Many of these peer-reviewed journal articles below are available for free (open access) through the links below. Please contact the lab for copies of materials that are not freely available.
Li SR, Gulieva RE, Helms L, Cruz NM, Vincent T, Fu H, Himmelfarb J, Freedman BS. Glucose absorption drives cystogenesis in a human organoid-on-chip model of polycystic kidney disease (2022). Nat Commun. 13(1):7918. By introducing flow into ‘organoids on chips’, we discover a surprising new cause of PKD, with potential for therapy.
Taguchi K, Elias BC, Sugahara S, Sant S, Freedman BS, Waikar SS, Pozzi A, Zent R, Harris RC, Parikh SM, Brooks CR (2022). Cyclin G1 induces maladaptive proximal tubule cell dedifferentiation and renal fibrosis through CDK5 activation. J Clin Invest. 132(23):e158096. Evidence in multiple research models including human organoids reveals a new target for kidney disease: Cyclin G1.
Xu Y, Kuppe C, Perales-Patón J, Hayat S, Kranz J, Abdallah AT, Nagai J, Li Z, Peisker F, Saritas T, Halder M, Menzel S, Hoeft K, Kenter A, Kim H, van Roeyen CRC, Lehrke M, Moellmann J, Speer T, Buhl EM, Hoogenboezem R, Boor P, Jansen J, Knopp C, Kurth I, Smeets B, Bindels E, Reinders MEJ, Baan C, Gribnau J, Hoorn EJ, Steffens J, Huber TB, Costa I, Floege J, Schneider RK, Saez-Rodriguez J, Freedman BS, Kramann R. Adult human kidney organoids originate from CD24+ cells and represent an advanced model for adult polycystic kidney disease (2022). Nature Genetics 54, 1690–1701. A new model system, kidney tubuloids, shows an ability to model polycystic kidney disease, including beneficial effects of vasopressin receptor antagonists.
Cruz NM, Reddy R, McFaline-Figueroa JL, Tran C, Fu H, Freedman BS. Modelling ciliopathy phenotypes in human tissues derived from pluripotent stem cells with genetically ablated cilia (2022). Nat Biomed Eng 6(4):463-475. Novel gene edited cell lines that are unable to form antennae (cilia) show changes in hedgehog signaling, kidney and neuronal differentiation, and polycystic kidney disease.
Freedman BS. Physiology Assays in Human Kidney Organoids (2022). Am. Journal Phys: Renal Phys 322: F625–F638. Can organoids pee? A summary of where organoids currently stand as models of human physiology.
Hunt AC, Case JB, Park YJ, Cao L, Wu K, Walls AC, Liu Z, Bowen JE, Yeh HW, Saini S, Helms L, Zhao YT, Hsiang TY, Starr TN, Goreshnik I, Kozodoy L, Carter L, Ravichandran R, Green LB, Matochko WL, Thomson CA, Vögeli B, Krüger-Gericke A, VanBlargan LA, Chen RE, Ying B, Bailey AL, Kafai NM, Boyken S, Ljubetič A, Edman N, Ueda G, Chow C, Addetia A, Panpradist N, Gale M, Freedman BS, Lutz BR, Bloom JD, Ruohola-Baker H, Whelan SPJ, Stewart L, Diamond MS, Veesler D, Jewett MC, Baker D. Multivalent designed proteins protect against SARS-CoV-2 variants of concern (2022). Science Translational Medicine 12:eabn1252. In this collaborative effort, next-generation therapeutics for COVID variants (such as Delta) are tested in a variety of genetic models, including kidney organoids.
Helms L, Marchiano Stanaway IB, Hsiang TY, Juliar BA, Saini S, Zhao YT, Khanna A, Menon R, Alakwaa F, Mikacenic C, Morrell ED, Wurfel MM, Kretzler M, Harder JL, Murry CE, Himmelfarb J, Ruohola-Baker H, Bhatraju PK, Gale Jr. M, and Freedman BS. Cross-validation of SARS-CoV-2 responses in kidney organoids and clinical populations. (2021) JCI Insight. Organoids lead to new insights into the impact of SARS-CoV-2 on the kidneys, including PKD, mechanisms, viral variants, and therapies.
Gopalan J, Omar M, Roy A, Cruz NM, Falcone J, Jones KN, Forbash KA, Himmelfarb J, Freedman BS, Scott JD. Targeting an anchored phosphatase-deacetylase unit restores renal ciliary hemostasis. (2021) eLife 10:e67828. A mechanistic investigation of the role of cilia in kidney cells, with relevance for polycystic kidney disease.
