Prof. Mak received his PhD from The University of Hong Kong and continued his postdoctoral training at the National Institute of Health (NIH). He started his own research program in the School of Biomedical Sciences in The Chinese University of Hong Kong as Assistant Professor. He worked at Guangzhou Institute of Regenerative Medicine of Health, Bioland Laboratory and Guangzhou National Laboratory as Principle Investigator before joining City University of Hong Kong. He received a number of awards for his research works including American Society of Bone and Mineral Research Young Investigator Award, Webster Jee Young Investigator Award, Gordon Conference Bone and Teeth Travel Award, Fellows Award for Research Excellence Travel Award, NIH and Talent awards from Guangzhou Province, China. Currently, his research focuses on dissecting the roles of key factors in regulating skeletal tissue regeneration and energy metabolism.

Research Interests

Our lab is interested in studying the roles of important signaling pathways in regulating tissue homeostasis, regeneration and disease pathogenesis. Specifically, we are interested to study the molecular mechanisms in the context of the skeletal system including the interactive regulations among chondrocytes, osteocytes, adipocytes, myocytes and tenocytes. The requirement for the niche establishment for the dynamic interactions with MSCs and HSCs within the bone marrow is also a focus in our lab. With the understanding of the interactions across different but closely related cell lineages in the skeletal system, we expect to set the foundation which essentially aid the development of new therapeutic approaches for tissue regeneration to help patients suffering with various skeletal diseases such as osteoarthritis, osteoporosis as well as certain skeletal cancers and metabolic disorders. In addition, we are also interested in studying the interactions between bone and energy metabolism. The skeleton is considered as one of the largest organs in mammals and it has been recently shown that bone is actively involved in glucose metabolism, energy expenditure as well as male fertility. These findings open up a totally new direction for the possible use of therapeutic treatments that are not previously considered. We aim to identify additional secretory factors derived from the bones that will regulate the metabolism of other organs. These findings will significantly advance the field of integrative physiology and delineate the important physiological functions of the bones, which previously misinterpreted as an inert organ.

