Subbroto Kumar Saha, PhD

Journal Publications 

(*Correspondence; †Equal contribution)

(https://www.ncbi.nlm.nih.gov/myncbi/subbroto.saha.1/bibliography/public/)

Research Articles

1. Sun, B., Reynolds, K. S.,Garland, M. A., McMahon, M., Saha, S. K., &Zhou, C. J. (2023). Epigenetic implications in maternal diabetes and metabolic syndrome-associated risk of orofacial clefts. Birth Defects Research,1–16. https://doi.org/10.1002/bdr2.222616SUNET AL.

2. Sun, B., Reynolds, K., Saha, SK, Zhang, S., McMahon, M., & Zhou, C. J. (2023). Ezh2-dependent methylation in oral epithelia promotes secondary palatogenesis. Birth Defects Research, 1– 15. https://doi.org/10.1002/bdr2.2216

3. Lee M, Seok J, Saha SK, Cho S, Jeong Y, Gil M, Kim A, Shin HY, Bae H, Do JT, Kim YB, Cho SG. 2023. Alterations and Co-Occurrence of C-MYC, N-MYC, and L-MYC Expression are Related to Clinical Outcomes in Various Cancers. Int J Stem Cells. 2023 Apr 30. (IF: 3.011) DOI: 10.15283/ijsc22188. (Co-Author)

4. Biswas, P.K.; Park, S.R.; An, J.; Lim, K.M.; Dayem, A.A.; Song, K.; Choi, H.Y.; Choi, Y.; Park, K.S.; Shin, H.J.; Kim, A.; Gil, M.; Saha, S.K.; Cho, S.-G. 2023. The Orphan GPR50 Receptor Regulates the Aggressiveness of Breast Cancer Stem-like Cells via Targeting the NF-kB Signaling Pathway. International Journal of Molecular Sciences, 24, 2804. (IF: 6.208; Q1) DOI: https://doi.org/10.3390/ijms24032804 (Co-Author)

5. Gu, R.†, Zhang, S.†, Saha, S. K.†, Ji, Y., Reynolds, K., McMahon, M., Sun, B., Islam, M., Trainor, P. A., Chen, YiP., Xu, Y., Chai, Y., Burkart-Waco, D., and Zhou, C. J., 2022. Single-cell transcriptomic signatures and gene regulatory networks modulated by Wls in mammalian midline facial formation and clefts. Development  149 (14), dev200533. (IF: 6.868; Q1) (Co-first Author)  

6. Zhao, T., McMahon, M., Reynolds, K., Saha, S. K., Stokes, A., and Zhou, C., 2022. The role of Lrp6-mediated Wnt/beta-catenin signaling in the cause and intervention of spinal neural tube defects in mice. Disease Models & Mechanisms, 15 (6), dmm049517. (IF: 5.758; Q1) DOI: https://doi.org/10.1242/dmm.049517 (Co-Author) 

7. Rahman, M., Biswas, P.K., Saha, S.K. et al. 2022. Identification of glycophorin C as a prognostic marker for human breast cancer using bioinformatic analysis. Network Modeling Analysis in Health Informatics and Bioinformatics,11, 7. DOI: https://doi.org/10.1007/s13721-021-00352-0 (Co-Author) 

8. Sabeh, M.E.†, Saha, S. K.†, Afrin, S., and Borahay, M.A., 2021. Simvastatin inhibits Wnt/β-catenin pathway in uterine leiomyoma. Endocrinology, 62 (12), bqab211. (IF: 4.736; Q1) DOI: 10.1210/endocr/bqab211 (Co-first Author)

9. Islam, S.M.R. †, Saha, S. K. †,*, El-Sappagh, S., Tariq, F.,  Das, J., Afzal, M., and Cho, S-G.*, 2021. Expression of GRINA Correlates with Prognosis in Human Cancers: A Pan-cancer Analysis. BioRxiv. Doi: https://doi.org/10.1101/2021.05.13.444089 (Co-first & Co-corresponding Author)

10. Seok, J., Gil, M., Dayem, A. A., Saha, S.K., Cho, S.-G. 2021. Multi-omics Analysis of SOX4, SOX11, and SOX12 Expression and the Associated Pathways in Human Cancers. Journal of Personalized Medicine, 11 (8), 823. (IF: 4.945; Q1) DOI: https://doi.org/10.3390/jpm11080823 (Co-Author)

