Emerging genomic and stem cell technologies are shaping the next frontier in biomedical research with nonhuman primates (NHP). They facilitate the development of genetically precise models of disease to study pathogenesis, identify biomarkers and therapeutic targets, and personalize therapeutic strategies.
The Precision Genomics and Stem Cell Therapies Unit, co-directed by Jenna Schmidt, PhD and Igor Slukvin, MD, PhD, provides guidance and resources to investigators interested in developing NHP genetic models, NHP stem cells and stem cell therapies.
The Precision Genomics and Stem Cell Therapies Unit aims to:
- Integrate embryonic and cellular genome editing to develop NHP models and advance in vivo cellular targeting.
- Discover “phenotype to genotype” associations by whole genome sequencing analyses.
- Develop NHP models for evaluation of iPSC-based regenerative therapies and immunotherapies.
- Provide fee-for-service sequencing and bioinformatics services.
- Offer cell lines available for distribution.
GENOMIC RESOURCES SUBUNIT
Cell and Embryo Genome Editing Technologies
- Design and use of CRISPR/Cas9 constructs to edit NHP cells (i.e., fibroblasts, stem cells, trophoblast stem cells) and embryos, including off-target analysis and methods for delivery.
- Macaque and marmoset gamete collection, in vitro embryo culture, embryo microinjection, and embryo transfer
- Sperm and embryo cryopreservation techniques for germplasm banking
Genomic Discovery
- Analysis of genomic data
- Provision of sequencing and bioinformatic support for WNPRC researchers and external investigators seeking to perform whole genome or exomes sequencing analysis
Contacts
Jenna Schmidt, PhD—Stem Cell Models, Assisted Reproduction, Genomics
Phone: (608)-263-3588
Email Dr. Schmidt
Jeffrey Rogers, PhD—Genomics
Email Dr. Rogers
Marina Emborg, PhD—Stem Cell Models, Cell Therapies
Phone: (608)-262-9714
Email Dr. Emborg
Jeanette Metzger, PhD— Microscopy
Email Dr. Metger
STEM CELL THERAPIES SUBUNIT
Stem Cell Technologies
- Derivation of transgene-free NHP iPSCs, including MHC homozygous and genome-specific cell lines for disease modeling and cell therapies.
- Engineering ESC/iPSCs to mitigate host immune response for preclinical evaluation in NHP models.
- Generation of genetically modified PSC lines for targeted immunotherapy of infectious diseases and cancers.
- Optimization of culture conditions to better support NHP stem cell cultures and differentiation protocols for the generation of immune cells from PSCs.
Cell Therapies
- Generation and characterization of immune effector cells derived from NHP-iPSCs.
- In vivo administration of iPSC-derived hematopoietic progenitors and immune cells.
- Genetic editing of HSCs and iPSCs using CRISPR/Cas9.
- Isolation of HSCs from bone marrow and peripheral blood.
- Transplantation of HSCs and developing novel conditioning regimens.
Contacts
Igor Slukvin, MD, PhD—Cell Therapies
Phone: (608) 263-0058
Email Dr. Slukvin
Saritha D’Souza, PhD—Cell Therapies
Email Dr. D’Souza
John Maufort, PhD—Stem Cell Resources
Phone:608-890-4244
Email Dr. Maufort
CELL LINES AVAILABLE FOR DISTRIBUTION
Cell lines can be distributed upon authorization of a material transfer agreement. New cell lines may be generated upon request. See the list of available cell lines here.
RECENT HIGHLIGHTED PUBLICATIONS
Scholz J, Secreto FJ, Wobig J, Kurian J, Hagen C, Zinnen A, Vu D, Johnson SJ, Cetta F, Qureshi Y, Reams R, Cannon B, Heyer CM, Chang M, Fadra N, Coonen J, Simmons HA, Mejia A, Hayes JM, Basu P, Capuano S, Bondarenko V, Metzger JM, Nelson TJ, Emborg ME. Human stem cell-derived cardiomyocytes integrate into the heart of monkeys with right ventricle pressure overload. Cell Transplant. 2024 Jan-Dec;33:963689724. PMID: 39487759.
