMNA Mutations in Patient-Specific iPSCs. In Press, Cell Stem Cell (2011)
Luong, M.X., Auerbach, J., Crook, J.M., Daheron, L., Hei, D., Lomax, G., Loring, J.F., Ludwig, T., Schlaeger, T.M., Smith, K.P., Stacey, G., Xu, R.H., Zeng, F., 2011. A Call for Standardized Naming and Reporting of Human ESC and iPSC Lines. Cell Stem Cell 8, 357-359.
Ku, S., Soragni, E., Campau, E., Thomas, E.A., Altun, G., Laurent, L.C., Loring, J.F., Napierala, M., and Gottesfeld, J.M. (2010). Friedreich's ataxia induced pluripotent stem cells model intergenerational GAATTC triplet repeat instability. Cell Stem Cell 7, 631-637.
Müller FJ, Goldmann J, Löser P, Loring JF. A call to standardize teratoma assays used to define human pluripotent cell lines. Cell Stem Cell. 2010 May 7;6(5):412-4. PMID: 20452314
Laurent LC, Wong E, Li G, Huynh T, Tsirigos A, Ong CT, Low HM, Sung KWK, Rigoutsos I*, Loring J*, Wei C-L*. Dynamic Changes in the Human Methylome During Differentiation. (*Co-Senior authors). Genome Research, 20(3):320-31.
Laurent LC, Nievergelt CM, Lynch C, Fakunle E, Harness J, Schmidt U, Galat V, Laslett, AL, Otonkoski T, Keirstead H, Schork A, Park H-S, Loring, JF. Restricted Ethnic Diversity in Human Embryonic Stem Cells. Nature Methods, 7(1):6-7. 2010. PMID: 20038950
Hansen, K., Muller, F.J., Messing, M., Zeigler, F., Loring, J.F., Lamszus, K., Westphal, M., and Schmidt, N.O. (2010). A 3-dimensional extracellular matrix as a delivery system for the transplantation of glioma-targeting neural stem/progenitor cells. Neuro Oncol.12(7): 645-654.
Altun G, Loring JF, Laurent LC. DNA Methylation in Embryonic Stem Cells. J Cell Biochem 109:1-6, 2010.
Blurton-Jones M, Kitazawa M, Martinez-Coria H, Castello NA, Müller FJ, Loring JF, Yamasaki TR, Poon WW, Green KN, Laferla FM. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc Natl Acad Sci U S A. 106(32):13594-9. 2009 PMCID: PMC2715325
Gonzalez R, Loring JF, Snyder EY. Preparation of autogenic human feeder cells for growth of human embryonic stem cells. Curr Protoc Stem Cell Biol. 2008; Mar; Chapter 1:Unit 1C.5.1-1C.5.15.
Müller FJ, Laurent LC, Kostka D, Ulitsky I, Williams R, Lu C, Park I-H, Rao MS, Shamir R, Schwartz PH, Schmidt NO, Loring JF. Regulatory networks define phenotypic classes of human stem cell lines. Nature 2008;455:401.
Laurent LC, Chen J, Ulitsky I, Mueller F-J, Lu C, Shamir R, Fan J-B and Loring JF. Comprehensive MicroRNA profiling reveals a unique human embryonic stem cell signature dominated by a single seed sequence. Stem Cells 2008;26:1506-16.
Guibinga GH, Song S, Loring J, Friedmann T. Characterization of the gene delivery properties of baculoviral-based virosomal vectors. J Virol Methods. 2008;148:277-82.
Bibikova M, Laurent LC, Ren B, Loring JF, Fan JB. Unraveling Epigenetic Regulation in Embryonic Stem Cells.
Cell Stem Cell. 2008 Feb 7;2(2):123-34. Review. PMID: 18371433 [PubMed - indexed for MEDLINE]
Gertow K, Przyborski S, Loring JF, Auerbach JM, Epifano O, Otonkoski T, Damjanov I, Ahrlund-Richter L. Isolation of human embryonic stem cell-derived teratomas for the assessment of pluripotency. Curr Protoc Stem Cell Biol. 2007 Oct; Chapter 1:Unit1B.4.
Bibikova M, Chudin E, Wu B, Zhou L, Garcia EW, Liu Y, Shin S, Plaia TW, Auerbach JM, Arking DE, Gonzalez R, Crook J, Davidson B, Schulz TC, Robins A, Khanna A, Sartipy P, Hyllner J, Vanguri P, Savant-Bhonsale S, Smith AK, Chakravarti A, Maitra A, Rao M, Barker DL, Loring JF, Fan JB.. Human embryonic stem cells have a unique epigenetic signature. Genome Res 2006;16:1075-1083. PMCID: PMC1557765.
Mueller FJ, Serobyan N, et al. Adhesive interactions between human neural stem cells and inflamed human vascular endothelium are mediated by integrins. Stem Cells 2006;24:2367-2372.
Cai J, Chen J, et al. Assessing self-renewal and differentiation in human embryonic stem cell lines. Stem Cells 2006;24:516-30. PMCID: PMC2528840
Li H, et al. Transcriptome coexpression map of human embryonic stem cells. BMC Genomics 2006;7:103. PMCID: PMC1523211.
Liu Y, Shin S, et al. Genome wide profiling of human embryonic stem cells (hESCs), their derivatives and embryonal carcinoma cells to develop base profiles of U.S. Federal government approved hESC lines. BMC Developmental Biology 2006;6:20. PMCID: PMC1523200.
Josephson G, Liu Y, et al. A molecular scheme for improved characterization of human embryonic stem cell lines. BMC Biol 2006;4:28.