11. Rahman, M.S.†, Hossain, M.S.†, Saha, S.K.†, Rahman, S., Sonne, C., Kim, K.-H., 2021. Homology Modeling and Probable Active Site Cavity Prediction of Uncharacterized Arsenate Reductase in Bacterial spp. Applied Biochemistry and Biotechnology, 193, 1-18. (IF: 2.926) DOI: https://doi.org/10.1007/s12010-020-03392-w (Co-first Author)  

12. Kwak, H. J., Gil, M., Chae, H., Seok, J., Soundrarajan, N., Saha, S.K., Kim, A., Park, K. S., Park, C., and Cho, S-G., 2020. Expression of ATP/GTP Binding Protein 1 Has Prognostic Value for the Clinical Outcomes in Non-Small Cell Lung Carcinoma. Journal of Personalized Medicine, 10 (4), 263. (IF: 4.945; Q1) DOI: https://doi.org/10.3390/jpm10040263 (Co-Author)

13. Chae, H., Gil, M., Saha, S.K., Kwak, H.J., Park, H.-W., Vellingiri, B., and Cho, S.-G., 2020. Sestrin2 expression has regulatory properties and prognostic value in lung cancer. Journal of Personalized Medicine, 10 (3), 109. (IF: 4.945; Q1) DOI: https://doi.org/10.3390/jpm10030109 (Co-Author)

14. Saha, S.K.†, Jeon, T.-I.†, Jang, S.B., Kim, S.J., Lim, K.M., Choi, Y.J., Kim, H.G., Kim, A., and Cho, S-G., 2020. Bioinformatic approach for identifying novel biomarkers and their signaling pathways involved in interstitial cystitis/bladder pain syndrome. Journal of Clinical Medicine, 9 (6), 1935. (IF: 5.688; Q1) DOI: https://doi.org/10.3390/jcm9061935 (Co-first Author)

15. Saha, S. K., Choi, H-Y., Yang, G-M., Biswas, P.K., Kim, K. S., Kang, G.H., Gil, M., and Cho, S-G., 2020. GPR50 promotes hepatocellular carcinoma progression via the Notch signaling pathway through direct interaction with ADAM17. Molecular Therapy-Oncolytics, 17, 332-349. (IF: 7.2; Q1) DOI: 10.1016/j.omto.2020.04.002 (First Author)

16. Saha, S. K. †,*, Islam, S.M.R. †, Kwak, K-S., Rahman, S., and Cho, S-G.*, 2020. PROM1 and PROM2 Expression Differentially Modulates Clinical Prognosis of Cancer: A Multiomics Analysis. Cancer Gene Therapy, 27 (3-4), 147-167. (IF: 5.987; Q1). DOI: 10.1038/s41417-019-0109-7 (Co-first & Co-corresponding Author)

17. Saha, S.K.†, Kader, M.A.†, Samad, A., Biswas, K.C., Rahman, M.A., Parvez, M.A.K., and Rahman, M.S., 2020. Prognostic and clinico-pathological significance of BIN1 in breast cancer. Informatics in Medicine Unlocked, 19, 100327. DOI: 10.1016/j.imu.2020.100327 (Co-first Author)

18. Barman, U.D.†, Saha, S. K.†, Kader, M.A., Jamal, M.A.H.M., Sharma, S.P., Samad, A., and Rahman, M.S., 2020. Clinicopathological and prognostic significance of GPC3 in human breast cancer and its 3D structure prediction. Network Modeling Analysis in Health Informatics and Bioinformatics, 9, 24. DOI: 10.1007/s13721-020-00234-x (Co-first Author)  

19. Kim, K.; Gil, M.; Dayem, A.A.; Choi, S.; Kang, G.-H.; Yang, G.-M.; Cho, S.; Jeong, Y.; Kim, S.J.; Seok, J.; Kwak, H.J.; Saha, S. K.; Kim, A.; Cho, S.-G. 2020. Improved Isolation and Culture of Urine-Derived Stem Cells (USCs) and Enhanced Production of Immune Cells from the USC-Derived Induced Pluripotent Stem Cells. Journal of Clinical Medicine, 9, 827. (IF: 5.688; Q1). DOI: 10.3390/jcm9030827 (Co-Author)

20. Rahman, S., Jamal, M.A.H.M., Biswas, P.K., Rahman, S.M., Sharma, S.P., Saha, S. K.*, Hong, S.T.*, and Islam, M.R.*, 2020.  Arsenic Remediation in Bangladeshi Rice Varieties with Enhance Plant Growth by Unique Arsenic-Resistant Bacterial Isolates. Geomicrobiology Journal, 37 (2), 130-142. (IF: 2.308). DOI: 10.1080/01490451.2019.1666938 (Co-corresponding Author)