Malukiewicz J, Warren K, Boere V, Bandeira ILC, Curi NHA, das Dores FT, Fitorra LS, Furuya HR, Igayara CS, Milanelo L, Moreira SB, Molina CV, Nardi MS, Nicola PA, Passamani M, Pedro VS, Pereira LCM, Petri B, Pissinatti A, Quirino AA, Rogers J, Ruiz-Miranda CR, Silva DL, Silva IO, Silva MOM, Summa JL, Zwarg T, Ackermann RR. Pelage variation and morphometrics of closely related Callithrix marmoset species and their hybrids. BMC Ecol Evol. 2024 Sep 20;24(1):122. PMID: 39304843.
Shaw TM, Huey D, Mousa-Makky M, Compaleo J, Nennig K, Shah AP, Jiang F, Qiu X, Klipsic D, Rowland RRR, Slukvin II, Sullender ME, Baldridge MT, Li H, Warren CJ, Bailey AL. The neonatal Fc receptor (FcRn) is a pan-arterivirus receptor. Nat Commun. 2024 Aug 7;15(1):6726. PMID: 39112502.
Emborg ME, Mancinelli A, Colwell JC, Zinnen AD, Pape B, Brunner K, Bondarenko V, Fitz C, Coonen J, Menna V, Fuchs K, Schultz-Darken N, Simmons HA, Tran H, Larson P, Olsen M, Hurley S, Bratt-Leal AM, Wirth E, Metzger JM. Preclinical evaluation of transaxial intraputaminal trajectory for enhanced distribution of grafted cells in Parkinson’s disease. J Neurosurg. 2024 Jul 26:1-13. PMID: 39059426.
Wang J, Wang M, Moshiri A, Harris RA, Raveendran M, Nguyen T, Kim S, Young L, Wang K, Wiseman R, O’Connor DH, Johnson Z, Martinez M, Montague MJ, Sayers K, Lyke M, Vallender E, Stout T, Li Y, Thomasy SM, Rogers J, Chen R. Genetic diversity of 1,845 rhesus macaques improves genetic variation interpretation and identifies disease models. Nat Commun. 2024 Jul 5;15(1):5658. PMID38969634.
Giese MA, Bennin DA, Schoen TJ, Peterson AN, Schrope JH, Brand J, Jung HS, Keller NP, Beebe DJ, Dinh HQ, Slukvin II, Huttenlocher A. PTP1B phosphatase dampens iPSC-derived neutrophil motility and antimicrobial function. J Leukoc Biol. 2024 Jun 28;116(1):118-131. PMID: 38417030.
Prall TM, Karl JA, Varghese JM, Baker DA, Minor NR, Raveendran M, Harris RA, Rogers J, Wiseman RW, O’Connor DH. Complete Genomic Assembly of Mauritian Cynomolgus Macaque Killer Ig-like Receptor and Natural Killer Group 2 Haplotypes. J Immunol. 2024 Jun 1;212(11)1754-1765. PMID: 38639635.
Shaw TM, Dettle ST, Mejia A, Hayes JM, Simmons HA, Basu P, Kuhn JH, Ramuta MD, Warren CJ, Jahrling PB, O’Connor DH, Huang L, Zaeem M, Seo J, Slukvin II, Brown ME, Bailey AL. Isolation of Diverse Simian Arteriviruses Causing Hemorrhagic Disease. Emerg Infect Dis. 2024 Apr;30(4):721-731. PMID: 38526136.
Emborg ME, Gambardella JC, Zhang A, Federoff HJ. Autologous vs heterologous cell replacement strategies for Parkinson disease and other neurologic diseases. Handb Clin Neurol. 2024;205:41-56. PMID: 39341662.
