Shyh-Han Tan Ph.D.

Education

National University of Singapore, B.Sc. (Hons)
National University of Singapore, Ph.D.

Biography

Dr. Tan obtained his B. Sc and Ph.D. at the National University of Singapore. For his Ph.D. thesis, he studied the transcriptional regulation of the Human Papillomavirus type-16 under the mentorship of Dr. Hans-Ulrich Bernard. He trained as a post-doctoral fellow with Dr. Mary Dasso at the NICHD, NIH, where he characterized the functional role of SUMO isopeptidase, SUSP1, in the formation of nuclear bodies. He began his research in prostate cancer with Dr. Marja Nevalainen at Georgetown University, and later at Thomas Jefferson University in Philadelphia.

At the CPDR, Dr. Tan led research that highlighted the role of ERG in blocking the differentiation of prostate epithelial cells while promoting EMT by repressing ANXA2 transcription and demonstrated the association of ANXA2 expression with higher grade and stage. These findings explain the reciprocal correlation of ERG and ANXA2 expression in prostate tumors, and suggest the potential use of ANXA2 as in the prognostic stratification of prostate cancer. He spearheaded the design, and subsequent validation and characterization of a highly specific monoclonal antibody (mAb) to detect ERG oncoprotein in prostate cancer. Application of the mAb in IHC simplified the confirmation of TMPRSS2-ERG fusion status. The mAb has been used to establish the clonal progression of ERG-positive tumors, stratify prostate cancer by ERG status, and detect ERG in vascular endothelial tumors.

His ongoing research focuses on identifying genomic signatures that contribute to ethnic disparity of prostate cancer, particularly among African American men who have higher prostate cancer incidence and mortality rates but are underrepresented in cancer research. Under the APOLLO Cancer Moonshot initiative, he co-leads a multi-disciplinary team to evaluate the proteo-genomics of prostate cancer. The goal is to identify early predictive proteogenomic signatures, biomarkers or therapeutic targets of metastatic progression that differentiate prostate cancers of African American and Caucasian American men.

Beyond the profiling of genome-wide alterations and changes in the global proteome, he is using novel approaches to understand the mechanisms underlying intratumoral heterogeneity and phenotypic diversity of prostate cancer. Ongoing projects include evaluating dysregulation of cancer driver genes and immune biomarker profiles in the tumor microenvironment using digital spatial profiling techniques, examining the role of epigenomic reprogramming in regulating EMT of prostate cancer cells and tumor progression, and integrating analyses of digital pathology, proteogenomics, and clinico-pathology data by using deep learning tools to predict survival and identify cancer subtypes.

Representative Bibliography

Schafer C, Young D, Singh H, Jayakrishnan R, Banerjee S, Song Y, Dobi A, Petrovics G, Srivastava S, Srivastava S, Sesterhenn IA, Chesnut GT, Tan SH. Development and characterization of an ETV1 rabbit monoclonal antibody for the immunohistochemical detection of ETV1 expression in cancer tissue specimens. J Immunol Methods. 2023 Jul;518:113493. doi: 10.1016/j.jim.2023.113493. Epub 2023 May 16. PMID: 37196930.

Jayakrishnan R, Schafer C, Tan SH. Prostate cancer autoantibodies - applications in diagnosis, prognosis, monitoring disease progression and immunotherapy. Am J Clin Exp Urol. 2023 Apr 15;11(2):79-102. PMID: 37168942; PMCID: PMC10165224.

Gesztes W, Schafer C, Young D, Fox J, Jiang J, Chen Y, Kuo HC, Mwamukonda KB, Dobi A, Burke AP, Moul JW, McLeod DG, Rosner IL, Petrovics G, Tan SH, Cullen J, Srivastava S, Sesterhenn IA. Focal p53 protein expression and lymphovascular invasion in primary prostate tumors predict metastatic progression. Sci Rep. 2022 Mar 30;12(1):5404. doi: 10.1038/s41598-022-08826-5. PubMed PMID: 35354846; PubMed Central PMCID: PMC8967869.

Kohaar I, Zhang X, Tan SH, Nousome D, Babcock K, Ravindranath L, Sukumar G, Mcgrath-Martinez E, Rosenberger J, Alba C, Ali A, Young D, Chen Y, Cullen J, Rosner IL, Sesterhenn IA, Dobi A, Chesnut G, Turner C, Dalgard C, Wilkerson MD, Pollard HB, Srivastava S, Petrovics G. Germline mutation landscape of DNA damage repair genes in African Americans with prostate cancer highlights potentially targetable RAD genes. Nat Commun. 2022 Mar 15;13(1):1361. doi: 10.1038/s41467-022-28945-x. PubMed PMID: 35292633; PubMed

Tan SH, Young D, Chen Y, Kuo HC, Srinivasan A, Dobi A, Petrovics G, Cullen J, Mcleod DG, Rosner IL, Srivastava S, Sesterhenn IA. Prognostic features of Annexin A2 expression in prostate cancer. Pathology. 2021 Feb;53(2):205-213. doi: 10.1016/j.pathol.2020.07.006. Epub 2020 Sep 20. PubMed PMID: 32967771; PubMed Central PMCID: PMC7855416.

Tan SH, Petrovics G, Srivastava S. Prostate Cancer Genomics: Recent Advances and the Prevailing Underrepresentation from Racial and Ethnic Minorities. Int J Mol Sci. 2018 Apr 22;19(4). doi: 10.3390/ijms19041255. Review. PubMed PMID: 29690565; PubMed Central PMCID: PMC5979433.

Petrovics G, Li H, Stümpel T, Tan SH, Young D, Katta S, Li Q, Ying K, Klocke B, Ravindranath L, Kohaar I, Chen Y, Ribli D, Grote K, Zou H, Cheng J, Dalgard CL, Zhang S, Csabai I, Kagan J, Takeda D, Loda M, Srivastava S, Scherf M, Seifert M, Gaiser T, McLeod DG, Szallasi Z, Ebner R, Werner T, Sesterhenn IA, Freedman M, Dobi A, Srivastava S. A novel genomic alteration of LSAMP associates with aggressive prostate cancer in African American men. EBioMedicine. 2015 Dec;2(12):1957-64. doi: 10.1016/j.ebiom.2015.10

Tan SH, Furusato B, Fang X, He F, Mohamed AA, Griner NB, Sood K, Saxena S, Katta S, Young D, Chen Y, Sreenath T, Petrovics G, Dobi A, McLeod DG, Sesterhenn IA, Saxena S, Srivastava S. Evaluation of ERG responsive proteome in prostate cancer. Prostate. 2014 Jan;74(1):70-89. doi: 10.1002/pros.22731. Epub 2013 Sep 21. PubMed PMID: 24115221; PubMed Central PMCID: PMC4075339.

Furusato B, Tan SH, Young D, Dobi A, Sun C, Mohamed AA, Thangapazham R, Chen Y, McMaster G, Sreenath T, Petrovics G, McLeod DG, Srivastava S, Sesterhenn IA. ERG oncoprotein expression in prostate cancer: clonal progression of ERG-positive tumor cells and potential for ERG-based stratification. Prostate Cancer Prostatic Dis. 2010 Sep;13(3):228-37. doi: 10.1038/pcan.2010.23. Epub 2010 Jun 29. PubMed PMID: 20585344; PubMed Central PMCID: PMC3010744.