21. Saha, S.K.†, Biswas, P.K.†, Gil, M.*, and Cho, S-G.*, 2019. High Expression of TTYH3 is Related to Poor Clinical Outcomes in Human Gastric Cancer. Journal of Clinical Medicine, 8 (11), 1762. (IF: 5.688; Q1). DOI: 10.3390/jcm8111762 (Co-first Author)

22. Saha, S. K., Kim, K. E., Islam, S.M.R., Cho, S-G., and Gil, M., 2019. Systematic Multiomics Analysis of Alterations in C1QBPmRNA Expression and Relevance for Clinical Outcomes in Cancers. Journal of Clinical Medicine, 8 (4), 513. (IF: 5.688; Q1). DOI: 10.3390/jcm8040513 (First Author) 

23. Saha, S. K. †,*, Islam, S.M.R. †, Abdullah-AL-Wadud, M., Islam, S., Ali, F., and Park, K. S., 2019. Multiomics Analysis Reveals GLS and GLS2 Differentially Modulate the Clinical Outcomes of Cancer. Journal of Clinical Medicine, 8 (3), 355. (IF: 5.688; Q1). DOI: 10.3390/jcm8030355 (Co-first & Corresponding Author) 

24. Choi, H-Y., Yang, G-M., Dayem, A. A., Saha, S. K., Kim, K. S., Yoo, Y., Hong, K., Kim, J-H., Yee, C., Lee, K-M., and Cho, S-G., 2019. Hydrodynamic shear stress promotes epithelial-mesenchymal transition by downregulating ERK and GSK3β activities. Breast Cancer Research, 21 (1), 6. (IF: 6.466; Q1). DOI: 10.1186/s13058-018-1071-2 (Co-Author)

25. Saha, S. K., Yin, Y.F., Chae, H. S., and Cho, S-G., 2019. Opposing regulation of cancer properties via KRT19-mediated differential modulation of Wnt/β-catenin/Notch signaling in breast and colon cancers. Cancers, 11 (1), 99. (IF: 6.639; Q1). DOI: 10.3390/cancers11010099 (First Author) 

26. Saha, S. K. †, Jong, Y. †, Cho, S., and Cho, S-G., 2018. Systematic expression alteration analysis of master reprogramming factor, octamer-binding transcription factor 4 (OCT4), in human cancer and their prognostic outcomes. Scientific Reports, 8, 14806. (IF: 4.379; Q1). DOI: 10.1038/s41598-018-33094-7 (Co-first Author)

27. Saha, S. K., Kim, K. S., Yang, G-M., Choi, H-Y., and Cho, S-G., 2018. Cytokeratin 19 (KRT19) has a Role in the Reprogramming of Cancer Stem Cell-Like Cells to Less Aggressive and More Drug-Sensitive Cells. International Journal of Molecular Sciences, 19 (5), 1423. (IF: 6.208; Q1). DOI: 10.3390/ijms19051423 (First Author)

28. Hossain, M. K.†, Saha, S. K. †, Dayem, A. A., Kim, J-H., Kim, K. S., Yang, G-M., Choi, H-Y., and Cho, S-G., 2018. Bax Inhibitor-1 Acts as an Anti-Influenza Factor by Inhibiting ROS Mediated Cell Death and Augmenting Heme-Oxygenase 1 Expression in Influenza Virus Infected Cells. International Journal of Molecular Sciences, 19 (3), 712. (IF: 6.208; Q1). DOI: 10.3390/ijms19030712 (Co-first Author) 

29. Saha, S. K., Yin, Y.F., Kim, K. S., Yang, G-M., Dayem, A. A., Choi, H-Y., and Cho, S-G., 2017. Valproic acid induces endocytosis-mediated doxorubicin internalization and shows synergistic cytotoxic effects in hepatocellular carcinoma cells. International Journal of Molecular Sciences, 18 (5), 1048. (IF: 6.208; Q1). DOI: 10.3390/ijms18051048 (First Author)

30. Saha, S. K., Choi, H-Y., Kim, B-W., Dayem, A. A., Yang, G-M., Kim, K. S., Yin, Y.F., and Cho, S-G., 2017. KRT19 directly interacts with β-catenin/RAC1 complex to regulate NUMB-dependent NOTCH signaling pathway and breast cancer properties. Oncogene, 36 (3), 332-349. (IF: 9.867; Q1). DOI: 10.1038/onc.2016.221 (First Author)

