Kehkooi Kee-School of Medicine, Tsinghua University

Cell and Molecular Biology

Kehkooi Kee

Tenured Professor

Contact Us:
Tel: +86-10-62794200
E-mail: kkee@tsinghua.edu.cn
WeChat public account:

Personal introduction:

Studying stem cell and reproductive biology, building cellular therapy and translational platform Kehkooi Kee graduated from Weill Cornell Medical College and Memorial Sloan-Kettering Cancer Center with PhD degree in Molecular, Cellular Biology and Genetics program in 2003. After postdoctoral trainings at Sloan-Kettering and UCSF, he became Research Associate at Stanford University in 2007. He joined School of Medicine, Tsinghua Univeristy and established his research team in 2010. He is the principal investigator of The Laboratory of Stem Cell and Reproductive Biology, PhD student advisor, and the associate director of the Department of Basic Medical Sciences.

Building in vitro systems to study human reproductive biology for infertility diseases and developing cellular therapies for translational applications

Germ cells transmit totipotency and generate genetic diversity from one generation to the next. When sperm and egg fuse, a new life begins to develop by their genetic blueprints while incorporating epigenetic instructions. Kehkooi and his research team are fascinated by these processes and focus on understanding the molecular mechanisms underlying these processes, especially RNA binding proteins involved in regulating germ cell development, initiation of meiosis, and molecular and genetic factors causing infertility. Studies of human germ cell development, especially early germ cells, had been hindered by sample procurement. Human embryonic stem cells provide them unprecedented opportunity to develop in vitro differentiation systems to study these mechanisms. They have successfully built many novel in vitro differentiation and induction systems for human germ cells and their neighboring somatic cells, including spermatids, oocytes, and Sertoli cells. These in vitro systems also allow them to study the effect of microgravity on development of human germ cells in spacecraft.

Moreover, the research team have induced human stem cells to Sertoli cells which create an immune-privileged microenvironment and applied the technology to eradicate immune rejection during tissue transplantation.

1.Li L, Yang R, Yin C,Kee K*. Studying human reproductive biology through single-cell analysis and in vitro differentiation of stem cells into germ cell-like cells.Hum Reprod Update. 2020. doi:10.1093/humupd/dmaa021.

2.Ye M, Yang ZY, Zhang Y, Xing YX, Xie QG, Zhou JH, Wang L, Xie W,Kee K*, Chian RC*. Single-cell multiomic analysis of in vivo and in vitro matured human oocytes.Hum Reprod. 2020 Apr 28;35(4):886-900. doi: 10.1093/humrep/deaa044.

3.Liang J, Wang N, He J, Du J, Guo Y, Li L, Wu W, Yao C, Li Z,Kee K*. Induction of Sertoli-like cells from human fibroblasts by NR5A1 and GATA4.Elife. 2019 Nov 11;8. pii: e48767. doi: 10.7554/eLife.48767.

4.Wang B, Li L, Zhu Y, Zhang W, Wang X, Chen B, Li T, Pan H, Wang J,Kee K*, Cao Y*. Sequence variants of KHDRBS1 as high penetrance susceptibility risks for primary ovarian insufficiency by mis-regulating mRNA alternative splicing.Hum Reprod.2017 Oct 1;32(10):2138-2146. doi: 10.1093/humrep/dex263.

5.Jung D, Xiong J, Ye M, Qin X, Li L, Cheng S, Luo M, Peng J, Dong J, Tang F, Shen W, Matzuk MM,Kee K*.In vitro differentiation of human embryonic stem cells into ovarian follicle-like cells.Nat Commun.2017 Jun 12;8:15680. doi: 10.1038/ncomms15680.

6.Li L, Wang B, Zhang W, Chen B, Luo M, Wang J, Wang X, Cao Y*,Kee K*. (2017). A homozygous NOBOX truncating variant causes defective transcriptional activation and leads to primary ovarian insufficiency.Hum Reprod32(1): 248-255. doi: 10.1093/humrep/dew271.

