The Cheng lab studies human stem cell biology and engineering to develop experimental models of and treatments for human blood diseases. The team has made several discoveries in understanding human stem cell self-renewal and hematopoietic (blood-forming) differentiation using adult hematopoietic stem cells and human pluripotent stem cells. They also poineered recently efficient methods to establish human induced pluripotent stem (iPS) cells from both blood cells and fibroblasts by plasmids without integrating into cellular chromosomes. In effort to develop better genetic models and gene therapy methods, the Cheng lab develops new methods for making genetic modifications in human cells using various methods such as human genome editing.
Peer-reviewed original research articles (?78)
1.: Cheng L
and Kelly TJ. Transcriptional activator Nuclear Factor I stimulates the replication of SV40 minichromosomes in vivo
and in vitro. Cell
. 1989; 59:541-551.
2.: Cheng L
, Workman JL, Kingston RE, Kelly TJ. Regulation of DNA replication in vitro by the transcriptional activation domain of GAL4-VP16. Proc. Natl. Acad. Sci.
(USA) 1992; 89: 589-593.
3.: Resnick JL, Bixler L, Cheng L
, Donovan PJ. Long-term proliferation of mouse primordial germ cell in culture. Nature
. 1992; 359: 550-551.
4.: Cheng L†
, Fu J, Tsukamoto A, Hawley RG. Use of green fluorescent protein (GFP) variants to monitor gene transfer and expression in mammalian cells. Nature Biotechnology
. 1996; 14: 606-609. (†
5.: Yang T-T, Cheng L
, Kain SL. Optimized codon usage and chromophore mutations provide enhanced sensitivity with green fluorescent protein in mammalian cells. Nucl. Acid. Res.
1996; 24: 4592-4593.
6.: Cui Y , Golob J, Kelleher E, Ye Z, Pardoll D, Cheng L
. Targeting transgene expression to antigen presenting cells derived from lentivirus transduced, engrafting human hematopoietic stem/progenitor cells. Blood
. 2002; 99: 399-408. Comment: http://www.nature.com/nbt/journal/v20/n3/full/nbt0302-241.html
7.: Cheng L
, Hammond H, Ye Z, Zhan X, Dravid G. Human adult marrow cells support prolonged expansion of human embryonic stem cells in culture. Stem Cells
, 2003; 20:121-132.
8.: Zhan X, Dravid G, Ye Z, Hammond H, Shamblott M, Gearhart J, Cheng L
. Functional antigen-presenting leukocytes derived from human embryonic stem cells in vitro. The Lancet
. 2004; 363:163-171.
9.: Chen G, Ye Z, Yu X, Zou J, Mali P, Brodsky RA, Cheng L
. Trophoblast differentiation defect in human embryonic stem cells lacking PIG-A and GPI-anchored cell surface proteins. Cell Stem Cell
. 2008; 2(4):345-355.
10. Yu X, Zou J, Ye Z, Hammond HH, Chen G, Tokunaga A, Mali P, Li YM, Civin CI, Gaiano N, Cheng L
. Notch signaling activation in human embryonic stem cells is required for embryonic but not trophoblastic lineage commitment. Cell Stem Cell
. 2008; 2(5):461-471.
11. Mali P, Ye Z, Hammond H, Yu X, Lin J, Chen G, Zou J, Cheng L
. Improved efficiency and pace of generating induced pluripotent stem cells from human adult and fetal fibroblasts. Stem Cells
. 2008; 26(8):1998-2005.
12. Zou J, Maeder ML, Mali P, Pruett-Miller SM, Thibodeau-Beganny S, Chou BK, Chen G, Ye Z, Park IH, Daley GQ, Porteus MH, Joung JK, Cheng L
. Gene targeting of a disease-related gene in human induced pluripotent stem cells and embryonic stem cells. Cell Stem Cell
. 2009; 5(1):97-110.
13. Ye Z, Zhan H, Mali P, Dowey S, Jang Y-Y, Dang CV, Spivak JL, Moliterno AR, Cheng L
. Human induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders. Blood
. 2009; 114:5473-5480.
14. Mali P, Chou, BK, Ye Z, Zou J, Yen J, Dowey S, Brodsky RA, Ohm JE, Yu W, Baylin SB, Yusa K, Bradley A, Meyers DJ, Mukherjee C, Cole PA, Cheng L
. Butyrate greatly enhances derivation of human induced pluripotent stem by promoting epigenetic remodeling and the expression of pluripotency-associated genes. Stem Cells
. 2010; 28(4): 713-720.
15. Ohm JE*, Mali P*, Van Neste L*, Berman DM, Liang L, Briggs K, Pandiyan K, Zhang W, Argani P, Simons B, Yu W, Matsui W, Van Criekinge W, Zambidis E, Rassool F, Schuebel K, Cope L, Yen J, Mohammad H, Cheng L+
, Baylin SB+
. Cancer-related Epigenome Changes Associated with Reprogramming to Induced Pluripotent Stem Cells. Cancer Research
, 2010; 70(19):7662-73. PMID: 20841480. (*Equal contributions; +
16. Chou BK, Mali P, Huang X, Ye Z, Dowey SN, Resar LMS, Zou C, Zhang YA, Tong J and Cheng L.
Efficient human iPS cell derivation by a non-integrating plasmid from blood cells with unique epigenetic and gene expression signatures. Cell Research
, 2011; 21(3):518-29.
Selected as one of the two Sanofi-Cell Research Outstanding Papers of 2011;http://www.nature.com/cr/journal/v22/n11/full/cr2012153a.html
17. Zou J†
, Mali P, Huang X, Dowey SN, and Cheng L†.
Site-specific gene correction of a point mutation in human iPS cells derived from sickle cell disease patient. Blood
, 2011; 118(17):4599-4608. (†
Both are corresponding authors).
18. Cheng L†
, Hansen NF, Zhao L, Du Y, Zou C, Donovan FX, Chou BK, Zhou G, Li S, Dowey SN, Ye Z, NISC Comparative Sequencing Program, Chandrasekharappa SC, Yang H, Mullikin JC and Liu PP†
. Low incidence of DNA sequence variation in human induced pluripotent stem cells generated by non-integrating plasmid expression. Cell Stem Cell
, 2012; 10(3):337-344 . (†
Both are corresponding authors).
1.: Mali P and Cheng L
. Human Cell Engineering: Cellular Reprogramming and Genome Editing. Stem Cells
, 2012; 30: 75-81
2.: Cheng L
, Blazar B, High K and Porteus M. Zinc fingers hit off-targets. Nature Medicine
, 2011; Oct. 11. 17(10): 1192-3.
Dr. Cheng ??s main laboratory is working on human stem cell biology and engineering, and their applications in regenerative medicine for curing blood diseases. One of their objectives is to understand genetic and epigenetic regulation of cell fate determination in hematopoiesis. The group currently focuses on using human pluripotent stem such as iPS cells from healthy donors and patients. They use both cellular differentiation and genetic approaches such as genome editing to orrect or create mutations in human stem cells. Their goals is to investigate human stem cell biology and diseases. More details are available on his lab website www.stemcelllab.org