Kuderna LFK,… Rogers J, et al. Identification of constrained sequence elements across 239 primate genomes. Nature. 2024 Jan;625(7996):735-742. PMID: 38030727.
Schmidt JK, Block LN, Jones KM, Hinkle HM, Mean KD, Bowman BD, Makulec AT, Golos TG. Atypical initial cleavage patterns minimally impact rhesus macaque in vitro embryo morphokinetics and embryo outgrowth development. Biol Reprod. 2023 Dec 11;109(6):812-820. PMID:37688580.
Harris RA, Raveendran M, Warren W, LaDeana HW, Tomlinson C, Graves-Lindsay T, Green RE, Schmidt JK, Colwell JC, Makulec AT, Cole SA, Cheeseman IH, Ross CN, Capuano S 3rd, Eichler EE, Levine JE, Rogers J. Whole Genome Analysis of SNV and Indel Polymorphism in Common Marmosets (Callithrix jacchus). Genes (Basel). 2023 Dec 7;14(12):2185. PMID: 38137007.
Gambardella JC, Schoephoerster W, Bondarenko V, Yandell BS, Emborg ME. Expression of tau and phosphorylated tau in the brain of normal and hemiparkinsonian rhesus macaques. J Comp Neurol. 2023 Aug;531(11):1198-1216. PMID: 37098996.
Fiziev PP, McRae J, Ulirsch JC, Dron JS, Hamp T, Yang Y, Wainschtein P, Ni Z, Schraiber JG, Gao H, Cable D, Field Y, Aguet F, Fasnacht M, Metwally A, Rogers J, Neuman SS, Metzger JM, Bondarenko V, Wang Y, Felton J, Levine JE, Saha K, Gong S, Emborg ME. Striatonigral distribution of a fluorescent reporter following intracerebral delivery of genome editors. Front Bioeng Biotechnol. 2023 Jul 26;11:1237613. PMID: 37564994.
Kuderna LFK,…Rogers J, et al. A global catalog of whole-genome diversity from 233 primate species. Science. 2023, June 2, 380(6648):906-913. PMID: 37262161.
Marques-Bonet T, Rehm HL, O’Donnell-Luria A, Khera AV, Farh KK. Rare penetrant mutations confer severe risk of common diseases. Science. 2023 Jun 2;380(6648):eabo1131. PMID: 37262146.
Gao H,…Rogers J, et al. The landscape of tolerated genetic variation in humans and primates. Science. 2023 Jun 2;380(6648):eabn8153. PMID: 37262156.
Shao Y,…Rogers J, et al. Phylogenomic analyses provide insights into primate evolution. Science. 2023 June 2;380(6648):913-924. PMID:37262173.
Baik J, Ortiz-Cordero C, Magli A, Azzag K, Crist SB, Yamashita A, Kiley J, Selvaraj S, Mondragon-Gonzalez R, Perrin E, Maufort JP, Janecek JL, Lee RM, Stone LH, Rangarajan P, Ramachandran S, Graham ML, Perlingeiro RCR. Establishment of Skeletal Myogenic Progenitors from Non-Human Primate Induced Pluripotent Stem Cells. Cells. 2023 Apr 13;12(8):1147. PMID: 37190056.
Jung HS, Suknuntha K, Kim YH, Liu P, Dettle ST, Sedzro DM, Smith PR, Thomson JA, Ong IM, Slukvin II. SOX18-enforced expression diverts hemogenic endothelium-derived progenitors from T towards NK lymphoid pathways. iScience. 2023 Apr 8;26(5):106621. PMID: 37250328.
Metzger JM, Wang Y, Neuman SS, Snow KJ, Murray SA, Lutz CM, Bondarenko V, Felton J, Gimse K, Xie R, Li D, Zhao Y, Flowers MT, Simmons HA, Roy S, Saha K, Levine JE, Emborg ME, Gong S. Efficient in vivo neuronal genome editing in the mouse brain using nanocapsules containing CRISPR-Cas9 ribonucleoproteins. Biomaterials. 2023 Feb;293:121959. PMID: 36527789.