Hongbing Wang, Paul C. Brown, Edwin C.Y. Chow, Lorna Ewart, Stephen S. Ferguson, Suzanne Fitzpatrick, Benjamin S. Freedman, Grace L. Guo, William Hedrich, Scott Heyward, James Hickman, Nina Isoherranen, Albert P. Li, Qi Liu, Shannon M. Mumenthaler, James Polli, William R. Proctor, Alexandre Ribeiro, Jian-Ying Wang, Ronald L. Wange, Shiew-Mei Huang. 3D Cell Culture Models: Drug Pharmacokinetics, Safety Assessment, and Regulatory Consideration (2021). Clin Transl Sci. 2021;00:1–22. A review of practical applications for human organoids and organs-on-chips in the regulatory framework of drug development.
Saha K, Sontheimer E, et al. The NIH Somatic Cell Genome Editing Program (2021). Nature 592(7853):195-204. Review of ongoing efforts on the part of a large genome editing consortium to test therapeutic approaches relevant to gene therapy.
Refaeli I, Hughes MR, Wong AK, Bissonnette MLZ, Roskelley CD, Wayne Vogl A, Barbour SJ, Freedman BS, McNagny KM. Distinct Functional Requirements for Podocalyxin in Immature and Mature Podocytes Reveal Mechanisms of Human Kidney Disease (2020). Sci Rep. 10(1):9419. The next step in our understanding of podocalyxin function in human glomeruli – outstanding effort led by our colleagues in the McNagny lab at UBC.
Luciani A and Freedman BS. Induced Pluripotent Stem Cells Provide Mega Insights into Kidney Disease (2020). Kidney Int. 98:54-57. Commentary on new work describing the use of iPS cells for studying the function of megalin, a key protein in the kidney proximal tubule.
Haase K ° and Freedman BS °. Once Upon a Dish: Engineering Multicellular Systems (2020). Development 147, dev188573. A review of a wonderful EMBL meeting in Barcelona on organoids of different stripes, which took place just before the pandemic hit in 2020.
MacDonald M, Fennel RT, Singanamalli A, Cruz NM, Yousefhussein M, Al Kofah Y, ° Freedman BS. ° Improved Automated Segmentation of Human Kidney Organoids Using Deep Convolutional Neural Networks (2020). SPIE Conference Proceedings, 113133B. A comparison of image analysis methods for identifying and measuring the properties of kidney organoids.
Liu E, Radmanesh B, Chung BH, Donnan MD, Yi D, Dadi A, Smith KD, Himmelfarb J, Li M, Freedman BS, ° Lin J °. Profiling APOL1 Nephropathy Risk Variants in Genome-Edited Kidney Organoids with Single-Cell Transcriptomics (2020). Kidney360 1:203-215. This pioneering study shows that kidney organoids can express apoliprotein L1, a major risk factor for glomerular disease, and used to study how disease may occur.
Barabino A, Flamier A, Hanna R, Héon E, Freedman BS, ° and Bernier G. ° Deregulation of neuro-developmental genes and primary cilium cytoskeleton anomalies in iPSC retinal sheets from human syndromic ciliopathies (2020). Stem Cell Reports 14:357–373. Phenotyping of new iPS cells derived from humans with disorders affecting the primary cilium, a specialized organelle involved in sensing the environment.
Nam SA, Seo E, Kim JW, Kim HW, Kim HL, Kim K, Kim TM, Ju JH, Gomez IG, Uchimura K, Humphreys BD, Yang CW, Lee JY, Kim J, Cho DW, Freedman BS, Kim YK. Graft immaturity and safety concerns in transplanted human kidney organoids. Exp Mol Med. 2019 Nov 28;51(11):145. Analysis of the potential for kidney organoids to regenerate kidneys finds evidence of partial maturation, but also identifies critical areas for improvement.
Cruz NM and Freedman BS. Differentiation of human kidney organoids from pluripotent stem cells (2019). Methods Cell Biol. 153:133-150. Book chapter describing detailed protocol for our simple, standard method for growing and characterizing kidney organoids.
Kaverina NV, Eng DG, Moeller MH, Freedman BS, Miner JH, Pippin JW, Shankland SJ (2019). Dual lineage tracing shows that glomerular parietal epithelial cells can transdifferentiate towards the adult podocyte fate. Kidney Int. 96:3, 597–611. Tracking cells after injury provides clean insight into how podocytes – the kidney’s irreplaceable cells – get replaced.
Freedman BS and Ratner B. Building Scaffolds to Rebuild Kidneys (2019). ACS Cent. Sci. doi: 10.1021/acscentsci.9b00099. Perspectives on a new method to promote productive repair of injured kidneys, co-authored with bioengineering legend Dr. Buddy Ratner.
Freedman BS. Producing Purer Podocytes (2019). J. Am. Soc. Nephrol. 30(2):183-184. Dr. Freedman’s thoughts on a new protocol that generates podocytes from iPS cells at ~ 90 % purity.