31. Rahman, M. S., Ahad, A., Saha, S. K., Hong, J., and Kim, K-H., 2017. Antibacterial and phytochemical properties of Aphanamixis polystachya essential oil. Analytical Science and Technology, 30 (3), 113-121. DOI: https://doi.org/10.5806/AST.2017.30.3.113 (Co-Author) 

32. Rahman, M. S., Hossain, R., Saikot. F. K., Rahman, S. M., Saha, S. K., Hong, J., and Kim, K-H., 2017. Insights into the in vitro germicidal activities of Acalypha indica. Analytical Science and Technology, 30 (1), 26-31. DOI: https://doi.org/10.5806/AST.2017.30.1.26 (Co-Author)

33. Dayem, A. A., Kim, B-W., Gurunathan, S., Choi, H-Y., Yang, G-M., Saha, S. K., Han, D., Han, J., Kim, K., Kim, J-H., and Cho, S-G., 2014. Biologically synthesized silver nanoparticles induce neuronal differentiation of SH-SY5Y cells via modulation of reactive oxygen species, phosphatases, and kinase signaling pathways. Biotechnology Journal, 9 (7), 934-943. (IF: 4.677; Q1). DOI: 10.1002/biot.201300555 (Co-Author)

34. Saha, S.K., and Kim, K.-H., 2013. Long-term variations of airborne cadmium (Cd) concentrations in major urban areas of Korea between 1991 and 2010. Aerosol and Air Quality Research, 13 (3), 1078–1089. (IF: 4.53; Q2). DOI: 10.4209/aaqr.2012.10.0268 (First Author)

35. Saha, S.K., Jo, S.-H., Song, H.-N., Brown, R.J.C., and Kim, K.-H., 2012. Contrasting recovery patterns of 2, 4-dinitrophenylhydrazones (DNPH) derivative of carbonyls between liquid and gas phase standards using HPLC-based analysis. Atmospheric Environment, 62, 562-565. (IF: 5.755; Q1). DOI: 10.1016/j.atmosenv.2012.09.005 (First Author)

36. Haque, M., Saha, S.K., Islam, D., and Islam, M., 2012. Comparative study between the effect of Coccinia cordiffolia (leaves and roots) on hypoglycemic and hypolipidemic activity of alloxan induced type 2 diabetic long-evans rats. Journal of Diabetes and Endocrinology, 3 (4), 37-43. DOI: 10.5897/JDE11.018 (Co-Author)

37. Saha, S.K.*, Haque, M., Islam, D., Rahman, M., Islam, M., Parvin, A., and Rahman, S., 2012. Comparative study between the effect of Momordica charantia (wild and hybrid variety) on hypoglycemic and hypolipidemic activity of alloxan induced type 2 diabetic long-evans rats. Journal of Diabetes Mellitus, 2 (1), 131-137. (IF: 0.49).  DOI: 10.4236/jdm.2012.21022 (First & Corresponding Author) 

Review Articles

37. Sun, B., Reynolds, K., Garland, M., McMahon, M., Saha, S. K., and Zhou, C., 2023. Epigenetic implications in maternal diabetes and metabolic syndrome-associated risk of orofacial clefts. Birth Defects Research. (Accepted).

38. Haque, S. T., Saha, S. K., Haque, M. E., and Biswas, N., 2021. Nanotechnology-based Therapeutic Applications: In Vitro, In Vivo Clinical Studies for Diabetic Wound Healing. Biomaterials Science, 9, 7705-7747. (IF: 7.59; Q1) Doi: https://doi.org/10.1039/D1BM01211H (Co-Author)

39. Saha, S. K. †,*, Islam, S.M.R. †, Saha, T., Gil, M., Nkenyereye, L., Kwak, K-S., and Cho, S-G.*, 2021. Prognostic role of EGR1 in breast cancer: a systematic review. BMB Reports, 54 (10) 497-504. (IF: 5.041; Q2) PMID: 34488929 (Co-first & Co-corresponding Author)

40. Sabeh, M.E.†, Saha, S. K.†, Afrin, S., Islam, M. S., and Borahay, M.A., 2021. Wnt/β-catenin signaling pathway in uterine leiomyoma: role in tumor biology and targeting opportunities. Molecular and Cellular Biochemistry, 476, 3513-3536. (IF: 3.842) Doi: https://doi.org/10.1007/s11010-021-04174-6 (Co-first Author)