7.Lin J, Chen H, Luo L, Lai Y, Xie W,Kee K*. (2015). Creating a monomeric endonuclease TALE-I-SceI with high specificity and low genotoxicity in human cells.Nucleic Acids Res43(2): 1112-1122. doi: 10.1093/nar/gku1339.

8.Kee K, Pera RA, Turek PJ*. (2010). Testicular germline stem cells.Nat Rev Urol7(2): 94-100. doi: 10.1038/nrurol.2009.263.

9.Kee K, Angeles VT, Flores M, Nguyen HN, Reijo Pera RA*. (2009). Human DAZL, DAZ and BOULE genes modulate primordial germ-cell and haploid gamete formation.Nature462(7270): 222-225. doi: 10.1038/nature08562.

10.International Stem Cell Initiative (2007). Characterization of human embryonic stem cell lines by the International Stem Cell Initiative.Nat Biotechnol25(7): 803-816. doi:10.1038/nbt1318.

11.Kee K, Gonsalves JM, Clark AT, Pera RA*. (2006). Bone morphogenetic proteins induce germ cell differentiation from human embryonic stem cells.Stem Cells Dev15(6): 831-837. doi: 10.1089/scd.2006.15.831.

12.Henderson KA,Kee K, Maleki S, Santini PA, Keeney S*. (2006). Cyclin-dependent kinase directly regulates initiation of meiotic recombination.Cell125(7): 1321-1332. doi: 10.1016/j.cell.2006.04.039.

13.Kee K, Protacio RU, Arora C, Keeney S*. (2004). Spatial organization and dynamics of the association of Rec102 and Rec104 with meiotic chromosomes.EMBO J23(8): 1815-1824. doi: 10.1038/sj.emboj.7600184.

14.Arora C,Kee K, Maleki S, Keeney S*. (2004). Antiviral protein Ski8 is a direct partner of Spo11 in meiotic DNA break formation, independent of its cytoplasmic role in RNA metabolism.Mol Cell13(4): 549-559. doi:10.1016/s1097-2765(04)00063-2.

15.Kee K, Keeney S*. (2002). Functional interactions between SPO11 and REC102 during initiation of meiotic recombination in Saccharomyces cerevisiae.Genetics160(1): 111-122.

16.Kee K, Niu L, Henderson E*. (1998). A Tetrahymena thermophila G4-DNA binding protein with dihydrolipoamide dehydrogenase activity.Biochemistry37(12): 4224-4234. doi: 10.1021/bi9716377

Awards:

2010, 2011,2017Bayer Investigator Award

2011Ten Outstanding Young Malaysian-Scientific and Technological development

2014Janssen Investigator Award

2014Tsinghua University ‘Outstanding Teaching Award’ (voted by students)


Lectures:

Medical cell biology

Stem cell biology


Extramural services:

2011-nowNational Natural Science Foundation of China(Grant Reviewer)

2012-2017Academic advisory board of State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Science

2013-nowThe Ministry of Science and Technology of China(Grant Reviewer)

2015-nowMedical Research Council, United Kingdom (Grant Reviewer)

2016-nowBeijing Municipal Science and Technology Commission(Grant Reviewer)

2017-nowInstitutional Review Broad for stem cell therapy, Peking Union Medical College

2019-now Advisory committee for life science and biotechnology of Chinese Spacecaft project


Patents:

US patent:9920300; Induction of germ cells from pluripotent cells; Inventors: Kee, Kehkooi; Reijo Pera, Renee.

China patent:201410730391.2;A chimeric nuclease specifically recognizes and edit mutations causing beta thalassemia, Chinese patent; Inventor: Jianfei Lin, Kehkooi Kee

China patent: 201710373412.3; In vitro differentiation of human embryonic stem cells into ovarian follicle and the culture medium; In ventor: Kehkooi Kee, Min Ye

China patent: 201810712206.5; A method to reprogram human fibroblasts to Sertoli cells and its application; Inventor:Kehkooi Kee, Jianlin Liang