Harder JL, Menon R, Otto EA, Zhou J, Eddy S, Wys NL, O’Connor C, Luo J, Nair V, Cebrian C, Spence JR, Bitzer M, Troyanskaya OG, Hodgin JB, Wiggins RC, Freedman BS, Kretzler M, European Renal cDNA Bank (ERCB), Nephrotic Syndrome Study Network (NEPTUNE). Organoid Single-Cell Profiling Identifies a Transcriptional Signature of Glomerular Disease (2019). JCI Insight 4(1):e122697. Use of single cell RNA sequencing in organoids reveals cell types, trajectories, and new information about how glomerular disease is a ‘reversal’ of kidney development. Open access!
Freedman BS. Better Being Single? Omics Improves Kidney Organoids (2018). Nephron, Dec 14;141(2):1-5. In-depth review by Dr. Freedman of a paper by Dr. Ben Humphrey’s lab comparing two organoid differentiation protocols using single cell RNA sequencing. Open access!
Czerniecki SM, Cruz NM, Harder JL, Menon R, Annis J, Otto EA, Gulieva RE, Islas LV, Kim YK, Tran LM, Martins TJ, Pippin JW, Fu H, Kretzler M, Shankland SJ, Himmelfarb J, Moon RT, Paragas N, Freedman BS. High-throughput screening enhances kidney organoid differentiation from human pluripotent stem cells and enables automated multidimensional phenotyping. Cell Stem Cell, doi: 10.1016/j.stem.2018.04.022. The use of automated robots to produce organoids takes kidney differentiation and phenotyping to the next level.
Cruz NM, Freedman BS† (2018). CRISPR gene editing in the kidney. Am. J. Kidney Dis. 71(6):874-883. A review of how CRISPR is revolutionizing nephrology research and clinical practice.
Hamatani H, Eng DG, Kaverina NV, Gross KW, Freedman BS, Pippin JW, Shankland SJ. Lineage tracing aged mouse kidneys show lower number of cells of renin lineage and reduce responsiveness to RAAS inhibition (2018). Am. J. Phys. – Renal Phys., doi: 10.1152/ajprenal.00570.2017. Studies of specialized ‘podocyte replacement’ cells reveals how aging affects kidney regeneration.
Jing P, Liu Y, Keeler EG, Cruz NM, Freedman BS, Lin LY (2018). Optical tweezers system for live stem cell organization at the single-cell level. Biomed. Optics Express 9:2, 772-779. Development of a new biophysical tool to manipulate and study stem cells.
Eng DG, Kaverina NV, Schneider RRS, Freedman BS, Gross KW, Miner JH, Pippin JW, Shankland SJ (2018). Detection of transdifferentiation in the kidney glomerulus with dual lineage tracing. Kidney International 93:1240-1246. A two-color labeling system provides strong evidence that renin lineage cells can transdifferentiate after injury to replace podocytes.
Cruz NM, Song X, Czerniecki SM, Gulieva RE, Churchill AJ, Kim YK, Winston K, Diaz M, Fu H, Finn LS, Pei Y, Himmelfarb J, Freedman BS (2017). Organoid cystogenesis reveals a critical role of microenvironment in human polycystic kidney disease. Nature Materials, 16:1112–1119. In permissive microenvironments, kidney organoids with PKD mutations swell up to sizes easily seen by the naked eye.
Kim YK, Refaeli I, Brooks CR, Jing P, Gulieva RE, Hughes MR, Cruz NM, Liu Y, Churchill AJ, Wang Y, Fu H, Pippin JW, Lin LY, Shankland SJ, Vogl AW, McNagny KM, Freedman BS (2017). Gene-edited human kidney organoids reveal mechanisms of disease in podocyte development. Stem Cells, 35:12, 2366-2378. CRISPR’d organoids reveal how the podocyte gets its legs.
Shankland SJ, Freedman BS, Pippin JW (2017). Can podocytes be regenerated in adults? Curr Opin Nephrol Hypertens. 26(3):154-164. In this review paper, we discuss the ability of podocytes, the kidney’s filtering cells, to regenerate naturally, and the ramifications of these findings for clinical nephrology.
Tögel F, Valerius MT, Freedman BS, Iatrino R, Grinstein M, Bonventre JV (2017). Repair after nephron ablation reveals limitations of neonatal neonephrogenesis. JCI Insight 2(2):e88848. In this study, we show that mammalian kidneys cannot regenerate new nephrons, even when injury occurs only shortly after birth.