41. Rahman, M.A.†, Saha, S. K. †, Rahman, M.S., Uddin, M.J., Uddin, M.S., Pang, M.-G., Rhim, H., andCho, S-G., 2020. Molecular Insights into Therapeutic Potential of Autophagy Modulation by Natural Products for Cancer Stem Cells. Frontiers in Cell and Developmental Biology, 8, 283. (IF: 6.684; Q1) DOI: 10.3389/fcell.2020.00283 (Co-first Author)

42. Tejwan, N., Saha, S. K.*, and Das, J.*, 2020. Multifaceted applications of green carbon dots synthesized from renewable sources. Advances in Colloid and Interface Science, 275, 102046. (IF: 15.19; Q1). DOI: 10.1016/j.cis.2019.102046 (Co-corresponding Author)

43. Saha, S. K. †,*, Saikot, F. K. †, Rahman, S. †, Jamal, M.A.H.M.†, Rahman, S. M.K. †, Islam, S.M.R.†, Kim, K.-H.†,*, 2019. Programmable molecular scissors: Applications of a new tool for genome editing in biotech. Molecular Therapy-Nucleic Acid, 14, 212-238. (IF: 10.183; Q1). DOI: 10.1016/j.omtn.2018.11.016 (Co-first & Co-corresponding Author)

44. Saha, S. K., Lee, S. B., Won, J., Choi, H-Y., Kim, K. S., Yang, G-M., Dayem, A. A., and Cho, S-G., 2017. Correlation between Oxidative Stress, Nutrition, and Cancer Progression. International Journal of Molecular Sciences, 18 (7), 1544. (IF: 6.208; Q1). DOI: 10.3390/ijms18071544 (First Author)

45. Ansari, A. †, Rahman, S. †, Saha, S. K. †, Saikot, F. K. †, Deep, A., and Kim, K.-H., 2017. Function of the SIRT3 mitochondrial deacetylase in cellular physiology, cancer, and neurodegenerative disease. Aging cell, 16 (1), 4-16. (IF: 11.005; Q1; <5%). DOI: 10.1111/acel.12538 (Co-first Author)

46. Dayem, A. A., Choi, H-Y., Yang, G-M., Kim, K. S., Saha, S. K., and Cho, S-G., 2016. The Anti-cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms. Nutrients, 8 (9), 581. (IF: 6.706; Q1). DOI: 10.3390/nu8090581 (Co-Author)

47. Dayem, A. A., Hossain, M. K., Lee, S., Kim, K. S., Saha, S. K., Yang, G-M., Choi, H-Y., and Cho, S-G., 2017. The role of reactive oxygen species (ROS) in the biological activities of metallic nanoparticles. International Journal of Molecular Sciences, 18 (1), 120. (IF: 6.208; Q2). DOI: 10.3390/ijms18010120 (Co-Author)

48. Dayem, A. A., Choi, H-Y., Yang, G-M., Kim, K. S., Saha, S. K., Kim, J-H., and Cho, S-G., 2016. The potential of nanoparticles in stem cell differentiation and further therapeutic applications. Biotechnology Journal, 11 (12), 1550–1560. (IF: 5.726; Q1). DOI: 10.1002/biot.201600453 (Co-Author)

49. Hossain, M. K., Dayem, A. A., Han, J., Yin, Y.F., Kim, K. S., Saha, S. K., Yang, G-M., Choi, H-Y., and Cho, S-G., 2016. Molecular Mechanisms of the Anti-Obesity and Anti-Diabetic Properties of Flavonoids. International Journal of Molecular Sciences, 17 (4), 569. (IF: 6.208; Q1). DOI:  10.3390/ijms17040569 (Co-Author)

50. Hossain, M. K., Dayem, A. A., Han, J., Saha, S. K., Yang, G-M., Choi, H-Y., and Cho, S-G., 2016. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells. International Journal of Molecular Sciences, 17 (2), 256. (IF: 6.208; Q1). DOI: 10.3390/ijms17020256 (Co-Author)

51. Choi, H-Y., Saha, S. K., Kim, K., Kim, S., Yang, G-M., Kim, B-W., Kim, J-H., and Cho, S-G., 2015. G protein-coupled receptors in stem cell maintenance and somatic reprogramming to pluripotent or cancer stem cells. BMB Reports, 48 (2), 68-80. (IF: 5.041; Q2). DOI:  10.5483/BMBRep.2015.48.2.250 (Co-Author)