Zhang J, Webster S, Duffin B, Bernstein MN, Steill J, Swanson S, Forsberg MH, Bolin J, Brown ME, Majumder A, Capitini CM, Stewart R, Thomson JA, Slukvin II. Generation of anti-GD2 CAR macrophages from human pluripotent stem cells for cancer immunotherapies. Stem Cell Reports. 2023 Feb 14;18(2):585-596. PMID: 36638788.
Olsen ME, Brodsky EK, Oler JA, Riedel MK, Mueller SAL, Vermilyea SC, Metzger JM, Tao Y, Brunner KG, Ahmed AS, Zhang SC, Emborg ME, Kalin NH, Block WF. Real-time trajectory guide tracking for intraoperative MRI-guided neurosurgery. Magn Reson Med. 2023 Feb;89(2):710-720.
Paulin LF, Raveendran M, Harris RA, Rogers J, von Haeseler A, Sedlazeck FJ. SVhound: detection of regions that harbor yet undetected structural variation. BMC Bioinformatics. 2023 Jan 20;24(1):23. PMID: 36670361.
Emborg ME. Reframing the Perception of Outliers and Negative Data in Translational Research. Brain Res Bull. 2023 Jan:192:203-207. PMID: 36464129.
Vallender EJ, Hotchkiss CE, Lewis AD, Rogers J, Stern JA, Peterson SM, Ferguson B, Sayers K. Nonhuman primate genetic models for the study of rare diseases. Orphanet J Rare Dis. 2023 Jan 31;18(1):20. PMID: 36721163.
Schmidt JK, Kim YH, Strelchenko N, Gierczic SR, Pavelec D, Golos TG, Slukvin II. Whole genome sequencing of CCR5 CRISPR-Cas9-edited Mauritian cynomolgus macaque blastomeres reveals large-scale deletions and off-target edits. Front Genome Ed. 2023 Jan 12;4:1031275. PMID: 36714391
D’Souza SS, Kumar A, Maufort J, Weinfurter JT, Raymond M, Strelchenko N, Perrin E, Coonen J, Mejia A, Simmons H, Torbett BE, Reynolds M, Thomson JA, Slukvin I. Assessment of Safety and Immunogenicity of MHC homozygous iPSC-derived CD34+ Hematopoietic Progenitors in a NHP Model. Blood Adv. 2022 Sep 27;6(18):5267-5278. PMID: 35404997.
Schmidt JK, Reynolds MR, Golos TG, Slukvin II. CRISPR/Cas9 genome editing to create nonhuman primate models for studying stem cell therapies for HIV infection. Retrovirology 2022 Aug 10;19(1):17. PMID: 35948929.
Weinfurter JT, D’Souza SS, Matschke LM, Bennett S, Kelnhofer-Millevolte LE, Suknuntha K, Kumar A, Coonen J, Capitini CM, Hematti P, Golos TG, Slukvin II, Reynolds MR. Allogeneic MHC-matched T-cell receptor α/β-depleted bone marrow transplants in SHIV-infected, ART-suppressed Mauritian cynomolgus macaques. Sci Rep. 2022 Jul 19;12(1):12345. PMID: 35853970.
Zinnen AD, Vichich J, Metzger JM, Gambardella JC, Bondarenko V, Simmons HA, Emborg ME. Alpha-synuclein and tau are abundantly expressed in the ENS of the human appendix and monkey cecum. PLoS One. 2022 June 17(6):e0269190. PMID: 35687573.
Uenishi GI, Jung HS, Slukvin II. Assessment of Endothelial-to-Hematopoietic Transition of Individual Hemogenic Endothelium and Bulk Populations in Defined Conditions. Methods Mol Biol. 2022;2429:103-124. PMID: 35507158.