Selected Publications

1. Liu Y, Wang Y, Xu C, Zhang Y, Wang Y, Qin J, Lan H, Wang L, Huang Y, Mak KK, Zheng Z, Xia Y. Activation of the YAP/KLF5 transcriptional cascade in renal tubular cells aggravates kidney injury. Molecular Therapy. 2024. Doi: 10.1016/j.ymthe.2024.02.031.
2. Yang KG, Chen H, Cheng K, Tang M, Wang Y, Hung AL, Cheng CY, Mak KK, Lee WY. Wnt16 interacting with Vitamin D generates synergistic effect on bone qualities in adolescent idiopathic scoliosis patients and health controls. Biomedicines. 2024 12(1) 250 doi.org/10.3390/biomedicines12010250
3. Zhang Y, Huang H, Kong Y, Xu C, Dai L, Geng X, Deng Y, Wang Y, Liu Y, Meng C, Zhang X, Li J, Qin J, Feng B, Mak KK, Wang L, Huang Y, Wang W, Lan H, Yang B, Lu HJ, Xia Y. Kidney tubular transcription co-activator, Yes-associated protein 1 (YAP), controls the expression of collecting duct aquaporins and water homeostasis. Kidney International. 2022 Nov 1; S0085-2538(22)00915-2. doi: 10.1016/j.kint.2022.10.007
4. Zhang Y, Wang Y, Huang H, Xu C, Zeng Y, Zhang X, Qin J, Dai C, Hambrock HO, Hartman U, Feng B, Mak KK, Liu Y, Lan HY, Huang Y, Xia Y. Follistatin-like 1 (FSTL1) interacts with Wnt ligands and Frizzled receptors to enhance Wnt/b-catenin signaling in obstructed kidneys in vivo. J Biol Chem. 2022 doi.org/10.1016/jbc:2022:102010
5. Zhang X, Wang D, Mak KK, Tuan RS, Ker DFE. Engineering Musculoskeletal Grafts for Multi-Tissue Unit Repair: Lessons from Developmental Biology and Wound Healing. Frontiers in Physiology. 2021, 12:691954. doi:10.3389/fphys.2021.691954.eCollection
6. Wang D^†, Zhang X^†, Huang S, Yang L, Fu BS, Mak KK, Blocki AM, Yung PS, Tuan RS, Ker DFE* Engineering Multi-Tissue Units for Regenerative Medicine: Bone-Tendon-Muscle Unites of the Rotator Cuff. Biomaterials. 2021 doi:10.1016/j.biomaterials.2021.120789
7. Sun X, Ren Z, Cun Y, Zhao C, Huang X, Zhou J, Hu R, Su X, Ji L, Li P, Mak KK, Gao F, Yang Y, Xu H, Ding J, Cao N, Li S, Zhang, W, Lan P, Sun H, Wang J, Yuan P. Hippo-YAP signaling controls lineage differentiation of mouse embryonic stem cells through modulating the formation of super-enhancers. Nucleic Acids Res. 2020 doi: 10.1093/nar/gkaa482
8. Meng C, Geng T, Xu C, Li X, Zhang Y, Wang Y, Qin J, Fok E, Hinton B, Mak KK, Shum W, and Chan WY, Xia Y. Hippo kinases MST1 and MST2 control the differentiation of the epididymal initial segment via the MEK-ERK pathway. Cell Death Diff. 2020 doi:10.1038/s41418-020-0544-x
9. Xu C, Wang L, Zhang Y, Li W, Li J, Wang Y, Meng C, Qin J, Zheng Z, Lan HY, Mak KK, Huang Y, Xia Y. Tubule-specific Mst1/2 Deficiency induces CKD via YAP and non-Yap mechanisms. Journal of the American Society of Nephrology. 2020 doi: 10.1681/ASN.2019101052
10. Tong W, Zeng Y, Chow DH, Yeung W, Xu J, Deng Y, Chen S, Zhao H, Zhang X, Ho KK, Qin L, Mak KK. Wn16 attenuates osteoarthritis progression through a PCP/JNK-mTORC1-PTHrP cascade. Ann Rheum Dis. 2019 doi:10.1136/annrheumdis-2018-214200
11. Deng Y, Wu A, Li W, Tong W, Qin L, Song H, Mak KK. Reciprocal inhibition of YAP/TAZ and NF-kB regulates osteoarthritic cartilage degradation. Nat Commun. 2018 9:4564 doi: 10.1038/s41467-018-07022-2 (Highlighted by Nature Reviews Rheumatology)
12. Li W, Deng Y, Feng B, Mak KK. Mst kinases modulate glucose uptake for osteoblast differentiation and bone formation. J Bone Miner Res. 2018 doi:10.1002/jbmr.3413
13. Wang Y, Zhang X, Xia Y, Yung PS, Chan KM, Mak KK. Osteocalcin expressing cells from tendon sheaths contribute to tendon repair by activating Hedgehog signalling. eLife. 2017 6e30474 doi:10.7554/eLife30474
14. Wang L, Luo J, Li B, Tian XY, Chen L, Huang Y, Liu J, Deng D, Lau CW, Wan S, Ai D, Mak KK, Tong KK, Kwan KM, Wang N, Chiu J, Zhu Y, Huang Y. Integrin-YAP/TAZ-JNK cascade mediates atheroprotective effect of unidirectional shear flow. Nature. 2016 doi: 10.1038/nature20602. (Impact factor:49.962; Featured in Nature Editorial)
15. Zhang X, Cheng Q, Wang Y, Leung PS, Mak KK. Hedgehog signaling in bone regulates whole body energy metabolism through a bone-adipose relay mediated by PTHrP and Adiponectin. Cell Death Diff. 2016 doi: 10.1038/cdd.2016.113
16. Deng Y, Li PS, Li G, Qin L, Mak KK. Yap1 regulates multiple steps of chondrocyte differentiation during skeletal development and bone repair. Cell Reports. 2016 14:2224-37(Featured in Cell Reports Homepage)
17. Tu J, Ng, SH, Luk ACS, Liao JJ, Jiang X, Feng B, Mak KK, Rennert O, Chan WY, Lee TL. MicroRNA-29b/Tet1 regulatory axis epigenetically modulates mesendoderm differentiation in mouse embryonic stem cells. Nucleic Acids Res. 2015 43(16):7805-22
18. Mak KK. White adipose tissue browning and cancer cachexia. J Cancer Sci. 2015; 2(1):2.
19. Li P, Chen Y, Mak KK, Wong CK, Wang CC, Yuan P. Functional role of Mst1/Mst2 in embryonic stem cell differentiation. PLoS One. 2013 8(11): e79867.doi:10.1371/journal.pone
20. Chan LH, Wang W, Yeung W, Deng Y, Yuan P, Mak KK. Hedgehog signaling induces osteosarcoma development through Yap1 and H19 overexpression. Oncogene. 2014 33:4857-66
21. Mak KK. Differential effects of Hedgehog Signaling on postnatal bone remodeling. IBMS BoneKEy. 2013 10:331
22. Yang Y, Zhou L, Jian P, Wang L, Hu L, Li X, Chan LKY, Yu J, Kwong J Cheung TH, Chung TKH, Mak KK, Sun H, Wang H. A Novel miR-193a-5p-yy1-APC Regulatory Axis in Human Endometrioid Endometrial Adenocarcinoma. Oncogene. 2013 32:3432-42
23. Song H*, Mak KK*, Topol L, Yun K, Hu J, Garrett L, Chen Y, Park O, Chang J, Simpson RM, Wang CY, Gao B, Jiang J, Yang Y. Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression. Proc Natl Acad Sci USA. 2010 107(4):1431-36. (* equal contribution)
24. Guo X, Mak KK, Maketo MM, Yang Y. The Wnt/ b-catenin pathway interacts differentially with PTHrP signaling to control chondrocyte hypertrophy and final maturation. PLoS One. 2009 4(6):e6067
25. Nemeth MJ, Mak KK, Yang Y, Bodine DM. b-catenin expression in the bone marrow microenvironment is required for long term maintenance of primitive haematopoitic cells. Stem Cells. 2009 27(5):1109-19
26. Mak KK, Bi Y, Wan C, Chuang PT, Clemens T, Young M, Yang Y. Hedgehog signaling in mature osteoblasts regulates bone formation and resorption by controlling PTHrP and RANKL expression. Dev. Cell. 2008 14:674-88. (Cover story)
27. Mak KK, Kronenberg HM, Chuang PT, Meckem S, Yang Y. Indian hedgehog signals independently of PTHrP to promote chondrocyte hypertrophy. Development. 2008 135:1947-56
28. Mak KK, Chen M, Day TF, Chuang PT, Yang Y. Wnt/b-catenin signaling interacts differentially with Ihh signaling in controlling endochondral bone and synovial joint formation. Development. 2006 133(18):3695-707
29. Mak KK, Chan SY. Epidermal growth factor as a biologic switch in hair growth cycle. J Biol Chem. 2003 278(28):26120-6
30. Wong RW, Kwan RW, Mak PH, Mak KK, Sham MH, Chan SY, Overexpression of epidermal growth factor induced hypospermatogenesis in transgenic mice. J Biol Chem. 2000 275(24):18297-301

27 February 2024