52. Rahman, S., Kim, K.-H., Saha, S. K., Swaraz, A. M., and Paul, D. K., 2014. Review of remediation techniques for arsenic (As) contamination: A novel approach utilizing bio-organisms. Journal of Environmental Management, 134, 175–185. (IF: 8.91; Q1). DOI: 10.1016/j.jenvman.2013.12.027 (Co-Author)

My area of research centers around epigenetics and post-translational modification of proteins in craniofacial development. To better understand this process, I am using knock-out/-in mouse models and a Cre/loxP conditional gene-targeting approach. Specifically, I am investigating how the Wnt/β-catenin signaling pathway is impacted by epigenetic regulation and post-translational modification in neural crest and mesenchymal cells during craniofacial development, particularly in midline facial formation and fusion. Additionally, I am interested in exploring how targeting key regulating genes can affect cancer progression and prognosis using tumorigenic/transgenic mice models. Over the years, my research has identified important functions of several gene biomarkers such as Wntless (Wls), G protein-coupled receptor 50 (GPR50), and Cytokeratin 19 (KRT19) in both craniofacial development and cancer progression. My previous and current research interests are as follows-

1. Cellular and molecular mechanisms of orofacial clefts and neural tube defects: 

My interest in developmental biology is a fundamental aspect of my research career, which has led me to evaluate the cellular and molecular mechanisms underlying facial morphogenesis and neural tube defects. Through our studies, we were able to gain a mechanistic insight into the modulation and integration of multiple signaling pathways by Wls, which is essential for the regulation of a core gene regulatory network (GRN) in the midfacial primordia. Furthermore, our research has identified several downstream target genes of GRN in the midfacial primordia, which are critical for the proper formation and fusion of the lip and palate during craniofacial development.

In addition to our work on facial morphogenesis, we also demonstrated the essential role of Lrp6-mediated Wnt/β-catenin signaling in posterior neuropore (PNP) closure. Our findings have the potential to provide a therapeutic target for neural tube defects (NTD) intervention by manipulating canonical Wnt/β-catenin signaling activities. Overall, our research provides valuable insights into the complex regulatory mechanisms underlying craniofacial development and neural tube closure, which have important implications for the diagnosis and treatment of craniofacial malformations and NTDs.

References:

1. Gu R*, Zhang S*, Saha SK*, Ji Y, Reynolds K, McMahon M, Sun B, Islam M, Trainor PA, Chen Y, Xu Y, Chai Y, Burkart-Waco D, Zhou CJ. Single-cell transcriptomic signatures and gene regulatory networks modulated by Wls in mammalian midline facial formation and clefts. Development. 2022 Jul 15;149(14) PubMed Central PMCID: PMC9382898.

2. Zhao T, McMahon M, Reynolds K, Saha SK, Stokes A, Zhou CJ. The role of Lrp6-mediated Wnt/β-catenin signaling in the development and intervention of spinal neural tube defects in mice. Dis Model Mech. 2022 Jun 1;15(6) PubMed Central PMCID: PMC9194482. 

2. Cytokeratin in Cancer Progression and Prognosis

Our interest on the cellular and molecular mechanism of breast cancer progression and prognosis. In our research, we utilized RNA Seq data from CD133high/CXCR4high/ALDH1high cancer stem-like cells (KU-CSLCs) and normal breast cells, which were obtained from breast cancer patients undergoing chemotherapy at Konkuk University Hospital. Our analysis revealed a significant decrease in the expression of various cytokeratins (KRTs) in KU-CSLCs, particularly KRT19, while high levels of KRT19 were detected in breast cancer cell lines. This led us to investigate the role of KRT19 in breast cancer progression and the underlying signaling mechanism. To accomplish this, we employed KRT19-targeted shRNA to knock down KRT19 in breast cancer cell lines and overexpressed KRT19 in KU-CSLCs. Our findings revealed that silencing KRT19 induced cancer properties, whereas overexpression of KRT19 attenuated KU-CSLCs properties. To elucidate the underlying mechanism of this phenomenon, we employed omics tools and found that KRT19 was linked to Wnt and Notch signaling. Experimental data confirmed that KRT19 positively regulates Wnt signaling-mediated NUMB transcription, which is a Notch signaling inhibitor, ultimately inhibiting Notch signaling-mediated cancer properties. Our Co-immunoprecipitation (Co-IP) assay further confirmed the interaction between KRT19, β-catenin, and RAC1. Furthermore, our chromatin-immunoprecipitation (CHIP), protein fraction western blot, and immunocytochemistry (ICC) assays confirmed the translocation of β-catenin and RAC1 onto the NUMB promoter, ultimately affecting the Notch signaling-mediated cancer properties. These findings could be beneficial for researchers working in this field.