Pang P, Abbott M, Chang SL, Abdi M, Chauhan N, Mistri M, Ghofrani J, Fucci QA, Walker C, Leonardi C, Grady S, Halim A, Hoffman R, Lu T, Cao H, Tullius SG, Malek S, Kumar S, Steele G, Kibel A, Freedman BS, Waikar SS, Siedlecki AM (2017). Human vascular progenitor cells derived from renal arteries are endothelial-like and assist in the repair of injured renal capillary networks. Kidney Int. 91(1): 129-143. A study by our collaborator Dr. Siedlecki identifying a new population of adult stem cells for repairing blood vessels.
Freedman BS, Zeidel ML, Steinman TI (2016). Technology and the future of kidney care. Nephrol. News Issues 30(11): 24-28 (review). A look at kidney medicine 30 years in the future.
Freedman BS (2015). Modeling kidney disease with iPS Cells. Biomarker Insights 2015:Suppl. 1 153-169 doi: 10.4137/BMI.S20054. A summary of recent progress in the field, including differentiation of kidney organoids and the use of genome editing techniques such as CRISPR.
Freedman BS, Brooks CR, Lam AQ, Fu H, Morizane R, Agrawal V, et al. (2015). Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids. Nat. Commun. 6:8715 doi: 10.1038/ncomms9715. This study describes a new, simple protocol for generating human mini-kidney organoids from stem cells, and uses gene-edited kidney organoids to re-create human kidney disease in a petri dish.
Morizane R, Lam AQ, Freedman BS, Kishi S, Valerius TM, Bonventre JV (2015). Nephron organoids derived from human pluripotent stem cells model kidney development and injury. Nat. Biotech doi:10.1038/nbt.3392. A new protocol for differentiating ES and iPS cells into kidney organoids that resemble kidney tissue.
Freedman BS, Steinman TI (2015). Stem cells represent a new area of kidney care. Nephrol. News Issues 29(8): 18-20 (review). An analysis of the potential for iPS cells in kidney clinical research and medicine.
Lam AQ, Freedman BS, Bonventre JV (2014). Directed differentiation of pluripotent stem cells to kidney cells. Semin Nephrol 34(4): 445-461 (review). A summary of recent progress and remaining challenges in using human pluripotent stem cells for kidney regeneration and disease modeling.
Lam AQ*, Freedman BS*, Morizane R*, Valerius MT, Bonventre JV (2014). Rapid and efficient differentiation of human pluripotent stem cells into intermediate mesoderm which forms tubules expressing kidney proximal tubular markers. J Am Soc Nephrol 25(6): 1211-1225. This paper introduces a new protocol for rapidly converting ES and iPS cells into mesoderm and subsequently kidney progenitor cells.
Freedman BS,* Lam AQ,* Sundsbak JL, Iatrino R, Su X, Koon SJ, Wu M, Daheron L, Harris PC, Zhou J, Bonventre JV (2013). Reduced ciliary polycystin-2 in iPS cells from PKD patients with PKD1 mutations. J Am Soc Nephrol 24: 1571-1586. In this paper, we generated iPS cells from patients with autosomal dominant and recessive PKD, and used them to identify a possible therapeutic approach.
Xiao B,* Freedman BS,* Miller KE, Heald R, and Marko JF (2012). Histone H1 compacts DNA under force and during chromatin assembly. Mol Biol Cell 23(24):4864-71. This paper measures that histone H1 compacts individual molecules of DNA under force, protecting them from shear stress during complex nuclear remodeling processes.
Fu H, Freedman BS, Lim CT, Heald R, and J Yan (2011). Atomic force microscope imaging of chromatin assembled in Xenopus laevis egg extract. Chromosoma 120(3):245-54. This paper introduces a novel method to examine chromatin structure under physiological conditions, in contrast to the highly purified and simplified conditions typically used in the lab.
Freedman BS, Miller KE, and R Heald (2010). Xenopus egg extracts increase dynamics of histone H1 on sperm chromatin. PLoS ONE 5(9): e13111. This paper shows that histone H1 rapidly binds and releases chromatin in physiological cytoplasm, but gets stuck on chromatin in non-physiological buffer. This paper is freely available.
Freedman BS and R Heald (2010). Functional comparison of H1 histones in Xenopus reveals isoform-specific regulation by Cdk1 and RanGTP. Current Biology 20(11):1048-1052. This paper shows that negative charges and cyclin-dependent phosphorylation of histone H1 at mitosis actually enhance its binding to chromosomes, contrary to the existing dogma in the field.
Maresca TJ, Freedman BS, and R Heald (2005). Histone H1 is essential for mitotic chromosome architecture and segregation in Xenopus laevis egg extracts. J. Cell Biol. 169(6):859-869. This paper shows that mitotic chromosomes assembled without histone H1 are long and “stringy,” causing problems during cell division. This paper is freely available.
* = co-first authors