References:

1. Saha SK, Yin Y, Chae HS, Cho SG. Opposing Regulation of Cancer Properties via KRT19-Mediated Differential Modulation of Wnt/β-Catenin/Notch Signaling in Breast and Colon Cancers. Cancers (Basel). 2019 Jan 15;11(1) PubMed Central PMCID: PMC6357186.

2. Saha SK, Kim K, Yang GM, Choi HY, Cho SG. Cytokeratin 19 (KRT19) has a Role in the Reprogramming of Cancer Stem Cell-Like Cells to Less Aggressive and More Drug-Sensitive Cells. Int J Mol Sci. 2018 May 9;19(5) PubMed Central PMCID: PMC5983664.

3. Saha SK, Choi HY, Kim BW, Dayem AA, Yang GM, Kim KS, Yin YF, Cho SG. KRT19 directly interacts with β-catenin/RAC1 complex to regulate NUMB-dependent NOTCH signaling pathway and breast cancer properties. Oncogene. 2017 Jan 19;36(3):332-349. PubMed Central PMCID: PMC5270332. 

3. Exploring biomarkers of cancer progression and prognosis using multi-omics tools 

My interest in cancer progression and prognosis led to the use of microarray and RNA sequencing data that can reveal widespread changes in tumor genomes, including alterations in mRNA expression, promoter methylation, mutations, and copy number alterations (CNAs). These changes can provide insights into the role of specific genes in cancer progression and prognosis. As a researcher, I analyze publicly available microarray and RNA sequencing data from TCGA, oncomine, and GEO to investigate mRNA expression, promoter methylation, CNAs, and clinical outcomes in various cancers. Using co-expressed and PPI data, I propose underlying mechanisms of genes through gene ontology (GO) and KEGG or Reactome pathway search, which could help develop new anti-cancer therapies. 

References:

1. Saha SK, Jeon TI, Jang SB, Kim SJ, Lim KM, Choi YJ, Kim HG, Kim A, Cho SG. Bioinformatics Approach for Identifying Novel Biomarkers and Their Signaling Pathways Involved in Interstitial Cystitis/Bladder Pain Syndrome with Hunner Lesion. J Clin Med. 2020 Jun 21;9(6) PubMed Central PMCID: PMC7356914.

2. Saha SK, Islam SMR, Kwak KS, Rahman MS, Cho SG. PROM1 and PROM2 expression differentially modulates clinical prognosis of cancer: a multiomics analysis. Cancer Gene Ther. 2020 Apr;27(3-4):147-167. PubMed Central PMCID: PMC7170805.

3. Saha SK, Islam SMR, Abdullah-Al-Wadud M, Islam S, Ali F, Park KS. Multiomics Analysis Reveals that GLS and GLS2 Differentially Modulate the Clinical Outcomes of Cancer. J Clin Med. 2019 Mar 13;8(3) PubMed Central PMCID: PMC6463114.

4. Saha, S. K. †, Jong, Y. †, Cho, S., and Cho, S-G., 2018. Systematic expression alteration analysis of master reprogramming factor, octamer-binding transcription factor 4 (OCT4), in human cancer and their prognostic outcomes. Scientific Reports, 8, 14806. 

4. G protein-coupled receptors (GPCRs) in Cancer Progression and Prognosis

Our interest was in the largest family of cell surface receptor proteins and its function in cancer progression and prognosis. G-protein coupled receptors (GPCRs) contain hundreds of different types of proteins and are targeted by nearly a third of all drugs. However, some GPCRs, known as orphan GPCRs, are thought to function independently of ligands. In my research, I focus on investigating the role of an orphan GPCR called GPR50 in hepatocellular carcinoma (HCC) progression and prognosis. While previous studies have suggested that GPR50 may be involved in the reprogramming of somatic cells to cancer stem cells, its precise function in cancer is still not well understood. To explore the potential of GPR50 as a target for cancer therapy, I used the CRISPR-Cas9 system to knock out GPR50 expression in HCC cells. This led to the suppression of HCC properties via the Notch signaling pathway, independent of ligands. Additionally, I found that GPR50 regulates the transcription of ADAM17 through the AKT/SP1 signaling axis, and my Co-IP data confirmed the direct interaction between GPR50 and ADAM17. Overexpression of GPR50 in normal hepatic cells induced cancer properties through the GPR50-ADAM17-Notch signaling cascade, providing valuable insights into the development of Notch-based HCC treatment strategies.

References:

1. Saha SK, Choi HY, Yang GM, Biswas PK, Kim K, Kang GH, Gil M, Cho SG. GPR50 Promotes Hepatocellular Carcinoma Progression via the Notch Signaling Pathway through Direct Interaction with ADAM17. Mol Ther Oncolytics. 2020 Jun 26;17:332-349. PubMed Central PMCID: PMC7210388.

2. Choi HY, Saha SK, Kim K, Kim S, Yang GM, Kim B, Kim JH, Cho SG. G protein-coupled receptors in stem cell maintenance and somatic reprogramming to pluripotent or cancer stem cells. BMB Rep. 2015 Feb;48(2):68-80. PubMed Central PMCID: PMC4352616.  

Future prospective 

In the future, there is great potential for advancements in our understanding of the genetic and molecular mechanisms underlying cancer and craniofacial abnormalities. With the advent of new technologies and research methods, it is likely that we will continue to uncover new insights into the complex nature of these disorders. There is also potential for the development of more targeted and personalized treatments for cancer and craniofacial abnormalities, based on an individual's unique genetic profile and disease characteristics. Additionally, with a greater understanding of the genetic basis of these disorders, it may be possible to develop preventative measures or early intervention strategies to reduce the incidence and severity of these conditions. Overall, the future looks promising for advancements in both our understanding and treatment of cancer and craniofacial abnormalities.    

Best Paper Award: The best of Nature Cancer Gene Therapy Journal 2018-2019  

2014-2016          Recipient of a Brain Korea 21plus (BK21plus) Fellowship for doctoral (PhD) research at Konkuk University, South Korea.

2016-2017          Recipient of a Scientific Research Center (SRC) Fellowship for doctoral (PhD) research at Konkuk University, South Korea.

2017-2018          Recipient of a University-Industry Cooperation Foundation (UICF) Fellowship for post-doctoral training at Konkuk University, South Korea.

2018-2020          Recipient of a Konkuk University (KU) Research Professorship at Konkuk University, South Korea.

2019                   Recipient of Appreciation for an invited talk at 77th KSRM Annual Meeting, Hanyang University, Seoul, South Korea. 

Editorial board

2018-present     Member of the Editorial Board, Experimental and Therapeutic Medicine

2018-present     Member of the Editorial Board, CPQ Medicine Journal

2023-                  Associate Editor, Frontiers in Cell and Developmental Biology - Molecular and Cellular Pathology

2019                   Lead Guest Editor, Journal of Oncology

                           Special issue title: Molecular Reprogramming of Cancer and Cancer Stem Cells

2020                   Handling Editor, Frontiers in Genetics

2021                   Handling Editor, Frontiers in Oncology

2018-present      Member of Reviewing Board, Cancers

2018-present      Reviewer, Cancer Medicine

2018-present      Reviewer, Cells

2018-present      Reviewer, Cancer Science

2018-present      Reviewer, International Journal of Biological Markers

2018-present      Reviewer, Oncology Letters

2018-present      Reviewer, World Journal of Surgical Oncology

2018-present      Reviewer, Network Modeling Analysis in Health Informatics and Bioinformatics

2018-present      Reviewer, Cancer Chemotherapy and Pharmacology

2018-present      Reviewer, Archives of Microbiology

2018-present      Reviewer, Viruses

2018-present      Reviewer, OncoTargets and Therapy

2018-present      Reviewer, Cancer Management and Research

2018-present      Reviewer, International Journal of Molecular Sciences

2018-present      Reviewer, Experimental and Therapeutic Medicine

2018-present   Reviewer, Frontiers in Genetics

Media coverage:

For Interstitial Cystitis/Bladder Pain Syndrome Paper

1] http://news.unn.net/news/articleView.html?idxno=231487&fbclid=IwAR3pdYUVTjHQ0_5

2] http://www.dhnews.co.kr/news/articleView.html?idxno=124592

3] http://www.kyosu.net/news/articleView.html?idxno=53877&fbclid=IwAR2Ipor4iba1UQIbxONSpzYGYa80cIwtCGn9pnpHft0Ewxi1sHOq6z3O1Gc

For KRT19 and breast cancer paper

1] https://www.konkuk.ac.kr/eng/jsp/Research/research_4.jsp